Literature

This section presents a list of the latest published scientific journal articles and preprints on COVID-19 and SARS-CoV-2 where at least one author has a Spanish affiliation. Items have been fetched from an automatic daily search from Europe PMC completed with other elements manually curated and uploaded from researchers.

There are filters at your disposal to navigate the list, i.e. publications with acknowledged funding to the “Fondo COVID19” extraordinary funds. Note that some articles have additional available data that have been curated manually and as such may not be exhaustive.

You can help us enriching this section by adding new papers not listed below or available associated data to existing ones (datasets, code repositories…) by filling in this formulaire. Please make sure that the information is not already in the table below and that the publication has at least one author affiliated in Spain.

Last update: 2021-05-31
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Fondo COVID19
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2020
2021
Publication Published Year Funder Publication type Available abstract Available related data DOI Title Authors Journal
The target landscape of N4-hydroxycytidine based on its chemical neighborhood
Jordi Mestres
preprint  bioRxiv
DOI: 10.1101/2020.03.30.016485
N4-hydroxycytidine (NHC) has been recently reported to have promising antiviral activity against SARS-CoV-2. To join worldwide efforts in identifying potential drug targets against this pandemic, the target landscape of NHC was defined by extracting all known targets of its chemical neighborhood, including drugs, analogues, and metabolites, and by performing target predictions from two independent platforms, following the recent Public Health Assessment via Structural Evaluation (PHASE) protocol. The analysis provides a list of over 30 protein targets that could be useful in future design activities of new COVID-19 antivirals. The relevance for existing drugs within the same chemical space, such as remdesivir, is also discussed.
2020-04-01 2020 other preprint abstract-available data-available 10.1101/2020.03.30.016485 The target landscape of N4-hydroxycytidine based on its chemical neighborhood Jordi Mestres bioRxiv
Simulating SARS-CoV-2 epidemics by region-specific variables and modeling contact tracing app containment
Alberto Ferrari, Enrico Santus, Davide Cirillo, Miguel Ponce-de-Leon, [...], Alfonso Valencia
npj Digital Medicine, volume 4, Article number: 9 (2021)
DOI: 10.1038/s41746-020-00374-4
Targeted contact-tracing through mobile phone apps has been proposed as an instrument to help contain the spread of COVID-19 and manage the lifting of nation-wide lock-downs currently in place in USA and Europe. However, there is an ongoing debate on its potential efficacy, especially in light of region-specific demographics. We built an expanded SIR model of COVID-19 epidemics that accounts for region-specific population densities, and we used it to test the impact of a contact-tracing app in a number of scenarios. Using demographic and mobility data from Italy and Spain, we used the model to simulate scenarios that vary in baseline contact rates, population densities, and fraction of app users in the population. Our results show that, in support of efficient isolation of symptomatic cases, app-mediated contact-tracing can successfully mitigate the epidemic even with a relatively small fraction of users, and even suppress altogether with a larger fraction of users. However, when regional differences in population density are taken into consideration, the epidemic can be significantly harder to contain in higher density areas, highlighting potential limitations of this intervention in specific contexts. This work corroborates previous results in favor of app-mediated contact-tracing as mitigation measure for COVID-19, and draws attention on the importance of region-specific demographic and mobility factors to achieve maximum efficacy in containment policies.
2021-01-14 2021 other article abstract-available data-available 10.1038/s41746-020-00374-4 Simulating SARS-CoV-2 epidemics by region-specific variables and modeling contact tracing app containment Alberto Ferrari, Enrico Santus, Davide Cirillo, Miguel Ponce-de-Leon, Nicola Marino, Maria Teresa Ferretti, Antonella Santuccione Chadha, Nikolaos Mavridis, Alfonso Valencia npj Digital Medicine, volume 4, Article number: 9 (2021)
RNA-Dependent RNA Polymerase From SARS-CoV-2. Mechanism Of Reaction And Inhibition By Remdesivir
Juan Aranda, Modesto Orozco
preprint  bioRxiv
DOI: 10.1101/2020.06.21.163592
We combine sequence analysis, molecular dynamics and hybrid quantum mechanics/molecular mechanics simulations to obtain the first description of the mechanism of reaction of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and of the inhibition of the enzyme by Remdesivir. Despite its evolutionary youth, the enzyme is highly optimized to have good fidelity in nucleotide incorporation and a good catalytic efficiency. Our simulations strongly suggest that Remdesivir triphosphate (the active form of drug) is incorporated into the nascent RNA replacing ATP, leading to a duplex RNA which is structurally very similar to an unmodified one. We did not detect any reason to explain the inhibitory activity of Remdesivir at the active site. Displacement of the nascent Remdesivir-containing RNA duplex along the exit channel of the enzyme can occur without evident steric clashes which would justify delayed inhibition. However, after the incorporation of three more nucleotides we found a hydrated Serine which is placed in a perfect arrangement to react through a Pinner’s reaction with the nitrile group of Remdesivir. Kinetic barriers for crosslinking and polymerization are similar suggesting a competition between polymerization and inhibition. Analysis of SARS-CoV-2 mutational landscape and structural analysis of polymerases across different species support the proposed mechanism and suggest that virus has not explored yet resistance to Remdesivir inhibition.
2020-06-21 2020 other preprint abstract-available data-available 10.1101/2020.06.21.163592 RNA-Dependent RNA Polymerase From SARS-CoV-2. Mechanism Of Reaction And Inhibition By Remdesivir Juan Aranda, Modesto Orozco bioRxiv
MasterOfPores: A Workflow for the Analysis of Oxford Nanopore Direct RNA Sequencing Datasets
Luca Cozzuto, Huanle Liu, Leszek P. Pryszcz, Toni Hermoso Pulido, [...], Eva Maria Novoa
Front. Genet. 11:211
DOI: 10.3389/fgene.2020.00211
The direct RNA sequencing platform offered by Oxford Nanopore Technologies allows for direct measurement of RNA molecules without the need of conversion to complementary DNA, fragmentation or amplification. As such, it is virtually capable of detecting any given RNA modification present in the molecule that is being sequenced, as well as provide polyA tail length estimations at the level of individual RNA molecules. Although this technology has been publicly available since 2017, the complexity of the raw Nanopore data, together with the lack of systematic and reproducible pipelines, have greatly hindered the access of this technology to the general user. Here we address this problem by providing a fully benchmarked workflow for the analysis of direct RNA sequencing reads, termed MasterOfPores. The pipeline starts with a pre-processing module, which converts raw current intensities into multiple types of processed data including FASTQ and BAM, providing metrics of the quality of the run, quality-filtering, demultiplexing, base-calling and mapping. In a second step, the pipeline performs downstream analyses of the mapped reads, including prediction of RNA modifications and estimation of polyA tail lengths. Four direct RNA MinION sequencing runs can be fully processed and analyzed in 10 h on 100 CPUs. The pipeline can also be executed in GPU locally or in the cloud, decreasing the run time fourfold. The software is written using the NextFlow framework for parallelization and portability, and relies on Linux containers such as Docker and Singularity for achieving better reproducibility. The MasterOfPores workflow can be executed on any Unix-compatible OS on a computer, cluster or cloud without the need of installing any additional software or dependencies, and is freely available in Github (https://github.com/biocorecrg/master_of_pores). This workflow simplifies direct RNA sequencing data analyses, facilitating the study of the (epi)transcriptome at single molecule resolution.
2020-03-17 2020 other article abstract-available data-available 10.3389/fgene.2020.00211 MasterOfPores: A Workflow for the Analysis of Oxford Nanopore Direct RNA Sequencing Datasets Luca Cozzuto, Huanle Liu, Leszek P. Pryszcz, Toni Hermoso Pulido, Anna Delgado-Tejedor, Julia Ponomarenko, Eva Maria Novoa Front. Genet. 11:211
Functional characterization of SARS-CoV-2 infection suggests a complex inflammatory response and metabolic alterations
Lucía Trilla-Fuertes, Ricardo Ramos, Natalia Blanca-López, Elena López-Camacho, [...], Angelo Gámez-Pozo
preprint  bioRxiv
DOI: 10.1101/2020.06.22.164384
Covid-19, caused by the SARS-CoV-2 virus, has reached the category of a worldwide pandemic. Even though intensive efforts, no effective treatments or a vaccine are available. Molecular characterization of the transcriptional response in Covid-19 patients could be helpful to identify therapeutic targets. In this study, RNAseq data from peripheral blood mononuclear cell samples from Covid-19 patients and healthy controls was analyzed from a functional point of view using probabilistic graphical models. Two networks were built: one based on genes differentially expressed between healthy and infected individuals and another one based on the 2,000 most variable genes in terms of expression in order to make a functional characterization. In the network based on differentially expressed genes, two inflammatory response nodes with different tendencies were identified, one related to cytokines and chemokines, and another one related to bacterial infections. In addition, differences in metabolism, which were studied in depth using Flux Balance Analysis, were identified. SARS-CoV2-infection caused alterations in glutamate, methionine and cysteine, and tetrahydrobiopterin metabolism. In the network based on 2,000 most variable genes, also two inflammatory nodes with different tendencies between healthy individuals and patients were identified. Similar to the other network, one was related to cytokines and chemokines. However, the other one, lower in Covid-19 patients, was related to allergic processes and self-regulation of the immune response. Also, we identified a decrease in T cell node activity and an increase in cell division node activity. In the current absence of treatments for these patients, functional characterization of the transcriptional response to SARS-CoV-2 infection could be helpful to define targetable processes. Therefore, these results may be relevant to propose new treatments.
2020-09-24 2020 other preprint abstract-available data-available 10.1101/2020.06.22.164384 Functional characterization of SARS-CoV-2 infection suggests a complex inflammatory response and metabolic alterations Lucía Trilla-Fuertes, Ricardo Ramos, Natalia Blanca-López, Elena López-Camacho, Laura Martín-Pedraza, Pablo Ryan Murua, Mariana Díaz-Almirón, Carlos Llorens, Toni Gabaldón, Andrés Moya, Juan Ángel Fresno Vara, Angelo Gámez-Pozo bioRxiv
Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection
Carlos Loucera, Marina Esteban-Medina, Kinza Rian, Matías M. Falco, [...], María Peña-Chilet
Sig Transduct Target Ther 5, 290 (2020)
DOI: 10.1038/s41392-020-00417-y
2020-12-11 2020 other article data-available 10.1038/s41392-020-00417-y Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection Carlos Loucera, Marina Esteban-Medina, Kinza Rian, Matías M. Falco, Joaquín Dopazo, María Peña-Chilet Sig Transduct Target Ther 5, 290 (2020)
DatAC: A visual analytics platform to explore climate and air quality indicators associated with the COVID-19 pandemic in Spain
Jordi Martorell-Marugán, Juan Antonio Villatoro-García, Adrián García-Moreno, Raúl López-Domínguez, [...], Pedro Carmona-Sáez
Science of The Total Environment, Volume 750, 2021, 141424, ISSN 0048-9697
DOI: 10.1016/j.scitotenv.2020.141424
The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented global health crisis, with several countries imposing lockdowns to control the coronavirus spread. Important research efforts are focused on evaluating the association of environmental factors with the survival and spread of the virus and different works have been published, with contradictory results in some cases. Data with spatial and temporal information is a key factor to get reliable results and, although there are some data repositories for monitoring the disease both globally and locally, an application that integrates and aggregates data from meteorological and air quality variables with COVID-19 information has not been described so far to the best of our knowledge. Here, we present DatAC (Data Against COVID-19), a data fusion project with an interactive web frontend that integrates COVID-19 and environmental data in Spain. DatAC is provided with powerful data analysis and statistical capabilities that allow users to explore and analyze individual trends and associations among the provided data. Using the application, we have evaluated the impact of the Spanish lockdown on the air quality, observing that NO2, CO, PM2.5, PM10 and SO2 levels decreased drastically in the entire territory, while O3 levels increased. We observed similar trends in urban and rural areas, although the impact has been more important in the former. Moreover, the application allowed us to analyze correlations among climate factors, such as ambient temperature, and the incidence of COVID-19 in Spain. Our results indicate that temperature is not the driving factor and without effective control actions, outbreaks will appear and warm weather will not substantially limit the growth of the pandemic. DatAC is available at https://covid19.genyo.es.
2020-06-23 2020 other article abstract-available data-available 10.1016/j.scitotenv.2020.141424 DatAC: A visual analytics platform to explore climate and air quality indicators associated with the COVID-19 pandemic in Spain Jordi Martorell-Marugán, Juan Antonio Villatoro-García, Adrián García-Moreno, Raúl López-Domínguez, Francisco Requena, Juan Julián Merelo, Marina Lacasaña, Juan de Dios Luna, Juan J. Díaz-Mochón, Jose A. Lorente, Pedro Carmona-Sáez Science of The Total Environment, Volume 750, 2021, 141424, ISSN 0048-9697
COVID-19 Outcomes in 4712 consecutively confirmed SARS-CoV2 cases in the city of Madrid
Sarah Heili-Frades, Pablo Minguez, Ignacio Mahillo Fernández, Tomás Prieto-Rumeau, [...], COVID FJD-TEAM
preprint  medRxiv
DOI: 10.1101/2020.05.22.20109850
There is limited information describing features and outcomes of patients requiring hospitalization for COVID19 disease and still no treatments have clearly demonstrated efficacy. Demographics and clinical variables on admission, as well as laboratory markers and therapeutic interventions were extracted from electronic Clinical Records (eCR) in 4712 SARS-CoV2 infected patients attending 4 public Hospitals in Madrid. Patients were stratified according to age and stage of severity. Using multivariate logistic regression analysis, cut-off points that best discriminated mortality were obtained for each of the studied variables. Principal components analysis and a neural network (NN) algorithm were applied. A high mortality incidence associated to age >70, comorbidities (hypertension, neurological disorders and diabetes), altered vitals such as fever, heart rhythm disturbances or elevated systolic blood pressure, and alterations in several laboratory tests. Remarkably, analysis of therapeutic options either taken individually or in combination drew a universal relationship between the use of Cyclosporine A and better outcomes as also a benefit of tocilizumab and/or corticosteroids in critically ill patients. We present a large Spanish population-based study addressing factors influencing survival in current SARS CoV2 pandemic, with particular emphasis on the effectivity of treatments. In addition, we have generated an NN capable of identifying severity predictors of SARS CoV2. A rapid extraction and management of data protocol from eCR and artificial intelligence in-house implementations allowed us to perform almost real time monitoring of the outbreak evolution.
2020-05-29 2020 other preprint abstract-available data-available 10.1101/2020.05.22.20109850 COVID-19 Outcomes in 4712 consecutively confirmed SARS-CoV2 cases in the city of Madrid Sarah Heili-Frades, Pablo Minguez, Ignacio Mahillo Fernández, Tomás Prieto-Rumeau, Antonio Herrero González, Lorena de la Fuente, María Jesús Rodríguez Nieto, Germán Peces-Barba Romero, Mario Peces-Barba, María del Pilar Carballosa de Miguel, Itziar Fernández Ormaechea, Alba Naya prieto, Farah Ezzine de Blas, Luis Jiménez Hiscock, Cesar Perez Calvo, Arnoldo Santos, Luis Enrique Muñoz Alameda, Fredeswinda Romero Bueno, Miguel Górgolas Hernández-Mora, Alfonso Cabello Úbeda, Beatriz Álvarez Álvarez, Elizabet Petkova, Nerea Carrasco, Dolores Martín Ríos, Nicolás González Mangado, Olga Sánchez Pernaute, COVID FJD-TEAM medRxiv
COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms
Marek Ostaszewski, Alexander Mazein, Marc E. Gillespie, Inna Kuperstein, [...], Reinhard Schneider
Sci Data 7, 136 (2020)
DOI: 10.1038/s41597-020-0477-8
2020-05-05 2020 other article data-available 10.1038/s41597-020-0477-8 COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms Marek Ostaszewski, Alexander Mazein, Marc E. Gillespie, Inna Kuperstein, Anna Niarakis, Henning Hermjakob, Alexander R. Pico, Egon L. Willighagen, Chris T. Evelo, Jan Hasenauer, Falk Schreiber, Andreas Dräger, Emek Demir, Olaf Wolkenhauer, Laura I. Furlong, Emmanuel Barillot, Joaquin Dopazo, Aurelio Orta-Resendiz, Francesco Messina, Alfonso Valencia, Akira Funahashi, Hiroaki Kitano, Charles Auffray, Rudi Balling, Reinhard Schneider Sci Data 7, 136 (2020)
Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs,
Camila Pontes, Victoria Ruiz-Serra, Rosalba Lepore, Alfonso Valencia
Computational and Structural Biotechnology Journal, Volume 19, 2021, Pages 759-766, ISSN 2001-0370.
DOI: 10.1016/j.csbj.2021.01.006
The recent emergence of the novel SARS-CoV-2 in China and its rapid spread in the human population has led to a public health crisis worldwide. Like in SARS-CoV, horseshoe bats currently represent the most likely candidate animal source for SARS-CoV-2. Yet, the specific mechanisms of cross-species transmission and adaptation to the human host remain unknown. Here we show that the unsupervised analysis of conservation patterns across the β-CoV spike protein family, using sequence information alone, can provide valuable insights on the molecular basis of the specificity of β-CoVs to different host cell receptors. More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). Furthermore, by integrating structural data, in silico mutagenesis and coevolution analysis we could elucidate the role of SDPs in mediating ACE2 binding across the Sarbecovirus lineage, either by engaging the receptor through direct intermolecular interactions or by affecting the local environment of the receptor binding motif. Finally, by the analysis of coevolving mutations across a paired MSA we were able to identify key intermolecular contacts occurring at the spike-ACE2 interface. These results show that effective mining of the evolutionary records held in the sequence of the spike protein family can help tracing the molecular mechanisms behind the evolution and host-receptor adaptation of circulating and future novel β-CoVs.
2021-01-12 2021 other article abstract-available data-available 10.1016/j.csbj.2021.01.006 Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs, Camila Pontes, Victoria Ruiz-Serra, Rosalba Lepore, Alfonso Valencia Computational and Structural Biotechnology Journal, Volume 19, 2021, Pages 759-766, ISSN 2001-0370.
Mental health impact of the first wave of COVID-19 pandemic on Spanish healthcare workers: A large cross-sectional survey.
Jordi Alonso, Gemma Vilagut, Philippe Mortier, Montse Ferrer, [...], MINDCOVID Working group (2020)
Revista de psiquiatria y salud mental, S1888-9891(20)30128-2. Advance online publication.
DOI: 10.1016/j.rpsm.2020.12.001
INTRODUCTION: Healthcare workers are vulnerable to adverse mental health impacts of the COVID-19 pandemic. We assessed prevalence of mental disorders and associated factors during the first wave of the pandemic among healthcare professionals in Spain. METHODS: All workers in 18 healthcare institutions (6 AACC) in Spain were invited to web-based surveys assessing individual characteristics, COVID-19 infection status and exposure, and mental health status (May 5 - September 7, 2020). We report: probable current mental disorders (Major Depressive Disorder-MDD- [PHQ-8≥10], Generalized Anxiety Disorder-GAD- [GAD-7≥10], Panic attacks, Posttraumatic Stress Disorder -PTSD- [PCL-5≥7]; and Substance Use Disorder -SUD-[CAGE-AID≥2]. Severe disability assessed by the Sheehan Disability Scale was used to identify probable "disabling" current mental disorders. RESULTS: 9,138 healthcare workers participated. Prevalence of screen-positive disorder: 28.1% MDD; 22.5% GAD, 24.0% Panic; 22.2% PTSD; and 6.2% SUD. Overall 45.7% presented any current and 14.5% any disabling current mental disorder. Workers with pre-pandemic lifetime mental disorders had almost twice the prevalence than those without. Adjusting for all other variables, odds of any disabling mental disorder were: prior lifetime disorders (TUS: OR=5.74; 95%CI 2.53-13.03; Mood: OR=3.23; 95%CI:2.27-4.60; Anxiety: OR=3.03; 95%CI:2.53-3.62); age category 18-29 years (OR=1.36; 95%CI:1.02-1.82), caring "all of the time" for COVID-19 patients (OR=5.19; 95%CI: 3.61-7.46), female gender (OR=1.58; 95%CI: 1.27-1.96) and having being in quarantine or isolated (OR= 1.60; 95CI:1.31-1.95). CONCLUSIONS: One in seven Spanish healthcare workers screened positive for a disabling mental disorder during the first wave of the COVID-19 pandemic. Workers reporting pre-pandemic lifetime mental disorders, those frequently exposed to COVID-19 patients, infected or quarantined/isolated, female workers, and auxiliary nurses should be considered groups in need of mental health monitoring and support.
2020-12-20 2020 other article abstract-available data-available 10.1016/j.rpsm.2020.12.001 Mental health impact of the first wave of COVID-19 pandemic on Spanish healthcare workers: A large cross-sectional survey. Jordi Alonso, Gemma Vilagut, Philippe Mortier, Montse Ferrer, Itxaso Alayo, Andrés Aragón-Peña, Enric Aragonès, Mireia Campos, Isabel D. Cura-González, José I. Emparanza, Meritxell Espuga, Maria João Forjaz, Ana González-Pinto, Josep M. Haro, Nieves López-Fresneña, Alma D. Martínez de Salázar, Juan D. Molina, Rafael M. Ortí-Lucas, Mara Parellada, José Maria Pelayo-Terán, Aurora Pérez-Zapata, José I. Pijoan, Nieves Plana, Maria Teresa Puig, Cristina Rius, Carmen Rodríguez-Blázquez, Ferran Sanz, Consol Serra, Ronald C. Kessler, Ronny Bruffaerts, Eduard Vieta, Víctor Pérez-Solà, MINDCOVID Working group (2020) Revista de psiquiatria y salud mental, S1888-9891(20)30128-2. Advance online publication.
COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms
Marek Ostaszewski, Anna Niarakis, Alexander Mazein, Inna Kuperstein, [...], the COVID-19 Disease Map Community
preprint  BioRxiv
DOI: 10.1101/2020.10.26.356014
We describe a large-scale community effort to build an open-access, interoperable, and computable repository of COVID-19 molecular mechanisms - the COVID-19 Disease Map. We discuss the tools, platforms, and guidelines necessary for the distributed development of its contents by a multi-faceted community of biocurators, domain experts, bioinformaticians, and computational biologists. We highlight the role of relevant databases and text mining approaches in enrichment and validation of the curated mechanisms. We describe the contents of the Map and their relevance to the molecular pathophysiology of COVID-19 and the analytical and computational modelling approaches that can be applied for mechanistic data interpretation and predictions. We conclude by demonstrating concrete applications of our work through several use cases and highlight new testable hypotheses.
2021-02-16 2021 other preprint abstract-available data-available 10.1101/2020.10.26.356014 COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms Marek Ostaszewski, Anna Niarakis, Alexander Mazein, Inna Kuperstein, Robert Phair, Aurelio Orta-Resendiz, Vidisha Singh, Sara Sadat Aghamiri, Marcio Luis Acencio, Enrico Glaab, Andreas Ruepp, Gisela Fobo, Corinna Montrone, Barbara Brauner, Goar Frishman, Luis Cristóbal Monraz Gómez, Julia Somers, Matti Hoch, Shailendra Kumar Gupta, Julia Scheel, Hanna Borlinghaus, Tobias Czauderna, Falk Schreiber, Arnau Montagud, Miguel Ponce de Leon, Akira Funahashi, Yusuke Hiki, Noriko Hiroi, Takahiro G. Yamada, Andreas Dräger, Alina Renz, Muhammad Naveez, Zsolt Bocskei, Francesco Messina, Daniela Börnigen, Liam Fergusson, Marta Conti, Marius Rameil, Vanessa Nakonecnij, Jakob Vanhoefer, Leonard Schmiester, Muying Wang, Emily E. Ackerman, Jason Shoemaker, Jeremy Zucker, Kristie Oxford, Jeremy Teuton, Ebru Kocakaya, Gökçe Yağmur Summak, Kristina Hanspers, Martina Kutmon, Susan Coort, Lars Eijssen, Friederike Ehrhart, D. A. B. Rex, Denise Slenter, Marvin Martens, Nhung Pham, Robin Haw, Bijay Jassal, Lisa Matthews, Marija Orlic-Milacic, Andrea Senff Ribeiro, Karen Rothfels, Veronica Shamovsky, Ralf Stephan, Cristoffer Sevilla, Thawfeek Varusai, Jean-Marie Ravel, Rupsha Fraser, Vera Ortseifen, Silvia Marchesi, Piotr Gawron, Ewa Smula, Laurent Heirendt, Venkata Satagopam, Guanming Wu, Anders Riutta, Martin Golebiewski, Stuart Owen, Carole Goble, Xiaoming Hu, Rupert W. Overall, Dieter Maier, Angela Bauch, Benjamin M. Gyori, John A. Bachman, Carlos Vega, Valentin Grouès, Miguel Vazquez, Pablo Porras, Luana Licata, Marta Iannuccelli, Francesca Sacco, Anastasia Nesterova, Anton Yuryev, Anita de Waard, Denes Turei, Augustin Luna, Ozgun Babur, Sylvain Soliman, Alberto Valdeolivas, Marina Esteban-Medina, Maria Peña-Chilet, Kinza Rian, Tomáš Helikar, Bhanwar Lal Puniya, Dezso Modos, Agatha Treveil, Marton Olbei, Bertrand De Meulder, Aurélien Dugourd, Aurélien Naldi, Vincent Noël, Laurence Calzone, Chris Sander, Emek Demir, Tamas Korcsmaros, Tom C. Freeman, Franck Augé, Jacques S. Beckmann, Jan Hasenauer, Olaf Wolkenhauer, Egon L. Wilighagen, Alexander R. Pico, Chris T. Evelo, Marc E. Gillespie, Lincoln D. Stein, Henning Hermjakob, Peter D’Eustachio, Julio Saez-Rodriguez, Joaquin Dopazo, Alfonso Valencia, Hiroaki Kitano, Emmanuel Barillot, Charles Auffray, Rudi Balling, Reinhard Schneider, the COVID-19 Disease Map Community BioRxiv
Update of the current knowledge on genetics, evolution, immunopathogenesis, and transmission for coronavirus disease 19 (COVID-19).
Tizaoui K, Zidi I, Lee KH, Ghayda RA, [...], Shin JI.
Int J Biol Sci. 2020; 16 (15)
DOI: 10.7150/ijbs.48812
In December 2019, an acute respiratory disease caused by novel species of coronavirus (SARS-CoV-2), emerged in China and has spread throughout the world. On 11th March 2020, the World Health Organization (WHO) officially declared coronavirus disease 19 (COVID-19) a pandemic, severe coronavirus-mediated human disease. Based on genomic and phylogenetic studies, SARS-CoV-2 might originate from bat coronaviruses and infects humans directly or through intermediate zoonotic hosts. However, the exact origin or the host intermediate remains unknown. Genetically, SARS-CoV-2 is similar to several existing coronaviruses, particularly SARS-CoV, but differs by silent and non-silent mutations. The virus uses different transmission routes and targets cells and tissues with angiotensin-converting enzyme 2 (ACE2) protein, which makes it contagious. COVID-19 shares both the main clinical features and excessive/dysregulated cell responses with the two previous Middle East respiratory syndrome coronavirus (MERS) and severe acute respiratory syndrome coronavirus (SARS) epidemics. In this review, we provide an update of the current knowledge on the COVID-19 pandemic. Gaining a deeper understanding of SARS-CoV-2 structure, transmission routes, and molecular responses, will assist in the prevention and control of COVID-19 outbreaks in the future.
2020-09-12 2020 other review-article; Review; Journal Article abstract-available 10.7150/ijbs.48812 Update of the current knowledge on genetics, evolution, immunopathogenesis, and transmission for coronavirus disease 19 (COVID-19). Tizaoui K, Zidi I, Lee KH, Ghayda RA, Hong SH, Li H, Smith L, Koyanagi A, Jacob L, Kronbichler A, Shin JI. Int J Biol Sci. 2020; 16 (15)
Emergence of Bat-Related Betacoronaviruses: Hazard and Risks.
Frutos R, Serra-Cobo J, Pinault L, Lopez Roig M, [...], Devaux CA.
Front Microbiol. 2021; 12
DOI: 10.3389/fmicb.2021.591535
The current Coronavirus Disease 2019 (COVID-19) pandemic, with more than 111 million reported cases and 2,500,000 deaths worldwide (mortality rate currently estimated at 2.2%), is a stark reminder that coronaviruses (CoV)-induced diseases remain a major threat to humanity. COVID-19 is only the latest case of betacoronavirus (β-CoV) epidemics/pandemics. In the last 20 years, two deadly CoV epidemics, Severe Acute Respiratory Syndrome (SARS; fatality rate 9.6%) and Middle East Respiratory Syndrome (MERS; fatality rate 34.7%), plus the emergence of HCoV-HKU1 which causes the winter common cold (fatality rate 0.5%), were already a source of public health concern. Betacoronaviruses can also be a threat for livestock, as evidenced by the Swine Acute Diarrhea Syndrome (SADS) epizootic in pigs. These repeated outbreaks of β-CoV-induced diseases raise the question of the dynamic of propagation of this group of viruses in wildlife and human ecosystems. SARS-CoV, SARS-CoV-2, and HCoV-HKU1 emerged in Asia, strongly suggesting the existence of a regional hot spot for emergence. However, there might be other regional hot spots, as seen with MERS-CoV, which emerged in the Arabian Peninsula. β-CoVs responsible for human respiratory infections are closely related to bat-borne viruses. Bats are present worldwide and their level of infection with CoVs is very high on all continents. However, there is as yet no evidence of direct bat-to-human coronavirus infection. Transmission of β-CoV to humans is considered to occur accidentally through contact with susceptible intermediate animal species. This zoonotic emergence is a complex process involving not only bats, wildlife and natural ecosystems, but also many anthropogenic and societal aspects. Here, we try to understand why only few hot spots of β-CoV emergence have been identified despite worldwide bats and bat-borne β-CoV distribution. In this work, we analyze and compare the natural and anthropogenic environments associated with the emergence of β-CoV and outline conserved features likely to create favorable conditions for a new epidemic. We suggest monitoring South and East Africa as well as South America as these regions bring together many of the conditions that could make them future hot spots.
2021-03-15 2021 other review-article; Review; Journal Article abstract-available 10.3389/fmicb.2021.591535 Emergence of Bat-Related Betacoronaviruses: Hazard and Risks. Frutos R, Serra-Cobo J, Pinault L, Lopez Roig M, Devaux CA. Front Microbiol. 2021; 12
Searching PubMed to Retrieve Publications on the COVID-19 Pandemic: Comparative Analysis of Search Strings.
Lazarus JV, Palayew A, Rasmussen LN, Andersen TH, [...], Norgaard O.
J Med Internet Res. 2020; 22 (11)
DOI: 10.2196/23449

Background

Since it was declared a pandemic on March 11, 2020, COVID-19 has dominated headlines around the world and researchers have generated thousands of scientific articles about the disease. The fast speed of publication has challenged researchers and other stakeholders to keep up with the volume of published articles. To search the literature effectively, researchers use databases such as PubMed.

Objective

The aim of this study is to evaluate the performance of different searches for COVID-19 records in PubMed and to assess the complexity of searches required.

Methods

We tested PubMed searches for COVID-19 to identify which search string performed best according to standard metrics (sensitivity, precision, and F-score). We evaluated the performance of 8 different searches in PubMed during the first 10 weeks of the COVID-19 pandemic to investigate how complex a search string is needed. We also tested omitting hyphens and space characters as well as applying quotation marks.

Results

The two most comprehensive search strings combining several free-text and indexed search terms performed best in terms of sensitivity (98.4%/98.7%) and F-score (96.5%/95.7%), but the single-term search COVID-19 performed best in terms of precision (95.3%) and well in terms of sensitivity (94.4%) and F-score (94.8%). The term Wuhan virus performed the worst: 7.7% for sensitivity, 78.1% for precision, and 14.0% for F-score. We found that deleting a hyphen or space character could omit a substantial number of records, especially when searching with SARS-CoV-2 as a single term.

Conclusions

Comprehensive search strings combining free-text and indexed search terms performed better than single-term searches in PubMed, but not by a large margin compared to the single term COVID-19. For everyday searches, certain single-term searches that are entered correctly are probably sufficient, whereas more comprehensive searches should be used for systematic reviews. Still, we suggest additional measures that the US National Library of Medicine could take to support all PubMed users in searching the COVID-19 literature.
2020-11-26 2020 other research-article; Journal Article abstract-available 10.2196/23449 Searching PubMed to Retrieve Publications on the COVID-19 Pandemic: Comparative Analysis of Search Strings. Lazarus JV, Palayew A, Rasmussen LN, Andersen TH, Nicholson J, Norgaard O. J Med Internet Res. 2020; 22 (11)
Should we discount the laboratory origin of COVID-19?
Segreto R, Deigin Y, McCairn K, Sousa A, [...], Zhang D.
Environ Chem Lett. 2021;
DOI: 10.1007/s10311-021-01211-0
2021-03-25 2021 other Editorial 10.1007/s10311-021-01211-0 Should we discount the laboratory origin of COVID-19? Segreto R, Deigin Y, McCairn K, Sousa A, Sirotkin D, Sirotkin K, Couey JJ, Jones A, Zhang D. Environ Chem Lett. 2021;
The Other Side of SARS-CoV-2 Infection: Neurological Sequelae in Patients.
Alonso-Bellido IM, Bachiller S, Vázquez G, Cruz-Hernández L, [...], Ruiz R.
Front Aging Neurosci. 2021; 13
DOI: 10.3389/fnagi.2021.632673
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the globe causing coronavirus disease 2019 (COVID-19). Because it affects the respiratory system, common symptoms are cough and breathing difficulties with fever and fatigue. Also, some cases progress to acute respiratory distress syndrome (ARDS). The acute phase of COVID-19 has been also related to nervous system symptoms, including loss of taste and smell as well as encephalitis and cerebrovascular disorders. However, it remains unclear if neurological complications are due to the direct viral infection of the nervous system, or they appear as a consequence of the immune reaction against the virus in patients who presented pre-existing deficits or had a certain detrimental immune response. Importantly, the medium and long-term consequences of the infection by SARS-CoV-2 in the nervous system remain at present unknown. This review article aims to give an overview of the current neurological symptoms associated with COVID-19, as well as attempting to provide an insight beyond the acute affectation.
2021-04-06 2021 other research-article; Journal Article abstract-available 10.3389/fnagi.2021.632673 The Other Side of SARS-CoV-2 Infection: Neurological Sequelae in Patients. Alonso-Bellido IM, Bachiller S, Vázquez G, Cruz-Hernández L, Martínez E, Ruiz-Mateos E, Deierborg T, Venero JL, Real LM, Ruiz R. Front Aging Neurosci. 2021; 13
Oral antiseptics against coronavirus: in-vitro and clinical evidence.
Mateos-Moreno MV, Mira A, Ausina-Márquez V, Ferrer MD.
J Hosp Infect. 2021; 113
DOI: 10.1016/j.jhin.2021.04.004
Angiotensin converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2, so ACE2-expressing cells can act as target cells and are susceptible to infection. ACE2 receptors are highly expressed in the oral cavity, so this may be a potential high-risk route for SARS-CoV-2 infection. Furthermore, the virus can be detected in saliva, even before COVID-19 symptoms appear, with the consequent high risk of virus transmission in asymptomatic/presymptomatic patients. Reducing oral viral load could lead to a lower risk of transmission via salivary droplets or aerosols and therefore contribute to the control of the pandemic. Our aim was to evaluate the available evidence testing the in-vitro and in-vivo effects of oral antiseptics to inactivate or eradicate coronaviruses. The criteria used were those described in the PRISMA declaration for performing systematic reviews. An electronic search was conducted in Medline (via PubMed) and in Web of Sciences, using the MeSH terms: 'mouthwash' OR 'oral rinse' OR 'mouth rinse' OR 'povidone iodine' OR 'hydrogen peroxide' OR 'cetylpyridinium chloride' AND 'COVID-19' OR 'SARS-CoV-2' OR 'coronavirus' OR 'SARS' OR 'MERS'. The initial search strategy identified 619 articles on two electronic databases. Seventeen articles were included assessing the virucidal efficacy of oral antiseptics against coronaviruses. In conclusion, there is sufficient in-vitro evidence to support the use of antiseptics to potentially reduce the viral load of SARS-CoV-2 and other coronaviruses. However, in-vivo evidence for most oral antiseptics is limited. Randomized clinical trials with a control group are needed to demonstrate its clinical efficacy.
2021-04-15 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.jhin.2021.04.004 Oral antiseptics against coronavirus: in-vitro and clinical evidence. Mateos-Moreno MV, Mira A, Ausina-Márquez V, Ferrer MD. J Hosp Infect. 2021; 113
The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak.
Lauxmann MA, Santucci NE, Autrán-Gómez AM.
Int Braz J Urol. 2020; 46 (suppl.1)
DOI: 10.1590/s1677-5538.ibju.2020.s101
The SARS-CoV-2, a newly identified β-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain, Italy, United Kingdom, Russia, France and Germany with over 223.000, 218.000, 215.000, 209.000, 176.000, and 171.000 cases, respectively.
2020-07-01 2020 other review-article; Review; Journal Article abstract-available 10.1590/s1677-5538.ibju.2020.s101 The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak. Lauxmann MA, Santucci NE, Autrán-Gómez AM. Int Braz J Urol. 2020; 46 (suppl.1)
Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates
Fakhri S, Nouri Z, Moradi S, Akkol E, [...], Echeverría J.
Molecules. 2021; 26 (10)
DOI:
Due to the complicated pathogenic pathways of coronavirus disease 2019 (COVID-19), related medicinal therapies have remained a clinical challenge. COVID-19 highlights the urgent need to develop mechanistic pathogenic pathways and effective agents for preventing/treating future epidemics. As a result, the destructive pathways of COVID-19 are in the line with clinical symptoms induced by severe acute coronary syndrome (SARS), including lung failure and pneumonia. Accordingly, revealing the exact signaling pathways, including inflammation, oxidative stress, apoptosis, and autophagy, as well as relative representative mediators such as tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), Bax/caspases, and Beclin/LC3, respectively, will pave the road for combating COVID-19. Prevailing host factors and multiple steps of SARS-CoV-2 attachment/entry, replication, and assembly/release would be hopeful strategies against COVID-19. This is a comprehensive review of the destructive signaling pathways and host–pathogen interaction of SARS-CoV-2, as well as related therapeutic targets and treatment strategies, including potential natural products-based candidates.
2021-05-01 2021 other review-article; Review; Journal Article abstract-available Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates Fakhri S, Nouri Z, Moradi S, Akkol E, Piri S, Sobarzo-Sánchez E, Farzaei M, Echeverría J. Molecules. 2021; 26 (10)
Immunological and physiopathological approach of COVID-19 in pregnancy.
Ferrer-Oliveras R, Mendoza M, Capote S, Pratcorona L, [...], Alijotas-Reig J.
Arch Gynecol Obstet. 2021; 304 (1)
DOI: 10.1007/s00404-021-06061-3
Coronavirus disease-2019 (COVID-19) related to Coronavirus-2 (SARS-CoV-2) is a worldwide health concern. Despite the majority of patients will evolve asymptomatic or mild-moderate upper respiratory tract infections, 20% will develop severe disease. Based on current pathogenetic knowledge, a severe COVID-19 form is mainly a hyperinflammatory, immune-mediated disorder, triggered by a viral infection. Due to their particular immunological features, pregnant women are supposed to be particularly susceptible to complicate by intracellular infections as well as immunological disturbances. As an example, immune-thrombosis has been identified as a common immune-mediated and pathogenic phenomenon both in COVID-19, in obstetric diseases and in COVID-19 pregnant women. According to extensive published clinical data, is rationale to expect an interference with the normal development of pregnancy in selected SARS-CoV-2-infected cases, mainly during third trimester.This manuscript provides insights of research to elucidate the potential harmful responses to SARS-CoV-2 and /or other coronavirus infections, as well as bidirectional interactions between COVID-19 and pregnancy to improve their respective management.
2021-05-04 2021 other review-article; Review; Journal Article abstract-available 10.1007/s00404-021-06061-3 Immunological and physiopathological approach of COVID-19 in pregnancy. Ferrer-Oliveras R, Mendoza M, Capote S, Pratcorona L, Esteve-Valverde E, Cabero-Roura L, Alijotas-Reig J. Arch Gynecol Obstet. 2021; 304 (1)
The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.
Osuchowski MF, Winkler MS, Skirecki T, Cajander S, [...], Rubio I.
Lancet Respir Med. 2021;
DOI: 10.1016/s2213-2600(21)00218-6
The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-inflammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.
2021-05-06 2021 other review-article; Review; Journal Article abstract-available 10.1016/s2213-2600(21)00218-6 The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Osuchowski MF, Winkler MS, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G, Monneret G, Venet F, Bauer M, Brunkhorst FM, Weis S, Garcia-Salido A, Kox M, Cavaillon JM, Uhle F, Weigand MA, Flohé SB, Wiersinga WJ, Almansa R, de la Fuente A, Martin-Loeches I, Meisel C, Spinetti T, Schefold JC, Cilloniz C, Torres A, Giamarellos-Bourboulis EJ, Ferrer R, Girardis M, Cossarizza A, Netea MG, van der Poll T, Bermejo-Martín JF, Rubio I. Lancet Respir Med. 2021;
Treatment and research lines for the patient with COVID-19. What do we have and where are we going?
Gotera C.
Int Braz J Urol. 2020; 46 (suppl.1)
DOI: 10.1590/s1677-5538.ibju.2020.s118
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the most significant global public health crisis of this generation. From the beginning of the pandemic, several publications and on-line resources about different treatment lines have been done, and development effort in response to the COVID-19 pandemic to investigate potential therapies is unprecedented. Unfortunately, until now, there is not enough evidence to recommend any specific anti-COVID19 treatment. Randomized clinical trials and high-quality evidence, even in the middle of a pandemic, are needed. We provide a review of the latest published literature on the therapeutic strategies and current investigational lines for SARS-CoV-2.
2020-07-01 2020 other review-article; Review; Journal Article abstract-available 10.1590/s1677-5538.ibju.2020.s118 Treatment and research lines for the patient with COVID-19. What do we have and where are we going? Gotera C. Int Braz J Urol. 2020; 46 (suppl.1)
Protection against COVID-19 in African population: Immunology, genetics, and malaria clues for therapeutic targets.
Altable M, de la Serna JM.
Virus Res. 2021; 299
DOI: 10.1016/j.virusres.2021.198347

Background

There is a marked discrepancy between SARS-CoV-2 seroprevalence and COVID-19 cases and deaths in Africa. MAIN: SARS-CoV-2 stimulates humoral and cellular immunity systems, as well as mitogen-activated protein kinase (MAPK) and nuclear NF-kB signalling pathways, which regulate inflammatory gene expression and immune cell differentiation. The result is pro-inflammatory cytokines release, hyperinflammatory condition, and cytokine storm, which provoke severe lung alterations that can lead to multi-organ failure in COVID-19. Multiple genetic and immunologic factors may contribute to the severity of COVID-19 in African individuals when compared to the rest of the global population. In this article, the role of malaria, NF-kB and MAPK pathways, caspase-12 expression, high level of LAIR-1-containing antibodies, and differential glycophorins (GYPA/B) expression in COVID-19 are discussed.

Conclusion

Understanding pathophysiological mechanisms can help identify target points for drugs and vaccines development against COVID-19. To our knowledge, this is the first study that explores this link and proposes a biological and molecular answer to the epidemiologic discrepancy in COVID-19 in Africa.
2021-02-22 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.virusres.2021.198347 Protection against COVID-19 in African population: Immunology, genetics, and malaria clues for therapeutic targets. Altable M, de la Serna JM. Virus Res. 2021; 299
Rhabdomyolysis as the main manifestation of coronavirus disease 2019.
Rivas-García S, Bernal J, Bachiller-Corral J.
Rheumatology (Oxford). 2020; 59 (8)
DOI: 10.1093/rheumatology/keaa351
2020-08-01 2020 other Letter; Comment 10.1093/rheumatology/keaa351 Rhabdomyolysis as the main manifestation of coronavirus disease 2019. Rivas-García S, Bernal J, Bachiller-Corral J. Rheumatology (Oxford). 2020; 59 (8)
The sharing of research data facing the COVID-19 pandemic.
Lucas-Dominguez R, Alonso-Arroyo A, Vidal-Infer A, Aleixandre-Benavent R.
Scientometrics. 2021;
DOI: 10.1007/s11192-021-03971-6
During the previous Ebola and Zika outbreaks, researchers shared their data, allowing many published epidemiological studies to be produced only from open research data, to speed up investigations and control of these infections. This study aims to evaluate the dissemination of the COVID-19 research data underlying scientific publications. Analysis of COVID-19 publications from December 1, 2019, to April 30, 2020, was conducted through the PubMed Central repository to evaluate the research data available through its publication as supplementary material or deposited in repositories. The PubMed Central search generated 5,905 records, of which 804 papers included complementary research data, especially as supplementary material (77.4%). The most productive journals were The New England Journal of Medicine, The Lancet and The Lancet Infectious Diseases, the most frequent keyword was pneumonia, and the most used repositories were GitHub and GenBank. An expected growth in the number of published articles following the course of the pandemics is confirmed in this work, while the underlying research data are only 13.6%. It can be deduced that data sharing is not a common practice, even in health emergencies, such as the present one. High-impact generalist journals have accounted for a large share of global publishing. The topics most often covered are related to epidemiological and public health concepts, genetics, virology and respiratory diseases, such as pneumonia. However, it is essential to interpret these data with caution following the evolution of publications and their funding in the coming months.
2021-04-26 2021 other research-article; Journal Article abstract-available 10.1007/s11192-021-03971-6 The sharing of research data facing the COVID-19 pandemic. Lucas-Dominguez R, Alonso-Arroyo A, Vidal-Infer A, Aleixandre-Benavent R. Scientometrics. 2021;
SARS-CoV-2: what it is, how it acts, and how it manifests in imaging studies☆ SARS-CoV-2: cómo es, cómo actúa y cómo se expresa en la imagen
Fernández-Pérez G, Oñate Miranda M, Fernández-Rodríguez P, Velasco Casares M, [...], Oñate Cuchat J.
Radiologi´a. 2021; 63 (2)
DOI:
COVID-19 is a disease with many clinical, biochemical, and radiological signs that has a predilection for the lungs, probably because of the high number of ACE-2 receptors in this organ. The infection of cells activates proinflammatory substances, causing diffuse alveolar damage, which is the histopathological basis of ARDS. The exudative phase would manifest as ground-glass opacities and consolidation, and the proliferative phase would manifest as a tendency toward a more linear morphology. Both CT and PET/CT findings support the inflammatory character of the lung lesions in the initial phase of the disease and in patients with mild-moderate disease. Severe cases have pulmonary hypoperfusion that is likely due to abnormal alveolar ventilation and perfusion. On the other hand, a prothrombotic state increases the risk of thromboembolic disease through the activation of coagulation and platelet pathways with the production of fibrin degradation products (D-dimer) and consumption of platelets.
2021-01-01 2021 other research-article; Journal Article abstract-available SARS-CoV-2: what it is, how it acts, and how it manifests in imaging studies☆ SARS-CoV-2: cómo es, cómo actúa y cómo se expresa en la imagen Fernández-Pérez G, Oñate Miranda M, Fernández-Rodríguez P, Velasco Casares M, Corral de la Calle M, Franco López Á, Díez Blanco M, Oñate Cuchat J. Radiologi´a. 2021; 63 (2)
Reinfección por SARS-CoV-2: la primera en una familia reportada en España Reinfection by SARS-CoV-2: the first one in a family reported in Spain.
Aguilar-Shea A, Gutiérrez-Martín-Arroyo J, Vacas-Córdoba M, Gallardo-Mayo C.
Med Clin (Barc). 2021;
DOI:
2021-05-07 2021 other Letter Reinfección por SARS-CoV-2: la primera en una familia reportada en España Reinfection by SARS-CoV-2: the first one in a family reported in Spain. Aguilar-Shea A, Gutiérrez-Martín-Arroyo J, Vacas-Córdoba M, Gallardo-Mayo C. Med Clin (Barc). 2021;
The soluble catalytic ectodomain of ACE2 a biomarker of cardiac remodelling: new insights for heart failure and COVID19.
García-Escobar A, Jiménez-Valero S, Galeote G, Jurado-Román A, [...], Moreno R.
Heart Fail Rev. 2021; 26 (4)
DOI: 10.1007/s10741-020-10066-6
The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that was discovered two decades ago. The ACE2 exists as a transmembrane protein and as a soluble catalytic ectodomain of ACE2, also known as the soluble ACE2 that can be found in plasma and other body fluids. ACE2 regulates the local actions of the renin-angiotensin system in cardiovascular tissues, and the ACE2/Angiotensin 1-7 axis exerts protective actions in cardiovascular disease. Increasing soluble ACE2 has been associated with heart failure, cardiovascular disease, and cardiac remodelling. This is a review of the molecular structure and biochemical functions of the ACE2, as well we provided an updated on the evidence, clinical applications, and emerging potential therapies with the ACE2 in heart failure, cardiovascular disease, lung injury, and COVID-19 infection.
2021-01-06 2021 other review-article; Review; Journal Article abstract-available 10.1007/s10741-020-10066-6 The soluble catalytic ectodomain of ACE2 a biomarker of cardiac remodelling: new insights for heart failure and COVID19. García-Escobar A, Jiménez-Valero S, Galeote G, Jurado-Román A, García-Rodríguez J, Moreno R. Heart Fail Rev. 2021; 26 (4)
The Renin-Angiotensin-Aldosterone System and Coronavirus Disease 2019.
Coto E, Avanzas P, Gómez J.
Eur Cardiol. 2021; 16
DOI: 10.15420/ecr.2020.30
The renin-aldosterone-angiotensin system (RAAS) plays an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2 and the host's expression of this membrane-bound protein could affect susceptibility to infection. The RAAS is an important regulator of cardiovascular physiology and ACE2 has an essential role. People with hypertension and other traits have shown to have an imbalance in ACE/ACE2 levels and reduced levels of ACE2 could enhance the risk of adverse outcome in patients with COVID-19. It has been hypothesised that the RAAS may mediate the interplay between cardiovascular disease and COVID-19 severity. Evidence shows that antihypertensive drugs that target the RAAS have no significant effect on the risk of infection and disease outcome. Variations in RAAS genes have been associated with the risk of developing hypertension and cardiovascular disease and could partly explain the heterogenous response to SARS-CoV-2 infection. This article explores the interplay between the RAAS and COVID-19, with emphasis on the possible relationship between genetic variations and disease severity.
2021-02-01 2021 other review-article; Review; Journal Article abstract-available 10.15420/ecr.2020.30 The Renin-Angiotensin-Aldosterone System and Coronavirus Disease 2019. Coto E, Avanzas P, Gómez J. Eur Cardiol. 2021; 16
Efficacy of Phytochemicals Derived from Avicennia officinalis for the Management of COVID-19: A Combined In Silico and Biochemical Study.
Mahmud S, Paul GK, Afroze M, Islam S, [...], Simal-Gandara J.
Molecules. 2021; 26 (8)
DOI: 10.3390/molecules26082210
The recent coronavirus disease 2019 (COVID-19) pandemic is a global threat for healthcare management and the economic system, and effective treatments against the pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for this disease have not yet progressed beyond the developmental phases. As drug refinement and vaccine progression require enormously broad investments of time, alternative strategies are urgently needed. In this study, we examined phytochemicals extracted from Avicennia officinalis and evaluated their potential effects against the main protease of SARS-CoV-2. The antioxidant activities of A. officinalis leaf and fruit extracts at 150 µg/mL were 95.97% and 92.48%, respectively. Furthermore, both extracts displayed low cytotoxicity levels against Artemia salina. The gas chromatography-mass spectroscopy analysis confirmed the identifies of 75 phytochemicals from both extracts, and four potent compounds, triacontane, hexacosane, methyl linoleate, and methyl palminoleate, had binding free energy values of -6.75, -6.7, -6.3, and -6.3 Kcal/mol, respectively, in complexes with the SARS-CoV-2 main protease. The active residues Cys145, Met165, Glu166, Gln189, and Arg188 in the main protease formed non-bonded interactions with the screened compounds. The root-mean-square difference (RMSD), root-mean-square fluctuations (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond data from a molecular dynamics simulation study confirmed the docked complexes' binding rigidity in the atomistic simulated environment. However, this study's findings require in vitro and in vivo validation to ensure the possible inhibitory effects and pharmacological efficacy of the identified compounds.
2021-04-12 2021 other research-article; Journal Article abstract-available 10.3390/molecules26082210 Efficacy of Phytochemicals Derived from <i>Avicennia officinalis</i> for the Management of COVID-19: A Combined In Silico and Biochemical Study. Mahmud S, Paul GK, Afroze M, Islam S, Gupt SBR, Razu MH, Biswas S, Zaman S, Uddin MS, Khan M, Cacciola NA, Emran TB, Saleh MA, Capasso R, Simal-Gandara J. Molecules. 2021; 26 (8)
Plitidepsin: a Repurposed Drug for the Treatment of COVID-19.
Martinez MA.
Antimicrob Agents Chemother. 2021; 65 (4)
DOI: 10.1128/aac.00200-21
Finding antivirals to reduce coronavirus disease 2019 (COVID-19) morbidity and mortality has been challenging. Large randomized clinical trials that aimed to test four repurposed drugs, hydroxychloroquine, lopinavir-ritonavir, interferon beta 1a, and remdesivir, have shown that these compounds lack an impact on the COVID-19 course. Although the phase III COVID-19 vaccine trial results are encouraging, the search for effective COVID-19 therapeutics should not stop. Recently, plitidepsin (aplidin) demonstrated highly effective preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its antiviral activity was 27.5-fold more potent than that of remdesivir (K. M. White, R. Rosales, S. Yildiz, T. Kehrer, et al., Science, 2021, https://science.sciencemag.org/content/early/2021/01/22/science.abf4058). Plitidepsin, a repurposed drug developed for the treatment of multiple myeloma, targets the host translation cofactor eEF1A. Plitidepsin has shown efficacy in animal models and phase I/II human trials. Although plitidepsin is administered intravenously and its toxicity profile remains to be fully characterized, this compound may be a promising alternative COVID-19 therapeutic.
2021-03-18 2021 other article-commentary; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1128/aac.00200-21 Plitidepsin: a Repurposed Drug for the Treatment of COVID-19. Martinez MA. Antimicrob Agents Chemother. 2021; 65 (4)
Flavonoids against the SARS-CoV-2 induced inflammatory storm.
Liskova A, Samec M, Koklesova L, Samuel SM, [...], Kubatka P.
Biomed Pharmacother. 2021; 138
DOI: 10.1016/j.biopha.2021.111430
The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CLpro) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities.
2021-02-25 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.biopha.2021.111430 Flavonoids against the SARS-CoV-2 induced inflammatory storm. Liskova A, Samec M, Koklesova L, Samuel SM, Zhai K, Al-Ishaq RK, Abotaleb M, Nosal V, Kajo K, Ashrafizadeh M, Zarrabi A, Brockmueller A, Shakibaei M, Sabaka P, Mozos I, Ullrich D, Prosecky R, La Rocca G, Caprnda M, Büsselberg D, Rodrigo L, Kruzliak P, Kubatka P. Biomed Pharmacother. 2021; 138
Pruebas Diagnosticas Covid-19: Importancia Del Contexto Clinico Covid-19 Diagnostic Tests: Importance Of The Clinical Context
Muntadas M, Sunyer I, Agustí A.
Med Clin (Barc). 2021;
DOI:
La actual pandemia de SARS-CoV-2 plantea numerosos retos sanitarios, entre los que destaca el uso adecuado e interpretación correcta de las pruebas diagnósticas disponibles en diferentes contextos clínicos. Como cualquier prueba diagnóstica, las de SARS-CoV-2 tienen limitaciones metodológicas de sensibilidad (S) y especificidad (E) que determinan su valor predictivo positivo (VPP) y negativo (VPN). Además, su rendimiento diagnóstico depende del contexto clínico en el que se evalúen, es decir de la probabilidad pretest. Este artículo revisa los principales aspectos metodológicos que influyen sobre la S, E, VPP y VPN de las pruebas diagnósticas de SARS-CoV-2 más habituales y discute su interpretación diagnóstica en diferentes escenarios clínicos.
2021-05-06 2021 other review-article; Review; Journal Article abstract-available Pruebas Diagnosticas Covid-19: Importancia Del Contexto Clinico Covid-19 Diagnostic Tests: Importance Of The Clinical Context Muntadas M, Sunyer I, Agustí A. Med Clin (Barc). 2021;
A Pandemic within Other Pandemics. When a Multiple Infection of a Host Occurs: SARS-CoV-2, HIV and Mycobacterium tuberculosis
González-Domenech C, Pérez-Hernández I, Gómez-Ayerbe C, Viciana Ramos I, [...], Santos J.
Viruses. 2021; 13 (5)
DOI:
By the middle of 2021, we are still immersed in the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The concurrence of this new pandemic in regions where human immunodeficiency virus (HIV) and tuberculosis (TB) infections possess the same epidemiological consideration, has arisen concerns about the prognosis, clinical management, symptomatology, and treatment of patients with triple infection. At the same time, healthcare services previously devoted to diagnosis and treatment of TB and HIV are being jeopardized by the urgent need of resources and attention for COVID-19 patients. The aim of this review was to collect any article considering the three conditions (HIV, TB, and SARS-CoV-2), included in PubMed/Medline and published in the English language since the beginning of the COVID-19 pandemic. We focused on detailed descriptions of the unusual cases describing the three co-infections. Eighty-four out of 184 publications retrieved met our inclusion criteria, but only three of them reported cases (five in total) with the three concomitant infections. The clinical evolution, management, and therapy of all of them were not different from mild/severe cases with exclusive COVID-19; the outcome was not worse either, with recovery for the five patients. Cases of patients with COVID-19 besides HIV and TB infections are scarce in literature, but studies deliberately embracing the triple infection as a priori inclusion criterion should be carried out in order to provide a complete understanding of joint influence.
2021-05-01 2021 other review-article; Review; Journal Article abstract-available A Pandemic within Other Pandemics. When a Multiple Infection of a Host Occurs: SARS-CoV-2, HIV and Mycobacterium tuberculosis González-Domenech C, Pérez-Hernández I, Gómez-Ayerbe C, Viciana Ramos I, Palacios-Muñoz R, Santos J. Viruses. 2021; 13 (5)
Clinical features and radiological manifestations of COVID-19 disease.
Landete P, Quezada Loaiza CA, Aldave-Orzaiz B, Muñiz SH, [...], Couñago F.
World J Radiol. 2020; 12 (11)
DOI: 10.4329/wjr.v12.i11.247
Coronavirus disease 2019 (COVID-19) was discovered after unusual cases of severe pneumonia emerged in December 2019 in Wuhan Province (China). Coronavirus is a family of single-stranded RNA viruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted from person to person. Although asymptomatic individuals can transmit the virus, symptomatic patients are more contagious. The incubation period ranges from 3-7 d and symptoms are mainly respiratory, including pneumonia or pulmonary embolism in severe cases. Elevated serum levels of interleukins (IL)-2, IL-6, IL-7 indicate the presence of cytokine release syndrome, which is associated with disease severity. The disease has three main phases: Viral infection, pulmonary involvement, and hyperinflammation. To date, no treatment has proved to be safe or effective. Chest X-ray and computed tomography (CT) are the primary imaging tests for diagnosis of SARS-CoV-2 pneumonia, follow-up, and detection of complications. The main radiological findings are ground-glass opacification and areas of consolidation. The long-term clinical course is unknown, although some patients may develop pulmonary fibrosis. Positron emission tomography-computed tomography (PET-CT) is useful to assess pulmonary involvement, to define the affected areas, and to assess treatment response. The pathophysiology and clinical course of COVID-19 infection remain poorly understood. However, patterns detected on CT and PET-CT may help to diagnose and guide treatment. In this mini review, we analyze the clinical manifestations and radiological findings of COVID-19 infection.
2020-11-01 2020 other review-article; Review; Journal Article abstract-available 10.4329/wjr.v12.i11.247 Clinical features and radiological manifestations of COVID-19 disease. Landete P, Quezada Loaiza CA, Aldave-Orzaiz B, Muñiz SH, Maldonado A, Zamora E, Sam Cerna AC, Del Cerro E, Alonso RC, Couñago F. World J Radiol. 2020; 12 (11)
Arthropod Ectoparasites Have Potential to Bind SARS-CoV-2 via ACE.
Lam SD, Ashford P, Díaz-Sánchez S, Villar M, [...], Orengo C.
Viruses. 2021; 13 (4)
DOI: 10.3390/v13040708
Coronavirus-like organisms have been previously identified in Arthropod ectoparasites (such as ticks and unfed cat flea). Yet, the question regarding the possible role of these arthropods as SARS-CoV-2 passive/biological transmission vectors is still poorly explored. In this study, we performed in silico structural and binding energy calculations to assess the risks associated with possible ectoparasite transmission. We found sufficient similarity between ectoparasite ACE and human ACE2 protein sequences to build good quality 3D-models of the SARS-CoV-2 Spike:ACE complex to assess the impacts of ectoparasite mutations on complex stability. For several species (e.g., water flea, deer tick, body louse), our analyses showed no significant destabilisation of the SARS-CoV-2 Spike:ACE complex, suggesting these species would bind the viral Spike protein. Our structural analyses also provide structural rationale for interactions between the viral Spike and the ectoparasite ACE proteins. Although we do not have experimental evidence of infection in these ectoparasites, the predicted stability of the complex suggests this is possible, raising concerns of a possible role in passive transmission of the virus to their human hosts.
2021-04-19 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13040708 Arthropod Ectoparasites Have Potential to Bind SARS-CoV-2 via ACE. Lam SD, Ashford P, Díaz-Sánchez S, Villar M, Gortázar C, de la Fuente J, Orengo C. Viruses. 2021; 13 (4)
One year into the pandemic: Short-term evolution of SARS-CoV-2 and emergence of new lineages.
González-Candelas F, Shaw MA, Phan T, Kulkarni-Kale U, [...], Sironi M.
Infect Genet Evol. 2021; 92
DOI: 10.1016/j.meegid.2021.104869
The COVID-19 pandemic was officially declared on March 11th, 2020. Since the very beginning, the spread of the virus has been tracked nearly in real-time by worldwide genome sequencing efforts. As of March 2021, more than 830,000 SARS-CoV-2 genomes have been uploaded in GISAID and this wealth of data allowed researchers to study the evolution of SARS-CoV-2 during this first pandemic year. In parallel, nomenclatures systems, often with poor consistency among each other, have been developed to designate emerging viral lineages. Despite general fears that the virus might mutate to become more virulent or transmissible, SARS-CoV-2 genetic diversity has remained relatively low during the first ~ 8 months of sustained human-to-human transmission. At the end of 2020/beginning of 2021, though, some alarming events started to raise concerns of possible changes in the evolutionary trajectory of the virus. Specifically, three new viral variants associated with extensive transmission have been described as variants of concern (VOC). These variants were first reported in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Their designation as VOCs was determined by an increase of local cases and by the high number of amino acid substitutions harboured by these lineages. This latter feature is reminiscent of viral sequences isolated from immunocompromised patients with long-term infection, suggesting a possible causal link. Here we review the events that led to the identification of these lineages, as well as emerging data concerning their possible implications for viral phenotypes, reinfection risk, vaccine efficiency and epidemic potential. Most of the available evidence is, to date, provisional, but still represents a starting point to uncover the potential threat posed by the VOCs. We also stress that genomic surveillance must be strengthened, especially in the wake of the vaccination campaigns.
2021-04-26 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.meegid.2021.104869 One year into the pandemic: Short-term evolution of SARS-CoV-2 and emergence of new lineages. González-Candelas F, Shaw MA, Phan T, Kulkarni-Kale U, Paraskevis D, Luciani F, Kimura H, Sironi M. Infect Genet Evol. 2021; 92
An integrative look at SARS‑CoV‑2 (Review).
Ortega MA, Fraile-Martínez O, García-Montero C, García-Gallego S, [...], De la Torre B.
Int J Mol Med. 2021; 47 (2)
DOI: 10.3892/ijmm.2020.4828
SARS‑CoV‑2 is a newly discovered member of the betacoronaviruses and the etiological agent of the disease COVID‑19. SARS‑CoV‑2 is responsible for the worldwide pandemic which has been taking place in 2020, and is causing a markedly higher number of infections and deaths compared to previous coronaviruses, such as SARS‑CoV or MERS‑CoV. Based on updated scientific literature, the present review compiles the most relevant knowledge of SARS‑CoV‑2, COVID‑19 and the clinical and typical responses that patients have exhibited against this virus, discussing current and future therapies, and proposing strategies with which to combat the disease and prevent a further global threat. The aggressiveness of SARS‑CoV‑2 arises from its capacity to infect, and spread easily and rapidly through its tight interaction with the human angiotensin‑converting enzyme 2 (ACE‑2) receptor. While not all patients respond in a similar manner and may even be asymptomatic, a wide range of manifestations associated with COVID‑19 have been described, particularly in vulnerable population groups, such as the elderly or individuals with other underlying conditions. The proper function of the immune system plays a key role in an individual's favorable response to SARS‑CoV‑2 infection. A hyperactivated response, on the contrary, could account for the more severe cases of COVID‑19, and this may finally lead to respiratory insufficiency and other complications, such as thrombotic or thromboembolic events. The development of novel therapies and vaccines designed to control and regulate a proper immune system response will be key to clinical management, prevention measures and effective population screening to attenuate the transmission of this novel RNA virus.
2020-12-22 2020 other research-article; Journal Article abstract-available 10.3892/ijmm.2020.4828 An integrative look at SARS‑CoV‑2 (Review). Ortega MA, Fraile-Martínez O, García-Montero C, García-Gallego S, Sánchez-Trujillo L, Torres-Carranza D, Álvarez-Mon MÁ, Pekarek L, García-Honduvilla N, Bujan J, Álvarez-Mon M, Asúnsolo Á, De la Torre B. Int J Mol Med. 2021; 47 (2)
The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19).
Domingo P, Mur I, Pomar V, Corominas H, [...], de Benito N.
EBioMedicine. 2020; 58
DOI: 10.1016/j.ebiom.2020.102887
The pathogenesis of coronavirus disease 2019 (COVID-19) may be envisaged as the dynamic interaction between four vicious feedback loops chained or happening at once. These are the viral loop, the hyperinflammatory loop, the non-canonical renin-angiotensin system (RAS) axis loop, and the hypercoagulation loop. Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1-7)/Mas1R axis. The viral feedback loop includes evading the host's innate response, uncontrolled viral replication, and turning on a hyperactive adaptative immune response. The inflammatory loop is composed of the exuberant inflammatory response feeding back until exploding in an actual cytokine storm. Downregulation of the ACE2/Ang-(1-7)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS. The coagulation loop is a hypercoagulable state caused by the interplay between inflammation and coagulation in an endless feedback loop. The result is a hyperinflammatory and hypercoagulable state producing acute immune-mediated lung injury and eventually, adult respiratory distress syndrome.
2020-07-29 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.ebiom.2020.102887 The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19). Domingo P, Mur I, Pomar V, Corominas H, Casademont J, de Benito N. EBioMedicine. 2020; 58
Histopathology features of the lung in COVID-19 patients.
Angeles Montero-Fernandez M, Pardo-Garcia R.
Diagn Histopathol (Oxf). 2021; 27 (3)
DOI: 10.1016/j.mpdhp.2020.11.009
COVID-19 is the infectious disease caused by the recently discovered coronavirus, SARS-CoV-2, unknown before the outbreak in Wuhan, China, in December 2019. COVID-19 is a pandemic, infectious disease that has simultaneously affected many countries globally. The leading cause of dead in patients with COVID-19 is hypoxic respiratory failure from acute respiratory distress syndrome (ARDS). Diffuse alveolar damage (DAD) is the histopathological pattern commonly described in all the postmortem series up to date. DAD is divided into two phases, and depending on the length of the disease, the morphological features seen in the specimens vary. There is an acute/exudative phase, which occurs during the first week after the pulmonary injury, following by the organizing/proliferative phase. Additional features detailed include vascular thrombosis, endothelialitis and angiogenesis. Interestingly, there is an ongoing discussion about the specificity of these changes, as diffuse alveolar damage seen in other viral infections show similar features.
2020-12-04 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.mpdhp.2020.11.009 Histopathology features of the lung in COVID-19 patients. Angeles Montero-Fernandez M, Pardo-Garcia R. Diagn Histopathol (Oxf). 2021; 27 (3)
Physical Exercise as a Multimodal Tool for COVID-19: Could It Be Used as a Preventive Strategy?
Fernández-Lázaro D, González-Bernal JJ, Sánchez-Serrano N, Navascués LJ, [...], Mielgo-Ayuso J.
Int J Environ Res Public Health. 2020; 17 (22)
DOI: 10.3390/ijerph17228496
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) is a novel coronavirus not previously recognized in humans until late 2019. On 31 December 2019, a cluster of cases of pneumonia of unspecified etiology was reported to the World Health Organization in China. The availability of adequate SARS-CoV-2 drugs is also limited, and the efficacy and safety of these drugs for COVID-2019 pneumonia patients need to be assessed by further clinical trials. For these reasons, there is a need for other strategies against COVID-19 that are capable of prevention and treatment. Physical exercise has proven to be an effective therapy for most chronic diseases and microbial infections with preventive/therapeutic benefits, considering that exercise involves primary immunological mediators and/or anti-inflammatory properties. This review aimed to provide an insight into how the implementation of a physical exercise program against COVID-19 may be a useful complementary tool for prevention, which can also enhance recovery, improve quality of life, and provide immune protection against SARS-CoV-2 virus infection in the long term. In summary, physical exercise training exerts immunomodulatory effects, controls the viral gateway, modulates inflammation, stimulates nitric oxide synthesis pathways, and establishes control over oxidative stress.
2020-11-17 2020 other review-article; Review; Journal Article abstract-available 10.3390/ijerph17228496 Physical Exercise as a Multimodal Tool for COVID-19: Could It Be Used as a Preventive Strategy? Fernández-Lázaro D, González-Bernal JJ, Sánchez-Serrano N, Navascués LJ, Ascaso-Del-Río A, Mielgo-Ayuso J. Int J Environ Res Public Health. 2020; 17 (22)
Similarities and differences between HIV and SARS-CoV-2.
Illanes-Álvarez F, Márquez-Ruiz D, Márquez-Coello M, Cuesta-Sancho S, [...], Girón-González JA.
Int J Med Sci. 2021; 18 (3)
DOI: 10.7150/ijms.50133
In the last 50 years we have experienced two big pandemics, the HIV pandemic and the pandemic caused by SARS-CoV-2. Both pandemics are caused by RNA viruses and have reached us from animals. These two viruses are different in the transmission mode and in the symptoms they generate. However, they have important similarities: the fear in the population, increase in proinflammatory cytokines that generate intestinal microbiota modifications or NETosis production by polymorphonuclear neutrophils, among others. They have been implicated in the clinical, prognostic and therapeutic attitudes.
2021-01-01 2021 other Historical Article; research-article; Review; Journal Article abstract-available 10.7150/ijms.50133 Similarities and differences between HIV and SARS-CoV-2. Illanes-Álvarez F, Márquez-Ruiz D, Márquez-Coello M, Cuesta-Sancho S, Girón-González JA. Int J Med Sci. 2021; 18 (3)
The quality of Internet information relating to 2019-nCov transmission control in dental practice.
Camacho-Alonso F, Lacal-Luján J.
J Clin Exp Dent. 2021; 13 (3)
DOI: 10.4317/jced.57573

Background

To date, the quality of the Internet information regarding the control and management of 2019-nCov virus transmission in dental clinics has not been evaluated. The aim of this study was to evaluate the quality of Internet information about the control of 2019-nCov transmission in dental practice.

Material and methods

Internet websites were identified daily using two search engines: Google and Yahoo! during the week from 20-06-2020 to 26-06-2020, applying the search term "2019-nCov transmission control in dental practice." The first 100 consecutive sites identified in each search were visited and classified. The quality of information contained in each website was analyzed using the Journal of the American Medical Association (JAMA) benchmarks, whether the website had been granted the Health on the Net Foundation Code of Conduct (HONcode), and a new tool for evaluating the quality of Internet websites providing information relating to 2019-nCov transmission control in dental practice, which awards a score of 0-40 points (8-13: poor; 14-26: medium; and 27-40 high).

Results

After the exclusion of duplicates, non-functioning websites, books/journals, irrelevant websites, or websites not in English, a total of 30 websites were evaluated. Only 6.66% fulfilled all four JAMA benchmarks, none had been granted the HONcode, and only 10% presented high quality information.

Conclusions

The quality of Internet information about 2019-nCov transmission control in dental practice is poor. This study points to the need to improve the quality of information available on the Internet relating to 2019-nCov transmission control in dental practice. Key words:2019-nCov, COVID-19, transmission control in dental practice, Internet, quality of information.
2021-03-01 2021 other research-article; Journal Article abstract-available 10.4317/jced.57573 The quality of Internet information relating to 2019-nCov transmission control in dental practice. Camacho-Alonso F, Lacal-Luján J. J Clin Exp Dent. 2021; 13 (3)
Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods.
Ginex T, Garaigorta U, Ramírez D, Castro V, [...], Gil C.
Pharmaceuticals (Basel). 2021; 14 (4)
DOI: 10.3390/ph14040332
The unprecedent situation generated by the COVID-19 global emergency has prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients. In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way. To this end a multi-target virtual screening approach focused on host-based targets related to viral entry, followed by the experimental evaluation of the antiviral activity of selected compounds, has been carried out. As a result, five different potentially repurposable drugs interfering with viral entry-cepharantine, clofazimine, metergoline, imatinib and efloxate-have been identified.
2021-04-06 2021 other research-article; Journal Article abstract-available 10.3390/ph14040332 Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods. Ginex T, Garaigorta U, Ramírez D, Castro V, Nozal V, Maestro I, García-Cárceles J, Campillo NE, Martinez A, Gastaminza P, Gil C. Pharmaceuticals (Basel). 2021; 14 (4)
Narrative review of the immune response against coronavirus: An overview, applicability for SARS-COV-2, and therapeutic implications.
García-Salido A.
An Pediatr (Engl Ed). 2020; 93 (1)
DOI: 10.1016/j.anpede.2020.04.006
The new coronavirus (SARS-CoV-2) that causes a severe acute respiratory syndrome emerges in Wuhan, China, in December 2019. It produces the aforementioned disease due to coronavirus 2019 (COVID-19), and has led to a declaration of a world public health emergency by the World Health Organisation. This new SARS-CoV-2 virus could share characteristics and an immune response similar to those described for other coronavirus. Given its activity on the interferon pathway, and the manner in which it dysregulates innate immunity, the use of treatments directed at modulating or containing this could be of interest. A narrative review was made of the current evidence about immunity against coronavirus and its applicability to SARS-CoV-2. The physiopathogenesis is also described, along with the underlying leucocyte activity, with the intention of clarifying the possible usefulness of inflammatory biomarkers and the development of personalised treatments.
2020-06-08 2020 other research-article; Journal Article abstract-available 10.1016/j.anpede.2020.04.006 Narrative review of the immune response against coronavirus: An overview, applicability for SARS-COV-2, and therapeutic implications. García-Salido A. An Pediatr (Engl Ed). 2020; 93 (1)
Current state of diagnostic, screening and surveillance testing methods for COVID-19 from an analytical chemistry point of view.
Martín J, Tena N, Asuero AG.
Microchem J. 2021; 167
DOI: 10.1016/j.microc.2021.106305
Since December 2019, we have been in the battlefield with a new threat to the humanity known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we describe the four main methods used for diagnosis, screening and/or surveillance of SARS-CoV-2: Real-time reverse transcription polymerase chain reaction (RT-PCR); chest computed tomography (CT); and different complementary alternatives developed in order to obtain rapid results, antigen and antibody detection. All of them compare the highlighting advantages and disadvantages from an analytical point of view. The gold standard method in terms of sensitivity and specificity is the RT-PCR. The different modifications propose to make it more rapid and applicable at point of care (POC) are also presented and discussed. CT images are limited to central hospitals. However, being combined with RT-PCR is the most robust and accurate way to confirm COVID-19 infection. Antibody tests, although unable to provide reliable results on the status of the infection, are suitable for carrying out maximum screening of the population in order to know the immune capacity. More recently, antigen tests, less sensitive than RT-PCR, have been authorized to determine in a quicker way whether the patient is infected at the time of analysis and without the need of specific instruments.
2021-04-19 2021 other research-article; Journal Article abstract-available 10.1016/j.microc.2021.106305 Current state of diagnostic, screening and surveillance testing methods for COVID-19 from an analytical chemistry point of view. Martín J, Tena N, Asuero AG. Microchem J. 2021; 167
Immune response in SARS-CoV-2.
Aguilar-Shea AL, Mayo CG.
J Family Med Prim Care. 2020; 9 (9)
DOI: 10.4103/jfmpc.jfmpc_1539_20
2020-09-30 2020 other letter; Journal Article 10.4103/jfmpc.jfmpc_1539_20 Immune response in SARS-CoV-2. Aguilar-Shea AL, Mayo CG. J Family Med Prim Care. 2020; 9 (9)
Undetectable viral RNA in oocytes from SARS-CoV-2 positive women.
Barragan M, Guillén JJ, Martin-Palomino N, Rodriguez A, [...], Vassena R.
Hum Reprod. 2021; 36 (2)
DOI: 10.1093/humrep/deaa284
A central concern for the safe provision of ART during the current coronavirus disease 2019 (COVID-19) pandemic is the possibility of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through gametes and preimplantation embryos. Unfortunately, data on SARS-CoV-2 viral presence in oocytes of infected individuals are not available to date. We describe the case of two women who underwent controlled ovarian stimulation and tested positive to SARS-CoV-2 infection by PCR on the day of oocyte collection. The viral RNA for gene N was undetectable in all the oocytes analyzed from the two women.
2021-01-01 2021 other Research Support, Non-U.S. Gov't; Journal Article; Case Reports; case-report abstract-available 10.1093/humrep/deaa284 Undetectable viral RNA in oocytes from SARS-CoV-2 positive women. Barragan M, Guillén JJ, Martin-Palomino N, Rodriguez A, Vassena R. Hum Reprod. 2021; 36 (2)
Impact of COVID-19 at the Ocular Level: A Citation Network Study.
Sánchez-Tena MÁ, Martinez-Perez C, Villa-Collar C, Alvarez-Peregrina C.
J Clin Med. 2021; 10 (7)
DOI: 10.3390/jcm10071340

Background

The main objective of this study was to use citation networks to analyze the relationship between different publications on the impact of COVID-19 at an ocular level and their authors. Furthermore, the different research areas will be identified, and the most cited publication will be determined.

Materials and methods

The publications were searched within the Web of Science database, using "ocular", "SARS-CoV-2", "ophthalmology", "eyesight", and "COVID-19" as keywords for the period between January 2020 and January 2021. The Citation Network Explorer and the CiteSpace software were used to analyze the different publications.

Results

A total of 389 publications with 890 citations generated on the web were found. It must be highlighted that July was the month with the largest number of publications. The most cited ones were "Characteristics of Ocular Findings of Patients with Coronavirus Disease 2019 (COVID-19) in Hubei Province, China" by Wu et al., which was published in May 2020. Three groups covering the different research areas in this field were found using the clustering functions: ocular manifestations, teleophthalmology, and personal protective equipment.

Conclusions

The citation network has shown a comprehensive and objective analysis of the main studies on the impact of COVID-19 in ocular disease.
2021-03-24 2021 other research-article; Journal Article abstract-available 10.3390/jcm10071340 Impact of COVID-19 at the Ocular Level: A Citation Network Study. Sánchez-Tena MÁ, Martinez-Perez C, Villa-Collar C, Alvarez-Peregrina C. J Clin Med. 2021; 10 (7)
Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target.
Veljkovic V, Vergara-Alert J, Segalés J, Paessler S.
F1000Res. 2020; 9
DOI: 10.12688/f1000research.22149.4
A novel coronavirus recently identified in Wuhan, China (SARS-CoV-2) has expanded the number of highly pathogenic coronaviruses affecting humans. The SARS-CoV-2 represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging SARS-CoV-2 is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Actin protein was also suggested as a host factor that participates in cell entry and pathogenesis of SARS-CoV-2; therefore, drugs modulating biological activity of this protein (e.g. ibuprofen) were suggested as potential candidates for treatment of this viral infection. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the SARS-CoV-2, and that domain 288-330 of S1 protein from the SARS-CoV-2 represents promising therapeutic and/or vaccine target.
2020-01-27 2020 other brief-report; Journal Article abstract-available 10.12688/f1000research.22149.4 Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. Veljkovic V, Vergara-Alert J, Segalés J, Paessler S. F1000Res. 2020; 9
Emerging therapies for COVID-19 pneumonia.
Battaglini D, Robba C, Ball L, Cruz FF, [...], Rocco PRM.
Expert Opin Investig Drugs. 2020; 29 (7)
DOI: 10.1080/13543784.2020.1771694
2020-06-01 2020 other Editorial 10.1080/13543784.2020.1771694 Emerging therapies for COVID-19 pneumonia. Battaglini D, Robba C, Ball L, Cruz FF, Silva PL, Pelosi P, Rocco PRM. Expert Opin Investig Drugs. 2020; 29 (7)
Effect of ramipril on kidney, lung and heart ACE2 in a diabetic mice model.
Vergara A, Jacobs-Cachá C, Molina-Van den Bosch M, Domínguez-Báez P, [...], Soler MJ.
Mol Cell Endocrinol. 2021; 529
DOI: 10.1016/j.mce.2021.111263

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19). The main organ affected in this infection is the lung and the virus uses the angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the target cells. In this context, a controversy raised regarding the use of renin-angiotensin system (RAAS) blockers, as these drugs might increase ACE2 expression in some tissues and potentially increase the risk for SARS-CoV-2 infection. This is specially concerning in diabetic patients as diabetes is a risk factor for COVID-19.

Methods

12-week old diabetic mice (db/db) were treated with ramipril, or vehicle control for 8 weeks. Non-diabetic db/m mice were included as controls. ACE2 expression and activity were studied in lung, kidney and heart of these animals.

Results

Kidney ACE2 activity was increased in the db/db mice as compared to the db/m (143.2% ± 23% vs 100% ± 22.3%, p = 0.004), whereas ramipril had no significant effect. In the lung, no differences were found in ACE2 when comparing db/db mice to db/m and ramipril also had no significant effect. In the heart, diabetes decreased ACE2 activity (83% ± 16.8%, vs 100% ± 23.1% p = 0.02), and ramipril increased ACE2 significantly (83% ± 16.8% vs 98.2% ± 15%, p = 0.04).

Conclusions

In a mouse model of type 2 diabetes, ramipril had no significant effect on ACE2 activity in either kidneys or in the lungs. Therefore, it is unlikely that RAAS blockers or at least angiotensin-converting enzyme inhibitors increase the risk of SARS-CoV-2 infection through increasing ACE2.
2021-03-31 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1016/j.mce.2021.111263 Effect of ramipril on kidney, lung and heart ACE2 in a diabetic mice model. Vergara A, Jacobs-Cachá C, Molina-Van den Bosch M, Domínguez-Báez P, Benito B, García-Carro C, Serón D, Soler MJ. Mol Cell Endocrinol. 2021; 529
COVID-19 and human reproduction: A pandemic that packs a serious punch.
Anifandis G, Tempest HG, Oliva R, Swanson GM, [...], Krawetz SA.
Syst Biol Reprod Med. 2021; 67 (1)
DOI: 10.1080/19396368.2020.1855271
The COVID-19 pandemic has led to a worldwide health emergency that has impacted 188 countries at last count. The rapid community transmission and relatively high mortality rates with COVID-19 in modern times are relatively unique features of this flu pandemic and have resulted in an unparalleled global health crisis. SARS-CoV-2, being a respiratory virus, mainly affects the lungs, but is capable of infecting other vital organs, such as brain, heart and kidney. Emerging evidence suggests that the virus also targets male and female reproductive organs that express its main receptor ACE2, although it is as yet unclear if this has any implications for human fertility. Furthermore, professional bodies have recommended discontinuing fertility services during the pandemic such that reproductive services have also been affected. Although increased safety measures have helped to mitigate the propagation of COVID-19 in a number of countries, it seems that there is no predictable timeline to containment of the virus, a goal likely to remain elusive until an effective vaccine becomes available  and widely distributed across the globe. In parallel, research on reproduction has been postponed for obvious reasons, while diagnostic tests that detect the virus or antibodies against it are of vital importance to support public health policies, such as social distancing and our obligation to wear masks in public spaces. This review aims to provide an overview of critical research and ethics issues that have been continuously emerging in the field of reproductive medicine as the COVID-19 pandemic tragically unfolds.Abbreviations: ACE2: angiotensin- converting enzyme 2; ART: Assisted reproductive technology; ASRM: American Society for Reproductive Medicine; CCR9: C-C Motif Chemokine Receptor 9; CDC: Centers for Disease Control and Prevention; COVID-19: Coronavirus disease 2019; Ct: Cycle threshold; CXCR6: C-X-C Motif Chemokine Receptor 6; ELISA: enzyme-linked immunosorbent assay; ESHRE: European Society of Human Reproduction and Embryology; ET: Embryo transfer; FSH: Follicle Stimulating Hormone; FFPE: formalin fixed paraffin embedded; FYCO1: FYVE And Coiled-Coil Domain Autophagy Adaptor 1; IFFS: International Federation of Fertility Societies; IUI: Intrauterine insemination; IVF: In vitro fertilization; LH: Luteinizing Hormone; LZTFL1: Leucine Zipper Transcription Factor Like 1; MAR: medically assisted reproduction services; MERS: Middle East Respiratory syndrome; NGS: Next Generation Sequencing; ORF: Open Reading Frame; PPE: personal protective equipment; RE: RNA Element; REDa: RNA Element Discovery algorithm; RT-PCR: Reverse=trascriptase transcriptase-polymerase chain reaction; SARS: Severe acute respiratory syndrome; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SLC6A20: Solute Carrier Family 6 Member 20; SMS: Single Molecule Sequencing; T: Testosterone; TMPRSS2: transmembrane serine protease 2; WHO: World Health Organization; XCR1: X-C Motif Chemokine Receptor.
2021-02-01 2021 other Review; Journal Article abstract-available 10.1080/19396368.2020.1855271 COVID-19 and human reproduction: A pandemic that packs a serious punch. Anifandis G, Tempest HG, Oliva R, Swanson GM, Simopoulou M, Easley CA, Primig M, Messini CI, Turek PJ, Sutovsky P, Ory SJ, Krawetz SA. Syst Biol Reprod Med. 2021; 67 (1)
Scientific effort in combating COVID-19 in obstetrics and gynecology.
Martinez-Portilla RJ, Gil MM, Poon LC.
Ultrasound Obstet Gynecol. 2021; 57 (2)
DOI: 10.1002/uog.23584
2021-02-01 2021 other article-commentary; Comment; Journal Article 10.1002/uog.23584 Scientific effort in combating COVID-19 in obstetrics and gynecology. Martinez-Portilla RJ, Gil MM, Poon LC. Ultrasound Obstet Gynecol. 2021; 57 (2)
Immunology of COVID-19: Mechanisms, clinical outcome, diagnostics, and perspectives-A report of the European Academy of Allergy and Clinical Immunology (EAACI).
Sokolowska M, Lukasik ZM, Agache I, Akdis CA, [...], Untersmayr E.
Allergy. 2020; 75 (10)
DOI: 10.1111/all.14462
With the worldwide spread of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.
2020-10-01 2020 other research-article; Review; Journal Article abstract-available 10.1111/all.14462 Immunology of COVID-19: Mechanisms, clinical outcome, diagnostics, and perspectives-A report of the European Academy of Allergy and Clinical Immunology (EAACI). Sokolowska M, Lukasik ZM, Agache I, Akdis CA, Akdis D, Akdis M, Barcik W, Brough HA, Eiwegger T, Eljaszewicz A, Eyerich S, Feleszko W, Gomez-Casado C, Hoffmann-Sommergruber K, Janda J, Jiménez-Saiz R, Jutel M, Knol EF, Kortekaas Krohn I, Kothari A, Makowska J, Moniuszko M, Morita H, O'Mahony L, Nadeau K, Ozdemir C, Pali-Schöll I, Palomares O, Papaleo F, Prunicki M, Schmidt-Weber CB, Sediva A, Schwarze J, Shamji MH, Tramper-Stranders GA, van de Veen W, Untersmayr E. Allergy. 2020; 75 (10)
Perspectives in Peptide-Based Vaccination Strategies for Syndrome Coronavirus 2 Pandemic.
Di Natale C, La Manna S, De Benedictis I, Brandi P, [...], Marasco D.
Front Pharmacol. 2020; 11
DOI: 10.3389/fphar.2020.578382
At the end of December 2019, an epidemic form of respiratory tract infection now named COVID-19 emerged in Wuhan, China. It is caused by a newly identified viral pathogen, the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which can cause severe pneumonia and acute respiratory distress syndrome. On January 30, 2020, due to the rapid spread of infection, COVID-19 was declared as a global health emergency by the World Health Organization. Coronaviruses are enveloped RNA viruses belonging to the family of Coronaviridae, which are able to infect birds, humans and other mammals. The majority of human coronavirus infections are mild although already in 2003 and in 2012, the epidemics of SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV), respectively, were characterized by a high mortality rate. In this regard, many efforts have been made to develop therapeutic strategies against human CoV infections but, unfortunately, drug candidates have shown efficacy only into in vitro studies, limiting their use against COVID-19 infection. Actually, no treatment has been approved in humans against SARS-CoV-2, and therefore there is an urgent need of a suitable vaccine to tackle this health issue. However, the puzzled scenario of biological features of the virus and its interaction with human immune response, represent a challenge for vaccine development. As expected, in hundreds of research laboratories there is a running out of breath to explore different strategies to obtain a safe and quickly spreadable vaccine; and among others, the peptide-based approach represents a turning point as peptides have demonstrated unique features of selectivity and specificity toward specific targets. Peptide-based vaccines imply the identification of different epitopes both on human cells and virus capsid and the design of peptide/peptidomimetics able to counteract the primary host-pathogen interaction, in order to induce a specific host immune response. SARS-CoV-2 immunogenic regions are mainly distributed, as well as for other coronaviruses, across structural areas such as spike, envelope, membrane or nucleocapsid proteins. Herein, we aim to highlight the molecular basis of the infection and recent peptide-based vaccines strategies to fight the COVID-19 pandemic including their delivery systems.
2020-12-03 2020 other review-article; Review; Journal Article abstract-available 10.3389/fphar.2020.578382 Perspectives in Peptide-Based Vaccination Strategies for Syndrome Coronavirus 2 Pandemic. Di Natale C, La Manna S, De Benedictis I, Brandi P, Marasco D. Front Pharmacol. 2020; 11
Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus.
Martinez MA.
Antimicrob Agents Chemother. 2020; 64 (5)
DOI: 10.1128/aac.00399-20
Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.
2020-04-21 2020 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1128/aac.00399-20 Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus. Martinez MA. Antimicrob Agents Chemother. 2020; 64 (5)
Pigs are not susceptible to SARS-CoV-2 infection but are a model for viral immunogenicity studies.
Vergara-Alert J, Rodon J, Carrillo J, Te N, [...], Segalés J.
Transbound Emerg Dis. 2020;
DOI: 10.1111/tbed.13861
Conventional piglets were inoculated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through different routes, including intranasal, intratracheal, intramuscular and intravenous ones. Although piglets were not susceptible to SARS-CoV-2 and lacked lesions or viral RNA in tissues/swabs, seroconversion was observed in pigs inoculated parenterally (intramuscularly or intravenously).
2020-10-02 2020 other brief-report; Journal Article abstract-available 10.1111/tbed.13861 Pigs are not susceptible to SARS-CoV-2 infection but are a model for viral immunogenicity studies. Vergara-Alert J, Rodon J, Carrillo J, Te N, Izquierdo-Useros N, Rodríguez de la Concepción ML, Ávila-Nieto C, Guallar V, Valencia A, Cantero G, Blanco J, Clotet B, Bensaid A, Segalés J. Transbound Emerg Dis. 2020;
[Scoping review of coronavirus case series (SARS-CoV, MERS-CoV and SARS-CoV-2) and their obstetric and neonatal results].
Rodríguez-Blanco N, Vegara-Lopez I, Aleo-Giner L, Tuells J.
Rev Esp Quimioter. 2020; 33 (5)
DOI: 10.37201/req/064.2020

Objective

The appearance of new infectious diseases, such as COVID-19, poses a challenge in monitoring pregnancy and preventing obstetric and neonatal complications. A scoping review has the objective to review the information available in pregnant women infected with the MERS-CoV, SARSCoV, SARS-CoV-2 coronaviruses to assess the similarities in terms of and differences in the clinical characteristics of the mothers and neonatal outcomes.

Methods

We carried out a bibliographic search (scoping review) according to the PRISMA guidelines between March and April 2020 in the MEDLINE, SciELO, and CUIDEN databases and the Elsevier COVID-19 Information Center.

Results

We analyzed 20 articles with a total of 102 cases. 9 of MERS-CoV, 14 of SARS-CoV and 79 of SARS-CoV-2. Fever (75.5%) and pneumonia (73.5%) were the most frequent symptoms in infected pregnant women. The most frequent obstetric complications were the threat of premature delivery (23.5%) and caesarean section (74.5%). No vertical transmission was documented in any of the infants.

Conclusions

All three coronaviruses produce pneumonia with very similar symptoms, being milder in the case of SARSCoV2. Despite documented obstetric complications, neonatal outcomes are mostly favorable. Increased knowledge is needed to improve and prevent obstetric and neonatal complications from these infections in pregnant women.
2020-07-20 2020 other research-article; Systematic Review abstract-available 10.37201/req/064.2020 [Scoping review of coronavirus case series (SARS-CoV, MERS-CoV and SARS-CoV-2) and their obstetric and neonatal results]. Rodríguez-Blanco N, Vegara-Lopez I, Aleo-Giner L, Tuells J. Rev Esp Quimioter. 2020; 33 (5)
SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus.
Muñoz-Basagoiti J, Perez-Zsolt D, Carrillo J, Blanco J, [...], Izquierdo-Useros N.
Membranes (Basel). 2021; 11 (1)
DOI: 10.3390/membranes11010064
Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.
2021-01-18 2021 other review-article; Review; Journal Article abstract-available 10.3390/membranes11010064 SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus. Muñoz-Basagoiti J, Perez-Zsolt D, Carrillo J, Blanco J, Clotet B, Izquierdo-Useros N. Membranes (Basel). 2021; 11 (1)
IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection.
Pérez A, Torregrosa I, D'Marco L, Juan I, [...], Gorriz JL.
Viruses. 2021; 13 (4)
DOI: 10.3390/v13040587
The renal involvement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported. The etiology of kidney injury appears to be tubular, mainly due to the expression of angiotensin-converting enzyme 2, the key joint receptor for SARS-CoV-2; however, cases with glomerular implication have also been documented. The multifactorial origin of this renal involvement could include virus-mediated injury, cytokine storm, angiotensin II pathway activation, complement dysregulation, hyper-coagulation, and microangiopathy. We present the renal histological findings from a patient who developed acute kidney injury and de novo nephrotic syndrome, highly suggestive of acute IgA-dominant infection-associated glomerulonephritis (IgA-DIAGN) after SARS-CoV-2 infection, as evidenced by the presence of this virus detected in the renal tissue of the patient via immunohistochemistry assay. In summary, we document the first case of IgA-DIAGN associated to SARS-CoV-2. Thus, SARS-CoV-2 S may act as a super antigen driving the development of multisystem inflammatory syndrome as well as cytokine storm in patients affected by COVID-19, reaching the glomerulus and leading to the development of this novel IgA-DIAGN.
2021-03-31 2021 other Case Reports; case-report abstract-available 10.3390/v13040587 IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection. Pérez A, Torregrosa I, D'Marco L, Juan I, Terradez L, Solís MÁ, Moncho F, Carda-Batalla C, Forner MJ, Gorriz JL. Viruses. 2021; 13 (4)
A COVID-19 Drug Repurposing Strategy through Quantitative Homological Similarities Using a Topological Data Analysis-Based Framework.
Pérez-Moraga R, Forés-Martos J, Suay-García B, Duval JL, [...], Climent J.
Pharmaceutics. 2021; 13 (4)
DOI: 10.3390/pharmaceutics13040488
Since its emergence in March 2020, the SARS-CoV-2 global pandemic has produced more than 116 million cases and 2.5 million deaths worldwide. Despite the enormous efforts carried out by the scientific community, no effective treatments have been developed to date. We applied a novel computational pipeline aimed to accelerate the process of identifying drug repurposing candidates which allows us to compare three-dimensional protein structures. Its use in conjunction with two in silico validation strategies (molecular docking and transcriptomic analyses) allowed us to identify a set of potential drug repurposing candidates targeting three viral proteins (3CL viral protease, NSP15 endoribonuclease, and NSP12 RNA-dependent RNA polymerase), which included rutin, dexamethasone, and vemurafenib. This is the first time that a topological data analysis (TDA)-based strategy has been used to compare a massive number of protein structures with the final objective of performing drug repurposing to treat SARS-CoV-2 infection.
2021-04-02 2021 other research-article; Journal Article abstract-available 10.3390/pharmaceutics13040488 A COVID-19 Drug Repurposing Strategy through Quantitative Homological Similarities Using a Topological Data Analysis-Based Framework. Pérez-Moraga R, Forés-Martos J, Suay-García B, Duval JL, Falcó A, Climent J. Pharmaceutics. 2021; 13 (4)
Is asthma a risk factor for COVID-19? Are phenotypes important?
Muñoz X, Pilia F, Ojanguren I, Romero-Mesones C, [...], Cruz MJ.
ERJ Open Res. 2021; 7 (1)
DOI: 10.1183/23120541.00216-2020
These results reaffirm the idea that asthma does not appear to be a risk factor for the development of #COVID19. However, most of the asthma patients in this study had a non-T2 phenotype. https://bit.ly/38hIp18.
2021-01-25 2021 other letter; Journal Article abstract-available 10.1183/23120541.00216-2020 Is asthma a risk factor for COVID-19? Are phenotypes important? Muñoz X, Pilia F, Ojanguren I, Romero-Mesones C, Cruz MJ. ERJ Open Res. 2021; 7 (1)
DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications?
Valencia I, Peiró C, Lorenzo Ó, Sánchez-Ferrer CF, [...], Romacho T.
Front Pharmacol. 2020; 11
DOI: 10.3389/fphar.2020.01161
COVID-19 outbreak, caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus has become an urgent health and economic challenge. Diabetes is a risk factor for severity and mortality of COVID-19. Recent studies support that COVID-19 has effects beyond the respiratory tract, with vascular complications arising as relevant factors worsening its prognosis, then making patients with previous vascular disease more prone to severity or fatal outcome. Angiotensin-II converting enzime-2 (ACE2) has been proposed as preferred receptor for SARS-CoV-2 host infection, yet specific proteins participating in the virus entry are not fully known. SARS-CoV-2 might use other co-receptor or auxiliary proteins allowing virus infection. In silico experiments proposed that SARS-CoV-2 might bind dipeptidyl peptidase 4 (DPP4/CD26), which was established previously as receptor for MERS-CoV. The renin-angiotensin-aldosterone system (RAAS) component ACE2 and DPP4 are proteins dysregulated in diabetes. Imbalance of the RAAS and direct effect of soluble DPP4 exert deleterious vascular effects. We hypothesize that diabetic patients might be more affected by COVID-19 due to increased presence ACE2 and DPP4 mediating infection and contributing to a compromised vasculature. Here, we discuss the role of ACE2 and DPP4 as relevant factors linking the risk of SARS-CoV-2 infection and severity of COVID-19 in diabetic patients and present an outlook on therapeutic potential of current drugs targeted against RAAS and DPP4 to treat or prevent COVID-19-derived vascular complications. Diabetes affects more than 400 million people worldwide, thus better understanding of how they are affected by COVID-19 holds an important benefit to fight against this disease with pandemic proportions.
2020-08-07 2020 other review-article; Review; Journal Article abstract-available 10.3389/fphar.2020.01161 DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications? Valencia I, Peiró C, Lorenzo Ó, Sánchez-Ferrer CF, Eckel J, Romacho T. Front Pharmacol. 2020; 11
Is the oral cavity relevant in SARS-CoV-2 pandemic?
Herrera D, Serrano J, Roldán S, Sanz M.
Clin Oral Investig. 2020; 24 (8)
DOI: 10.1007/s00784-020-03413-2

Objectives

Recent scientific evidences suggest a relevant role of the oral cavity in the transmission and pathogenicity of SARS-CoV-2.

Methods

A literature search was performed in PubMed, up to April 30, 2020, focusing on SARS-CoV-2, COVID-19, oral cavity, and antimicrobial agents.

Results

Oral viral load of SARS-CoV-2 has been associated with the severity of COVID-19, and thus, a reduction in the oral viral load could be associated with a decrease in the severity of the condition. Similarly, a decrease in the oral viral load would diminish the amount of virus expelled and reduce the risk of transmission, since (i) during the first 10 days, the virus mainly accumulates at the nasal, oral, and pharyngeal area; (ii) the number of angiotensin-converting enzyme (ACE2) receptor is greater in the salivary glands as compared with the lungs; and (iii) salivary droplets represent the most relevant transmission route. To reduce the oral viral load, antiseptic agents may be used, although the evidence on its efficacy is indirect and weak.

Conclusions

Antiseptic mouth rinses, such as those containing cetylpyridinium chloride or povidone-iodine, may be able to decrease the severity of COVID-19 by reducing oral viral load in infected subjects and decreasing the risk of transmission by limiting viral load in droplets, generated in normal life, or in aerosols, produced during dental procedures. Well-designed clinical and preclinical research must be conducted to support these hypotheses.

Clinical relevance

Antiseptic mouth rinses may help in decreasing the severity of COVID-19 and in reducing the risk of transmission.
2020-06-23 2020 other research-article; Journal Article abstract-available 10.1007/s00784-020-03413-2 Is the oral cavity relevant in SARS-CoV-2 pandemic? Herrera D, Serrano J, Roldán S, Sanz M. Clin Oral Investig. 2020; 24 (8)
Extrathoracic manifestations of COVID-19 in adults and presentation of the disease in children☆ Manifestaciones extratorácicas de la COVID-19 en adultos y presentación de la enfermedad en niños
Plasencia-Martínez J, Rovira À, Caro Domínguez P, Barber I, [...], Arenas-Jiménez J.
Radiologi´a. 2021;
DOI:
In March 2020, the World Health Organization declared a global pandemic of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); epidemic conditions continue in nearly all countries today. Although the symptoms and imaging manifestations of COVID-19 predominantly involve the respiratory system, it is fundamental to know the manifestations of the disease and its possible complications in other organs to help in diagnosis and orient the prognosis. To improve the diagnostic process without increasing the risk of contagion unnecessarily, it is crucial to know when extrathoracic imaging tests are indicated and which tests are best in each situation. This paper aims to provide answers to these questions. To this end, we describe and illustrate the extrathoracic imaging manifestations of COVID-19 in adults as well as the entire spectrum of imaging findings in children.
2021-05-19 2021 other research-article; Journal Article abstract-available Extrathoracic manifestations of COVID-19 in adults and presentation of the disease in children☆ Manifestaciones extratorácicas de la COVID-19 en adultos y presentación de la enfermedad en niños Plasencia-Martínez J, Rovira À, Caro Domínguez P, Barber I, García-Garrigós E, Arenas-Jiménez J. Radiologi´a. 2021;
Subacute thyroiditis following COVID-19 infection☆ Tiroiditis subaguda tras infección por COVID-19
de la Higuera López-Frías M, Perdomo C, Galofré J.
Rev Clin Esp (Barc). 2021; 221 (6)
DOI:
2021-01-01 2021 other Letter Subacute thyroiditis following COVID-19 infection☆ Tiroiditis subaguda tras infección por COVID-19 de la Higuera López-Frías M, Perdomo C, Galofré J. Rev Clin Esp (Barc). 2021; 221 (6)
Neurological Symptoms of COVID-19: The Zonulin Hypothesis.
Llorens S, Nava E, Muñoz-López M, Sánchez-Larsen Á, [...], Segura T.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.665300
The irruption of SARS-CoV-2 during 2020 has been of pandemic proportions due to its rapid spread and virulence. COVID-19 patients experience respiratory, digestive and neurological symptoms. Distinctive symptom as anosmia, suggests a potential neurotropism of this virus. Amongst the several pathways of entry to the nervous system, we propose an alternative pathway from the infection of the gut, involving Toll-like receptor 4 (TLR4), zonulin, protease-activated receptor 2 (PAR2) and zonulin brain receptor. Possible use of zonulin antagonists could be investigated to attenuate neurological manifestations caused by SARS-CoV-19 infection.
2021-04-26 2021 other research-article; Review; Journal Article abstract-available 10.3389/fimmu.2021.665300 Neurological Symptoms of COVID-19: The Zonulin Hypothesis. Llorens S, Nava E, Muñoz-López M, Sánchez-Larsen Á, Segura T. Front Immunol. 2021; 12
Structural analysis of SARS-CoV-2 genome and predictions of the human interactome.
Vandelli A, Monti M, Milanetti E, Armaos A, [...], Tartaglia GG.
Nucleic Acids Res. 2020; 48 (20)
DOI: 10.1093/nar/gkaa864
Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of >2000 coronaviruses and computed >100 000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genomic regions display different degrees of conservation. SARS-CoV-2 domain encompassing nucleotides 22 500-23 000 is conserved both at the sequence and structural level. The regions upstream and downstream, however, vary significantly. This part of the viral sequence codes for the Spike S protein that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2). Thus, variability of Spike S is connected to different levels of viral entry in human cells within the population. Our predictions indicate that the 5' end of SARS-CoV-2 is highly structured and interacts with several human proteins. The binding proteins are involved in viral RNA processing, include double-stranded RNA specific editases and ATP-dependent RNA-helicases and have strong propensity to form stress granules and phase-separated assemblies. We propose that these proteins, also implicated in viral infections such as HIV, are selectively recruited by SARS-CoV-2 genome to alter transcriptional and post-transcriptional regulation of host cells and to promote viral replication.
2020-11-01 2020 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/nar/gkaa864 Structural analysis of SARS-CoV-2 genome and predictions of the human interactome. Vandelli A, Monti M, Milanetti E, Armaos A, Rupert J, Zacco E, Bechara E, Delli Ponti R, Tartaglia GG. Nucleic Acids Res. 2020; 48 (20)
Lack of Effectiveness of Repurposed Drugs for COVID-19 Treatment.
Martinez MA.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.635371
2021-03-11 2021 other discussion; Journal Article 10.3389/fimmu.2021.635371 Lack of Effectiveness of Repurposed Drugs for COVID-19 Treatment. Martinez MA. Front Immunol. 2021; 12
Assessing the risks of SARS-CoV-2 in wildlife.
Delahay RJ, de la Fuente J, Smith GC, Sharun K, [...], Gortazar C.
One Health Outlook. 2021; 3
DOI: 10.1186/s42522-021-00039-6
The novel coronavirus SARS-CoV-2 likely emerged from a wildlife source with transmission to humans followed by rapid geographic spread throughout the globe and severe impacts on both human health and the global economy. Since the onset of the pandemic, there have been many instances of human-to-animal transmission involving companion, farmed and zoo animals, and limited evidence for spread into free-living wildlife. The establishment of reservoirs of infection in wild animals would create significant challenges to infection control in humans and could pose a threat to the welfare and conservation status of wildlife. We discuss the potential for exposure, onward transmission and persistence of SARS-CoV-2 in an initial selection of wild mammals (bats, canids, felids, mustelids, great apes, rodents and cervids). Dynamic risk assessment and targeted surveillance are important tools for the early detection of infection in wildlife, and here we describe a framework for collating and synthesising emerging information to inform targeted surveillance for SARS-CoV-2 in wildlife. Surveillance efforts should be integrated with information from public and veterinary health initiatives to provide insights into the potential role of wild mammals in the epidemiology of SARS-CoV-2.
2021-04-07 2021 other review-article; Review; Journal Article abstract-available 10.1186/s42522-021-00039-6 Assessing the risks of SARS-CoV-2 in wildlife. Delahay RJ, de la Fuente J, Smith GC, Sharun K, Snary EL, Flores Girón L, Nziza J, Fooks AR, Brookes SM, Lean FZX, Breed AC, Gortazar C. One Health Outlook. 2021; 3
Sex Hormones and Hormone Therapy during COVID-19 Pandemic: Implications for Patients with Cancer.
Cattrini C, Bersanelli M, Latocca MM, Conte B, [...], Boccardo F.
Cancers (Basel). 2020; 12 (8)
DOI: 10.3390/cancers12082325
The novel coronavirus disease 2019 (COVID-19) shows a wide spectrum of clinical presentations, severity, and fatality rates. The reason older patients and males show increased risk of severe disease and death remains uncertain. Sex hormones, such as estradiol, progesterone, and testosterone, might be implicated in the age-dependent and sex-specific severity of COVID-19. High testosterone levels could upregulate transmembrane serine protease 2 (TMPRSS2), facilitating the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells via angiotensin-converting enzyme 2 (ACE2). Data from patients with prostate cancer treated with androgen-deprivation therapy seem to confirm this hypothesis. Clinical studies on TMPRSS2 inhibitors, such as camostat, nafamostat, and bromhexine, are ongoing. Antiandrogens, such as bicalutamide and enzalutamide, are also under investigation. Conversely, other studies suggest that the immune modulating properties of androgens could protect from the unfavorable cytokine storm, and that low testosterone levels might be associated with a worse prognosis in patients with COVID-19. Some evidence also supports the notion that estrogens and progesterone might exert a protective effect on females, through direct antiviral activity or immune-mediated mechanisms, thus explaining the higher COVID-19 severity in post-menopausal women. In this perspective, we discuss the available evidence on sex hormones and hormone therapy in patients infected with SARS-CoV-2, and we highlight the possible implications for cancer patients, who can receive hormonal therapies during their treatment plans.
2020-08-18 2020 other other; Journal Article abstract-available 10.3390/cancers12082325 Sex Hormones and Hormone Therapy during COVID-19 Pandemic: Implications for Patients with Cancer. Cattrini C, Bersanelli M, Latocca MM, Conte B, Vallome G, Boccardo F. Cancers (Basel). 2020; 12 (8)
Phytonutrient and Nutraceutical Action against COVID-19: Current Review of Characteristics and Benefits.
Pastor N, Collado MC, Manzoni P.
Nutrients. 2021; 13 (2)
DOI: 10.3390/nu13020464
The trend toward using phytonutrients and/or nutraceuticals (P/Ns) with the aim of impacting immune health has increased in recent years. The main reason is that properties of P/Ns are associated with possible immunomodulating effects in the prevention and complementary treatment of viral diseases, including COVID-19 and other respiratory infections. In the present review, we assess the scientific plausibility of specific P/Ns for this purpose of preventative and therapeutic interventions against COVID-19, with an emphasis on safety, validity, and evidence of efficacy against other viruses. Five potential candidates have been identified after reviewing available studies (in silico, in vitro, and in vivo) in which certain flavonoids have demonstrated a potential for use as adjuvant therapeutic agents against viral infections, including COVID-19. As these are often better tolerated than pharmacological treatments, their use could be more widely considered if additional detailed studies can validate the existing evidence.
2021-01-30 2021 other review-article; Review; Journal Article abstract-available 10.3390/nu13020464 Phytonutrient and Nutraceutical Action against COVID-19: Current Review of Characteristics and Benefits. Pastor N, Collado MC, Manzoni P. Nutrients. 2021; 13 (2)
Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of in vitro, in vivo, and clinical trials.
Han YJ, Lee KH, Yoon S, Nam SW, [...], Shin JI.
Theranostics. 2021; 11 (3)
DOI: 10.7150/thno.48342
Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-β1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.
2021-01-01 2021 other Systematic Review; review-article; Journal Article abstract-available 10.7150/thno.48342 Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of <i>in vitro</i>, <i>in vivo</i>, and clinical trials. Han YJ, Lee KH, Yoon S, Nam SW, Ryu S, Seong D, Kim JS, Lee JY, Yang JW, Lee J, Koyanagi A, Hong SH, Dragioti E, Radua J, Smith L, Oh H, Ghayda RA, Kronbichler A, Effenberger M, Kresse D, Denicolò S, Kang W, Jacob L, Shin H, Shin JI. Theranostics. 2021; 11 (3)
The presence of SARS-CoV-2 RNA in human sewage in Santa Catarina, Brazil, November 2019.
Fongaro G, Stoco PH, Souza DSM, Grisard EC, [...], Rodríguez-Lázaro D.
Sci Total Environ. 2021; 778
DOI: 10.1016/j.scitotenv.2021.146198
Human sewage from Florianopolis (Santa Catarina, Brazil) was analyzed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) from October 2019 until March 2020. Twenty five ml of sewage samples were clarified and viruses concentrated using a glycine buffer method coupled with polyethylene glycol precipitation, and viral RNA extracted using a commercial kit. SARS-CoV-2 RNA was detected by RT-qPCR using oligonucleotides targeting N1, S and two RdRp regions. The results of all positive samples were further confirmed by a different RT-qPCR system in an independent laboratory. S and RdRp amplicons were sequenced to confirm identity with SARS-CoV-2. Genome sequencing was performed using two strategies; a sequence-independent single-primer amplification (SISPA) approach, and by direct metagenomics using Illumina's NGS. SARS-CoV-2 RNA was detected on 27th November 2019 (5.49 ± 0.02 log10 SARS-CoV-2 genome copies (GC) L-1), detection being confirmed by an independent laboratory and genome sequencing analysis. The samples in the subsequent three events were positive by all RT-qPCR assays; these positive results were also confirmed by an independent laboratory. The average load was 5.83 ± 0.12 log10 SARS-CoV-2 GC L-1, ranging from 5.49 ± 0.02 log10 GC L-1 (27th November 2019) to 6.68 ± 0.02 log10 GC L-1 (4th March 2020). Our findings demonstrate that SARS-CoV-2 was likely circulating undetected in the community in Brazil since November 2019, earlier than the first reported case in the Americas (21st January 2020).
2021-03-08 2021 other brief-report; Journal Article abstract-available 10.1016/j.scitotenv.2021.146198 The presence of SARS-CoV-2 RNA in human sewage in Santa Catarina, Brazil, November 2019. Fongaro G, Stoco PH, Souza DSM, Grisard EC, Magri ME, Rogovski P, Schörner MA, Barazzetti FH, Christoff AP, de Oliveira LFV, Bazzo ML, Wagner G, Hernández M, Rodríguez-Lázaro D. Sci Total Environ. 2021; 778
SARS-CoV-2 infection in K18-ACE2 transgenic mice replicates human pulmonary disease in COVID-19.
Arce VM, Costoya JA.
Cell Mol Immunol. 2021; 18 (3)
DOI: 10.1038/s41423-020-00616-1
2021-01-14 2021 other brief-report; Journal Article 10.1038/s41423-020-00616-1 SARS-CoV-2 infection in K18-ACE2 transgenic mice replicates human pulmonary disease in COVID-19. Arce VM, Costoya JA. Cell Mol Immunol. 2021; 18 (3)
Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19.
De Toma I, Dierssen M.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-81451-w
SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection or poorer clinical outcomes. In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we identified the genes associated with the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We then analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) and created a DS-SARS-CoV-2 network. We detected COVID-19 protective and risk factors among HSA21 genes and interactors and/or DS deregulated genes that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome. Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells. However, as the anti-viral interferon I signaling is also upregulated in DS, this might increase the initial anti-viral response, inhibiting viral genome release, viral replication and viral assembly. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.
2021-01-21 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-021-81451-w Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19. De Toma I, Dierssen M. Sci Rep. 2021; 11 (1)
COVID-19 infection in patients with mast cell disorders including mastocytosis does not impact mast cell activation symptoms.
Giannetti MP, Weller E, Alvarez-Twose I, Torrado I, [...], Castells M.
J Allergy Clin Immunol Pract. 2021; 9 (5)
DOI: 10.1016/j.jaip.2021.02.023
2021-02-23 2021 other brief-report; Journal Article 10.1016/j.jaip.2021.02.023 COVID-19 infection in patients with mast cell disorders including mastocytosis does not impact mast cell activation symptoms. Giannetti MP, Weller E, Alvarez-Twose I, Torrado I, Bonadonna P, Zanotti R, Dwyer DF, Foer D, Akin C, Hartmann K, Rama TA, Sperr WR, Valent P, Teodosio C, Orfao A, Castells M. J Allergy Clin Immunol Pract. 2021; 9 (5)
nObesity as an Adipose tissue dysfunction disease and A Risk Factor for Infections – Covid-19 as a case study
MF L, M M, B R, I B, [...], Frühbeck G.
Eur J Intern Med. 2021;
DOI:
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) disease (COVID-19) is a novel threat that hampers life expectancy especially in obese individuals. Though this association is clinically relevant, the underlying mechanisms are not fully elucidated. SARS CoV2 enters host cells via the Angiotensin Converting Enzyme 2 receptor, that is also expressed in adipose tissue. Moreover, adipose tissue is also a source of many proinflammatory mediators and adipokines that might enhance the characteristic COVID-19 cytokine storm due to a chronic low-grade inflammatory preconditioning. Further obesity-dependent thoracic mechanical constraints may also incise negatively into the prognosis of obese subjects with COVID-19. This review summarizes the current body of knowledge on the obesity-dependent circumstances triggering an increased risk for COVID-19 severity, and their clinical relevance.
2021-04-02 2021 other review-article; Review; Journal Article abstract-available nObesity as an Adipose tissue dysfunction disease and A Risk Factor for Infections – Covid-19 as a case study MF L, M M, B R, I B, Frühbeck G. Eur J Intern Med. 2021;
Emerging SARS-CoV-2 Variants and Impact in Global Vaccination Programs against SARS-CoV-2/COVID-19.
Gómez CE, Perdiguero B, Esteban M.
Vaccines (Basel). 2021; 9 (3)
DOI: 10.3390/vaccines9030243
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants in different continents is causing a major concern in human global health. These variants have in common a higher transmissibility, becoming dominant within populations in a short time, and an accumulation of a high number of mutations in the spike (S) protein, especially within the amino terminal domain (NTD) and the receptor binding domain (RBD). These mutations have direct implications on virus infection rates through higher affinity of S RBD for the cellular angiotensin-converting enzyme-2 (ACE-2) receptor. There are also signs of enhanced virulence, re-infection frequency, and increased resistance to the action of monoclonal and polyclonal antibodies from convalescence sera and in vaccinated individuals in regions where the variants spread dominantly. In this review, we describe the different SARS-CoV-2 variants that have thus far been identified in various parts of the world with mutational changes and biological properties as well as their impact in medical countermeasures and human health.
2021-03-11 2021 other review-article; Review; Journal Article abstract-available 10.3390/vaccines9030243 Emerging SARS-CoV-2 Variants and Impact in Global Vaccination Programs against SARS-CoV-2/COVID-19. Gómez CE, Perdiguero B, Esteban M. Vaccines (Basel). 2021; 9 (3)
A Comprehensive Review of Coronavirus Disease 2019: Epidemiology, Transmission, Risk Factors, and International Responses.
Li H, Burm SW, Hong SH, Ghayda RA, [...], Shin JI.
Yonsei Med J. 2021; 62 (1)
DOI: 10.3349/ymj.2021.62.1.1
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide pandemic. The first reports of patients with COVID-19 were provided to World Health Organization on December 21, 2019 and were presumably associated with seafood markets in Wuhan, China. As of October 25, 2020, more than 42 million cases have been confirmed worldwide, with more than 1.1 million deaths. Asymptomatic transmission contributes significantly to transmission, and clinical features are non-specific to the disease. Thus, the diagnosis of COVID-19 requires specific viral RNA testing. The disease demonstrates extensive human-to-human transmissibility and has infected healthcare workers at high rates. Clinical awareness of the epidemiology and the risk factors for nosocomial transmission of COVID-19 is essential to preventing infection. Moreover, effective control measures should be further identified by comprehensive evaluation of hospital and community responses. In this review, we provide a comprehensive update on the epidemiology, presentation, transmission, risk factors, and public health measures associated with COVID-19. We also review past insights from previous coronavirus epidemics [i.e., severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)] to suggest measures to reduce transmission.
2021-01-01 2021 other review-article; Review; Journal Article abstract-available 10.3349/ymj.2021.62.1.1 A Comprehensive Review of Coronavirus Disease 2019: Epidemiology, Transmission, Risk Factors, and International Responses. Li H, Burm SW, Hong SH, Ghayda RA, Kronbichler A, Smith L, Koyanagi A, Jacob L, Lee KH, Shin JI. Yonsei Med J. 2021; 62 (1)
Coronavirus Disease 2019 (COVID-19) and Its Neuroinvasive Capacity: Is It Time for Melatonin?
Romero A, Ramos E, López-Muñoz F, Gil-Martín E, [...], Reiter RJ.
Cell Mol Neurobiol. 2020;
DOI: 10.1007/s10571-020-00938-8
The world faces an exceptional new public health concern caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequently termed the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). Although the clinical symptoms mostly have been characterized, the scientific community still doesn´t know how SARS-CoV-2 successfully reaches and spreads throughout the central nervous system (CNS) inducing brain damage. The recent detection of SARS-CoV-2 in the cerebrospinal fluid (CSF) and in frontal lobe sections from postmortem examination has confirmed the presence of the virus in neural tissue. This finding reveals a new direction in the search for a neurotherapeutic strategy in the COVID-19 patients with underlying diseases. Here, we discuss the COVID-19 outbreak in a neuroinvasiveness context and suggest the therapeutic use of high doses of melatonin, which may favorably modulate the immune response and neuroinflammation caused by SARS-CoV-2. However, clinical trials elucidating the efficacy of melatonin in the prevention and clinical management in the COVID-19 patients should be actively encouraged.
2020-08-09 2020 other review-article; Review; Journal Article abstract-available 10.1007/s10571-020-00938-8 Coronavirus Disease 2019 (COVID-19) and Its Neuroinvasive Capacity: Is It Time for Melatonin? Romero A, Ramos E, López-Muñoz F, Gil-Martín E, Escames G, Reiter RJ. Cell Mol Neurobiol. 2020;
A Founder Effect Led Early SARS-CoV-2 Transmission in Spain.
Díez-Fuertes F, Iglesias-Caballero M, García-Pérez J, Monzón S, [...], Casas I.
J Virol. 2021; 95 (3)
DOI: 10.1128/jvi.01583-20
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome analysis has identified five large clades worldwide which emerged in 2019 (19A and 19B) and in 2020 (20A, 20B, and 20C). This study aimed to analyze the diffusion of SARS-CoV-2 in Spain using maximum-likelihood phylogenetic and Bayesian phylodynamic analyses. The most recent common ancestor (MRCA) of the SARS-CoV-2 pandemic was estimated to have emerged in Wuhan, China, around 24 November 2019. Phylogenetic analyses of the first 12,511 SARS-CoV-2 whole-genome sequences obtained worldwide, including 290 from 11 different regions of Spain, revealed 62 independent introductions of the virus in the country. Most sequences from Spain were distributed in clades characterized by a D614G substitution in the S gene (20A, 20B, and 20C) and an L84S substitution in ORF8 (19B) with 163 and 118 sequences, respectively, with the remaining sequences branching in 19A. A total of 110 (38%) sequences from Spain grouped in four different monophyletic clusters of clade 20A (20A-Sp1 and 20A-Sp2) and 19B clade (19B-Sp1 and 19B-Sp2) along with sequences from 29 countries worldwide. The MRCAs of clusters 19A-Sp1, 20A-Sp1, 19A-Sp2, and 20A-Sp2 were estimated to have occurred in Spain around 21 and 29 January and 6 and 17 February 2020, respectively. The prevalence of clade 19B in Spain (40%) was by far higher than in any other European country during the first weeks of the epidemic, probably as a result of a founder effect. However, this variant was replaced by G614-bearing viruses in April. In vitro assays showed an enhanced infectivity of pseudotyped virions displaying the G614 substitution compared with those having D614, suggesting a fitness advantage of D614G.IMPORTANCE Multiple SARS-CoV-2 introductions have been detected in Spain, and at least four resulted in the emergence of locally transmitted clusters that originated not later than mid-February, with further dissemination to many other countries around the world, and a few weeks before the explosion of COVID-19 cases detected in Spain during the first week of March. The majority of the earliest variants detected in Spain branched in the clade 19B (D614 viruses), which was the most prevalent clade during the first weeks of March, pointing to a founder effect. However, from mid-March to June 2020, G614-bearing viruses (clades 20A, 20B, and 20C) overcame D614 variants in Spain, probably as a consequence of an evolutionary advantage of this substitution in the spike protein. A higher infectivity of G614-bearing viruses than D614 variants was detected, suggesting that this substitution in SARS-CoV-2 spike protein could be behind the variant shift observed in Spain.
2021-01-13 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1128/jvi.01583-20 A Founder Effect Led Early SARS-CoV-2 Transmission in Spain. Díez-Fuertes F, Iglesias-Caballero M, García-Pérez J, Monzón S, Jiménez P, Varona S, Cuesta I, Zaballos Á, Jiménez M, Checa L, Pozo F, Pérez-Olmeda M, Thomson MM, Alcamí J, Casas I. J Virol. 2021; 95 (3)
Congenital, Intrapartum and Postnatal Maternal-Fetal-Neonatal SARS-CoV-2 Infections: A Narrative Review.
Caparros-Gonzalez RA, Pérez-Morente MA, Hueso-Montoro C, Álvarez-Serrano MA, [...], de la Torre-Luque A.
Nutrients. 2020; 12 (11)
DOI: 10.3390/nu12113570

Background

There is inconclusive evidence regarding congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. A narrative review was conducted with the aim of guiding clinicians on the management of pregnant women with respect to congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections and breastfeeding during the COVID-19 pandemic.

Methods

Searches were conducted in Web of Science, PubMed, Scopus, Dialnet, CUIDEN, Scielo, and Virtual Health Library to identify observational, case series, case reports, and randomized controlled trial studies assessing the transmission of SARS-CoV-2 from mother to baby and/or through breastfeeding during the COVID-19 pandemic.

Results

A total of 49 studies was included in this review, comprising 329 pregnant women and 331 neonates (two pregnant women delivered twins). The studies were performed in China (n = 26), USA (n = 7), Italy (n = 3), Iran (n = 2), Switzerland (n = 1), Spain (n = 1), Turkey (n = 1), Australia (n = 1), India (n = 1), Germany (n = 1), France (n = 1), Canada (n = 1), Honduras (n = 1), Brazil (n = 1), and Peru (n = 1). Samples from amniotic fluid, umbilical cord blood, placenta, cervical secretion, and breastmilk were collected and analyzed. A total of 15 placental swabs gave positive results for SARS-CoV-2 ribonucleic acid (RNA) on the fetal side of the placenta. SARS-CoV-2 RNA was found in seven breastmilk samples. One umbilical cord sample was positive for SARS-CoV-2. One amniotic fluid sample tested positive for SARS-CoV-2.

Conclusions

This study presents some evidence to support the potential of congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. Mothers should follow recommendations including wearing a facemask and hand washing before and after breastfeeding.
2020-11-20 2020 other review-article; Review; Journal Article abstract-available 10.3390/nu12113570 Congenital, Intrapartum and Postnatal Maternal-Fetal-Neonatal SARS-CoV-2 Infections: A Narrative Review. Caparros-Gonzalez RA, Pérez-Morente MA, Hueso-Montoro C, Álvarez-Serrano MA, de la Torre-Luque A. Nutrients. 2020; 12 (11)
Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2.
Sanclemente-Alaman I, Moreno-Jiménez L, Benito-Martín MS, Canales-Aguirre A, [...], Gómez-Pinedo U.
Front Immunol. 2020; 11
DOI: 10.3389/fimmu.2020.02163

Introduction

The response to the SARS-CoV-2 coronavirus epidemic requires increased research efforts to expand our knowledge of the disease. Questions related to infection rates and mechanisms, the possibility of reinfection, and potential therapeutic approaches require us not only to use the experimental models previously employed for the SARS-CoV and MERS-CoV coronaviruses but also to generate new models to respond to urgent questions.

Development

We reviewed the different experimental models used in the study of central nervous system (CNS) involvement in COVID-19 both in different cell lines that have enabled identification of the virus' action mechanisms and in animal models (mice, rats, hamsters, ferrets, and primates) inoculated with the virus. Specifically, we reviewed models used to assess the presence and effects of SARS-CoV-2 on the CNS, including neural cell lines, animal models such as mouse hepatitis virus CoV (especially the 59 strain), and the use of brain organoids.

Conclusion

Given the clear need to increase our understanding of SARS-CoV-2, as well as its potential effects on the CNS, we must endeavor to obtain new information with cellular or animal models, with an appropriate resemblance between models and human patients.
2020-08-28 2020 other review-article; Review; Journal Article abstract-available 10.3389/fimmu.2020.02163 Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2. Sanclemente-Alaman I, Moreno-Jiménez L, Benito-Martín MS, Canales-Aguirre A, Matías-Guiu JA, Matías-Guiu J, Gómez-Pinedo U. Front Immunol. 2020; 11
Can COVID-19 Increase the Risk of Herpes Zoster? A Narrative Review.
Diez-Domingo J, Parikh R, Bhavsar AB, Cisneros E, [...], Lecrenier N.
Dermatol Ther (Heidelb). 2021;
DOI: 10.1007/s13555-021-00549-1
Herpes zoster (HZ) is associated with substantial morbidity. It is caused by reactivation of the latent varicella zoster virus (VZV) following decline in cell-mediated immunity, which is commonly age-related, but also occurs in individuals with immunosuppressive diseases and/or treatment. Since coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with T cell immune dysfunction and there have been reports of HZ in COVID-19 patients, we have performed a review of available literature on whether COVID-19 could trigger HZ. We identified 27 cases of HZ following COVID-19, which most frequently occurred within 1-2 weeks of COVID-19, and the majority of cases had typical presentation. Atypical presentations of HZ were noted especially in patients with lymphopenia. It has been hypothesized that VZV reactivation occurs as a consequence of T cell dysfunction (including lymphopenia and lymphocyte exhaustion) in COVID-19 patients. Based on current evidence, which is limited to case reports and case series, it is not possible to determine whether COVID-19 increases the risk of HZ. Practitioners should be aware of the possible increased risk of HZ during the pandemic period and consider timely therapeutic and preventive measures against it.
2021-05-17 2021 other review-article; Review; Journal Article abstract-available 10.1007/s13555-021-00549-1 Can COVID-19 Increase the Risk of Herpes Zoster? A Narrative Review. Diez-Domingo J, Parikh R, Bhavsar AB, Cisneros E, McCormick N, Lecrenier N. Dermatol Ther (Heidelb). 2021;
SARS-CoV 2; Possible alternative virus receptors and pathophysiological determinants.
Pruimboom L.
Med Hypotheses. 2021; 146
DOI: 10.1016/j.mehy.2020.110368
Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highjacks epithelial cells and infiltrates the lung, as well as other organs and tissues, is essential for developing treatment strategies and vaccines against this highly contagious virus. Another major goal is to fully elucidate the mechanisms by which SARS-CoV- 2 bypasses the innate immune system and induces a cytokine storm, and its effects on mortality. Currently, SARS- CoV-2 is thought to evade innate antiviral immunity, undergo endocytosis, and fuse with the host cell membrane by exploiting ACE2 receptors and the protease TMMPRSS2, with cathepsin B/L as alternative protease, for entry into the epithelial cells of tissues vulnerable to developing coronavirus disease 2019 (COVID-19) symptoms. However, the incorporation of new and unique binding sites, i.e., O-linked glycans, and the preservation and augmentation of effective binding sites (N-linked glycans) on the outer membrane of SARS-CoV-2 may represent other strategies of infecting the human host. Here, I will rationalize the possibility that other host molecules-i.e., sugar molecules and the sialic acidsN-glycolylneuraminic acid, N-acetylneuraminic acid, and their derivates could be viable candidates for the use as virus receptors by SARS-CoV-2 and/or serve as determinants for the adherence on ACE2 of SARS-CoV-2.
2020-11-06 2020 other research-article; Review; Journal Article abstract-available 10.1016/j.mehy.2020.110368 SARS-CoV 2; Possible alternative virus receptors and pathophysiological determinants. Pruimboom L. Med Hypotheses. 2021; 146
The Rheumatology Drugs for COVID-19 Management: Which and When?
Atzeni F, Masala IF, Rodríguez-Carrio J, Ríos-Garcés R, [...], Cervera R.
J Clin Med. 2021; 10 (4)
DOI: 10.3390/jcm10040783

Introduction

While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. 'Repurposing' immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patients.
2021-02-16 2021 other review-article; Review; Journal Article abstract-available 10.3390/jcm10040783 The Rheumatology Drugs for COVID-19 Management: Which and When? Atzeni F, Masala IF, Rodríguez-Carrio J, Ríos-Garcés R, Gerratana E, La Corte L, Giallanza M, Nucera V, Riva A, Espinosa G, Cervera R. J Clin Med. 2021; 10 (4)
Obesity - A Risk Factor for Psoriasis and COVID-19.
Llamas-Velasco M, Ovejero-Merino E, Salgado-Boquete L.
Actas Dermosifiliogr. 2021;
DOI: 10.1016/j.adengl.2021.03.013
Obesity is a major health problem whose well-known association with psoriasis has been amply described. The importance of obesity as a risk factor for poor prognosis in the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has recently been demonstrated. This review examines a possible relationship between obesity, psoriasis, and COVID-19, analyzing the pathophysiological links and their practical implications. On the one hand, a higher body mass index increases the risk of psoriasis and is also a factor in metabolic syndrome, which is common in patients with psoriasis and has been implicated in reducing the effectiveness of psoriasis treatments. On the other hand, obesity is a risk factor for severe COVID-19 and mortality. Obesity also promotes a proinflammatory state in the lung, where it compromises respiratory mechanics.
2021-03-19 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.adengl.2021.03.013 Obesity - A Risk Factor for Psoriasis and COVID-19. Llamas-Velasco M, Ovejero-Merino E, Salgado-Boquete L. Actas Dermosifiliogr. 2021;
Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)A, Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)B, Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)D, Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)E, Österreichische Gesellschaft für Pneumologie (ÖGP)F in co-operation with the German, Austrian, and Swiss ARIA groupsG, and the European Academy of Allergy and Clinical Immunology (EAACI)H.
Klimek L, Pfaar O, Worm M, Eiwegger T, [...], Jutel M.
Allergol Select. 2020; 4
DOI: 10.5414/alx02166e

Background

Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.

Materials and methods

A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.

Results

In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.

Conclusion

The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.
2020-09-07 2020 other research-article; Journal Article abstract-available 10.5414/alx02166e Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)<sup>A</sup>, Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)<sup>B</sup>, Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)<sup>C</sup>, Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)<sup>D</sup>, Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)<sup>E</sup>, Österreichische Gesellschaft für Pneumologie (ÖGP)<sup>F</sup> in co-operation with the German, Austrian, and Swiss ARIA groups<sup>G</sup>, and the European Academy of Allergy and Clinical Immunology (EAACI)<sup>H</sup>. Klimek L, Pfaar O, Worm M, Eiwegger T, Hagemann J, Ollert M, Untersmayr E, Hoffmann-Sommergruber K, Vultaggio A, Agache I, Bavbek S, Bossios A, Casper I, Chan S, Chatzipetrou A, Vogelberg C, Firinu D, Kauppi P, Kolios A, Kothari A, Matucci A, Palomares O, Szépfalusi Z, Pohl W, Hötzenecker W, Rosenkranz AR, Bergmann KC, Bieber T, Buhl R, Buters J, Darsow U, Keil T, Kleine-Tebbe J, Lau S, Maurer M, Merk H, Mösges R, Saloga J, Staubach P, Jappe U, Rabe KF, Rabe U, Vogelmeier C, Biedermann T, Jung K, Schlenter W, Ring J, Chaker A, Wehrmann W, Becker S, Freudelsperger L, Mülleneisen N, Nemat K, Czech W, Wrede H, Brehler R, Fuchs T, Tomazic PV, Aberer W, Fink-Wagner AH, Horak F, Wöhrl S, Niederberger-Leppin V, Pali-Schöll I, Pohl W, Roller-Wirnsberger R, Spranger O, Valenta R, Akdis M, Matricardi PM, Spertini F, Khaltaev N, Michel JP, Nicod L, Schmid-Grendelmeier P, Idzko M, Hamelmann E, Jakob T, Werfel T, Wagenmann M, Taube C, Jensen-Jarolim E, Korn S, Hentges F, Schwarze J, O Mahony L, Knol EF, Del Giacco S, Chivato Pérez T, Bousquet J, Bedbrook A, Zuberbier T, Akdis C, Jutel M. Allergol Select. 2020; 4
Pulmonary Endothelial Dysfunction and Thrombotic Complications in Patients with COVID-19.
Rodríguez C, Luque N, Blanco I, Sebastian L, [...], Tura-Ceide O.
Am J Respir Cell Mol Biol. 2021; 64 (4)
DOI: 10.1165/rcmb.2020-0359ps
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new strain of a Coronaviridae virus that presents 79% genetic similarity to the severe acute respiratory syndrome coronavirus, has been recently recognized as the cause of a global pandemic by the World Health Organization, implying a major threat to world public health. SARS-CoV-2 infects host human cells by binding through the viral spike proteins to the ACE-2 (angiotensin-converting enzyme 2) receptor, fuses with the cell membrane, enters, and starts its replication process to multiply its viral load. Coronavirus disease (COVID-19) was initially considered a respiratory infection that could cause pneumonia. However, in severe cases, it extends beyond the respiratory system and becomes a multiorgan disease. This transition from localized respiratory infection to multiorgan disease is due to two main complications of COVID-19. On the one hand, it is due to the so-called cytokine storm: an uncontrolled inflammatory reaction of the immune system in which defensive molecules become aggressive for the body itself. On the other hand, it is due to the formation of a large number of thrombi that can cause myocardial infarction, stroke, and pulmonary embolism. The pulmonary endothelium actively participates in these two processes, becoming the last barrier before the virus spreads throughout the body. In this review, we examine the role of the pulmonary endothelium in response to COVID-19, the existence of potential biomarkers, and the development of novel therapies to restore vascular homeostasis and to protect and/or treat coagulation, thrombosis patients. In addition, we review the thrombotic complications recently observed in patients with COVID-19 and its potential threatening sequelae.
2021-04-01 2021 other research-article; Review; Journal Article abstract-available 10.1165/rcmb.2020-0359ps Pulmonary Endothelial Dysfunction and Thrombotic Complications in Patients with COVID-19. Rodríguez C, Luque N, Blanco I, Sebastian L, Barberà JA, Peinado VI, Tura-Ceide O. Am J Respir Cell Mol Biol. 2021; 64 (4)
SARS-CoV-2, COVID-19, skin and immunology - What do we know so far?
Novak N, Peng W, Naegeli MC, Galvan C, [...], Catala A.
Allergy. 2021; 76 (3)
DOI: 10.1111/all.14498
The pandemic condition coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2-positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial, and maculopapular eruptions and livedo, necrosis, and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors, and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical, and histologic features of virus- and drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.
2020-08-12 2020 other Research Support, Non-U.S. Gov't; research-article; Review; Journal Article abstract-available 10.1111/all.14498 SARS-CoV-2, COVID-19, skin and immunology - What do we know so far? Novak N, Peng W, Naegeli MC, Galvan C, Kolm-Djamei I, Brüggen C, Cabanillas B, Schmid-Grendelmeier P, Catala A. Allergy. 2021; 76 (3)
Abnormal Liver Function Test in Patients Infected with Coronavirus (SARS-CoV-2): A Retrospective Single-Center Study from Spain.
Benedé-Ubieto R, Estévez-Vázquez O, Flores-Perojo V, Macías-Rodríguez RU, [...], Nevzorova YA.
J Clin Med. 2021; 10 (5)
DOI: 10.3390/jcm10051039
The outbreak of the novel coronavirus SARS-CoV-2 epidemic has rapidly spread and still poses a serious threat to healthcare systems worldwide. In the present study, electronic medical records containing clinical indicators related to liver injury in 799 COVID-19-confirmed patients admitted to a hospital in Madrid (Spain) were extracted and analyzed. Correlation between liver injury and disease outcome was also evaluated. Serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyltransferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and AST/ALT ratio were elevated above the Upper Limit of Normal (ULN) in 25.73%, 49.17%, 34.62%, 24.21%, 55.84% and 75% of patients, respectively. Interestingly, significant positive correlation between LDH levels and the AST/ALT ratio with disease outcome was found. Our data showed that SARS-CoV-2 virus infection leads to mild, but significant changes in serum markers of liver injury. The upregulated LDH levels as well as AST/ALT ratios upon admission may be used as additional diagnostic characteristic for COVID-19 patients.
2021-03-03 2021 other research-article; Journal Article abstract-available 10.3390/jcm10051039 Abnormal Liver Function Test in Patients Infected with Coronavirus (SARS-CoV-2): A Retrospective Single-Center Study from Spain. Benedé-Ubieto R, Estévez-Vázquez O, Flores-Perojo V, Macías-Rodríguez RU, Ruiz-Margáin A, Martínez-Naves E, Regueiro JR, Ávila MA, Trautwein C, Bañares R, Bosch J, Cubero FJ, Nevzorova YA. J Clin Med. 2021; 10 (5)
A pharmacological perspective of chloroquine in SARS-CoV-2 infection: An old drug for the fight against a new coronavirus?
Oscanoa TJ, Romero-Ortuno R, Carvajal A, Savarino A.
Int J Antimicrob Agents. 2020; 56 (3)
DOI: 10.1016/j.ijantimicag.2020.106078
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having serious consequences on health and the economy worldwide. All evidence-based treatment strategies need to be considered to combat this new virus. Drugs need to be considered on scientific grounds of efficacy, safety and cost. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used in the treatment of malaria. Moreover, their antiviral properties have been previously studied, including against coronaviruses, where evidence of efficacy has been found. In the current race against time triggered by the COVID-19 pandemic, the search for new antivirals is very important. However, consideration should be given to old drugs with known anti-coronavirus activity, such as CQ and HCQ. These could be integrated into current treatment strategies while novel treatments are awaited, also in light of the fact that they display an anticoagulant effect that facilitates the activity of low-molecular-weight heparin, aimed at preventing acute respiratory distress syndrome (ARDS)-associated thrombotic events. The safety of CQ and HCQ has been studied for over 50 years, however recently published data raise concerns for cardiac toxicity of CQ/HCQ in patients with COVID-19. This review also re-examines the real information provided by some of the published alarming reports, although concluding that cardiac toxicity should in any case be stringently monitored in patients receiving CQ/HCQ.
2020-07-04 2020 other research-article; Review; Journal Article abstract-available 10.1016/j.ijantimicag.2020.106078 A pharmacological perspective of chloroquine in SARS-CoV-2 infection: An old drug for the fight against a new coronavirus? Oscanoa TJ, Romero-Ortuno R, Carvajal A, Savarino A. Int J Antimicrob Agents. 2020; 56 (3)
The SARS-CoV-2 envelope (E) protein has evolved towards membrane topology robustness.
Duart G, García-Murria MJ, Mingarro I.
Biochim Biophys Acta Biomembr. 2021; 1863 (7)
DOI: 10.1016/j.bbamem.2021.183608
2021-03-24 2021 other brief-report; Research Support, Non-U.S. Gov't; Journal Article 10.1016/j.bbamem.2021.183608 The SARS-CoV-2 envelope (E) protein has evolved towards membrane topology robustness. Duart G, García-Murria MJ, Mingarro I. Biochim Biophys Acta Biomembr. 2021; 1863 (7)
Small Resistance Artery Disease and ACE2 in Hypertension: A New Paradigm in the Context of COVID-19.
Galán M, Jiménez-Altayó F.
Front Cardiovasc Med. 2020; 7
DOI: 10.3389/fcvm.2020.588692
Cardiovascular disease causes almost one third of deaths worldwide, and more than half are related to primary arterial hypertension (PAH). The occurrence of several deleterious events, such as hyperactivation of the renin-angiotensin system (RAS), and oxidative and inflammatory stress, contributes to the development of small vessel disease in PAH. Small resistance arteries are found at various points through the arterial tree, act as the major site of vascular resistance, and actively regulate local tissue perfusion. Experimental and clinical studies demonstrate that alterations in small resistance artery properties are important features of PAH pathophysiology. Diseased small vessels in PAH show decreased lumens, thicker walls, endothelial dysfunction, and oxidative stress and inflammation. These events may lead to altered blood flow supply to tissues and organs, and can increase the risk of thrombosis. Notably, PAH is prevalent among patients diagnosed with COVID-19, in whom evidence of small vessel disease leading to cardiovascular pathology is reported. The SARS-Cov2 virus, responsible for COVID-19, achieves cell entry through an S (spike) high-affinity protein binding to the catalytic domain of the angiotensin-converting enzyme 2 (ACE2), a negative regulator of the RAS pathway. Therefore, it is crucial to examine the relationship between small resistance artery disease, ACE2, and PAH, to understand COVID-19 morbidity and mortality. The scope of the present review is to briefly summarize available knowledge on the role of small resistance artery disease and ACE2 in PAH, and critically discuss their clinical relevance in the context of cardiovascular pathology associated to COVID-19.
2020-10-30 2020 other review-article; Review; Journal Article abstract-available 10.3389/fcvm.2020.588692 Small Resistance Artery Disease and ACE2 in Hypertension: A New Paradigm in the Context of COVID-19. Galán M, Jiménez-Altayó F. Front Cardiovasc Med. 2020; 7
Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease.
Halpin DMG, Criner GJ, Papi A, Singh D, [...], Vogelmeier CF.
Am J Respir Crit Care Med. 2021; 203 (1)
DOI: 10.1164/rccm.202009-3533so
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required. It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic. It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2. During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery. Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering. Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination. Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management. Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications. Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging. If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered. Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation. Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome. Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols. Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy.
2021-01-01 2021 other research-article; Review; Journal Article abstract-available 10.1164/rccm.202009-3533so Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease. Halpin DMG, Criner GJ, Papi A, Singh D, Anzueto A, Martinez FJ, Agusti AA, Vogelmeier CF. Am J Respir Crit Care Med. 2021; 203 (1)
Proteomics Insights Into the Molecular Basis of SARS-CoV-2 Infection: What We Can Learn From the Human Olfactory Axis.
Lachén-Montes M, Corrales FJ, Fernández-Irigoyen J, Santamaría E.
Front Microbiol. 2020; 11
DOI: 10.3389/fmicb.2020.02101
Like other RNA viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in host cells, continuously modulating the molecular environment. It encodes 28 multifunctional proteins that induce an imbalance in the metabolic and proteostatic homeostasis in infected cells. Recently, proteomic approaches have allowed the evaluation of the impact of SARS-CoV-2 infection in human cells. Here, we discuss the current use of proteomics in three major application areas: (i) virus-protein interactomics, (ii) differential proteotyping to map the virus-induced changes in different cell types, and (iii) diagnostic methods for coronavirus infectious disease 2019 (COVID-19). Since the nasal cavity is one of the entry sites for SARS-CoV-2, we will also discuss the potential application of olfactory proteomics to provide novel insights into the olfactory dysfunction triggered by SARS-CoV-2 in patients with COVID-19.
2020-09-22 2020 other review-article; Review; Journal Article abstract-available 10.3389/fmicb.2020.02101 Proteomics Insights Into the Molecular Basis of SARS-CoV-2 Infection: What We Can Learn From the Human Olfactory Axis. Lachén-Montes M, Corrales FJ, Fernández-Irigoyen J, Santamaría E. Front Microbiol. 2020; 11
Human recombinant soluble ACE2 in severe COVID-19.
Zoufaly A, Poglitsch M, Aberle JH, Hoepler W, [...], Penninger JM.
Lancet Respir Med. 2020; 8 (11)
DOI: 10.1016/s2213-2600(20)30418-5
2020-09-24 2020 other Research Support, Non-U.S. Gov't; Journal Article; Case Reports; case-report 10.1016/s2213-2600(20)30418-5 Human recombinant soluble ACE2 in severe COVID-19. Zoufaly A, Poglitsch M, Aberle JH, Hoepler W, Seitz T, Traugott M, Grieb A, Pawelka E, Laferl H, Wenisch C, Neuhold S, Haider D, Stiasny K, Bergthaler A, Puchhammer-Stoeckl E, Mirazimi A, Montserrat N, Zhang H, Slutsky AS, Penninger JM. Lancet Respir Med. 2020; 8 (11)
Potential of pulsed light technology for control of SARS-CoV-2 in hospital environments.
Jean J, Rodríguez-López MI, Jubinville E, Núñez-Delicado E, [...], Gómez-López VM.
J Photochem Photobiol B. 2021; 215
DOI: 10.1016/j.jphotobiol.2020.112106
The emergence of the SARS-CoV-2 infection and its potential transmission through touching surfaces in clinical environments have impelled the use of conventional and novel methods of disinfection to prevent its spreading. Among the latter, pulsed light may be an effective, non-chemical decontamination alternative. Pulsed light technology inactivates microorganisms and viruses by using high intensity polychromatic light pulses, which degrades nucleic acids and proteins. This review describes this technology, compiles and critically analyzes the evidence about the virucidal efficacy of pulsed light technology with view on its potential use against SARS-CoV-2 in touching surfaces in health-care facilities. The efficacy of pulsed light proved against many different kind of viruses allows to conclude that is a suitable candidate to inactivate SARS-CoV-2 as long as the required fluence is applied and the appropriated exposure to contaminated surfaces is guaranteed.
2020-12-28 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.jphotobiol.2020.112106 Potential of pulsed light technology for control of SARS-CoV-2 in hospital environments. Jean J, Rodríguez-López MI, Jubinville E, Núñez-Delicado E, Gómez-López VM. J Photochem Photobiol B. 2021; 215
Review of the Microbiological Diagnostic Approaches of COVID-19.
Melo-Vallès A, Ballesté-Delpierre C, Vila J.
Front Public Health. 2021; 9
DOI: 10.3389/fpubh.2021.592500
On March 12, the World Health Organization declared a pandemic following the exponential increase of SARS-CoV-2 cases. The rapid spread of the virus is due to both its high infectivity and the free circulation of unrecognized infectious cases. Thus, diagnostic testing is a key element to prevent further dissemination of the virus. Urged by WHO's call, laboratories worldwide have been working on nucleic acid tests protocols and immunoassays that became available, albeit poorly validated, within a comparatively short time. Since then, external studies evaluating these diagnostic tests have been published. The present study is a review of the COVID-19 diagnostic approaches, discussing both direct and indirect microbiological diagnoses. A compendium of the literature on commercial assays kits available to date is provided together with the conclusions drawn as well as RT-PCR protocols published by the WHO. Briefly, diagnostic accuracy varies according to time elapsed since symptom onset and evolves together with understanding of the COVID-19 disease. Taking into account all these variables will allow determining the most adequate diagnostic test to use and how to optimize diagnostic testing for COVID-19.
2021-04-27 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fpubh.2021.592500 Review of the Microbiological Diagnostic Approaches of COVID-19. Melo-Vallès A, Ballesté-Delpierre C, Vila J. Front Public Health. 2021; 9
Chemosensory Dysfunction in Patients with COVID-19: What Do We Learn from the Global Outbreak?
Zeng M, Wang DY, Mullol J, Liu Z.
Curr Allergy Asthma Rep. 2021; 21 (2)
DOI: 10.1007/s11882-020-00987-5

Purpose of review

Chemosensory dysfunction in the patients with COVID-19 has been reported frequently in the studies from different regions of the world. However, the prevalence of smell and/or taste disorders presents significant ethnic and geographic variability. In addition, the pathogenesis of chemosensory dysfunction remains unclarified.

Recent findings

This is a narrative review on the recent state of the prevalence, mechanism, and diagnostic and therapeutic strategy of chemosensory dysfunction in COVID-19 patients during the global pandemic. The chemosensory dysfunction was analysis based on recent studies, which either used questionnaires, Likert scales (0-10), or smell tests to estimate the smell and taste dysfunction. The ethnic and geographic difference of the prevalence of smell and/or taste disorders and the potential underlying mechanisms have been discussed. Several suggestions on the diagnosis and treatment of COVID-19 patients with smell and taste disorders were summarized for the physicians. This review provides a comprehensive overview of the current studies regarding the chemosensory dysfunction during the COVID-19 worldwide outbreak.
2021-02-03 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1007/s11882-020-00987-5 Chemosensory Dysfunction in Patients with COVID-19: What Do We Learn from the Global Outbreak? Zeng M, Wang DY, Mullol J, Liu Z. Curr Allergy Asthma Rep. 2021; 21 (2)
A protocol for adding knowledge to Wikidata: aligning resources on human coronaviruses.
Waagmeester A, Willighagen EL, Su AI, Kutmon M, [...], Koehorst JJ.
BMC Biol. 2021; 19 (1)
DOI: 10.1186/s12915-020-00940-y

Background

Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a "commons." Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions.

Results

As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates.

Conclusions

Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).
2021-01-22 2021 other research-article; Journal Article abstract-available 10.1186/s12915-020-00940-y A protocol for adding knowledge to Wikidata: aligning resources on human coronaviruses. Waagmeester A, Willighagen EL, Su AI, Kutmon M, Gayo JEL, Fernández-Álvarez D, Groom Q, Schaap PJ, Verhagen LM, Koehorst JJ. BMC Biol. 2021; 19 (1)
Position statement for a pragmatic approach to immunotherapeutics in patients with inflammatory skin diseases during the coronavirus disease 2019 pandemic and beyond.
Beecker J, Papp KA, Dutz J, Vender RB, [...], Puig L.
J Eur Acad Dermatol Venereol. 2021; 35 (4)
DOI: 10.1111/jdv.17075
Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, a novel RNA virus that was declared a global pandemic on 11 March 2020. The efficiency of infection with SARS-CoV-2 is reflected by its rapid global spread. The SARS-CoV-2 pandemic has implications for patients with inflammatory skin diseases on systemic immunotherapy who may be at increased risk of infection or more severe infection. This position paper is a focused examination of current evidence considering the mechanisms of action of immunotherapeutic drugs in relation to immune response to SARS-CoV-2. We aim to provide practical guidance for dermatologists managing patients with inflammatory skin conditions on systemic therapies during the current pandemic and beyond. Considering the limited and rapidly evolving evidence, mechanisms of action of therapies, and current knowledge of SARS-CoV-2 infection, we propose that systemic immunotherapy can be continued, with special considerations for at risk patients or those presenting with symptoms.
2021-02-03 2021 other research-article; Journal Article abstract-available 10.1111/jdv.17075 Position statement for a pragmatic approach to immunotherapeutics in patients with inflammatory skin diseases during the coronavirus disease 2019 pandemic and beyond. Beecker J, Papp KA, Dutz J, Vender RB, Gniadecki R, Cooper C, Gisondi P, Gooderham M, Hong CH, Kirchhof MG, Lynde CW, Maari C, Poulin Y, Puig L. J Eur Acad Dermatol Venereol. 2021; 35 (4)
Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge.
Winkler MS, Skirecki T, Brunkhorst FM, Cajander S, [...], Osuchowski MF.
EBioMedicine. 2021; 66
DOI: 10.1016/j.ebiom.2021.103291
Many milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered on clinical studies. However, several animal SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting clinical evidence rapidly emerge. In this review, we characterize the existing animal models exposing their relevance and limitations as well as outline their utility in COVID-19 drug and vaccine development. Concurrently, we summarize the status of clinical trial research and discuss the novel tactics utilized in the largest multi-center trials aiming to accelerate generation of reliable results that may subsequently shape COVID-19 clinical treatment practices. We also highlight areas of improvement for animal studies in order to elevate their translational utility. In pandemics, to optimize the use of strained resources in a short time-frame, optimizing and strengthening the synergy between the preclinical and clinical domains is pivotal.
2021-04-01 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.ebiom.2021.103291 Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge. Winkler MS, Skirecki T, Brunkhorst FM, Cajander S, Cavaillon JM, Ferrer R, Flohé SB, García-Salido A, Giamarellos-Bourboulis EJ, Girardis M, Kox M, Lachmann G, Martin-Loeches I, Netea MG, Spinetti T, Schefold JC, Torres A, Uhle F, Venet F, Weis S, Scherag A, Rubio I, Osuchowski MF. EBioMedicine. 2021; 66
Evidences of SARS-CoV-2 virus air transmission indoors using several untouched surfaces: A pilot study.
Orenes-Piñero E, Baño F, Navas-Carrillo D, Moreno-Docón A, [...], Ramírez P.
Sci Total Environ. 2021; 751
DOI: 10.1016/j.scitotenv.2020.142317
Nowadays, there is an important controversy about coronavirus air transmission. The aim of this study was to determine aerosol transmission from patients with coronavirus infection using "COVID-19 traps" that included different untouched surfaces within them. 42 swab samples of 6 different surfaces placed in the rooms of 6 patients with a positive diagnostic of COVID-19 were analyzed with RT-PCR technique to evaluate the presence of the virus and its stability. Samples were collected at 24, 48 and 72 h. Patients were in an intensive care unit (ICU) and in a COVID-19 ward unit (CWU) at a Spanish referral hospital. None of the samples placed in the ICU unit were positive for COVID-19. However, two surfaces, placed in a CWU room with a patient that required the use of respiratory assistance were positive for coronavirus at 72 h. Surfaces could not be touched by patients or health workers, so viral spreading was unequivocally produced by air transmission. Thus, fomites should be considered as a possible mode of transmission of coronavirus and frequent disinfection of surfaces should be taken into account. Our results, although preliminary, point the importance of SARS-CoV-2 virus air transmission indoors and may shed some light in this debate.
2020-09-08 2020 other brief-report; Journal Article abstract-available 10.1016/j.scitotenv.2020.142317 Evidences of SARS-CoV-2 virus air transmission indoors using several untouched surfaces: A pilot study. Orenes-Piñero E, Baño F, Navas-Carrillo D, Moreno-Docón A, Marín JM, Misiego R, Ramírez P. Sci Total Environ. 2021; 751
Respiratory viruses in foods and their potential transmission through the diet: A review of the literature.
González N, Marquès M, Domingo JL.
Environ Res. 2021; 195
DOI: 10.1016/j.envres.2021.110826
Respiratory viruses are the main agents causing respiratory tract diseases. Nowadays, coronaviruses - and specifically, SARS-CoV-1, MERS-CoV and SARS-CoV-2 - are the principal responsible for the major epidemic outbreaks of the 21st century. The major routes of transmission for respiratory viruses - including coronaviruses - are via direct and indirect contacts. However, transmission through contaminated foods has not been extensively assessed. The present paper was aimed at reviewing scientific data on the transmission of respiratory viruses through potentially contaminated foods. While the current data seem to suggest that this route of transmission is not likely to occur, in order to increase the knowledge on this issue further investigations are still clearly necessary for a more complete prevention of the risks. Studies should include fresh produce and cooked foods. Anyway, prevention measures and good hygienic practices for both consumers and workers are mandatory when handling and cooking foods.
2021-01-30 2021 other research-article; Review; Journal Article abstract-available 10.1016/j.envres.2021.110826 Respiratory viruses in foods and their potential transmission through the diet: A review of the literature. González N, Marquès M, Domingo JL. Environ Res. 2021; 195
Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection.
Monteil V, Dyczynski M, Lauschke VM, Kwon H, [...], Mirazimi A.
EMBO Mol Med. 2021; 13 (1)
DOI: 10.15252/emmm.202013426
There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely, Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials.
2020-12-14 2020 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.15252/emmm.202013426 Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection. Monteil V, Dyczynski M, Lauschke VM, Kwon H, Wirnsberger G, Youhanna S, Zhang H, Slutsky AS, Hurtado Del Pozo C, Horn M, Montserrat N, Penninger JM, Mirazimi A. EMBO Mol Med. 2021; 13 (1)
Neuropathogenesis in COVID-19.
Altable M, Moisés de la Serna J.
J Neuropathol Exp Neurol. 2020; 79 (11)
DOI: 10.1093/jnen/nlaa116
2020-11-01 2020 other Letter; Review 10.1093/jnen/nlaa116 Neuropathogenesis in COVID-19. Altable M, Moisés de la Serna J. J Neuropathol Exp Neurol. 2020; 79 (11)
Aplicación del Valor Umbral del Número de Ciclos (Ct) de PCR en la COVID-19 Application of the PCR Number of Cycle Threshold Value (Ct) in COVID-19
Garcia A, Segura-Fragoso A, Olmo-Quintana V, Pérez R, [...], Serrano-Cumplido A.
Semergen. 2021;
DOI:
La pandemia por el SARS-CoV-2 persiste con toda su virulencia a pesar de haberse administrado 650.382.819 dosis de vacuna anti-COVID a nivel mundial. La prueba de referencia para la identificación de la infección es la reacción en cadena de la polimerasa con transcriptasa inversa (RT-qPCR). La utilidad de esta prueba puede disminuir al simplificar su resultado como positivo o negativo. Determinar el número de ciclos (Ct) en las pruebas RT-qPCR positivas puede ayudar en la toma de decisiones cuando se interpretan en el contexto clínico de los pacientes.
2021-05-27 2021 other review-article; Review; Journal Article abstract-available Aplicación del Valor Umbral del Número de Ciclos (Ct) de PCR en la COVID-19 Application of the PCR Number of Cycle Threshold Value (Ct) in COVID-19 Garcia A, Segura-Fragoso A, Olmo-Quintana V, Pérez R, Barquilla-García A, Morán-Bayón A, Serrano-Cumplido A. Semergen. 2021;
Do hydrogen peroxide mouthwashes have a virucidal effect? A systematic review.
Ortega KL, Rech BO, El Haje GLC, Gallo CB, [...], Braz-Silva PH.
J Hosp Infect. 2020; 106 (4)
DOI: 10.1016/j.jhin.2020.10.003

Background

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva has alerted health professionals to the possibility of contamination by aerosols generated in a number of procedures. The indication of preoperative mouthwash containing 1% hydrogen peroxide for reducing the viral load of SARS-CoV-2 in saliva prior to oral procedures has been significantly disseminated through several citations and influenced various dental associations in the elaboration of dental care protocols during this pandemic period, including patients admitted to hospital wards and intensive care units.

Aim

To Our aim was to perform a systematic review to answer the following question: does hydrogen peroxide mouthwash (at any concentration) have a virucidal effect?

Methods

The Cochrane, LILACS, PubMed, Scopus, and Embase databases were searched by using the following key-words: 'hydrogen peroxide', 'mouthwash', 'mouth rinse', 'rinse', 'oral rinse', 'mouth bath', 'mouth wash', and 'mouth washes'. Reviews, letters to the editor, personal opinions, book chapters, case reports, congress abstracts, studies with animals and studies on mouthwash containing other compounds other than hydrogen peroxide were excluded.

Findings

During the initial search 1342 articles were identified on the five electronic databases. After excluding some duplicates, 976 articles remained. Only studies assessing the virucidal effect of hydrogen peroxide mouthwash were selected, regardless of publication date.

Conclusion

After reading titles and abstracts, no article met the eligibility criteria. In conclusion, there is no scientific evidence supporting the indication of hydrogen peroxide mouthwash for control of the viral load regarding SARS-CoV-2 or any other viruses in saliva.
2020-10-12 2020 other Systematic Review; review-article; Journal Article abstract-available 10.1016/j.jhin.2020.10.003 Do hydrogen peroxide mouthwashes have a virucidal effect? A systematic review. Ortega KL, Rech BO, El Haje GLC, Gallo CB, Pérez-Sayáns M, Braz-Silva PH. J Hosp Infect. 2020; 106 (4)
Anthropogenic Infection of Cats during the 2020 COVID-19 Pandemic.
Hosie MJ, Hofmann-Lehmann R, Hartmann K, Egberink H, [...], Möstl K.
Viruses. 2021; 13 (2)
DOI: 10.3390/v13020185
COVID-19 is a severe acute respiratory syndrome (SARS) caused by a new coronavirus (CoV), SARS-CoV-2, which is closely related to SARS-CoV that jumped the animal-human species barrier and caused a disease outbreak in 2003. SARS-CoV-2 is a betacoronavirus that was first described in 2019, unrelated to the commonly occurring feline coronavirus (FCoV) that is an alphacoronavirus associated with feline infectious peritonitis (FIP). SARS-CoV-2 is highly contagious and has spread globally within a few months, resulting in the current pandemic. Felids have been shown to be susceptible to SARS-CoV-2 infection. Particularly in the Western world, many people live in very close contact with their pet cats, and natural infections of cats in COVID-19-positive households have been described in several countries. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of experts in feline medicine from 11 European Countries, discusses the current status of SARS-CoV infections in cats. The review examines the host range of SARS-CoV-2 and human-to-animal transmissions, including infections in domestic and non-domestic felids, as well as mink-to-human/-cat transmission. It summarises current data on SARS-CoV-2 prevalence in domestic cats and the results of experimental infections of cats and provides expert opinions on the clinical relevance and prevention of SARS-CoV-2 infection in cats.
2021-01-26 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3390/v13020185 Anthropogenic Infection of Cats during the 2020 COVID-19 Pandemic. Hosie MJ, Hofmann-Lehmann R, Hartmann K, Egberink H, Truyen U, Addie DD, Belák S, Boucraut-Baralon C, Frymus T, Lloret A, Lutz H, Marsilio F, Pennisi MG, Tasker S, Thiry E, Möstl K. Viruses. 2021; 13 (2)
Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm.
Lippi G, Sanchis-Gomar F, Henry BM.
Ann Transl Med. 2020; 8 (7)
DOI: 10.21037/atm.2020.03.157
The "novel" coronavirus disease 2019 (abbreviated "COVID-19") is the third coronavirus outbreak emerging during the past two decades. This infectious disease, sustained by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has been recently declared a global pandemic by the World Health Organization. Despite the concerning epidemiological burden, many people, including some policymakers, are underestimating this pandemic and are remaining enigmatically inactive against a human pathology which, for a combination of reasons, can be reasonably defined as a perfect storm (i.e., the "wrong virus" at the "wrong time"). These many paradigmatic aspects include SARS-CoV-2 structure and peculiar biology of infection, high risk of inter-human transmission, long incubation time combined with early and sustained viral load, existence of asymptomatic or mildly-symptomatic carriers, viral shedding for days after symptom relief, unfavorable progression towards respiratory distress and death in up to 5-10% of patients thus causing dramatic healthcare challenges, as well as environmental contamination. Last but not least, the combination of the current case fatality rate with the extraordinary number of people that could be potentially infected by SARS-CoV-2 would permit to estimate that the worldwide deaths for COVID-19 may even approximate those recorded during World War II if appropriate restrictive measures for preventing human-to-human transmission are not readily undertaken. Everybody should be inexcusably aware that this is not a drill, and that the consequences of inadequate action will be tragedy.
2020-04-01 2020 other review-article; Review; Journal Article abstract-available 10.21037/atm.2020.03.157 Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm. Lippi G, Sanchis-Gomar F, Henry BM. Ann Transl Med. 2020; 8 (7)
Endocrine and metabolic aspects of the COVID-19 pandemic.
Marazuela M, Giustina A, Puig-Domingo M.
Rev Endocr Metab Disord. 2020; 21 (4)
DOI: 10.1007/s11154-020-09569-2
COVID-19 infection has tremendously impacted our daily clinical practice as well as our social living organization. Virtually all organs and biological systems suffer from this new coronavirus infection, either because the virus targets directly specific tissues or because of indirect effects. Endocrine diseases are not an exception and some of endocrine organs are at risk of direct or indirect lesion by COVID-19. Although there is still no evidence of higher predisposition to contract the infection in patients with diabetes and/or obesity, the coexistence of these conditions contributes to a worse prognosis because both conditions confer an impaired immunologic system. Cytokines storm can be amplified by these two latter conditions thereby leading to multisystemic failure and death. Glycaemic control has been demonstrated to be crucial to avoiding long hospital stays, ICU requirement and also prevention of excessive mortality. Endocrine treatment modifications as a consequence of COVID-19 infection are required in a proactive manner, in order to avoid decompensation and eventual hospital admission. This is the case of diabetes and adrenal insufficiency in which prompt increase of insulin dosage and substitutive adrenal steroids through adoption of the sick day's rules should be warranted, as well as easy contact with the health care provider through telematic different modalities. New possible endocrinological targets of COVID-19 have been recently described and warrant a full study in the next future.
2020-12-01 2020 other review-article; Review; Journal Article abstract-available 10.1007/s11154-020-09569-2 Endocrine and metabolic aspects of the COVID-19 pandemic. Marazuela M, Giustina A, Puig-Domingo M. Rev Endocr Metab Disord. 2020; 21 (4)
A compendium answering 150 questions on COVID-19 and SARS-CoV-2.
Riggioni C, Comberiati P, Giovannini M, Agache I, [...], Akdis CA.
Allergy. 2020; 75 (10)
DOI: 10.1111/all.14449
In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a "cytokine storm" leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.
2020-07-20 2020 other review-article; Review; Journal Article abstract-available 10.1111/all.14449 A compendium answering 150 questions on COVID-19 and SARS-CoV-2. Riggioni C, Comberiati P, Giovannini M, Agache I, Akdis M, Alves-Correia M, Antó JM, Arcolaci A, Azkur AK, Azkur D, Beken B, Boccabella C, Bousquet J, Breiteneder H, Carvalho D, De Las Vecillas L, Diamant Z, Eguiluz-Gracia I, Eiwegger T, Eyerich S, Fokkens W, Gao YD, Hannachi F, Johnston SL, Jutel M, Karavelia A, Klimek L, Moya B, Nadeau KC, O'Hehir R, O'Mahony L, Pfaar O, Sanak M, Schwarze J, Sokolowska M, Torres MJ, van de Veen W, van Zelm MC, Wang Y, Zhang L, Jiménez-Saiz R, Akdis CA. Allergy. 2020; 75 (10)
Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection.
Fuentes-Prior P.
J Biol Chem. 2020;
DOI: 10.1074/jbc.rev120.015980
The ongoing COVID-19 pandemic has already caused over a million deaths worldwide, and this death toll will be much higher before effective treatments and vaccines are available. The causative agent of the disease, the coronavirus SARS-CoV-2, shows important similarities with the previously emerged SARS-CoV-1, but also striking differences. First, SARS-CoV-2 possesses a significantly higher transmission rate and infectivity than SARS-CoV-1 and has infected in a few months over 60 million people. Moreover, COVID-19 has a systemic character, as in addition to the lungs it also affects heart, liver, and kidneys among other organs of the patients, and causes frequent thrombotic and neurological complications. In fact, the term "viral sepsis" has been recently coined to describe the clinical observations. Here I review current structure-function information on the viral spike proteins and the membrane fusion process to provide plausible explanations for these observations. I hypothesize that several membrane-associated serine proteinases (MASPs), in synergy with or in place of TMPRSS2, contribute to activate the SARS-CoV-2 spike protein. Relative concentrations of the attachment receptor, ACE2, MASPs, their endogenous inhibitors (the Kunitz-type transmembrane inhibitors, HAI-1/SPINT1 and HAI-2/SPINT2, as well as major circulating serpins) would determine the infection rate of host cells. The exclusive or predominant expression of major MASPs in specific human organs suggests a direct role of these proteinases in e.g. heart infection and myocardial injury, liver dysfunction, kidney damage, as well as neurological complications. Thorough consideration of these factors could have a positive impact on the control of the current COVID-19 pandemic.
2020-12-02 2020 other review-article; Review; Journal Article abstract-available 10.1074/jbc.rev120.015980 Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection. Fuentes-Prior P. J Biol Chem. 2020;
Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19.
Steardo L, Steardo L, Zorec R, Verkhratsky A.
Acta Physiol (Oxf). 2020; 229 (3)
DOI: 10.1111/apha.13473
2020-04-11 2020 other research-article; Review; Journal Article 10.1111/apha.13473 Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19. Steardo L, Steardo L, Zorec R, Verkhratsky A. Acta Physiol (Oxf). 2020; 229 (3)
Macrolides May Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Entry into Cells: A Quantitative Structure Activity Relationship Study and Experimental Validation.
Galvez J, Zanni R, Galvez-Llompart M, Benlloch JM.
J Chem Inf Model. 2021; 61 (4)
DOI: 10.1021/acs.jcim.0c01394
The global pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening the health and economic systems worldwide. Despite the enormous efforts of scientists and clinicians around the world, there is still no drug or vaccine available worldwide for the treatment and prevention of the infection. A rapid strategy for the identification of new treatments is based on repurposing existing clinically approved drugs that show antiviral activity against SARS-CoV-2 infection. In this study, after developing a quantitative structure activity relationship analysis based on molecular topology, several macrolide antibiotics are identified as promising SARS-CoV-2 spike protein inhibitors. To confirm the in silico results, the best candidates were tested against two human coronaviruses (i.e., 229E-GFP and SARS-CoV-2) in cell culture. Time-of-addition experiments and a surrogate model of viral cell entry were used to identify the steps in the virus life cycle inhibited by the compounds. Infection experiments demonstrated that azithromycin, clarithromycin, and lexithromycin reduce the intracellular accumulation of viral RNA and virus spread as well as prevent virus-induced cell death, by inhibiting the SARS-CoV-2 entry into cells. Even though the three macrolide antibiotics display a narrow antiviral activity window against SARS-CoV-2, it may be of interest to further investigate their effect on the viral spike protein and their potential in combination therapies for the coronavirus disease 19 early stage of infection.
2021-03-18 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1021/acs.jcim.0c01394 Macrolides May Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Entry into Cells: A Quantitative Structure Activity Relationship Study and Experimental Validation. Galvez J, Zanni R, Galvez-Llompart M, Benlloch JM. J Chem Inf Model. 2021; 61 (4)
COVID-19 natural herd immunity and risk of neuropsychiatric disorders.
Losilla-Rodríguez B, Maldonado N, Moreno-Mellado E, López-Díaz Á.
Rev Psiquiatr Salud Ment (Engl Ed). 2020; 13 (4)
DOI: 10.1016/j.rpsm.2020.07.002
2020-08-24 2020 other Letter; Comment 10.1016/j.rpsm.2020.07.002 COVID-19 natural herd immunity and risk of neuropsychiatric disorders. Losilla-Rodríguez B, Maldonado N, Moreno-Mellado E, López-Díaz Á. Rev Psiquiatr Salud Ment (Engl Ed). 2020; 13 (4)
The cognitive aftermath of COVID-19
Lleó A, Alcolea D.
Brain Commun. 2020;
DOI:
2020-05-27 2020 other Comment; discussion The cognitive aftermath of COVID-19 Lleó A, Alcolea D. Brain Commun. 2020;
ACE2: the molecular doorway to SARS-CoV-2.
Medina-Enríquez MM, Lopez-León S, Carlos-Escalante JA, Aponte-Torres Z, [...], Wegman-Ostrosky T.
Cell Biosci. 2020; 10 (1)
DOI: 10.1186/s13578-020-00519-8
The angiotensin-converting enzyme 2 (ACE2) is the host functional receptor for the new virus SARS-CoV-2 causing Coronavirus Disease 2019. ACE2 is expressed in 72 different cell types. Some factors that can affect the expression of the ACE2 are: sex, environment, comorbidities, medications (e.g. anti-hypertensives) and its interaction with other genes of the renin-angiotensin system and other pathways. Different factors can affect the risk of infection of SARS-CoV-2 and determine the severity of the symptoms. The ACE2 enzyme is a negative regulator of RAS expressed in various organ systems. It is with immunity, inflammation, increased coagulopathy, and cardiovascular disease. In this review, we describe the genetic and molecular functions of the ACE2 receptor and its relation with the physiological and pathological conditions to better understand how this receptor is involved in the pathogenesis of COVID-19. In addition, it reviews the different comorbidities that interact with SARS-CoV-2 in which also ACE2 plays an important role. It also describes the different factors that interact with the virus that have an influence in the expression and functional activities of the receptor. The goal is to provide the reader with an understanding of the complexity and importance of this receptor.
2020-12-30 2020 other review-article; Review; Journal Article abstract-available 10.1186/s13578-020-00519-8 ACE2: the molecular doorway to SARS-CoV-2. Medina-Enríquez MM, Lopez-León S, Carlos-Escalante JA, Aponte-Torres Z, Cuapio A, Wegman-Ostrosky T. Cell Biosci. 2020; 10 (1)
Novel Coronavirus Disease-2019 and the Gastrointestinal Tract: Lessons Learned from Human Organoids.
Jurado-Gomez A, Giraldez MD.
Gastroenterology. 2020; 159 (6)
DOI: 10.1053/j.gastro.2020.09.039
2020-10-01 2020 other Comment; discussion; Journal Article 10.1053/j.gastro.2020.09.039 Novel Coronavirus Disease-2019 and the Gastrointestinal Tract: Lessons Learned from Human Organoids. Jurado-Gomez A, Giraldez MD. Gastroenterology. 2020; 159 (6)
New-onset psychosis: A case report of brief psychosis related to COVID-19 infection.
Alba L, Coll C, Sáez S, Alonso L, [...], Ortiz S.
Psychiatry Res. 2021; 301
DOI: 10.1016/j.psychres.2021.113975
2021-04-29 2021 other Letter 10.1016/j.psychres.2021.113975 New-onset psychosis: A case report of brief psychosis related to COVID-19 infection. Alba L, Coll C, Sáez S, Alonso L, Pérez H, Palma S, Vallés V, Ortiz S. Psychiatry Res. 2021; 301
Neutralization assay with SARS-CoV-1 and SARS-CoV-2 spike pseudotyped murine leukemia virions.
Zheng Y, Larragoite ET, Williams ESCP, Lama J, [...], Planelles V.
Virol J. 2021; 18 (1)
DOI: 10.1186/s12985-020-01472-1

Background

Virus neutralization by antibodies is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal murine leukemia virus genome encoding firefly luciferase. This assay design is intended for use in laboratories with biocontainment level 2 and therefore circumvents the need for the biocontainment level 3 that would be required for replication-competent SARS-CoV-2 virus. To validate the pseudovirion assay, we set up comparisons with other available antibody tests including those from Abbott, Euroimmun and Siemens, using archived, known samples.

Results

11 out of 12 SARS-CoV-2-infected patient serum samples showed neutralizing activity against SARS-CoV-2-spike pseudotyped MLV viruses, with neutralizing titers-50 (NT50) that ranged from 1:25 to 1:1,417. Five historical samples from patients hospitalized for severe influenza infection in 2016 tested negative in the neutralization assay (NT50 < 25). Three serum samples with high neutralizing activity against SARS-CoV-2/MLV pseudoviruses showed no detectable neutralizing activity (NT50 < 25) against SARS-CoV-1/MLV pseudovirions. We also compared the semiquantitative Siemens SARS-CoV-2 IgG test, which measures binding of IgG to recombinantly expressed receptor binding domain of SARS-CoV-2 spike glycoprotein with the neutralization titers obtained in the pseudovirion assay and the results show high concordance between the two tests (R2 = 0.9344).

Conclusions

SARS-CoV-2 spike/MLV pseudovirions provide a practical means of assessing neutralizing activity of antibodies in serum or plasma from infected patients under laboratory conditions consistent with biocontainment level 2. This assay offers promise also in evaluating immunogenicity of spike glycoprotein-based candidate vaccines in the near future.
2021-01-04 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.1186/s12985-020-01472-1 Neutralization assay with SARS-CoV-1 and SARS-CoV-2 spike pseudotyped murine leukemia virions. Zheng Y, Larragoite ET, Williams ESCP, Lama J, Cisneros I, Delgado JC, Slev P, Rychert J, Innis EA, Coiras M, Rondina MT, Spivak AM, Planelles V. Virol J. 2021; 18 (1)
Coronavirus and other airborne agents with pandemic potential.
Fernandez-Montero JV, Soriano V, Barreiro P, de Mendoza C, [...], Artacho MÁ.
Curr Opin Environ Sci Health. 2020; 17
DOI: 10.1016/j.coesh.2020.09.001
The recent emergence of a novel coronavirus (severe acute respiratory syndrome coronavirus 2) has caused a pandemic, which is the most severe infectious disease outbreak in many decades. Other infective agents such as influenza as well as other neglected viruses such as Lassa virus, Nipah virus or poxviruses are also a cause for concern owing to their attack rate and potential for global spread. Drug-resistant bacteria, such as Mycobacterium tuberculosis, are already a significant public health issue in many countries, and it is expected that they will be expanding in the near future. Finally, airborne bioterrorism agents have high morbidity and mortality rates and should be looked with concern in the current international unrest.
2020-09-24 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.coesh.2020.09.001 Coronavirus and other airborne agents with pandemic potential. Fernandez-Montero JV, Soriano V, Barreiro P, de Mendoza C, Artacho MÁ. Curr Opin Environ Sci Health. 2020; 17
Longitudinal Development of Antibody Responses in COVID-19 Patients of Different Severity with ELISA, Peptide, and Glycan Arrays: An Immunological Case Series.
Heidepriem J, Dahlke C, Kobbe R, Santer R, [...], On Behalf Of The Id-Uke Covid-Study Group.
Pathogens. 2021; 10 (4)
DOI: 10.3390/pathogens10040438
The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A better understanding of its immunogenicity can be important for the development of improved diagnostics, therapeutics, and vaccines. Here, we report the longitudinal analysis of three COVID-19 patients with moderate (#1) and mild disease (#2 and #3). Antibody serum responses were analyzed using spike glycoprotein enzyme linked immunosorbent assay (ELISA), full-proteome peptide, and glycan microarrays. ELISA immunoglobulin A, G, and M (IgA, IgG, and IgM) signals increased over time for individuals #1 and #2, whereas #3 only showed no clear positive IgG and IgM result. In contrast, peptide microarrays showed increasing IgA/G signal intensity and epitope spread only in the moderate patient #1 over time, whereas early but transient IgA and stable IgG responses were observed in the two mild cases #2 and #3. Glycan arrays showed an interaction of antibodies to fragments of high-mannose and core N-glycans, present on the viral shield. In contrast to protein ELISA, microarrays allow for a deeper understanding of IgA, IgG, and IgM antibody responses to specific epitopes of the whole proteome and glycans of SARS-CoV-2 in parallel. In the future, this may help to better understand and to monitor vaccination programs and monoclonal antibodies as therapeutics.
2021-04-06 2021 other research-article; Journal Article abstract-available 10.3390/pathogens10040438 Longitudinal Development of Antibody Responses in COVID-19 Patients of Different Severity with ELISA, Peptide, and Glycan Arrays: An Immunological Case Series. Heidepriem J, Dahlke C, Kobbe R, Santer R, Koch T, Fathi A, Seco BMS, Ly ML, Schmiedel S, Schwinge D, Serna S, Sellrie K, Reichardt NC, Seeberger PH, Addo MM, Loeffler FF, On Behalf Of The Id-Uke Covid-Study Group. Pathogens. 2021; 10 (4)
COVID-19: Drug Targets and Potential Treatments.
Gil C, Ginex T, Maestro I, Nozal V, [...], Martinez A.
J Med Chem. 2020; 63 (21)
DOI: 10.1021/acs.jmedchem.0c00606
Currently, humans are immersed in a pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which threatens public health worldwide. To date, no drug or vaccine has been approved to treat the severe disease caused by this coronavirus, COVID-19. In this paper, we will focus on the main virus-based and host-based targets that can guide efforts in medicinal chemistry to discover new drugs for this devastating disease. In principle, all CoV enzymes and proteins involved in viral replication and the control of host cellular machineries are potentially druggable targets in the search for therapeutic options for SARS-CoV-2. This Perspective provides an overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response to coronavirus infection and the related therapeutic options will be presented.
2020-06-26 2020 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1021/acs.jmedchem.0c00606 COVID-19: Drug Targets and Potential Treatments. Gil C, Ginex T, Maestro I, Nozal V, Barrado-Gil L, Cuesta-Geijo MÁ, Urquiza J, Ramírez D, Alonso C, Campillo NE, Martinez A. J Med Chem. 2020; 63 (21)
Clinical Trials of Repurposed Antivirals for SARS-CoV-2.
Martinez MA.
Antimicrob Agents Chemother. 2020; 64 (9)
DOI: 10.1128/aac.01101-20
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir-ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized, controlled trials are showing poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.
2020-08-20 2020 other article-commentary; Research Support, Non-U.S. Gov't; Review; Journal Article abstract-available 10.1128/aac.01101-20 Clinical Trials of Repurposed Antivirals for SARS-CoV-2. Martinez MA. Antimicrob Agents Chemother. 2020; 64 (9)
Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins.
Díez JM, Romero C, Vergara-Alert J, Belló-Perez M, [...], Gajardo R.
Immunotherapy. 2020; 12 (17)
DOI: 10.2217/imt-2020-0220
Background: Cross-reactivity against human coronaviruses with Flebogamma® DIF and Gamunex®-C, two available intravenous immunoglobulins (IVIG), has been reported. In this study, these IVIG were tested for neutralization activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Materials & methods: Neutralization capacity of lots of IVIG manufactured prior to COVID-19 pandemic was assessed against these viruses in cell culture. Infectivity neutralization was quantified by percent reduction in plaque-forming units and/or cytopathic/cytotoxic methods. Results: All IVIG preparations showed neutralization of SARS-CoV-2 isolates. All IVIG lots produced neutralization of SARS-CoV. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion: The tested IVIG contain antibodies with significant in vitro cross-neutralization capacity against SARS-CoV-2 and SARS-CoV, but not MERS-CoV. These preparations are currently under evaluation as potential therapies for COVID-19.
2020-09-08 2020 other brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.2217/imt-2020-0220 Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins. Díez JM, Romero C, Vergara-Alert J, Belló-Perez M, Rodon J, Honrubia JM, Segalés J, Sola I, Enjuanes L, Gajardo R. Immunotherapy. 2020; 12 (17)
Silver nanoparticles as a potential treatment against SARS-CoV-2: A review.
Pilaquinga F, Morey J, Torres M, Seqqat R, [...], Piña MLN.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021;
DOI: 10.1002/wnan.1707
Several human coronaviruses (HCoVs) are distinguished by the ability to generate epidemics or pandemics, with their corresponding diseases characterized by severe respiratory illness, such as that which occurs in severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and, today, in SARS-CoV-2, an outbreak that has struck explosively and uncontrollably beginning in December 2019 and has claimed the lives of more than 1.9 M people worldwide as of January 2021. The development of vaccines has taken one year, which is why it is necessary to investigate whether some already-existing alternatives that have been successfully developed in recent years can mitigate the pandemic's advance. Silver nanoparticles (AgNPs) have proved effective in antiviral action. Thus, in this review, several in vitro and in vivo studies of the effect of AgNPs on viruses that cause respiratory diseases are analyzed and discussed to promote an understanding of the possible interaction of AgNPs with SARS-CoV-2. The study focuses on several in vivo toxicological studies of AgNPs and a dose extrapolation to humans to determine the chief avenue of exposure. It can be concluded that the use of AgNPs as a possible treatment for SARS-CoV-2 could be viable, based on comparing the virus' behavior to that of similar viruses in in vivo studies, and that the suggested route of administration in terms of least degree of adverse effects is inhalation. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.
2021-02-27 2021 other review-article; Review; Journal Article abstract-available 10.1002/wnan.1707 Silver nanoparticles as a potential treatment against SARS-CoV-2: A review. Pilaquinga F, Morey J, Torres M, Seqqat R, Piña MLN. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021;
Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features.
Hassan SS, Ghosh S, Attrish D, Choudhury PP, [...], Brufsky AM.
Molecules. 2020; 25 (24)
DOI: 10.3390/molecules25245906
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.
2020-12-13 2020 other research-article; Journal Article abstract-available 10.3390/molecules25245906 Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features. Hassan SS, Ghosh S, Attrish D, Choudhury PP, Aljabali AAA, Uhal BD, Lundstrom K, Rezaei N, Uversky VN, Seyran M, Pizzol D, Adadi P, Soares A, El-Aziz TMA, Kandimalla R, Tambuwala MM, Azad GK, Sherchan SP, Baetas-da-Cruz W, Takayama K, Serrano-Aroca Á, Chauhan G, Palu G, Brufsky AM. Molecules. 2020; 25 (24)
Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19.
Faheem, Kumar BK, Sekhar KVGC, Kunjiappan S, [...], Sankaranarayanan M.
Bioorg Chem. 2020; 104
DOI: 10.1016/j.bioorg.2020.104269
COVID-19 caused by the novel SARS-CoV-2 has been declared a pandemic by the WHO is causing havoc across the entire world. As of May end, about 6 million people have been affected, and 367 166 have died from COVID-19. Recent studies suggest that the SARS-CoV-2 genome shares about 80% similarity with the SARS-CoV-1 while their protein RNA dependent RNA polymerase (RdRp) shares 96% sequence similarity. Remdesivir, an RdRp inhibitor, exhibited potent activity against SARS-CoV-2 in vitro. 3-Chymotrypsin like protease (also known as Mpro) and papain-like protease, have emerged as the potential therapeutic targets for drug discovery against coronaviruses owing to their crucial role in viral entry and host-cell invasion. Crystal structures of therapeutically important SARS-CoV-2 target proteins, namely, RdRp, Mpro, endoribonuclease Nsp15/NendoU and receptor binding domain of CoV-2 spike protein has been resolved, which have facilitated the structure-based design and discovery of new inhibitors. Furthermore, studies have indicated that the spike proteins of SARS-CoV-2 use the Angiotensin Converting Enzyme-2 (ACE-2) receptor for its attachment similar to SARS-CoV-1, which is followed by priming of spike protein by Transmembrane protease serine 2 (TMPRSS2) which can be targeted by a proven inhibitor of TMPRSS2, camostat. The current treatment strategy includes repurposing of existing drugs that were found to be effective against other RNA viruses like SARS, MERS, and Ebola. This review presents a critical analysis of druggable targets of SARS CoV-2, new drug discovery, development, and treatment opportunities for COVID-19.
2020-09-08 2020 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.bioorg.2020.104269 Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19. Faheem, Kumar BK, Sekhar KVGC, Kunjiappan S, Jamalis J, Balaña-Fouce R, Tekwani BL, Sankaranarayanan M. Bioorg Chem. 2020; 104
Pharmacological considerations for the treatment of COVID-19 in people living with HIV (PLWH).
Gutierrez MDM, Mur I, Mateo MG, Vidal F, [...], Domingo P.
Expert Opin Pharmacother. 2021;
DOI: 10.1080/14656566.2021.1887140

Introduction

When coronavirus infectious disease-2019 (COVID-19) blew up, ill-fated auguries on the collision between COVID-19 and the human immunodeficiency virus (HIV) epidemics loomed.

Areas covered

Data from observational studies suggest similar incidence attacks of SARS-CoV-2 infection in people living with HIV (PLWH) and HIV-uninfected populations. The mortality rate of COVID-19 is similar in both populations too. The authors discuss the role of combination antiretroviral therapy (cART) in preventing infection or reducing COVID-19 severity. They also discuss the pharmacological interventions for COVID-19 in PLWH.

Expert opinion

Management of COVID-19 in PLWH is no different from the general population. It should be based on careful supportive care, emphasizing lung-protective ventilation, and wise pharmacological interventions. The antiviral drug remdesivir and dexamethasone are the only pharmacological interventions with clinical benefit for COVID-19, whereas anticoagulation may prevent thrombotic complications. The experience with using these drugs in PLWH is limited, which prevents from rendering well-founded conclusions. Until more data on COVID-19 in PLWH become available, the best weapons within our reach are sound supportive care and sensible use of RDV and dexamethasone, bearing in mind the potential for drug-drug interactions of most corticosteroids and antiretroviral drugs.
2021-02-26 2021 other research-article; Journal Article abstract-available 10.1080/14656566.2021.1887140 Pharmacological considerations for the treatment of COVID-19 in people living with HIV (PLWH). Gutierrez MDM, Mur I, Mateo MG, Vidal F, Domingo P. Expert Opin Pharmacother. 2021;
Citation Network Analysis of the Novel Coronavirus Disease 2019 (COVID-19).
Martinez-Perez C, Alvarez-Peregrina C, Villa-Collar C, Sánchez-Tena MÁ.
Int J Environ Res Public Health. 2020; 17 (20)
DOI: 10.3390/ijerph17207690

Background

The first outbreaks of the new coronavirus disease, named COVID-19, occurred at the end of December 2019. This disease spread quickly around the world, with the United States, Brazil and Mexico being the countries the most severely affected. This study aims to analyze the relationship between different publications and their authors through citation networks, as well as to identify the research areas and determine which publication has been the most cited.

Methods

The search for publications was carried out through the Web of Science database using terms such as "COVID-19" and "SARS-CoV-2" for the period between January and July 2020. The Citation Network Explorer software was used for publication analysis.

Results

A total of 14,335 publications were found with 42,374 citations generated in the network, with June being the month with the largest number of publications. The most cited publication was "Clinical Characteristics of Coronavirus Disease 2019 in China" by Guan et al., published in April 2020. Nine groups comprising different research areas in this field, including clinical course, psychology, treatment and epidemiology, were found using the clustering functionality.

Conclusions

The citation network offers an objective and comprehensive analysis of the main papers on COVID-19 and SARS-CoV-2.
2020-10-21 2020 other research-article; Journal Article abstract-available 10.3390/ijerph17207690 Citation Network Analysis of the Novel Coronavirus Disease 2019 (COVID-19). Martinez-Perez C, Alvarez-Peregrina C, Villa-Collar C, Sánchez-Tena MÁ. Int J Environ Res Public Health. 2020; 17 (20)
The Nucleocapsid protein triggers the main humoral immune response in COVID-19 patients.
Smits VAJ, Hernández-Carralero E, Paz-Cabrera MC, Cabrera E, [...], Freire R.
Biochem Biophys Res Commun. 2021; 543
DOI: 10.1016/j.bbrc.2021.01.073
In order to control the COVID-19 pandemic caused by SARS-CoV-2 infection, serious progress has been made to identify infected patients and to detect patients with a positive immune response against the virus. Currently, attempts to generate a vaccine against the coronavirus are ongoing. To understand SARS-CoV-2 immunoreactivity, we compared the IgG antibody response against SARS-CoV-2 in infected versus control patients by dot blot using recombinant viral particle proteins: N (Nucleocapsid), M (Membrane) and S (Spike). In addition, we used different protein fragments of the N and S protein to map immune epitopes. Most of the COVID-19 patients presented a specific immune response against the full length and fragments of the N protein and, to lesser extent, against a fragment containing amino acids 300-685 of the S protein. In contrast, immunoreactivity against other S protein fragments or the M protein was low. This response is specific for COVID-19 patients as very few of the control patients displayed immunoreactivity, likely reflecting an immune response against other coronaviruses. Altogether, our results may help develop method(s) for measuring COVID-19 antibody response, selectivity of methods detecting such SARS-CoV-2 antibodies and vaccine development.
2021-01-22 2021 other brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1016/j.bbrc.2021.01.073 The Nucleocapsid protein triggers the main humoral immune response in COVID-19 patients. Smits VAJ, Hernández-Carralero E, Paz-Cabrera MC, Cabrera E, Hernández-Reyes Y, Hernández-Fernaud JR, Gillespie DA, Salido E, Hernández-Porto M, Freire R. Biochem Biophys Res Commun. 2021; 543
Impact of systemic corticosteroids on mortality in older adults with critical COVID-19 pneumonia.
Piniella-Ruiz E, Bellver-Álvarez MT, Mestre-Gómez B, Escolano-Fernández B, [...], Torres-Macho J.
J Gerontol A Biol Sci Med Sci. 2021;
DOI: 10.1093/gerona/glab074

Background

The most susceptible population group to critical and fatal coronavirus disease 2019 (COVID-19) is older adults. In SARS-CoV-2 infection, the host immune response is thought to play a key role in the pathophysiological effects of lung damage. Therefore, corticosteroid therapy could modulate inflammation-mediated pulmonary injury and thereby reduce progression to severe respiratory failure and death. The aim of this study was to analyse the safety and clinical efficacy of corticosteroid therapy in older adults with severe COVID-19 pneumonia.

Method

We reviewed the clinical records of confirmed COVID-19 patients aged 75 years or older admitted to our hospital over a three months period (March 1, to May 31, 2020). A total of 143 patients were included in the study cohort. From 2 April, 2020, in accordance with World Health Organization (WHO) guidance on COVID-19, our hospital protocol added corticosteroid for COVID-19 treatment. We compared in-hospital mortality among patients with critical COVID-19 who received corticosteroids therapy and those who did not.

Results

88 patients (61.5%) were treated with corticosteroids, and 55 patients (38.4%) were not. Both groups were similar in baseline characteristics. The median age was 85 years (IQR, 82-89), and 61.5% (88/143) were male. In-hospital mortality was lower in the corticosteroid group (68.2%) compared with patients in the non-corticosteroid group (81.8%). Treatment with corticosteroids was an independent survival factor (HR=0.61; 95% CI, 0.41-0.93; P=0.006).

Conclusions

In critically ill older adults with COVID-19 pneumonia, the use of corticosteroid treatment resulted in lower mortality without severe adverse events.
2021-03-12 2021 other brief-report; Journal Article abstract-available 10.1093/gerona/glab074 Impact of systemic corticosteroids on mortality in older adults with critical COVID-19 pneumonia. Piniella-Ruiz E, Bellver-Álvarez MT, Mestre-Gómez B, Escolano-Fernández B, Vinat-Prado S, Cabezas-Olea R, Acedo-Gutiérrez MS, Akasbi-Montalvo M, Ryan-Murua P, Bustamante-Fermosel A, Muñoz-Rivas N, Santamaría-García C, Pardo-Guimerá V, Ulla-Anés M, Franco-Moreno A, Torres-Macho J. J Gerontol A Biol Sci Med Sci. 2021;
Coronavirus in cat flea: findings and questions regarding COVID-19.
Villar M, Fernández de Mera IG, Artigas-Jerónimo S, Contreras M, [...], de la Fuente J.
Parasit Vectors. 2020; 13 (1)
DOI: 10.1186/s13071-020-04292-y
The coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. Recent evidence raised the question about the possibility that cats may be a domestic host for SARS-CoV-2 with unknown implications in disease dissemination. Based on the fact that the domestic cat flea, Ctenocephalides felis, are abundant ectoparasites infesting humans, companion animals and wildlife and that coronavirus-like agents have been identified in the ectoparasite tick vector, Ixodes uriae of seabirds, herein we considered the presence of coronaviruses in general and SARS-CoV-2 in particular in C. felis. We identified coronavirus-derived and cell receptor angiotensin-converting enzyme RNA/proteins in C. felis. Although current evidence suggests that pets are probably dead-end-hosts with small risk of transmission to humans, our results suggested that cat flea may act as biological and/or mechanical vectors of SARS-CoV. Although preliminary, these results indicate a possibility of ectoparasites acting as reservoirs and vectors of SARS-CoV and related beta-coronavirus although with little disease risk due to systemic transmission route, low viremia, virus attenuation or other unknown factors. These results support the need to further study the role of animal SARS-CoV-2 hosts and their ectoparasite vectors in COVID-19 disease spread.
2020-08-10 2020 other Letter abstract-available 10.1186/s13071-020-04292-y Coronavirus in cat flea: findings and questions regarding COVID-19. Villar M, Fernández de Mera IG, Artigas-Jerónimo S, Contreras M, Gortázar C, de la Fuente J. Parasit Vectors. 2020; 13 (1)
The different manifestations of COVID-19 in adults and children: a cohort study in an intensive care unit.
Girona-Alarcon M, Bobillo-Perez S, Sole-Ribalta A, Hernandez L, [...], Kids Corona Platform.
BMC Infect Dis. 2021; 21 (1)
DOI: 10.1186/s12879-021-05786-5

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has collapsed health systems worldwide. In adults, the virus causes severe acute respiratory distress syndrome (ARDS), while in children the disease seems to be milder, although a severe multisystem inflammatory syndrome (MIS-C) has been described. The aim was to describe and compare the characteristics of the severe COVID-19 disease in adults and children.

Methods

This prospective observational cohort study included the young adults and children infected with SARS-CoV-2 between March-June 2020 and admitted to the paediatric intensive care unit. The two populations were analysed and compared focusing on their clinical and analytical characteristics and outcomes.

Results

Twenty patients were included. There were 16 adults (80%) and 4 children (20%). No mortality was recorded. All the adults were admitted due to ARDS. The median age was 32 years (IQR 23.3-41.5) and the most relevant previous pathology was obesity (n = 7, 43.7%). Thirteen (81.3%) needed mechanical ventilation, with a median PEEP of 13 (IQR 10.5-14.5). Six (37.5%) needed inotropic support due to the sedation. Eight (50%) developed a healthcare-associated infection, the most frequent of which was central line-associated bloodstream infection (n = 7, 71.4%). One patient developed a partial pulmonary thromboembolism, despite him being treated with heparin. All the children were admitted due to MIS-C. Two (50%) required mechanical ventilation. All needed inotropic support, with a median vasoactive-inotropic score of 27.5 (IQR 17.5-30). The difference in the inotropic requirements between the two populations was statistically significant (37.5% vs. 100%, p < 0.001). The biomarker values were higher in children than in adults: mid-regional pro-adrenomedullin 1.72 vs. 0.78 nmol/L (p = 0.017), procalcitonin 5.7 vs. 0.19 ng/mL (p = 0.023), and C-reactive protein 328.2 vs. 146.9 mg/L (p = 0.005). N-terminal pro-B-type natriuretic peptide and troponins were higher in children than in adults (p = 0.034 and p = 0.039, respectively).

Conclusions

Adults and children had different clinical manifestations. Adults developed severe ARDS requiring increased respiratory support, whereas children presented MIS-C with greater inotropic requirements. Biomarkers could be helpful in identifying susceptible patients, since they might change depending on the clinical features.
2021-01-20 2021 other research-article; Journal Article abstract-available 10.1186/s12879-021-05786-5 The different manifestations of COVID-19 in adults and children: a cohort study in an intensive care unit. Girona-Alarcon M, Bobillo-Perez S, Sole-Ribalta A, Hernandez L, Guitart C, Suarez R, Balaguer M, Cambra FJ, Jordan I, KIDS-Corona study group, Kids Corona Platform. BMC Infect Dis. 2021; 21 (1)
Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: A delayed pandemic?? Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada?
Serrano-Castro P, Estivill-Torrús G, Cabezudo-García P, Reyes-Bueno J, [...], Rodríguez de Fonseca F.
Neurología (English Edition). 2020; 35 (4)
DOI:
Introduction SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. Development We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. Conclusions SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.
2020-05-01 2020 other review-article; Review; Journal Article abstract-available Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: A delayed pandemic?? Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada? Serrano-Castro P, Estivill-Torrús G, Cabezudo-García P, Reyes-Bueno J, Ciano Petersen N, Aguilar-Castillo M, Suárez-Pérez J, Jiménez-Hernández M, Moya-Molina M, Oliver-Martos B, Arrabal-Gómez C, Rodríguez de Fonseca F. Neurología (English Edition). 2020; 35 (4)
Liquid-based cytological and immunohistochemical study of nasopharyngeal swab from persons under investigation for SARS-CoV-2 infection.
Parada D, Peña KB, Gumà J, Guilarte C, [...], Riu F.
Histopathology. 2021; 78 (4)
DOI: 10.1111/his.14257

Introduction

We describe cytologic and immunohistologic findings in virus transport medium on cases under investigation of SARS-CoV-2 infection.

Methods

Cytologic findings in cases under investigation of SARS-CoV-2 infection from one hundred consecutive nasopharyngeal swab were reviewed. Immunohistochemistry and SARSCoV-2 RT-PCR determination were performed to detect virus.

Results

No viral inclusions were noted in squamous cells obtained from virus transport medium. Immunohistochemical study with monoclonal antibody against SARS-CoV-2 viral nucleoprotein showed positivity in squamous cells. No positivity was present in others cellular components.

Conclusions

SARS-CoV-2 predominantly localizes squamous cells in cytology samples of patients with RT-PCR positive determination of SARSCoV-2. The results of the current study support the notion that the nasopharyngeal region is the anatomical station that SARS-CoV-2 infects first, and the infection can lead to the migration of the virus into the lower airways.
2020-11-21 2020 other research-article; Journal Article abstract-available 10.1111/his.14257 Liquid-based cytological and immunohistochemical study of nasopharyngeal swab from persons under investigation for SARS-CoV-2 infection. Parada D, Peña KB, Gumà J, Guilarte C, Riu F. Histopathology. 2021; 78 (4)
Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review.
Güemes-Villahoz N, Burgos-Blasco B, Vidal-Villegas B, Garcia-Feijoo J, [...], Konstas AG.
Adv Ther. 2020; 37 (10)
DOI: 10.1007/s12325-020-01442-7
SARS-CoV-2 is a highly transmissible virus that spreads mainly via person-to-person contact through respiratory droplets, or through contact with contaminated objects or surfaces from an infected person. At present we are passing through a phase of slow and painful understanding of the origin, epidemiological profile, clinical spectrum, and risk profile of the virus. To the best of our knowledge there is only limited and contradictory evidence concerning SARS-CoV-2 transmission through other routes. Importantly, the eye may constitute not only a potential site of virus replication but also an alternative transmission route of the virus from the ocular surface to the respiratory and gastrointestinal tract. It is therefore imperative to gain a better insight into the potential ophthalmological transmission route of the virus and establish directions on best practice and future models of care for ophthalmological patients. This review article critically evaluates available evidence on the ophthalmological mode of viral transmission and the value of earlier identification of the virus on the eye. More evidence is urgently needed to better evaluate the need for protective measures and reliable ocular diagnostic tests to diminish further pandemic spread.
2020-08-18 2020 other review-article; Review; Journal Article abstract-available 10.1007/s12325-020-01442-7 Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review. Güemes-Villahoz N, Burgos-Blasco B, Vidal-Villegas B, Garcia-Feijoo J, Arriola-Villalobos P, Martínez-de-la-Casa JM, Diaz-Valle D, Konstas AG. Adv Ther. 2020; 37 (10)
Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2.
Hassan SS, Attrish D, Ghosh S, Choudhury PP, [...], Brufsky AM.
Int J Biol Macromol. 2021; 181
DOI: 10.1016/j.ijbiomac.2021.03.199
The current Coronavirus Disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) shows similar pathology to MERS and SARS-CoV, with a current estimated fatality rate of 1.4%. Open reading frame 10 (ORF10) is a unique SARS-CoV-2 accessory protein, which contains eleven cytotoxic T lymphocyte (CTL) epitopes each of nine amino acids in length. Twenty-two unique SARS-CoV-2 ORF10 variants have been identified based on missense mutations found in sequence databases. Some of these mutations are predicted to decrease the stability of ORF10 in silico physicochemical and structural comparative analyses were carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid (aa) homology. Though there is a high degree of ORF10 protein similarity of SARS-CoV-2 and Pangolin-CoV, there are differences of these two ORF10 proteins related to their sub-structure (loop/coil region), solubility, antigenicity and shift from strand to coil at aa position 26 (tyrosine). SARS-CoV-2 ORF10, which is apparently expressed in vivo since reactive T cell clones are found in convalescent patients should be monitored for changes which could correlate with the pathogenesis of COVID-19.
2021-04-16 2021 other research-article; Journal Article abstract-available 10.1016/j.ijbiomac.2021.03.199 Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2. Hassan SS, Attrish D, Ghosh S, Choudhury PP, Uversky VN, Aljabali AAA, Lundstrom K, Uhal BD, Rezaei N, Seyran M, Pizzol D, Adadi P, Soares A, Abd El-Aziz TM, Kandimalla R, Tambuwala MM, Azad GK, Sherchan SP, Baetas-da-Cruz W, Lal A, Palù G, Takayama K, Serrano-Aroca Á, Barh D, Brufsky AM. Int J Biol Macromol. 2021; 181
COVID-19 Disease and Ophthalmology: An Update.
Amesty MA, Alió Del Barrio JL, Alió JL.
Ophthalmol Ther. 2020; 9 (3)
DOI: 10.1007/s40123-020-00260-y
The worldwide outbreak of the severe and acute respiratory coronavirus disease (COVID-19) caused by the coronavirus strain SARS-CoV-2 is currently the focal point of discussion due to the suffering this syndrome is causing to humanity. However, the ophthalmological implications of this syndrome has not yet been well described. Both eyes and tears as portals of entry and sources of contagion have been the subject of debate by many authors. The purpose of this review is to summarize the evidence currently available on COVID-19 and its ocular implications and manifestations, in both animals and humans, with the aim to facilitate prevention and educate the ophthalmological community on this subject. A review of the literature revealed that the results of some studies suggest that ocular symptoms commonly appear in patients with severe COVID-19 pneumonia and that it is possible to isolate the virus from the conjunctival sac of these patients. Conjunctivitis is not a common manifestation of the disease, but contact with infected eyes could be one route of transmission. Consequently, ophthalmologists need to have correct prevention strategies in place. Some guidelines regarding the prevention and management of ophthalmology clinics are reviewed. However, well-designed trials should be conducted to rule out other ocular manifestations that may result from COVID-19 infection and to understand the transmission of the virus through the eyes.
2020-05-22 2020 other review-article; Review; Journal Article abstract-available 10.1007/s40123-020-00260-y COVID-19 Disease and Ophthalmology: An Update. Amesty MA, Alió Del Barrio JL, Alió JL. Ophthalmol Ther. 2020; 9 (3)
The Multifacets of COVID-19 in Adult Patients: A Concise Clinical Review on Pulmonary and Extrapulmonary Manifestations for Healthcare Physicians.
Canatan D, Vives Corrons JL, De Sanctis V.
Acta Biomed. 2020; 91 (4)
DOI: 10.23750/abm.v91i4.10665
COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Most people with COVID-19 have a mild to moderate respiratory illness; others experience severe illness, such as COVID-19 pneumonia. The first and most accessible diagnostic information is from symptoms and signs from clinical examination. Infected patients present with a variety of manifestations. Formal diagnosis requires laboratory analysis of nose and throat samples, or imaging tests like CT scans. Emerging data suggest that coronavirus disease 2019 (COVID-19) has extrapulmonary manifestations. Sometimes these extra-respiratory manifestations may be the initial or only symptom of COVID-19, prior to fever or respiratory manifestations. In summary, our concise review shows that there is a wide range of symptoms that can be presented by COVID-19 patients. Extra-respiratory manifestations of SARS-CoV-2 infection have recently been observed in the rapidly increasing number of COVID-19 cases. Considering the broad spectrum of clinical manifestations and the increasing worldwide burden of the disease, there is an urgent need to rapidly scale up the diagnostic capacity to detect COVID-19 and its complications.
2020-11-10 2020 other review-article; Review; Journal Article abstract-available 10.23750/abm.v91i4.10665 The Multifacets of COVID-19 in Adult Patients: A Concise Clinical Review on Pulmonary and Extrapulmonary Manifestations for Healthcare Physicians. Canatan D, Vives Corrons JL, De Sanctis V. Acta Biomed. 2020; 91 (4)
Does the maternal-fetal transmission of SARS-CoV-2 occur during pregnancy?
Hijona Elósegui JJ, Carballo García AL, Fernández Risquez AC, Bermúdez Quintana M, [...], Expósito Montes JF.
Rev Clin Esp (Barc). 2021; 221 (2)
DOI: 10.1016/j.rceng.2020.06.002

Background and objetive

On January 7th, 2020, a new coronavirus, SARS-CoV-2, was identified, as responsible for a new human disease: COVID-19. Given its recent appearance, our current knowledge about the possible influence that this disease can exert on pregnancy is very limited. One of the unknowns to be solved is whether there is a vertical transmission of the infection during pregnancy.

Patients and methods

Using the Real-time Polymerase Chain Reaction techniques for SARS-CoV-2 nucleic acids, the possible presence of this germ in vaginal discharge and amniotic fluid was investigated in four pregnant Caucasian patients affected by mild acute symptoms of COVID-19 during the second trimester of pregnancy.

Results

There is no laboratory evidence to suggest a possible passage of SARS-CoV-2 from the infected mother to the amniotic fluid.

Conclusions

It is necessary to expand the investigation of COVID-19 cases diagnosed during pregnancy to clarify the real influence that SARS-CoV-2 has on pregnant women and their offspring, as well as those factors that modulate the disease.
2020-07-10 2020 other brief-report; Journal Article abstract-available 10.1016/j.rceng.2020.06.002 Does the maternal-fetal transmission of SARS-CoV-2 occur during pregnancy? Hijona Elósegui JJ, Carballo García AL, Fernández Risquez AC, Bermúdez Quintana M, Expósito Montes JF. Rev Clin Esp (Barc). 2021; 221 (2)
Animal models for COVID-19.
Muñoz-Fontela C, Dowling WE, Funnell SGP, Gsell PS, [...], Barouch DH.
Nature. 2020; 586 (7830)
DOI: 10.1038/s41586-020-2787-6
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.
2020-09-23 2020 other research-article; Review; Journal Article abstract-available 10.1038/s41586-020-2787-6 Animal models for COVID-19. Muñoz-Fontela C, Dowling WE, Funnell SGP, Gsell PS, Riveros-Balta AX, Albrecht RA, Andersen H, Baric RS, Carroll MW, Cavaleri M, Qin C, Crozier I, Dallmeier K, de Waal L, de Wit E, Delang L, Dohm E, Duprex WP, Falzarano D, Finch CL, Frieman MB, Graham BS, Gralinski LE, Guilfoyle K, Haagmans BL, Hamilton GA, Hartman AL, Herfst S, Kaptein SJF, Klimstra WB, Knezevic I, Krause PR, Kuhn JH, Le Grand R, Lewis MG, Liu WC, Maisonnasse P, McElroy AK, Munster V, Oreshkova N, Rasmussen AL, Rocha-Pereira J, Rockx B, Rodríguez E, Rogers TF, Salguero FJ, Schotsaert M, Stittelaar KJ, Thibaut HJ, Tseng CT, Vergara-Alert J, Beer M, Brasel T, Chan JFW, García-Sastre A, Neyts J, Perlman S, Reed DS, Richt JA, Roy CJ, Segalés J, Vasan SS, Henao-Restrepo AM, Barouch DH. Nature. 2020; 586 (7830)
Statins in COVID-19: Is there any foundation?☆ Estatinas en COVID-19: ¿existe algún fundamento?
Lima Martínez M, Contreras M, Marín W, D’Marco L.
Clínica e Investigación en Arteriosclerosis (English Edition). 2020; 32 (6)
DOI:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19). Acute respiratory distress syndrome is the main cause of death from COVID-19 and occurs due to an exaggerated inflammatory response that causes the release of pro-inflammatory cytokines such as interleukins and tumor necrosis factor-alpha (TNF-α). Statins are lipid lowering drugs with pleiotropic effects. They have shown benefit in the management of inflammatory and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Furthermore, due to their immunomodulatory properties, they have been used in the treatment of various infectious diseases such as community-acquired pneumonia and influenza. In this review we analyze the pathophysiological foundations that support the use of statins as an adjunctive treatment in patients with COVID-19.
2020-01-01 2020 other review-article; Review; Journal Article abstract-available Statins in COVID-19: Is there any foundation?☆ Estatinas en COVID-19: ¿existe algún fundamento? Lima Martínez M, Contreras M, Marín W, D’Marco L. Clínica e Investigación en Arteriosclerosis (English Edition). 2020; 32 (6)
Pathological findings in organs and tissues of patients with COVID-19: A systematic review.
Peiris S, Mesa H, Aysola A, Manivel J, [...], Reveiz L.
PLoS One. 2021; 16 (4)
DOI: 10.1371/journal.pone.0250708

Background

Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings

A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions

The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.
2021-04-28 2021 other research-article; Systematic Review; Journal Article abstract-available 10.1371/journal.pone.0250708 Pathological findings in organs and tissues of patients with COVID-19: A systematic review. Peiris S, Mesa H, Aysola A, Manivel J, Toledo J, Borges-Sa M, Aldighieri S, Reveiz L. PLoS One. 2021; 16 (4)
COVID-19 vaccine candidates based on modified vaccinia virus Ankara expressing the SARS-CoV-2 spike induce robust T- and B-cell immune responses and full efficacy in mice.
García-Arriaza J, Garaigorta U, Pérez P, Lázaro-Frías A, [...], Esteban M.
J Virol. 2021;
DOI: 10.1128/jvi.02260-20
Vaccines against SARS-CoV-2, the causative agent of the COVID-19 pandemic, are urgently needed. We developed two COVID-19 vaccines based on modified vaccinia virus Ankara (MVA) vectors expressing the entire SARS-CoV-2 spike (S) protein (MVA-CoV2-S); their immunogenicity was evaluated in mice using DNA/MVA or MVA/MVA prime/boost immunizations. Both vaccines induced robust, broad and polyfunctional S-specific CD4+ (mainly Th1) and CD8+ T-cell responses, with a T effector memory phenotype. DNA/MVA immunizations elicited higher T-cell responses. All vaccine regimens triggered high titers of IgG antibodies specific for the S, as well as for the receptor-binding domain; the predominance of the IgG2c isotype was indicative of Th1 immunity. Notably, serum samples from vaccinated mice neutralized SARS-CoV-2 in cell cultures, and those from MVA/MVA immunizations showed a higher neutralizing capacity. Remarkably, one or two doses of MVA-CoV2-S protect humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2. In addition, two doses of MVA-CoV2-S confer full inhibition of virus replication in the lungs. These results demonstrate the robust immunogenicity and full efficacy of MVA-based COVID-19 vaccines in animal models and support its translation to the clinic.IMPORTANCE The continuous dissemination of the novel emerging SARS-CoV-2 virus, with more than 78 million infected cases worldwide and higher than 1,700,000 deaths as of December 23, 2020, highlights the urgent need for the development of novel vaccines against COVID-19. With this aim, we have developed novel vaccine candidates based on the poxvirus modified vaccinia virus Ankara (MVA) strain expressing the full-length SARS-CoV-2 spike (S) protein, and we have evaluated their immunogenicity in mice using DNA/MVA or MVA/MVA prime/boost immunization protocols. The results showed the induction of a potent S-specific T-cell response and high titers of neutralizing antibodies. Remarkably, humanized K18-hACE2 mice immunized with one or two doses of the MVA-based vaccine were 100% protected from SARS-CoV-2 lethality. Moreover, two doses of the vaccine prevented virus replication in lungs. Our findings prove the robust immunogenicity and efficacy of MVA-based COVID-19 vaccines in animal models and support its translation to the clinic.
2021-01-07 2021 other research-article; Journal Article abstract-available 10.1128/jvi.02260-20 COVID-19 vaccine candidates based on modified vaccinia virus Ankara expressing the SARS-CoV-2 spike induce robust T- and B-cell immune responses and full efficacy in mice. García-Arriaza J, Garaigorta U, Pérez P, Lázaro-Frías A, Zamora C, Gastaminza P, Del Fresno C, Casasnovas JM, Sorzano CÓS, Sancho D, Esteban M. J Virol. 2021;
COVID-19 Infection During Pregnancy and Risk of Neurodevelopmental Disorders in Offspring: Time for Collaborative Research.
López-Díaz Á, Ayesa-Arriola R, Crespo-Facorro B, Ruiz-Veguilla M.
Biol Psychiatry. 2021; 89 (5)
DOI: 10.1016/j.biopsych.2020.09.011
2020-10-31 2020 other Letter 10.1016/j.biopsych.2020.09.011 COVID-19 Infection During Pregnancy and Risk of Neurodevelopmental Disorders in Offspring: Time for Collaborative Research. López-Díaz Á, Ayesa-Arriola R, Crespo-Facorro B, Ruiz-Veguilla M. Biol Psychiatry. 2021; 89 (5)
COVID-19 and oral lesions, short communication and review.
Egido-Moreno S, Valls-Roca-Umbert J, Jané-Salas E, López-López J, [...], Estrugo-Devesa A.
J Clin Exp Dent. 2021; 13 (3)
DOI: 10.4317/jced.57981

Background

The COVID-19 disease first appeared in December 2019 in Wuhan, China. The World Health Organization (WHO) declared the pandemic in March 2020, with 40 million cases and a million deaths in October 2020. COVID-19 also includes manifestations on the skin and mucous mucosal membrane. Objective: To evaluate the prevalence of the oral lesions associated to COVID-19 disease; and evaluate their clinical presentation and the hypothesized etiology.

Material and methods

An electronic literature search was performed in PubMed, Scopus and Índice Médico Español databases. The following combination of keywords and Boolean operators were used: "COVID-19 AND oral manifestations"; "COVID-19 AND oral lesions"; "COVID-19 AND mucosal lesions" ; "COVID-19 AND mucosal manifestations"; "SARS-COV-2 AND oral manifestations"; "SARS-COV-2 AND oral lesions"; "SARS-COV-2 AND mucosal lesions"; "SARS-COV-2 AND mucosal manifestations". Furthermore, the bibliography was reviewed to manually include additional articles. The risk of bias in individual studies was assessed by two blinded reviewers using the Joanna Briggs Institute (JBI) and the evidence levels of the articles found will be cataloged according to the level of evidence and grade of recommendation of Oxford Centre for Evidence-Based Medicine (CEBM).

Results

249 articles were found in the Medline / Pubmed database. There are no additional articles in the Scopus and Índice Médico Español databases. We selected 14 articles plus 5 more articles due to manual searching. Patients presented a wide variety of oral manifestations. The most prevalent were lesions with a solution of continuity (n = 48, 73.85%) and the most frequent area was the tongue (n = 41, 52.56%). The preferred treatment for the lesions is a localized one by using rinses.

Conclusions

To conclude, after the bibliographic review was performed, we can expect that the COVID-19 disease can cause cutaneous and mucosal lesions as secondary manifestations. Despite more studies being needed to confirm this. Key words:COVID-19, SARS-COV-2, oral lesions, oral manifestations.
2021-03-01 2021 other review-article; Review; Journal Article abstract-available 10.4317/jced.57981 COVID-19 and oral lesions, short communication and review. Egido-Moreno S, Valls-Roca-Umbert J, Jané-Salas E, López-López J, Estrugo-Devesa A. J Clin Exp Dent. 2021; 13 (3)
From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances.
Zeouk I, Bekhti K, Lorenzo-Morales J.
Microorganisms. 2020; 8 (6)
DOI: 10.3390/microorganisms8060850
The emergence of a novel human coronavirus (SARS-CoV-2) causing severe contagious respiratory tract infections presents a serious threat to public health worldwide. To date, there are no specific antiviral agents available for this disease, currently known as COVID-19. Therefore, genomic sequencing and therapeutic clinical trials are being conducted to develop effective antiviral agents. Several reports have investigated FDA-approved drugs as well as in silico virtual screening approaches such as molecular docking and modeling to find novel antiviral agents. Until now, antiparasitic drugs such as chloroquine have shown the most relevant results. Furthermore, there is an urgent need to understand the pathogenesis of this novel coronavirus, its transmission routes, surface survival and evolution in the environment. So far, the scientific community has indicated a possible transmission of COVID-19 via blood transfusion which is challenging in the case of asymptomatic individuals. Protocols for pathogen inactivation are also needed. In this paper, we reviewed recent findings about this life-threatening pandemic.
2020-06-04 2020 other review-article; Review; Journal Article abstract-available 10.3390/microorganisms8060850 From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances. Zeouk I, Bekhti K, Lorenzo-Morales J. Microorganisms. 2020; 8 (6)
Frequency and predictive validity of olfactory and taste dysfunction in patients with SARS-CoV-2 infection☆ Frecuencia de aparición y validez predictiva de la disfunción olfatoria y del gusto en pacientes con infección por SARS-CoV-2
Pérula de Torres L, González-Lama J, Jiménez García C, Sánchez Montero R, [...], EPICOVID Collaborative Group.
Med Clin (Engl Ed). 2021;
DOI:

Background and objective

Olfactory and taste dysfunction (OD, TD) have been considered symptoms of SARS-CoV-2 infection. However, its presence in certain populations, especially those with mild clinical symptoms, has not been clarified. The objective was to estimate the frequency of OD and TD, and its predictive validity in patients detected in Primary Care.

Patients and methods

A cross-sectional study was carried out in the Spanish National Health System. An epidemiological survey was administered to patients who were requested the PCR test for SARS-CoV-2. Odds ratio (OR) were estimated to measure the magnitude of the association between OD and TD and the existence of SARS-CoV-2 infection. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of these symptoms in SARS-CoV-2 infection were calculated.

Results

Of 1038 patients screened, 20.1% had SARS-CoV-2 infection. OD and DG were present in 64.4% (95% CI 56.0–72.1) and 56.2% (95% CI 47.9–64.2) of the subjects with infection, respectively. The OR for OD was 12.2 (95% CI 8.26–18.06) and for TD was 7.95 (95% CI 5.48–11.53). TD presented a sensitivity of 41.1% (95% CI 34.4–46.1), a specificity of 91.9% (95% CI 89.8–93.7), a PPV of 56.2% (95% CI48.0–64.2) and a NPV of 86.1% (95% CI 83.6–88.3), while the OD showed a sensitivity of 45.0% (95% CI 37.6–51.5), a specificity of 93.7% (95% CI 91.8–95.0), a PPV of 64.4% (95% CI 56.0–72.1) and a NPV of 87.1% (95% CI 84.7–89.2).

Conclusions

More than half of the subjects with SARS-CoV-2 infection have OD or TD. The presence of OD or TD could be of diagnostic utility due to its ability to predict infection in more than half of the cases.
2021-05-24 2021 other research-article; Journal Article abstract-available Frequency and predictive validity of olfactory and taste dysfunction in patients with SARS-CoV-2 infection☆ Frecuencia de aparición y validez predictiva de la disfunción olfatoria y del gusto en pacientes con infección por SARS-CoV-2 Pérula de Torres L, González-Lama J, Jiménez García C, Sánchez Montero R, Rider Garrido F, Ortega López Y, Pajares Conde D, Ramírez Baena M, Párraga Martínez I, Romero-Rodríguez E, EPICOVID Collaborative Group. Med Clin (Engl Ed). 2021;
COVID-19 Infection and Its Influence in Otorhinolaryngology-Head and Neck Surgery.
Parilli-Troconis D, Baptista P, Marcano-Lozada M, Goncalves S, [...], Chiossone-Kerdel JA.
Int Arch Otorhinolaryngol. 2020; 24 (4)
DOI: 10.1055/s-0040-1715586
Introduction  The novel coronavirus disease 2019 pandemic has rapidly spread worldwide, challenging healthcare resources and communities to an unprecedent degree. Simultaneously, the amount of clinical and scientific information released has overwhelmed journal platforms. Objectives  This review aims to summarize the available diagnostic tools and current guidelines to safely assist patients while limiting the exposure of otolaryngologists during this pandemic. Data Synthesis  Key articles were retrieved from the following databases: PubMed, Lancet, Springer Nature, BioMed Central, JAMA network and MEDLINE, as well as updated documents from the Spanish Ministry of Health, World Health Organization, Centers for Disease Control and Prevention, Spanish Association of Surgeons, ENT-UK, American College of Surgeons, and American Academy of Otolaryngology-Head and Neck Surgery. The terms used for the search were: COVID-19 , Test COVID , Surgery in COVID , 2019-nCoV , ' coronavirus' , and SARS-CoV-2 . A total of 10,245 papers were retrieved. The inclusion criteria for the review included: COVID-19 testing ( n  = 531), society guidelines for otolaryngology-head and neck surgery patient care in the outpatient clinic ( n  = 10) and surgical ( n  = 18) settings. Studies not related to COVID-19 diagnosis were excluded. Conclusion  Healthcare institutions around the world are outlining their own protocols regarding laboratory testing and personnel protective equipment usage based upon medical societies recommendations during the COVID-19 pandemic. We have summarized the available laboratory tests and their respective sensitivity and specificity. Moreover, clinical guidelines from different societies were reviewed and summarized to facilitate guidance for otolaryngologists in the operating room and in the clinical settings.
2020-09-24 2020 other review-article; Review; Journal Article abstract-available 10.1055/s-0040-1715586 COVID-19 Infection and Its Influence in Otorhinolaryngology-Head and Neck Surgery. Parilli-Troconis D, Baptista P, Marcano-Lozada M, Goncalves S, Shahal D, Chiossone-Kerdel JA. Int Arch Otorhinolaryngol. 2020; 24 (4)
The structural basis of accelerated host cell entry by SARS-CoV-2†.
Seyran M, Takayama K, Uversky VN, Lundstrom K, [...], Uhal BD.
FEBS J. 2020;
DOI: 10.1111/febs.15651
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19) that exhibits an overwhelming contagious capacity over other human coronaviruses (HCoVs). This structural snapshot describes the structural bases underlying the pandemic capacity of SARS-CoV-2 and explains its fast motion over respiratory epithelia that allow its rapid cellular entry. Based on notable viral spike (S) protein features, we propose that the flat sialic acid-binding domain at the N-terminal domain (NTD) of the S1 subunit leads to more effective first contact and interaction with the sialic acid layer over the epithelium, and this, in turn, allows faster viral 'surfing' of the epithelium and receptor scanning by SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE-2) protein on the epithelial surface is the primary entry receptor for SARS-CoV-2, and protein-protein interaction assays demonstrate high-affinity binding of the spike protein (S protein) to ACE-2. To date, no high-frequency mutations were detected at the C-terminal domain of the S1 subunit in the S protein, where the receptor-binding domain (RBD) is located. Tight binding to ACE-2 by a conserved viral RBD suggests the ACE2-RBD interaction is likely optimal. Moreover, the viral S subunit contains a cleavage site for furin and other proteases, which accelerates cell entry by SARS-CoV-2. The model proposed here describes a structural basis for the accelerated host cell entry by SARS-CoV-2 relative to other HCoVs and also discusses emerging hypotheses that are likely to contribute to the development of antiviral strategies to combat the pandemic capacity of SARS-CoV-2.
2020-12-02 2020 other article-commentary; Journal Article abstract-available 10.1111/febs.15651 The structural basis of accelerated host cell entry by SARS-CoV-2†. Seyran M, Takayama K, Uversky VN, Lundstrom K, Palù G, Sherchan SP, Attrish D, Rezaei N, Aljabali AAA, Ghosh S, Pizzol D, Chauhan G, Adadi P, Mohamed Abd El-Aziz T, Soares AG, Kandimalla R, Tambuwala M, Hassan SS, Azad GK, Pal Choudhury P, Baetas-da-Cruz W, Serrano-Aroca Á, Brufsky AM, Uhal BD. FEBS J. 2020;
Seroprevalence of SARS-CoV-2 antibodies in over 6000 healthcare workers in Spain.
Varona JF, Madurga R, Peñalver F, Abarca E, [...], Castellano Vázquez JM.
Int J Epidemiol. 2021; 50 (2)
DOI: 10.1093/ije/dyaa277

Background

Spain has one of the highest incidences of coronavirus disease 2019 (COVID-19) worldwide, so Spanish health care workers (HCW) are at high risk of exposure. Our objective was to determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence amongst HCW and factors associated with seropositivity.

Methods

A cross-sectional study evaluating 6190 workers (97.8% of the total workforce of a healthcare-system of 17 hospitals across four regions in Spain) was carried out between April and June 2020, by measuring immunoglobulin G (IgG)-SARS-CoV-2 antibody titres and related clinical data. Exposure risk was categorized as high (clinical environment; prolonged/direct contact with patients), moderate (clinical environment; non-intense/no patient contact) and low (non-clinical environment).

Results

A total of 6038 employees (mean age 43.8 years; 71% female) were included in the final analysis. A total of 662 (11.0%) were seropositive for IgG against SARS-CoV-2 (39.4% asymptomatic). Adding available PCR-testing, 713 (11.8%) employees showed evidence of previous SARS-CoV-2 infection. However, before antibody testing, 482 of them (67%) had no previous diagnosis of SARS-CoV-2-infection. Seroprevalence was higher in high- and moderate-risk exposure (12.1 and 11.4%, respectively) compared with low-grade risk subjects (7.2%), and in Madrid (13.8%) compared with Barcelona (7.6%) and Coruña (2.0%). High-risk [odds ratio (OR): 2.06; 95% confidence interval (CI): 1.63-2.62] and moderate-risk (OR: 1.77; 95% CI: 1.32-2.37) exposures were associated with positive IgG-SARS-CoV-2 antibodies after adjusting for region, age and sex. Higher antibody titres were observed in moderate-severe disease (median antibody-titre: 13.7 AU/mL) compared with mild (6.4 AU/mL) and asymptomatic (5.1 AU/mL) infection, and also in older (>60 years: 11.8 AU/mL) compared with younger (<30 years: 4.2 AU/mL) people.

Conclusions

Seroprevalence of IgG-SARS-CoV-2 antibodies in HCW is a little higher than in the general population and varies depending on regional COVID-19 incidence. The high rates of subclinical and previously undiagnosed infection observed in this study reinforce the utility of antibody screening. An occupational risk for SARS-CoV-2 infection related to working in a clinical environment was demonstrated in this HCW cohort.
2021-05-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/ije/dyaa277 Seroprevalence of SARS-CoV-2 antibodies in over 6000 healthcare workers in Spain. Varona JF, Madurga R, Peñalver F, Abarca E, Almirall C, Cruz M, Ramos E, Castellano Vázquez JM. Int J Epidemiol. 2021; 50 (2)
False-negative results of initial RT-PCR assays for COVID-19: A systematic review.
Arevalo-Rodriguez I, Buitrago-Garcia D, Simancas-Racines D, Zambrano-Achig P, [...], Zamora J.
PLoS One. 2020; 15 (12)
DOI: 10.1371/journal.pone.0242958

Background

A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19.

Methods

We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020.

Results

We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues.

Conclusions

There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence).

Systematic review registration

Protocol available on the OSF website: https://tinyurl.com/vvbgqya.
2020-12-10 2020 other research-article; Systematic Review; Journal Article abstract-available 10.1371/journal.pone.0242958 False-negative results of initial RT-PCR assays for COVID-19: A systematic review. Arevalo-Rodriguez I, Buitrago-Garcia D, Simancas-Racines D, Zambrano-Achig P, Del Campo R, Ciapponi A, Sued O, Martinez-García L, Rutjes AW, Low N, Bossuyt PM, Perez-Molina JA, Zamora J. PLoS One. 2020; 15 (12)
Reply to Althuwaybi et al.: Hospitalization Outcomes for COVID-19 in Patients with Interstitial Lung Disease: A Potential Role for Aerodigestive Pathophysiology?
Chaudhuri N, George PM, Kreuter M, Molina-Molina M, [...], Jenkins RG.
Am J Respir Crit Care Med. 2021; 203 (4)
DOI: 10.1164/rccm.202011-4146le
2021-02-01 2021 other Letter; Comment 10.1164/rccm.202011-4146le Reply to Althuwaybi <i>et al.</i>: Hospitalization Outcomes for COVID-19 in Patients with Interstitial Lung Disease: A Potential Role for Aerodigestive Pathophysiology? Chaudhuri N, George PM, Kreuter M, Molina-Molina M, Rivera-Ortega P, Stella GM, Stewart I, Spencer LG, Wells AU, Jenkins RG. Am J Respir Crit Care Med. 2021; 203 (4)
Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity.
Carrillo J, Izquierdo-Useros N, Ávila-Nieto C, Pradenas E, [...], Blanco J.
Biochem Biophys Res Commun. 2021; 538
DOI: 10.1016/j.bbrc.2020.10.108
The magnitude and the quality of humoral responses against SARS-CoV-2 have been associated with clinical outcome. Although the elicitation of humoral responses against different viral proteins is rapid and occurs in most infected individuals, its magnitude is highly variable among them and positively correlates with COVID-19 disease severity. This rapid response is characterized by the almost concomitant appearance of virus-specific IgG, IgA and IgM antibodies that contain neutralizing antibodies directed against different epitopes of the Spike glycoprotein. Of particularly interest, the antibodies against domain of the Spike that interacts with the cellular receptor ACE2, known as the receptor binding domain (RBD), are present in most infected individuals and are block viral entry and infectivity. Such neutralizing antibodies protect different animal species when administered before virus exposure; therefore, its elicitation is the main target of current vaccine approaches and their clinical use as recombinant monoclonal antibodies (mAbs) is being explored. Yet, little information exists on the duration of humoral responses during natural infection. This is a key issue that will impact the management of the pandemic and determine the utility of seroconversion studies and the level of herd immunity. Certainly, several cases of reinfection have been reported, suggesting that immunity could be transient, as reported for other coronaviruses. In summary, although the kinetics of the generation of antibodies against SASR-CoV-2 and their protective activity have been clearly defined, their role in COVID-19 pathogenesis and the length of these responses are still open questions.
2020-11-07 2020 other brief-report; Research Support, Non-U.S. Gov't; Review; Journal Article abstract-available 10.1016/j.bbrc.2020.10.108 Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity. Carrillo J, Izquierdo-Useros N, Ávila-Nieto C, Pradenas E, Clotet B, Blanco J. Biochem Biophys Res Commun. 2021; 538
Coronavirus Disease-19: An Interim Evidence Synthesis of the World Association for Infectious Diseases and Immunological Disorders (Waidid).
Abu-Raya B, Migliori GB, O'Ryan M, Edwards K, [...], Esposito S.
Front Med (Lausanne). 2020; 7
DOI: 10.3389/fmed.2020.572485
Coronavirus disease 2019 (COVID-19) is a rapidly evolving, highly transmissible, and potentially lethal pandemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of June 11 2020, more than 7,000,000 COVID-19 cases have been reported worldwide, and more than 400,000 patients have died, affecting at least 188 countries. While literature on the disease is rapidly accumulating, an integrated, multinational perspective on clinical manifestations, immunological effects, diagnosis, prevention, and treatment of COVID-19 can be of global benefit. We aimed to synthesize the most relevant literature and experiences in different parts of the world through our global consortium of experts to provide a consensus-based document at this early stage of the pandemic.
2020-10-30 2020 other review-article; Review; Journal Article abstract-available 10.3389/fmed.2020.572485 Coronavirus Disease-19: An Interim Evidence Synthesis of the World Association for Infectious Diseases and Immunological Disorders (Waidid). Abu-Raya B, Migliori GB, O'Ryan M, Edwards K, Torres A, Alffenaar JW, Märtson AG, Centis R, D'Ambrosio L, Flanagan K, Hung I, Lauretani F, Leung CC, Leuridan E, Maertens K, Maggio MG, Nadel S, Hens N, Niesters H, Osterhaus A, Pontali E, Principi N, Rossato Silva D, Omer S, Spanevello A, Sverzellati N, Tan T, Torres-Torreti JP, Visca D, Esposito S. Front Med (Lausanne). 2020; 7
SARS-CoV-2 Seroprevalence in Household Domestic Ferrets (Mustela putorius furo).
Giner J, Villanueva-Saz S, Tobajas AP, Pérez MD, [...], Fernández A.
Animals (Basel). 2021; 11 (3)
DOI: 10.3390/ani11030667
Animal infections with SARS-CoV-2 have been reported in different countries and several animal species have been proven to be susceptible to infection with SARS-CoV-2 both naturally and by experimental infection. Moreover, infections under natural conditions in more than 20 mink farms have been reported where humans could have been the source of infection for minks. However, little information is available about the susceptibility of pet animals under natural conditions and currently there is no SARS-CoV-2 epidemiological assessment occurrence in household ferrets. In this study, the presence of SARS-CoV-2 antibodies was evaluated in serum samples obtained from 127 household ferrets (Mustela putorius furo) in the Province of Valencia (Spain). Two ferrets tested positive to SARS-CoV-2 (1.57%) by in-house enzyme-linked immunosorbent assay based on receptor binding domain (RBD) of Spike antigen. Furthermore, anti-RBD SARS-CoV-2 antibodies persisted at detectable levels in a seropositive SARS-CoV-2 domestic ferret beyond 129 days since the first time antibodies were detected. This study reports for the first time the evidence of household pet ferrets exposure to SARS-CoV-2 in Spain to date.
2021-03-02 2021 other research-article; Journal Article abstract-available 10.3390/ani11030667 SARS-CoV-2 Seroprevalence in Household Domestic Ferrets (<i>Mustela putorius furo</i>). Giner J, Villanueva-Saz S, Tobajas AP, Pérez MD, González A, Verde M, Yzuel A, García-García A, Taleb V, Lira-Navarrete E, Hurtado-Guerrero R, Pardo J, Santiago L, Paño JR, Ruíz H, Lacasta D, Fernández A. Animals (Basel). 2021; 11 (3)
Diabetic Kidney Disease and COVID-19: The Crash of Two Pandemics.
D'Marco L, Puchades MJ, Romero-Parra M, Gorriz JL.
Front Med (Lausanne). 2020; 7
DOI: 10.3389/fmed.2020.00199
2020-05-06 2020 other discussion; Journal Article 10.3389/fmed.2020.00199 Diabetic Kidney Disease and COVID-19: The Crash of Two Pandemics. D'Marco L, Puchades MJ, Romero-Parra M, Gorriz JL. Front Med (Lausanne). 2020; 7
COVID-19 and endocrine and metabolic diseases. An updated statement from the European Society of Endocrinology.
Puig-Domingo M, Marazuela M, Yildiz BO, Giustina A.
Endocrine. 2021; 72 (2)
DOI: 10.1007/s12020-021-02734-w

Background

COVID-19 has completely changed our daily clinical practice as well as our social relations. Many organs and biological systems are involved in SARS-Cov-2 infection, either due to direct virus-induced damage or to indirect effects that can have systemic consequences. Endocrine system is not only an exception but its involvement in COVID-19 is so relevant that an "endocrine phenotype" of COVID-19 has progressively acquired clinical relevance.

Aim

We have been appointed by the European Society of Endocrinology (ESE) to update with the current statement ESE members and the whole endocrine community on the emerging endocrine phenotype of COVID-19 and its implication for the prevention and management of the disease.

Conclusions

Diabetes has a major role in this phenotype since it is one of the most frequent comorbidities associated with severity and mortality of COVID-19. Careful management including treatment modifications may be required for protecting our patients rather with known diabetes from the most dangerous consequences of COVID-19 or hospitalized with COVID-19, but also in patients with SARS-CoV-2 induced newly onset diabetes. Obesity increases susceptibility to SARS-CoV-2 and the risk for COVID-19 adverse outcome. Adequate nutritional management needs to be granted to patients with obesity or undernourishment in order to limit their increased susceptibility and severity of COVID-19 infection. Lack of vitamin D, hypocalcemia and vertebral fractures have also emerged as frequent findings in the hospitalized COVID-19 population and may negatively impact on the outcome of such patients. Also, in patients with adrenal insufficiency prompt adaptation of glucocorticoid doses may be needed. Moreover, in this updated statement role of sex hormones as well as peculiar pituitary and thyroid aspects of COVID-19 have been included. Finally, in view of the mass vaccination, potential implications for endocrine patients should be considered.
2021-05-08 2021 other research-article; Journal Article abstract-available 10.1007/s12020-021-02734-w COVID-19 and endocrine and metabolic diseases. An updated statement from the European Society of Endocrinology. Puig-Domingo M, Marazuela M, Yildiz BO, Giustina A. Endocrine. 2021; 72 (2)
COVID-19 and emerging spinal cord complications: A systematic review
Mondal R, Deb S, Shome G, Ganguly U, [...], Benito-León J.
Mult Scler Relat Disord. 2021; 51
DOI:

Background

: Spinal cord complications associated with coronavirus infectious disease of 2019 (COVID-19) are being widely reported. The purpose of this systematic review was to summarize so far available pieces of evidence documenting de novo novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) mediated spinal cord demyelinating diseases. Indeed, the spinal demyelinating disorders that have been reported in those patients who have suffered from COVID-19 rather than on the people already living with diagnosed or undiagnosed primary demyelinating disorders.

Methods

: We used the existing PRISMA consensus statement. Data were collected from PubMed, NIH Litcovid, EMBASE and Cochrane library databases, as well as Pre-print servers (medRxiv, bioRxiv, and pre-preints.org), until September 10, 2020, using pre-specified searching strategies.

Results

: The 21 selected articles were all case reports and included 11 (52%) men and 10 (48%) women. The mean age was of 46.7 ± 18.0. The neurological manifestations included weakness, sensory deficit, autonomic dysfunction and ataxia. In most cases, elevated cerebrospinal fluid protein as well as lymphocytic pleocytosis were found. SARS-CoV-2 was detected in five (24%) patients, meanwhile in 13 (62%) patients, the testing was negative. Testing was not performed in two cases and, in one, data were unavailable. Nearly half of the cases (N = 9) were associated with isolated long extensive transverse myelitis (LETM), whereas a combination of both LETM and patchy involvement was found in two. Only five patients had isolated short segment involvement and two patchy involvement. Furthermore, concomitant demyelination of both brain and spine was reported in six patients. Concerning the prognosis, most of the patients improved and the mortality rate was low (N = 2, <10%).

Conclusion

: Spinal cord demyelination should be added to the plethora of immune mediated neurologic complications associated with COVID-19.
2021-03-21 2021 other research-article; Journal Article abstract-available COVID-19 and emerging spinal cord complications: A systematic review Mondal R, Deb S, Shome G, Ganguly U, Lahiri D, Benito-León J. Mult Scler Relat Disord. 2021; 51
Drugs Repurposing Using QSAR, Docking and Molecular Dynamics for Possible Inhibitors of the SARS-CoV-2 Mpro Protease.
Tejera E, Munteanu CR, López-Cortés A, Cabrera-Andrade A, [...], Pérez-Castillo Y.
Molecules. 2020; 25 (21)
DOI: 10.3390/molecules25215172
Wuhan, China was the epicenter of the first zoonotic transmission of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) in December 2019 and it is the causative agent of the novel human coronavirus disease 2019 (COVID-19). Almost from the beginning of the COVID-19 outbreak several attempts were made to predict possible drugs capable of inhibiting the virus replication. In the present work a drug repurposing study is performed to identify potential SARS-CoV-2 protease inhibitors. We created a Quantitative Structure-Activity Relationship (QSAR) model based on a machine learning strategy using hundreds of inhibitor molecules of the main protease (Mpro) of the SARS-CoV coronavirus. The QSAR model was used for virtual screening of a large list of drugs from the DrugBank database. The best 20 candidates were then evaluated in-silico against the Mpro of SARS-CoV-2 by using docking and molecular dynamics analyses. Docking was done by using the Gold software, and the free energies of binding were predicted with the MM-PBSA method as implemented in AMBER. Our results indicate that levothyroxine, amobarbital and ABP-700 are the best potential inhibitors of the SARS-CoV-2 virus through their binding to the Mpro enzyme. Five other compounds showed also a negative but small free energy of binding: nikethamide, nifurtimox, rebimastat, apomine and rebastinib.
2020-11-06 2020 other research-article; Journal Article abstract-available 10.3390/molecules25215172 Drugs Repurposing Using QSAR, Docking and Molecular Dynamics for Possible Inhibitors of the SARS-CoV-2 M<sup>pro</sup> Protease. Tejera E, Munteanu CR, López-Cortés A, Cabrera-Andrade A, Pérez-Castillo Y. Molecules. 2020; 25 (21)
The calm after the storm: re-starting ART treatments safely in the wake of the COVID-19 pandemic.
ESHRE COVID-19 Working Group, Gianaroli L, Ata B, Lundin K, [...], Mocanu E.
Hum Reprod. 2021; 36 (2)
DOI: 10.1093/humrep/deaa285
The coronavirus disease 2019 (COVID-19) pandemic created a significant impact on medically assisted reproduction (MAR) services. ESHRE decided to mobilize resources in order to collect, analyse, monitor, prepare and disseminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) knowledge specifically related to ART and early pregnancy. This article presents the impact of the SARS-CoV-2 pandemic focusing on reproductive healthcare. It details the rationale behind the guidance prepared to support MAR services in organizing and managing the re-start of treatments or in case of any future wave of COVID-19 disease. The guidance includes information on patient selection and informed consent, staff and patient triage and testing, adaptation of ART services, treatment planning and code of conduct. The initiatives detailed in this article are not necessarily COVID-specific and such action plans could be applied effectively to manage similar emergency situations in different areas of medicine, in the future.
2021-01-01 2021 other Practice Guideline; review-article; Journal Article abstract-available 10.1093/humrep/deaa285 The calm after the storm: re-starting ART treatments safely in the wake of the COVID-19 pandemic. ESHRE COVID-19 Working Group, Gianaroli L, Ata B, Lundin K, Rautakallio-Hokkanen S, Tapanainen JS, Vermeulen N, Veiga A, Mocanu E. Hum Reprod. 2021; 36 (2)
Qualitative assessment of SARS-CoV-2-specific antibody avidity by lateral flow immunochromatographic IgG/IgM antibody assay.
Valdivia A, Torres I, Huntley D, Alcaraz MJ, [...], Navarro D.
J Med Virol. 2021; 93 (2)
DOI: 10.1002/jmv.26344
Knowledge of the precise timing of SARS-CoV-2 infection may be of clinical and epidemiological relevance. The presence of low-avidity IgGs has conventionally been considered an indicator of recent infection. Here, we carried out qualitative assessment of SARS-CoV-2-specific antibody avidity using an urea (6M) dissociation test performed on a lateral flow immunochromatographic IgG/IgM device. We included a total of 76 serum specimens collected from 57 COVID-19 patients, of which 39 tested positive for both IgG and IgM and 37 only for IgG. Sera losing IgG reactivity after urea treatment (n = 28) were drawn significantly earlier (P = .04) after onset of symptoms than those which preserved it (n = 48). This assay may be helpful to estimate the time of acquisition of infection in patients with mild to severe COVID-19.
2020-08-02 2020 other brief-report; Journal Article abstract-available 10.1002/jmv.26344 Qualitative assessment of SARS-CoV-2-specific antibody avidity by lateral flow immunochromatographic IgG/IgM antibody assay. Valdivia A, Torres I, Huntley D, Alcaraz MJ, Albert E, Colomina J, Ferrer J, Carratalá A, Navarro D. J Med Virol. 2021; 93 (2)
Epitope-Based Immunoinformatics Approach on Nucleocapsid Protein of Severe Acute Respiratory Syndrome-Coronavirus-2.
Rakib A, Sami SA, Islam MA, Ahmed S, [...], Simal-Gandara J.
Molecules. 2020; 25 (21)
DOI: 10.3390/molecules25215088
With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019), as a global pandemic. Additionally, the positive cases are still following an upward trend worldwide and as a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication and interferes with host immune responses. We comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we predicted the most immunogenic epitope for the T-cell and B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.
2020-11-02 2020 other research-article; Journal Article abstract-available 10.3390/molecules25215088 Epitope-Based Immunoinformatics Approach on Nucleocapsid Protein of Severe Acute Respiratory Syndrome-Coronavirus-2. Rakib A, Sami SA, Islam MA, Ahmed S, Faiz FB, Khanam BH, Marma KKS, Rahman M, Uddin MMN, Nainu F, Emran TB, Simal-Gandara J. Molecules. 2020; 25 (21)
SAFETY PROFILE OF TREATMENTS ADMINISTERED IN COVID 19 INFECTION IN PREGNANT WOMEN.
Martínez-Sánchez N, De la Calle Fernández-Miranda M, Bartha JL.
Clin Invest Ginecol Obstet. 2021;
DOI: 10.1016/j.gine.2021.01.004
SARS-CoV-2 infection has unexpectedly arrived in our society. In pregnant women, the situation has been similar to general population. Some drugs have been used empirically, and obstetricians have to consider whether the same treatments used in the general population were valid for pregnant women with severe disease, according to their safety profile for both the mother and the foetus. There has been a wide experience with the use of hydroxychloroquine and lopinavir/ritonavir in pregnant women. Tocilizumab and interferon beta could be used if benefits exceed risks. There is no experience using remdesivir in pregnancy.
2021-02-25 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.gine.2021.01.004 SAFETY PROFILE OF TREATMENTS ADMINISTERED IN COVID 19 INFECTION IN PREGNANT WOMEN. Martínez-Sánchez N, De la Calle Fernández-Miranda M, Bartha JL. Clin Invest Ginecol Obstet. 2021;
Corona Virus Disease 2019 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition.
Turner D, Huang Y, Martín-de-Carpi J, Aloi M, [...], Paediatric IBD Porto group of ESPGHAN.
J Pediatr Gastroenterol Nutr. 2020; 70 (6)
DOI: 10.1097/mpg.0000000000002729

Introduction

With the current coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised about the risk to children with inflammatory bowel diseases (IBD). We aimed to collate global experience and provide provisional guidance for managing paediatric IBD (PIBD) in the era of COVID-19.

Methods

An electronic reporting system of children with IBD infected with SARS-CoV-2 has been circulated among 102 PIBD centres affiliated with the Porto and Interest-group of ESPGHAN. A survey has been completed by major PIBD centres in China and South-Korea to explore management during the pandemic. A third survey collected current practice of PIBD treatment. Finally, guidance points for practice have been formulated and voted upon by 37 PIBD authors and Porto group members.

Results

Eight PIBD children had COVID-19 globally, all with mild infection without needing hospitalization despite treatment with immunomodulators and/or biologics. No cases have been reported in China and South Korea but biologic treatment has been delayed in 79 children, of whom 17 (22%) had exacerbation of their IBD. Among the Porto group members, face-to-face appointments were often replaced by remote consultations but almost all did not change current IBD treatment. Ten guidance points for clinicians caring for PIBD patients in epidemic areas have been endorsed with consensus rate of 92% to 100%.

Conclusions

Preliminary data for PIBD patients during COVID-19 outbreak are reassuring. Standard IBD treatments including biologics should continue at present through the pandemic, especially in children who generally have more severe IBD course on one hand, and milder SARS-CoV-2 infection on the other.
2020-06-01 2020 other research-article; Journal Article abstract-available 10.1097/mpg.0000000000002729 Corona Virus Disease 2019 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition. Turner D, Huang Y, Martín-de-Carpi J, Aloi M, Focht G, Kang B, Zhou Y, Sanchez C, Kappelman MD, Uhlig HH, Pujol-Muncunill G, Ledder O, Lionetti P, Dias JA, Ruemmele FM, Russell RK, Paediatric IBD Porto group of ESPGHAN. J Pediatr Gastroenterol Nutr. 2020; 70 (6)
A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies.
Wang C, van Haperen R, Gutiérrez-Álvarez J, Li W, [...], Bosch BJ.
Nat Commun. 2021; 12 (1)
DOI: 10.1038/s41467-021-21968-w
The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth.
2021-03-17 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.1038/s41467-021-21968-w A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies. Wang C, van Haperen R, Gutiérrez-Álvarez J, Li W, Okba NMA, Albulescu I, Widjaja I, van Dieren B, Fernandez-Delgado R, Sola I, Hurdiss DL, Daramola O, Grosveld F, van Kuppeveld FJM, Haagmans BL, Enjuanes L, Drabek D, Bosch BJ. Nat Commun. 2021; 12 (1)
Impact of novel coronavirus infection in patients with uveitis associated with an autoimmune disease: Result of the COVID-19-GEAS patient survey☆ Impacto de la infección por el nuevo coronavirus en los pacientes con uveítis asociada a una enfermedad autoinmune: resultado de la encuesta COVID-19-GEAS pacientes
Fanlo P, Espinosa G, Adán A, Arnáez R, [...], Pallarés L.
Arch Soc Esp Oftalmol (Engl Ed). 2021;
DOI:

Introduction

The objective of these study is to know the characteristics of COVID-19 in patients with uveitis associated with Systemic Autoimmune Disease (SAD) through telematic survey.

Material and methods

Internal Medicine Society and Group of Systemic Autoimmune disease conducted a telematic survey of patients with SAD to learn about the characteristics of COVID-19 in this population.

Results

A total of 2,789 patients answered the survey, of which 28 had a diagnosis of uveitis associated with SAE. The majority (82%) were female and caucasian (82%), with a mean age of 48 years. The most frequent SAEs were Behçet’s disease followed by sarcoidosis and systemic lupus erythematosus. 46% of the patients were receiving corticosteroid treatment at a mean prednisone dose of 11 mg/day. Regarding infection, 14 (50%) patients reported symptoms compatible with SARS-CoV-2 infection. RT-PCR was performed on the nasopharyngeal smear in two patients and in one of them (4%) it was positive.

Conclusions

Both asymptomatic and symptomatic COVID-19 patients with ASD-associated UNI had received similar immunosuppressive treatment.
2021-05-19 2021 other research-article; Journal Article abstract-available Impact of novel coronavirus infection in patients with uveitis associated with an autoimmune disease: Result of the COVID-19-GEAS patient survey☆ Impacto de la infección por el nuevo coronavirus en los pacientes con uveítis asociada a una enfermedad autoinmune: resultado de la encuesta COVID-19-GEAS pacientes Fanlo P, Espinosa G, Adán A, Arnáez R, Fonollosa A, Heras H, Oteiza J, del Carmelo Gracia Tello B, Sáez Comet L, Pallarés L. Arch Soc Esp Oftalmol (Engl Ed). 2021;
Endoplasmic reticulum as a potential therapeutic target for covid-19 infection management?
Sureda A, Alizadeh J, Nabavi SF, Berindan-Neagoe I, [...], Ghavami S.
Eur J Pharmacol. 2020; 882
DOI: 10.1016/j.ejphar.2020.173288
In December 2019, many pneumonia cases with unidentified sources appeared in Wuhan, Hubei, China, with clinical symptoms like viral pneumonia. Deep sequencing analysis of samples from lower respiratory tract revealed a novel coronavirus, called 2019 novel coronavirus (2019-nCoV). Currently there is a rapid global spread. World Health Organization declare the disease a pandemic condition. The pathologic source of this disease was a new RNA virus from Coronaviridae family, which was named COVID-19. SARS-CoV-2 entry starts with the binding of the spike glycoprotein expressed on the viral envelope to ACE2 on the alveolar surface followed by clathrin-dependent endocytosis of the SARS-CoV-2 and ACE2 complex. SARS-CoV-2 enters the cells through endocytosis process, which is possibly facilitated, via a pH dependent endosomal cysteine protease cathepsins. Once inside the cells, SARS-CoV-2 exploits the endogenous transcriptional machinery of alveolar cells to replicate and spread through the entire lung. Endosomal acidic pH for SARS-CoV-2 processing and internalization is critical. After entering the cells, it possibly activates or hijack many intracellular pathways in favor of its replication. In the current opinion article, we will explain the possible involvement of unfolded protein response as a cellular stress response to the SARS-CoV-2 infection.
2020-06-17 2020 other research-article; Journal Article abstract-available 10.1016/j.ejphar.2020.173288 Endoplasmic reticulum as a potential therapeutic target for covid-19 infection management? Sureda A, Alizadeh J, Nabavi SF, Berindan-Neagoe I, Cismaru CA, Jeandet P, Łos MJ, Clementi E, Nabavi SM, Ghavami S. Eur J Pharmacol. 2020; 882
Describing variability in pig genes involved in coronavirus infections for a One Health perspective in conservation of animal genetic resources.
Bovo S, Schiavo G, Ribani A, Utzeri VJ, [...], Fontanesi L.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-82956-0
Coronaviruses silently circulate in human and animal populations, causing mild to severe diseases. Therefore, livestock are important components of a "One Health" perspective aimed to control these viral infections. However, at present there is no example that considers pig genetic resources in this context. In this study, we investigated the variability of four genes (ACE2, ANPEP and DPP4 encoding for host receptors of the viral spike proteins and TMPRSS2 encoding for a host proteinase) in 23 European (19 autochthonous and three commercial breeds and one wild boar population) and two Asian Sus scrofa populations. A total of 2229 variants were identified in the four candidate genes: 26% of them were not previously described; 29 variants affected the protein sequence and might potentially interact with the infection mechanisms. The results coming from this work are a first step towards a "One Health" perspective that should consider conservation programs of pig genetic resources with twofold objectives: (i) genetic resources could be reservoirs of host gene variability useful to design selection programs to increase resistance to coronaviruses; (ii) the described variability in genes involved in coronavirus infections across many different pig populations might be part of a risk assessment including pig genetic resources.
2021-02-09 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-021-82956-0 Describing variability in pig genes involved in coronavirus infections for a One Health perspective in conservation of animal genetic resources. Bovo S, Schiavo G, Ribani A, Utzeri VJ, Taurisano V, Ballan M, Muñoz M, Alves E, Araujo JP, Bozzi R, Charneca R, Di Palma F, Djurkin Kušec I, Etherington G, Fernandez AI, García F, García-Casco J, Karolyi D, Gallo M, Martins JM, Mercat MJ, Núñez Y, Quintanilla R, Radović Č, Razmaite V, Riquet J, Savić R, Škrlep M, Usai G, Zimmer C, Ovilo C, Fontanesi L. Sci Rep. 2021; 11 (1)
Reducing transmission of SARS-CoV-2 with intranasal prophylaxis.
Boiardi F, Stebbing J.
EBioMedicine. 2021; 63
DOI: 10.1016/j.ebiom.2020.103170
2020-12-16 2020 other discussion; Journal Article 10.1016/j.ebiom.2020.103170 Reducing transmission of SARS-CoV-2 with intranasal prophylaxis. Boiardi F, Stebbing J. EBioMedicine. 2021; 63
Inflammatory-Related Clinical and Metabolic Outcomes in COVID-19 Patients.
Martinez-Urbistondo M, Mora-Vargas A, Expósito-Palomo E, Castejón R, [...], Martinez JA.
Mediators Inflamm. 2020; 2020
DOI: 10.1155/2020/2914275

Background

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) infection elicits inflammatory manifestations that relate with a "cytokine storm."

Objective

The aim of this research was to assess the role of circulating interleukin 6 (IL-6) levels and other inflammatory markers in patients with coronavirus disease 2019 (COVID-19) on metabolic functions and accompanying clinical complications. Patients and Methods. A total of 165 patients diagnosed with COVID-19 pneumonia were examined for medical features and inflammatory markers such as blood IL-6, CRP, ferritin, LDH, neutrophil/lymphocyte index (NLI), D-Dimer, and Red Cell Distribution Width (RDW). Regression analyses concerning electronically collected medical data were adjusted by appropriate factors and confounding variables. Results. Plasma IL-6 determinations evidenced a consistent association with hospital stay days, Intensive Care Unit (ICU) admission, and mortality rates. Similar trends were found for other proinflammatory variables, where ferritin and NLI showed a remarkable value as surrogates. Hyperglycaemia and the Charlson Comorbidity Index Score were positively associated with the inflammatory response induced by the SARS-COV-2 infection. An unhealthy lifestyle such as smoking and alcoholic drinks consumption as well as excessive body adiposity influenced inflammatory-related outcomes in the screened patients.

Conclusion

IL-6 together with other inflammatory biomarkers accompanied poor clinical and metabolic outcomes in COVID-19-infected patients. IL-6 may result in a suitable proxy to individually categorise patients in order to manage this infectious pandemic.
2020-11-25 2020 other research-article; Journal Article abstract-available 10.1155/2020/2914275 Inflammatory-Related Clinical and Metabolic Outcomes in COVID-19 Patients. Martinez-Urbistondo M, Mora-Vargas A, Expósito-Palomo E, Castejón R, Citores MJ, Rosado S, de Mendoza C, Baños I, Fernández-Cruz A, Daimiel L, San-Cristóbal R, Vargas JA, Martinez JA. Mediators Inflamm. 2020; 2020
Cardiovascular Damage in COVID-19: Therapeutic Approaches Targeting the Renin-Angiotensin-Aldosterone System.
Lumpuy-Castillo J, Lorenzo-Almorós A, Pello-Lázaro AM, Sánchez-Ferrer C, [...], Lorenzo Ó.
Int J Mol Sci. 2020; 21 (18)
DOI: 10.3390/ijms21186471
Coronavirus disease 2019 (COVID-19) is usually more severe and associated with worst outcomes in individuals with pre-existing cardiovascular pathologies, including hypertension or atherothrombosis. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can differentially infect multiple tissues (i.e., lung, vessel, heart, liver) in different stages of disease, and in an age- and sex-dependent manner. In particular, cardiovascular (CV) cells (e.g., endothelial cells, cardiomyocytes) could be directly infected and indirectly disturbed by systemic alterations, leading to hyperinflammatory, apoptotic, thrombotic, and vasoconstrictive responses. Until now, hundreds of clinical trials are testing antivirals and immunomodulators to decrease SARS-CoV-2 infection or related systemic anomalies. However, new therapies targeting the CV system might reduce the severity and lethality of disease. In this line, activation of the non-canonical pathway of the renin-angiotensin-aldosterone system (RAAS) could improve CV homeostasis under COVID-19. In particular, treatments with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) may help to reduce hyperinflammation and viral propagation, while infusion of soluble ACE2 may trap plasma viral particles and increase cardioprotective Ang-(1-9) and Ang-(1-7) peptides. The association of specific ACE2 polymorphisms with increased susceptibility of infection and related CV pathologies suggests potential genetic therapies. Moreover, specific agonists of Ang-(1-7) receptor could counter-regulate the hypertensive, hyperinflammatory, and hypercoagulable responses. Interestingly, sex hormones could also regulate all these RAAS components. Therefore, while waiting for an efficient vaccine, we suggest further investigations on the non-canonical RAAS pathway to reduce cardiovascular damage and mortality in COVID-19 patients.
2020-09-04 2020 other review-article; Review; Journal Article abstract-available 10.3390/ijms21186471 Cardiovascular Damage in COVID-19: Therapeutic Approaches Targeting the Renin-Angiotensin-Aldosterone System. Lumpuy-Castillo J, Lorenzo-Almorós A, Pello-Lázaro AM, Sánchez-Ferrer C, Egido J, Tuñón J, Peiró C, Lorenzo Ó. Int J Mol Sci. 2020; 21 (18)
Lung ACE2 and ADAM17 in pulmonary arterial hypertension: Implications for COVID-19?
Pérez-Vizcaíno F.
J Heart Lung Transplant. 2020; 39 (10)
DOI: 10.1016/j.healun.2020.07.003
2020-07-14 2020 other Letter; Comment 10.1016/j.healun.2020.07.003 Lung ACE2 and ADAM17 in pulmonary arterial hypertension: Implications for COVID-19? Pérez-Vizcaíno F. J Heart Lung Transplant. 2020; 39 (10)
Determination of the Concentration of IgG against the Spike Receptor-Binding Domain That Predicts the Viral Neutralizing Activity of Convalescent Plasma and Serum against SARS-CoV-2.
Santiago L, Uranga-Murillo I, Arias M, González-Ramírez AM, [...], Pardo J.
Biology (Basel). 2021; 10 (3)
DOI: 10.3390/biology10030208
Several hundred millions of people have been diagnosed of coronavirus disease 2019 (COVID-19), causing millions of deaths and a high socioeconomic burden. SARS-CoV-2, the causative agent of COVID-19, induces both specific T- and B-cell responses, being antibodies against the virus detected a few days after infection. Passive immunization with hyperimmune plasma from convalescent patients has been proposed as a potentially useful treatment for COVID-19. Using an in-house quantitative ELISA test, we found that plasma from 177 convalescent donors contained IgG antibodies specific to the spike receptor-binding domain (RBD) of SARS-CoV-2, although at very different concentrations which correlated with previous disease severity and gender. Anti-RBD IgG plasma concentrations significantly correlated with the plasma viral neutralizing activity (VN) against SARS-CoV-2 in vitro. Similar results were found using an independent cohort of serum from 168 convalescent health workers. These results validate an in-house RBD IgG ELISA test in a large cohort of COVID-19 convalescent patients and indicate that plasma from all convalescent donors does not contain a high enough amount of anti-SARS-CoV-2-RBD neutralizing IgG to prevent SARS-CoV-2 infection in vitro. The use of quantitative anti-RBD IgG detection systems might help to predict the efficacy of the passive immunization using plasma from patients recovered from SARS-CoV-2.
2021-03-10 2021 other research-article; Journal Article abstract-available 10.3390/biology10030208 Determination of the Concentration of IgG against the Spike Receptor-Binding Domain That Predicts the Viral Neutralizing Activity of Convalescent Plasma and Serum against SARS-CoV-2. Santiago L, Uranga-Murillo I, Arias M, González-Ramírez AM, Macías-León J, Moreo E, Redrado S, García-García A, Taleb V, Lira-Navarrete E, Hurtado-Guerrero R, Aguilo N, Del Mar Encabo-Berzosa M, Hidalgo S, Galvez EM, Ramirez-Labrada A, de Miguel D, Benito R, Miranda P, Fernández A, Domingo JM, Serrano L, Yuste C, Villanueva-Saz S, Paño-Pardo JR, Pardo J. Biology (Basel). 2021; 10 (3)
Oromucosal immunomodulation as clinical spectrum mitigating factor in SARS-CoV-2 infection.
Rodríguez-Argente F, Alba-Domínguez M, Ortiz-Muñoz E, Ortega-González Á.
Scand J Immunol. 2021; 93 (1)
DOI: 10.1111/sji.12972
Mounting evidence supports the importance of mucosal immunity in the immune response to SARS-CoV-2. Active virus replication in the upper respiratory tract for the first days of infection opens a new perspective in immunological strategies to counteract viral pathogenicity. An effective mucosal innate immune response to SARS-CoV-2 paves the way to an also effective adaptive immune response. A strong local immune response seems to be crucial in the initial contention of the virus by the organism and for triggering the production of the necessary neutralizing antibodies in sera and mucosal secretions. However, if the innate immune response fails to overcome the immune evasion mechanisms displayed by the virus, the infection will progress and the lack of an adaptive immune response will take the patient to an overreactive but ineffective innate immune response. To revert this scenario, an immune strategy based on enhancement of immunity in the first days of infection would be theoretically well come. But serious concerns about cytokine response syndrome prevent us to do so. Fortunately, it is possible to enhance immune system response without causing inflammation through immunomodulation. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate our mucosal immunity, which could send an early an effective warning to the adaptive immune system. There are studies on immunotherapeutic management of upper respiratory tract infections in children that can place us in the right path to design an immune strategy able to mitigate COVID-19 symptoms and reduce clinical progression.
2020-09-18 2020 other research-article; Journal Article abstract-available 10.1111/sji.12972 Oromucosal immunomodulation as clinical spectrum mitigating factor in SARS-CoV-2 infection. Rodríguez-Argente F, Alba-Domínguez M, Ortiz-Muñoz E, Ortega-González Á. Scand J Immunol. 2021; 93 (1)
Coronavirus Disease 2019-Associated Thrombosis and Coagulopathy: Review of the Pathophysiological Characteristics and Implications for Antithrombotic Management.
Ortega-Paz L, Capodanno D, Montalescot G, Angiolillo DJ.
J Am Heart Assoc. 2021; 10 (3)
DOI: 10.1161/jaha.120.019650
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2, which has posed a significant threat to global health. Although the infection is frequently asymptomatic or associated with mild symptoms, in a small proportion of patients it can produce an intense inflammatory and prothrombotic state that can lead to acute respiratory distress syndrome, multiple organ failure, and death. Angiotensin-converting enzyme 2, highly expressed in the respiratory system, has been identified as a functional receptor for severe acute respiratory syndrome coronavirus-2. Notably, angiotensin-converting enzyme 2 is also expressed in the cardiovascular system, and there are multiple cardiovascular implications of COVID-19. Cardiovascular risk factors and cardiovascular disease have been associated with severe manifestations and poor prognosis in patients with COVID-19. More important, patients with COVID-19 may have thrombotic and coagulation abnormalities, promoting a hypercoagulable state and resulting in an increased rate of thrombotic and thromboembolic events. This review will describe the pathophysiological characteristics of the cardiovascular involvement following infection by severe acute respiratory syndrome coronavirus-2, with a focus on thrombotic and thromboembolic manifestations and implications for antithrombotic management.
2020-11-24 2020 other review-article; Review; Journal Article abstract-available 10.1161/jaha.120.019650 Coronavirus Disease 2019-Associated Thrombosis and Coagulopathy: Review of the Pathophysiological Characteristics and Implications for Antithrombotic Management. Ortega-Paz L, Capodanno D, Montalescot G, Angiolillo DJ. J Am Heart Assoc. 2021; 10 (3)
Gestation and COVID-19: clinical and microbiological observational study (Gesta-COVID19).
Suy A, Garcia-Ruiz I, Carbonell M, Garcia-Manau P, [...], Gesta-COVID19 Collaboration Group.
BMC Pregnancy Childbirth. 2021; 21 (1)
DOI: 10.1186/s12884-021-03572-4

Background

The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known.

Methods

Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres.

Discussion

There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population.
2021-01-22 2021 fondo-covid research-article; Journal Article abstract-available 10.1186/s12884-021-03572-4 Gestation and COVID-19: clinical and microbiological observational study (Gesta-COVID19). Suy A, Garcia-Ruiz I, Carbonell M, Garcia-Manau P, Rodo C, Maiz N, Sulleiro E, Anton A, Esperalba J, Fernández-Hidalgo N, Frick MA, Camba F, Pumarola T, Carreras E, Gesta-COVID19 Collaboration Group. BMC Pregnancy Childbirth. 2021; 21 (1)
Usefulness of chest ultrasound in a neonatal infection due to SARS-CoV-2.
Pineda Caplliure A, Porcar Almela M, Navarro Albert A, Muñoz Vicente E, [...], Mansilla Roig B.
An Pediatr (Engl Ed). 2021;
DOI: 10.1016/j.anpede.2021.04.001
2021-04-21 2021 other Case Reports; case-report 10.1016/j.anpede.2021.04.001 Usefulness of chest ultrasound in a neonatal infection due to SARS-CoV-2. Pineda Caplliure A, Porcar Almela M, Navarro Albert A, Muñoz Vicente E, Mansilla Roig B. An Pediatr (Engl Ed). 2021;
SARS-CoV-2 and COVID-19: A genetic, epidemiological, and evolutionary perspective.
Sironi M, Hasnain SE, Rosenthal B, Phan T, [...], Genetics and Evolution.
Infect Genet Evol. 2020; 84
DOI: 10.1016/j.meegid.2020.104384
In less than five months, COVID-19 has spread from a small focus in Wuhan, China, to more than 5 million people in almost every country in the world, dominating the concern of most governments and public health systems. The social and political distresses caused by this epidemic will certainly impact our world for a long time to come. Here, we synthesize lessons from a range of scientific perspectives rooted in epidemiology, virology, genetics, ecology and evolutionary biology so as to provide perspective on how this pandemic started, how it is developing, and how best we can stop it.
2020-05-29 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.meegid.2020.104384 SARS-CoV-2 and COVID-19: A genetic, epidemiological, and evolutionary perspective. Sironi M, Hasnain SE, Rosenthal B, Phan T, Luciani F, Shaw MA, Sallum MA, Mirhashemi ME, Morand S, González-Candelas F, Editors of Infection, Genetics and Evolution. Infect Genet Evol. 2020; 84
A molecular modelling approach for identifying antiviral selenium-containing heterocyclic compounds that inhibit the main protease of SARS-CoV-2: an in silico investigation.
Rakib A, Nain Z, Sami SA, Mahmud S, [...], Simal-Gandara J.
Brief Bioinform. 2021; 22 (2)
DOI: 10.1093/bib/bbab045
Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (Mpro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a vital role in immune functions, both directly and indirectly. Thus, we hypothesised that Se-containing heterocyclic compounds might curb the activity of SARS-CoV-2 Mpro. We performed a molecular docking analysis and found that several of the selected selenocompounds showed potential binding affinities for SARS-CoV-2 Mpro, especially ethaselen (49), which exhibited a docking score of -6.7 kcal/mol compared with the -6.5 kcal/mol score for GC376 (positive control). Drug-likeness calculations suggested that these compounds are biologically active and possess the characteristics of ideal drug candidates. Based on the binding affinity and drug-likeness results, we selected the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. We also validated the structural integrity and stability of the drug candidate through molecular dynamics simulation. Using further in vitro and in vivo experiments, we believe that the targeted compound identified in this study (ethaselen) could pave the way for the development of prospective drugs to combat SARS-CoV-2 infections and trigger specific host immune responses.
2021-03-01 2021 other Journal Article; case-report abstract-available 10.1093/bib/bbab045 A molecular modelling approach for identifying antiviral selenium-containing heterocyclic compounds that inhibit the main protease of SARS-CoV-2: an in silico investigation. Rakib A, Nain Z, Sami SA, Mahmud S, Islam A, Ahmed S, Siddiqui ABF, Babu SMOF, Hossain P, Shahriar A, Nainu F, Emran TB, Simal-Gandara J. Brief Bioinform. 2021; 22 (2)
Drug Repurposing Approach against Novel Coronavirus Disease (COVID-19) through Virtual Screening Targeting SARS-CoV-2 Main Protease.
Chowdhury KH, Chowdhury MR, Mahmud S, Tareq AM, [...], Simal-Gandara J.
Biology (Basel). 2020; 10 (1)
DOI: 10.3390/biology10010002
Novel coronavirus disease (COVID-19) was identified from China in December 2019 and spread rapidly through human-to-human transmission, affecting so many people worldwide. Until now, there has been no specific treatment against the disease and repurposing of the drug. Our investigation aimed to screen potential inhibitors against coronavirus for the repurposing of drugs. Our study analyzed sequence comparison among SARS-CoV, SARS-CoV-2, and MERS-CoV to determine the identity matrix using discovery studio. SARS-CoV-2 Mpro was targeted to generate an E-pharmacophore hypothesis to screen drugs from the DrugBank database having similar features. Promising drugs were used for docking-based virtual screening at several precisions. Best hits from virtual screening were subjected to MM/GBSA analysis to evaluate binding free energy, followed by the analysis of binding interactions. Furthermore, the molecular dynamics simulation approaches were carried out to assess the docked complex's conformational stability. A total of 33 drug classes were found from virtual screening based on their docking scores. Among them, seven potential drugs with several anticancer, antibiotic, and immunometabolic categories were screened and showed promising MM/GBSA scores. During interaction analysis, these drugs exhibited different types of hydrogen and hydrophobic interactions with amino acid residue. Besides, 17 experimental drugs selected from virtual screening might be crucial for drug discovery against COVID-19. The RMSD, RMSF, SASA, Rg, and MM/PBSA descriptors from molecular dynamics simulation confirmed the complex's firm nature. Seven promising drugs for repurposing against SARS-CoV-2 main protease (Mpro), namely sapanisertib, ornidazole, napabucasin, lenalidomide, daniquidone, indoximod, and salicylamide, could be vital for the treatment of COVID-19. However, extensive in vivo and in vitro studies are required to evaluate the mentioned drug's activity.
2020-12-23 2020 other research-article; Journal Article abstract-available 10.3390/biology10010002 Drug Repurposing Approach against Novel Coronavirus Disease (COVID-19) through Virtual Screening Targeting SARS-CoV-2 Main Protease. Chowdhury KH, Chowdhury MR, Mahmud S, Tareq AM, Hanif NB, Banu N, Reza ASMA, Emran TB, Simal-Gandara J. Biology (Basel). 2020; 10 (1)
Pharmacokinetics/Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drugs and Other Supportive Measures: A Comprehensive Review by the PK/PD of Anti-Infectives Study Group of the European Society of Antimicrobial Agents.
Zeitlinger M, Koch BCP, Bruggemann R, De Cock P, [...], Infectious Diseases (ESCMID).
Clin Pharmacokinet. 2020; 59 (10)
DOI: 10.1007/s40262-020-00924-9
There is an urgent need to identify optimal antiviral therapies for COVID-19 caused by SARS-CoV-2. We have conducted a rapid and comprehensive review of relevant pharmacological evidence, focusing on (1) the pharmacokinetics (PK) of potential antiviral therapies; (2) coronavirus-specific pharmacodynamics (PD); (3) PK and PD interactions between proposed combination therapies; (4) pharmacology of major supportive therapies; and (5) anticipated drug-drug interactions (DDIs). We found promising in vitro evidence for remdesivir, (hydroxy)chloroquine and favipiravir against SARS-CoV-2; potential clinical benefit in SARS-CoV-2 with remdesivir, the combination of lopinavir/ritonavir (LPV/r) plus ribavirin; and strong evidence for LPV/r plus ribavirin against Middle East Respiratory Syndrome (MERS) for post-exposure prophylaxis in healthcare workers. Despite these emerging data, robust controlled clinical trials assessing patient-centred outcomes remain imperative and clinical data have already reduced expectations with regard to some drugs. Any therapy should be used with caution in the light of potential drug interactions and the uncertainty of optimal doses for treating mild versus serious infections.
2020-10-01 2020 other Research Support, Non-U.S. Gov't; Systematic Review; review-article; Journal Article abstract-available 10.1007/s40262-020-00924-9 Pharmacokinetics/Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drugs and Other Supportive Measures: A Comprehensive Review by the PK/PD of Anti-Infectives Study Group of the European Society of Antimicrobial Agents. Zeitlinger M, Koch BCP, Bruggemann R, De Cock P, Felton T, Hites M, Le J, Luque S, MacGowan AP, Marriott DJE, Muller AE, Nadrah K, Paterson DL, Standing JF, Telles JP, Wölfl-Duchek M, Thy M, Roberts JA, PK/PD of Anti-Infectives Study Group (EPASG) of the European Society of Clinical Microbiology, Infectious Diseases (ESCMID). Clin Pharmacokinet. 2020; 59 (10)
Humoral responses to SARS-CoV-2 by healthy and sick dogs during the COVID-19 pandemic in Spain.
Perisé-Barrios AJ, Tomeo-Martín BD, Gómez-Ochoa P, Delgado-Bonet P, [...], Barbero-Fernández A.
Vet Res. 2021; 52 (1)
DOI: 10.1186/s13567-021-00897-y
COVID-19 is a zoonotic disease caused by SARS-CoV-2. Infections of animals with SARS-CoV-2 have recently been reported, and an increase of severe lung pathologies in domestic dogs has also been detected by veterinarians in Spain. Therefore, further descriptions of the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19 would be highly valuable. The potential for companion animals to contribute to the continued transmission and community spread of this known human-to-human disease is an urgent issue to be considered. Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound analysis, and computed tomography. Nasopharyngeal and rectal swabs were analyzed to detect canine pathogens, including SARS-CoV-2. An additional twenty healthy dogs living in SARS-CoV-2-positive households were included. Immunoglobulin detection by several immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial patterns with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. The forty sick dogs were negative for SARS-CoV-2 but Mycoplasma spp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2. Here we report that despite detecting dogs with α-SARS-CoV-2 IgG, we never obtained a positive RT-qPCR for SARS-SoV-2, not even in dogs with severe pulmonary disease; suggesting that even in the case of canine infection, transmission would be unlikely. Moreover, dogs living in COVID-19-positive households could have been more highly exposed to infection with SARS-CoV-2.
2021-02-15 2021 fondo-covid research-article; Journal Article abstract-available 10.1186/s13567-021-00897-y Humoral responses to SARS-CoV-2 by healthy and sick dogs during the COVID-19 pandemic in Spain. Perisé-Barrios AJ, Tomeo-Martín BD, Gómez-Ochoa P, Delgado-Bonet P, Plaza P, Palau-Concejo P, González J, Ortiz-Díez G, Meléndez-Lazo A, Gentil M, García-Castro J, Barbero-Fernández A. Vet Res. 2021; 52 (1)
Immune Response and COVID-19: A mirror image of Sepsis.
López-Collazo E, Avendaño-Ortiz J, Martín-Quirós A, Aguirre LA.
Int J Biol Sci. 2020; 16 (14)
DOI: 10.7150/ijbs.48400
The emergence of SARS-CoV-2 virus and its associated disease COVID-19 have triggered significant threats to public health, in addition to political and social changes. An important number of studies have reported the onset of symptoms compatible with pneumonia accompanied by coagulopathy and lymphocytopenia during COVID-19. Increased cytokine levels, the emergence of acute phase reactants, platelet activation and immune checkpoint expression are some of the biomarkers postulated in this context. As previously observed in prolonged sepsis, T-cell exhaustion due to SARS-CoV-2 and even their reduction in numbers due to apoptosis hinder the response to the infection. In this review, we synthesized the immune changes observed during COVID-19, the role of immune molecules as severity markers for patient stratification and their associated therapeutic options.
2020-07-09 2020 other review-article; Review; Journal Article abstract-available 10.7150/ijbs.48400 Immune Response and COVID-19: A mirror image of Sepsis. López-Collazo E, Avendaño-Ortiz J, Martín-Quirós A, Aguirre LA. Int J Biol Sci. 2020; 16 (14)
Ramipril in High-Risk Patients With COVID-19.
Amat-Santos IJ, Santos-Martinez S, López-Otero D, Nombela-Franco L, [...], San Román JA.
J Am Coll Cardiol. 2020; 76 (3)
DOI: 10.1016/j.jacc.2020.05.040

Background

Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory-syndrome coronavirus-2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2. This interaction has been proposed as a potential risk factor in patients treated with RAAS inhibitors.

Objectives

This study analyzed whether RAAS inhibitors modify the risk for COVID-19.

Methods

The RASTAVI (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation) trial is an ongoing randomized clinical trial randomly allocating subjects to ramipril or control groups after successful transcatheter aortic valve replacement at 14 centers in Spain. A non-pre-specified interim analysis was performed to evaluate ramipril's impact on COVID-19 risk in this vulnerable population.

Results

As of April 1, 2020, 102 patients (50 in the ramipril group and 52 in the control group) were included in the trial. Mean age was 82.3 ± 6.1 years, 56.9% of the participants were male. Median time of ramipril treatment was 6 months (interquartile range: 2.9 to 11.4 months). Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving ramipril; hazard ratio: 1.150; 95% confidence interval: 0.351 to 3.768). The risk of COVID-19 was increased in older patients (p = 0.019) and those with atrial fibrillation (p = 0.066), lower hematocrit (p = 0.084), and more comorbidities according to Society of Thoracic Surgeons score (p = 0.065). Admission and oxygen supply was required in 4.9% of patients (2 in the ramipril group and 3 in the control group), and 4 of them died (2 in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p = 0.039).

Conclusions

In a high-risk population of older patients with cardiovascular disease, randomization to ramipril had no impact on the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS inhibitor treatment during the COVID-19 crisis. (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation [RASTAVI]; NCT03201185).
2020-05-26 2020 other research-article; Multicenter Study; Journal Article abstract-available 10.1016/j.jacc.2020.05.040 Ramipril in High-Risk Patients With COVID-19. Amat-Santos IJ, Santos-Martinez S, López-Otero D, Nombela-Franco L, Gutiérrez-Ibanes E, Del Valle R, Muñoz-García E, Jiménez-Diaz VA, Regueiro A, González-Ferreiro R, Benito T, Sanmartin-Pena XC, Catalá P, Rodríguez-Gabella T, Delgado-Arana JR, Carrasco-Moraleja M, Ibañez B, San Román JA. J Am Coll Cardiol. 2020; 76 (3)
Reduced macular vessel density in COVID-19 patients with and without associated thrombotic events using optical coherence tomography angiography.
Guemes-Villahoz N, Burgos-Blasco B, Vidal-Villegas B, Donate-López J, [...], García-Feijoó J.
Graefes Arch Clin Exp Ophthalmol. 2021;
DOI: 10.1007/s00417-021-05186-0

Purpose

Thrombotic events (TE) represent one of the major complications of SARS-CoV-2 infection. The objective is to evaluate vessel density (VD) and perfusion density (PD) by optical coherence tomography angiography (OCTA) in COVID-19 patients, and compare the findings with healthy controls. The secondary objective is to evaluate if there are differences in OCTA parameters between COVID-19 patients with and without associated TE.

Methods

Cross-sectional case-control study that included patients with laboratory-confirmed diagnosis of COVID-19 with and without TE related to the infection and age-matched healthy controls. Ophthalmological examination and OCTA were performed 12 weeks after diagnosis. Demographic data and medical history were collected. Macular OCTA parameters in the superficial retinal plexus were analyzed according to ETDRS sectors.

Results

Ninety patients were included, 19 (20%) COVID-19 patients with associated TE, 47 (49.5%) COVID-19 patients without TE, and 29 (30.5%) healthy controls. Fifty-three (55.7%) were male, mean age 54.4 (SD 10.2) years. COVID-19 patients presented significantly lower VD than healthy controls: central (p = 0.003), inner ring (p = 0.026), outer ring (p = 0.001). PD was also significantly decreased: outer ring (p = 0.003), full area (p = 0.001). No differences in OCTA parameters were found between COVID-19 patients with and without TE.

Conclusions

OCTA represents a promising tool for the in vivo assessment of microvascular changes in COVID-19. Patients with SARS-CoV-2 infection show lower VD and PD compared to healthy controls. However, no differences were found between COVID-19 when considering TE. Prospective studies are required to further evaluate the retinal microvascular involvement of SARS-CoV-2 and its impact on the vasculature of other organs.
2021-05-07 2021 other research-article; Journal Article abstract-available 10.1007/s00417-021-05186-0 Reduced macular vessel density in COVID-19 patients with and without associated thrombotic events using optical coherence tomography angiography. Guemes-Villahoz N, Burgos-Blasco B, Vidal-Villegas B, Donate-López J, de la Muela MH, López-Guajardo L, Martín-Sánchez FJ, García-Feijoó J. Graefes Arch Clin Exp Ophthalmol. 2021;
Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?
Vela JM.
Front Pharmacol. 2020; 11
DOI: 10.3389/fphar.2020.582310
Outbreaks of emerging infections, such as COVID-19 pandemic especially, confront health professionals with the unique challenge of treating patients. With no time to discover new drugs, repurposing of approved drugs or in clinical development is likely the only solution. Replication of coronaviruses (CoVs) occurs in a modified membranous compartment derived from the endoplasmic reticulum (ER), causes host cell ER stress and activates pathways to facilitate adaptation of the host cell machinery to viral needs. Accordingly, modulation of ER remodeling and ER stress response might be pivotal in elucidating CoV-host interactions and provide a rationale for new therapeutic, host-based antiviral approaches. The sigma-1 receptor (Sig-1R) is a ligand-operated, ER membrane-bound chaperone that acts as an upstream modulator of ER stress and thus a candidate host protein for host-based repurposing approaches to treat COVID-19 patients. Sig-1R ligands are frequently identified in in vitro drug repurposing screens aiming to identify antiviral compounds against CoVs, including severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Sig-1R regulates key mechanisms of the adaptive host cell stress response and takes part in early steps of viral replication. It is enriched in lipid rafts and detergent-resistant ER membranes, where it colocalizes with viral replicase proteins. Indeed, the non-structural SARS-CoV-2 protein Nsp6 interacts with Sig-1R. The activity of Sig-1R ligands against COVID-19 remains to be specifically assessed in clinical trials. This review provides a rationale for targeting Sig-1R as a host-based drug repurposing approach to treat COVID-19 patients. Evidence gained using Sig-1R ligands in unbiased in vitro antiviral drug screens and the potential mechanisms underlying the modulatory effect of Sig-1R on the host cell response are discussed. Targeting Sig-1R is not expected to reduce dramatically established viral replication, but it might interfere with early steps of virus-induced host cell reprogramming, aid to slow down the course of infection, prevent the aggravation of the disease and/or allow a time window to mature a protective immune response. Sig-1R-based medicines could provide benefit not only as early intervention, preventive but also as adjuvant therapy.
2020-11-09 2020 other review-article; Review; Journal Article abstract-available 10.3389/fphar.2020.582310 Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy? Vela JM. Front Pharmacol. 2020; 11
Potential Applications of Plant Biotechnology against SARS-CoV-2.
Capell T, Twyman RM, Armario-Najera V, Ma JK, [...], Christou P.
Trends Plant Sci. 2020; 25 (7)
DOI: 10.1016/j.tplants.2020.04.009
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for an ongoing human pandemic (COVID-19). There is a massive international effort underway to develop diagnostic reagents, vaccines, and antiviral drugs in a bid to slow down the spread of the disease and save lives. One part of that international effort involves the research community working with plants, bringing researchers from all over the world together with commercial enterprises to achieve the rapid supply of protein antigens and antibodies for diagnostic kits, and scalable production systems for the emergency manufacturing of vaccines and antiviral drugs. Here, we look at some of the ways in which plants can and are being used in the fight against COVID-19.
2020-04-24 2020 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.tplants.2020.04.009 Potential Applications of Plant Biotechnology against SARS-CoV-2. Capell T, Twyman RM, Armario-Najera V, Ma JK, Schillberg S, Christou P. Trends Plant Sci. 2020; 25 (7)
The European tiered approach for virucidal efficacy testing - rationale for rapidly selecting disinfectants against emerging and re-emerging viral diseases.
Eggers M, Schwebke I, Suchomel M, Fotheringham V, [...], Steinhauer K.
Euro Surveill. 2021; 26 (3)
DOI: 10.2807/1560-7917.es.2021.26.3.2000708
When facing an emerging virus outbreak such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a quick reaction time is key to control the spread. It takes time to develop antivirals and vaccines, and implement vaccination campaigns. Therefore, preventive measures such as rapid isolation of cases and identification and early quarantine of cases' close contacts-as well as masks, physical distancing, hand hygiene, surface disinfection and air control-are crucial to reduce the risk of transmission. In this context, disinfectants and antiseptics with proven efficacy against the outbreak virus should be used. However, biocidal formulations are quite complex and may include auxiliary substances such as surfactants or emollients in addition to active substances. In order to evaluate disinfectants' efficacy objectively, meaningful efficacy data are needed. Therefore, the European Committee for Standardisation technical committee 216 'Chemical disinfectants and antiseptics' Working Group 1 (medical area) has developed standards for efficacy testing. The European tiered approach grades the virucidal efficacy in three levels, with corresponding marker test viruses. In the case of SARS-CoV-2, disinfectants with proven activity against vaccinia virus, the marker virus for the European claim 'active against enveloped viruses', should be used to ensure effective hygiene procedures to control the pandemic.
2021-01-01 2021 other discussion; Journal Article abstract-available 10.2807/1560-7917.es.2021.26.3.2000708 The European tiered approach for virucidal efficacy testing - rationale for rapidly selecting disinfectants against emerging and re-emerging viral diseases. Eggers M, Schwebke I, Suchomel M, Fotheringham V, Gebel J, Meyer B, Morace G, Roedger HJ, Roques C, Visa P, Steinhauer K. Euro Surveill. 2021; 26 (3)
Role of Monocytes/Macrophages in Covid-19 Pathogenesis: Implications for Therapy.
Gómez-Rial J, Rivero-Calle I, Salas A, Martinón-Torres F.
Infect Drug Resist. 2020; 13
DOI: 10.2147/idr.s258639
Emerging studies from SARS-CoV-2-infected patients indicate a preponderant role of monocytes/macrophages in the pathogenesis of this viral infection, in a similar way to that previously observed in other coronavirus outbreaks (SARS and MERS). The clinical presentation of severe patients resembles viral-associated hemophagocytic syndrome, a rare condition previously seen during lethal influenza pandemics and during previous SARS and MERS coronavirus outbreaks. SARS-CoV-2 infection triggers an over-exuberant inflammatory response due to the development of a cytokine storm and the depletion of the adaptative immune compartment, which may prelude sepsis in many cases. The present review summarizes past evidence on the role of monocytes/macrophages in previous coronavirus outbreaks and the emerging knowledge on their role in COVID-19 pathogenesis. Treatment strategies incorporating the blockade of migration and differentiation of monocyte-macrophage, such as granulocyte macrophage-colony stimulating factor inhibitors, might enhance the promising results seen so far with selective cytokine blockade.
2020-07-22 2020 other review-article; Review; Journal Article abstract-available 10.2147/idr.s258639 Role of Monocytes/Macrophages in Covid-19 Pathogenesis: Implications for Therapy. Gómez-Rial J, Rivero-Calle I, Salas A, Martinón-Torres F. Infect Drug Resist. 2020; 13
Where do we stand to oversee the coronaviruses in aqueous and aerosol environment? Characteristics of transmission and possible curb strategies.
Ji B, Zhao Y, Esteve-Núñez A, Liu R, [...], Wang Y.
Chem Eng J. 2021; 413
DOI: 10.1016/j.cej.2020.127522
By 17 October 2020, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused confirmed infection of more than 39,000,000 people in 217 countries and territories globally and still continues to grow. As environmental professionals, understanding how SARS-CoV-2 can be transmitted via water and air environment is a concern. We have to be ready for focusing our attention to the prompt diagnosis and potential infection control procedures of the virus in integrated water and air system. This paper reviews the state-of-the-art information from available sources of published papers, newsletters and large number of scientific websites aimed to provide a comprehensive profile on the transmission characteristics of the coronaviruses in water, sludge, and air environment, especially the water and wastewater treatment systems. The review also focused on proposing the possible curb strategies to monitor and eventually cut off the coronaviruses under the authors' knowledge and understanding.
2020-10-27 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.cej.2020.127522 Where do we stand to oversee the coronaviruses in aqueous and aerosol environment? Characteristics of transmission and possible curb strategies. Ji B, Zhao Y, Esteve-Núñez A, Liu R, Yang Y, Nzihou A, Tai Y, Wei T, Shen C, Yang Y, Ren B, Wang X, Wang Y. Chem Eng J. 2021; 413
Neurological manifestations and implications of COVID-19 pandemic.
Tsivgoulis G, Palaiodimou L, Katsanos AH, Caso V, [...], Tsiodras S.
Ther Adv Neurol Disord. 2020; 13
DOI: 10.1177/1756286420932036
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide, with a vast majority of confirmed cases presenting with respiratory symptoms. Potential neurological manifestations and their pathophysiological mechanisms have not been thoroughly established. In this narrative review, we sought to present the neurological manifestations associated with coronavirus disease 2019 (COVID-19). Case reports, case series, editorials, reviews, case-control and cohort studies were evaluated, and relevant information was abstracted. Various reports of neurological manifestations of previous coronavirus epidemics provide a roadmap regarding potential neurological complications of COVID-19, due to many shared characteristics between these viruses and SARS-CoV-2. Studies from the current pandemic are accumulating and report COVID-19 patients presenting with dizziness, headache, myalgias, hypogeusia and hyposmia, but also with more serious manifestations including polyneuropathy, myositis, cerebrovascular diseases, encephalitis and encephalopathy. However, discrimination between causal relationship and incidental comorbidity is often difficult. Severe COVID-19 shares common risk factors with cerebrovascular diseases, and it is currently unclear whether the infection per se represents an independent stroke risk factor. Regardless of any direct or indirect neurological manifestations, the COVID-19 pandemic has a huge impact on the management of neurological patients, whether infected or not. In particular, the majority of stroke services worldwide have been negatively influenced in terms of care delivery and fear to access healthcare services. The effect on healthcare quality in the field of other neurological diseases is additionally evaluated.
2020-06-09 2020 other review-article; Review; Journal Article abstract-available 10.1177/1756286420932036 Neurological manifestations and implications of COVID-19 pandemic. Tsivgoulis G, Palaiodimou L, Katsanos AH, Caso V, Köhrmann M, Molina C, Cordonnier C, Fischer U, Kelly P, Sharma VK, Chan AC, Zand R, Sarraj A, Schellinger PD, Voumvourakis KI, Grigoriadis N, Alexandrov AV, Tsiodras S. Ther Adv Neurol Disord. 2020; 13
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2.
Monteil V, Kwon H, Prado P, Hagelkrüys A, [...], Penninger JM.
Cell. 2020; 181 (4)
DOI: 10.1016/j.cell.2020.04.004
We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.
2020-04-24 2020 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1016/j.cell.2020.04.004 Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, Leopoldi A, Garreta E, Hurtado Del Pozo C, Prosper F, Romero JP, Wirnsberger G, Zhang H, Slutsky AS, Conder R, Montserrat N, Mirazimi A, Penninger JM. Cell. 2020; 181 (4)
Evolution of SARS-CoV-2 Envelope, Membrane, Nucleocapsid, and Spike Structural Proteins from the Beginning of the Pandemic to September 2020: A Global and Regional Approach by Epidemiological Week.
Troyano-Hernáez P, Reinosa R, Holguín Á.
Viruses. 2021; 13 (2)
DOI: 10.3390/v13020243
Monitoring acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity and emerging mutations in this ongoing pandemic is crucial for understanding its evolution and assuring the performance of diagnostic tests, vaccines, and therapies against coronavirus disease (COVID-19). This study reports on the amino acid (aa) conservation degree and the global and regional temporal evolution by epidemiological week for each residue of the following four structural SARS-CoV-2 proteins: spike, envelope, membrane, and nucleocapsid. All, 105,276 worldwide SARS-CoV-2 complete and partial sequences from 117 countries available in the Global Initiative on Sharing All Influenza Data (GISAID) from 29 December 2019 to 12 September 2020 were downloaded and processed using an in-house bioinformatics tool. Despite the extremely high conservation of SARS-CoV-2 structural proteins (>99%), all presented aa changes, i.e., 142 aa changes in 65 of the 75 envelope aa, 291 aa changes in 165 of the 222 membrane aa, 890 aa changes in 359 of the 419 nucleocapsid aa, and 2671 changes in 1132 of the 1273 spike aa. Mutations evolution differed across geographic regions and epidemiological weeks (epiweeks). The most prevalent aa changes were D614G (81.5%) in the spike protein, followed by the R203K and G204R combination (37%) in the nucleocapsid protein. The presented data provide insight into the genetic variability of SARS-CoV-2 structural proteins during the pandemic and highlights local and worldwide emerging aa changes of interest for further SARS-CoV-2 structural and functional analysis.
2021-02-04 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13020243 Evolution of SARS-CoV-2 Envelope, Membrane, Nucleocapsid, and Spike Structural Proteins from the Beginning of the Pandemic to September 2020: A Global and Regional Approach by Epidemiological Week. Troyano-Hernáez P, Reinosa R, Holguín Á. Viruses. 2021; 13 (2)
Pleural diseases and COVID-19: ubi fumus, ibi ignis.
Porcel JM.
Eur Respir J. 2020; 56 (5)
DOI: 10.1183/13993003.03308-2020
2020-11-19 2020 other Comment; Editorial 10.1183/13993003.03308-2020 Pleural diseases and COVID-19: <i>ubi fumus, ibi ignis</i>. Porcel JM. Eur Respir J. 2020; 56 (5)
Recommendations on the clinical management of the COVID-19 infection by the «new coronavirus» SARS-CoV2. Spanish Paediatric Association working group.
Calvo C, López-Hortelano MG, Vicente JCC, Martínez JLV, [...], colaboradores con el Ministerio de Sanidad.
An Pediatr (Engl Ed). 2020; 92 (4)
DOI: 10.1016/j.anpede.2020.02.002
On 31 December 2019, the Wuhan Municipal Committee of Health and Healthcare (Hubei Province, China) reported that there were 27 cases of pneumonia of unknown origin with symptoms starting on the 8 December. There were 7 serious cases with common exposure in market with shellfish, fish, and live animals, in the city of Wuhan. On 7 January 2020, the Chinese authorities identified that the agent causing the outbreak was a new type of virus of the Coronaviridae family, temporarily called «new coronavirus», 2019-nCoV. On January 30th, 2020, the World Health Organisation (WHO) declared the outbreak an International Emergency. On 11 February 2020 the WHO assigned it the name of SARS-CoV2 and COVID-19 (SARS-CoV2 and COVID-19). The Ministry of Health summoned the Specialties Societies to prepare a clinical protocol for the management of COVID-19. The Spanish Paediatric Association appointed a Working Group of the Societies of Paediatric Infectious Diseases and Paediatric Intensive Care to prepare the present recommendations with the evidence available at the time of preparing them.
2020-04-25 2020 other research-article; Journal Article abstract-available 10.1016/j.anpede.2020.02.002 Recommendations on the clinical management of the COVID-19 infection by the «new coronavirus» SARS-CoV2. Spanish Paediatric Association working group. Calvo C, López-Hortelano MG, Vicente JCC, Martínez JLV, Grupo de trabajo de la Asociación Española de Pediatría para el brote de infección por Coronavirus, colaboradores con el Ministerio de Sanidad. An Pediatr (Engl Ed). 2020; 92 (4)
Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens.
Díez JM, Romero C, Gajardo R.
Immunotherapy. 2020; 12 (8)
DOI: 10.2217/imt-2020-0095
Aim: There is a critical need for effective therapies that are immediately available to control the spread of COVID-19 disease. Material & methods: Gamunex®-C and Flebogamma® DIF (Grifols) intravenous immunoglobulin (IVIG) products were tested using ELISA techniques for antibodies against several antigens of human common betacoronaviruses that may crossreact with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Results: Both IVIGs showed consistent reactivity to components of the tested viruses. Positive crossreactivity was seen in SARS-CoV, middle east respiratory syndrome-CoV and SARS-CoV-2. For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 μg/ml with Gamunex-C to 1 mg/ml with Flebogamma 5% DIF. Conclusion: Gamunex-C and Flebogamma DIF contain antibodies reacting against SARS-CoV-2 antigens. Studies to confirm the utility of IVIG preparations for COVID-19 management may be warranted.
2020-05-12 2020 other brief-report; Journal Article abstract-available 10.2217/imt-2020-0095 Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens. Díez JM, Romero C, Gajardo R. Immunotherapy. 2020; 12 (8)
After corona: there is life after the pandemic.
Tesarik J.
Reprod Biomed Online. 2020; 40 (6)
DOI: 10.1016/j.rbmo.2020.04.002
The current pandemic of Coronavirus Disease 2019 (COVID-19) has focused the attention of medical-care providers away from non-life-threatening diseases, including infertility. Although infertility does not jeopardize the physical survival of infertile couples, it does jeopardize their future quality of life. Human infertility can be caused by a number of factors, some of which are age-dependent, and their effects may become irreversible if appropriate measures are not taken in time to prevent irreversible childlessness. Accordingly, each case of infertility should be evaluated comprehensively to establish its position of priority. Assisted reproductive technology (ART) makes it possible to separate fertilization and pregnancy in time. Whereas pregnant women infected with coronavirus may have an increased risk of adverse neonatal outcomes, gametes do not transmit COVID-19. Thus, performing ovarian stimulation and fertilization without delay, freezing the resulting embryos and delaying embryo transfer until the end of the pandemic appears to be the best strategy at present.
2020-04-08 2020 other Comment; discussion; Journal Article abstract-available 10.1016/j.rbmo.2020.04.002 After corona: there is life after the pandemic. Tesarik J. Reprod Biomed Online. 2020; 40 (6)
Biomarker Research and Development for Coronavirus Disease 2019 (COVID-19): European Medical Research Infrastructures Call for Global Coordination.
Oldoni E, van Gool A, García Bermejo L, Scherer A, [...], Andreu AL.
Clin Infect Dis. 2021; 72 (10)
DOI: 10.1093/cid/ciaa1250
An effective response to the coronavirus disease 2019 (COVID-19) pandemic requires a better understanding of the biology of the infection and the identification of validated biomarker profiles that would increase the availability, accuracy, and speed of COVID-19 testing. Here, we describe the strategic objectives and action lines of the European Alliance of Medical Research Infrastructures (AMRI), established to improve the research process and tackle challenges related to diagnostic tests and biomarker development. Recommendations include: the creation of a European taskforce for validation of novel diagnostic products, the definition and promotion of criteria for COVID-19 samples biobanking, the identification and validation of biomarkers as clinical endpoints for clinical trials, and the definition of immune biomarker signatures at different stages of the disease. An effective management of the COVID-19 pandemic is possible only if there is a high level of knowledge and coordination between the public and private sectors within a robust quality framework.
2021-05-01 2021 other review-article; Journal Article abstract-available 10.1093/cid/ciaa1250 Biomarker Research and Development for Coronavirus Disease 2019 (COVID-19): European Medical Research Infrastructures Call for Global Coordination. Oldoni E, van Gool A, García Bermejo L, Scherer A, Mayrhofer MT, Florindi F, Demotes J, Kubiak C, Fauvel AC, Bietrix F, Ussi A, Andreu AL. Clin Infect Dis. 2021; 72 (10)
SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates.
Kyriakidis NC, López-Cortés A, González EV, Grimaldos AB, [...], Prado EO.
NPJ Vaccines. 2021; 6 (1)
DOI: 10.1038/s41541-021-00292-w
The new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.
2021-02-22 2021 other review-article; Review; Journal Article abstract-available 10.1038/s41541-021-00292-w SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. Kyriakidis NC, López-Cortés A, González EV, Grimaldos AB, Prado EO. NPJ Vaccines. 2021; 6 (1)
Guillain-Barré syndrome associated with leptomeningeal enhancement following SARS-CoV-2 infection.
Sancho-Saldaña A, Lambea-Gil Á, Liesa JLC, Caballo MRB, [...], Serrano-Ponz M.
Clin Med (Lond). 2020; 20 (4)
DOI: 10.7861/clinmed.2020-0213

Introduction

Patients with coronavirus disease 2019 (COVID-19) typically present with respiratory symptoms, but little is known about the disease's potential neurological complications.We report a case of Guillain-Barré syndrome (GBS) following a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, in association with leptomeningeal enhancement.

Case presentation

A 56-year-old woman presented with recent unsteadiness and paraesthesia in both hands. Fifteen days earlier, she complained of fever, dry cough and shortness of breath. Her chest X-ray showed a lobar consolidation and PCR was positive for SARS-CoV-2; she was admitted due to mild COVID-19 pneumonia.In the first 48 hours of hospitalisation, she started to experience lumbar pain and weakness of the proximal lower extremities, progressing to bilateral facial nerve palsy, oropharyngeal weakness and severe proximal tetraparesis with cervical flexion 2/5 on the MRC scale. Full spine magnetic resonance imaging (MRI) showed a brainstem and cervical leptomeningeal enhancement. Analysis of cerebrospinal fluid (CSF) revealed albumin-cytological dissociation. Microbiological studies on CSF, including SARS-CoV-2, were negative. Nerve conduction studies were consistent with demyelinating neuropathy. She was treated with intravenous immunoglobulin, with significant neurological improvement noted over the next 2 weeks.

Conclusion

Leptomeningeal enhancement is an atypical feature in GBS, but could be a marker of its association with SARS-CoV-2 infection.
2020-06-09 2020 other research-article; Journal Article; Case Reports abstract-available 10.7861/clinmed.2020-0213 Guillain-Barré syndrome associated with leptomeningeal enhancement following SARS-CoV-2 infection. Sancho-Saldaña A, Lambea-Gil Á, Liesa JLC, Caballo MRB, Garay MH, Celada DR, Serrano-Ponz M. Clin Med (Lond). 2020; 20 (4)
Cognitive and Neuropsychiatric Manifestations of COVID-19 and Effects on Elderly Individuals With Dementia.
Alonso-Lana S, Marquié M, Ruiz A, Boada M.
Front Aging Neurosci. 2020; 12
DOI: 10.3389/fnagi.2020.588872
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide and has had unprecedented effects in healthcare systems, economies and society. COVID-19 clinical presentation primarily affects the respiratory system causing bilateral pneumonia, but it is increasingly being recognized as a systemic disease, with neurologic manifestations reported in patients with mild symptoms but, most frequently, in those in a severe condition. Elderly individuals are at high risk of developing severe forms of COVID-19 due to factors associated with aging and a higher prevalence of medical comorbidities and, therefore, they are more vulnerable to possible lasting neuropsychiatric and cognitive impairments. Several reports have described insomnia, depressed mood, anxiety, post-traumatic stress disorder and cognitive impairment in a proportion of patients after discharge from the hospital. The potential mechanisms underlying these symptoms are not fully understood but are probably multifactorial, involving direct neurotrophic effect of SARS-CoV-2, consequences of long intensive care unit stays, the use of mechanical ventilation and sedative drugs, brain hypoxia, systemic inflammation, secondary effects of medications used to treat COVID-19 and dysfunction of peripheral organs. Chronic diseases such as dementia are a particular concern not only because they are associated with higher rates of hospitalization and mortality but also because COVID-19 further exacerbates the vulnerability of those with cognitive impairment. In patients with dementia, COVID-19 frequently has an atypical presentation with mental status changes complicating the early identification of cases. COVID-19 has had a dramatical impact in long-term care facilities, where rates of infection and mortality have been very high. Community measures implemented to slow the spread of the virus have forced to social distancing and cancelation of cognitive stimulation programs, which may have contributed to generate loneliness, behavioral symptoms and worsening of cognition in patients with dementia. COVID-19 has impacted the functioning of Memory Clinics, research programs and clinical trials in the Alzheimer's field, triggering the implementation of telemedicine. COVID-19 survivors should be periodically evaluated with comprehensive cognitive and neuropsychiatric assessments, and specific mental health and cognitive rehabilitation programs should be provided for those suffering long-term cognitive and psychiatric sequelae.
2020-10-26 2020 other review-article; Review; Journal Article abstract-available 10.3389/fnagi.2020.588872 Cognitive and Neuropsychiatric Manifestations of COVID-19 and Effects on Elderly Individuals With Dementia. Alonso-Lana S, Marquié M, Ruiz A, Boada M. Front Aging Neurosci. 2020; 12
COVID-19 vaccination challenge: history lessons from a dermatologist's perspective.
Fernandez-Nieto D, Ortega-Quijano D, Jimenez-Cauhe J, Burgos-Blasco P, [...], Bea-Ardebol S.
Int J Dermatol. 2021; 60 (5)
DOI: 10.1111/ijd.15449
2021-03-04 2021 other research-article; Journal Article 10.1111/ijd.15449 COVID-19 vaccination challenge: history lessons from a dermatologist's perspective. Fernandez-Nieto D, Ortega-Quijano D, Jimenez-Cauhe J, Burgos-Blasco P, Bea-Ardebol S. Int J Dermatol. 2021; 60 (5)
Haemophagocytic syndrome and COVID-19.
Retamozo S, Brito-Zerón P, Sisó-Almirall A, Flores-Chávez A, [...], Ramos-Casals M.
Clin Rheumatol. 2021; 40 (4)
DOI: 10.1007/s10067-020-05569-4
Primary and secondary haemophagocytic lymphohistiocytosis (HLH) are hyperferritinaemic hyperinflammatory syndromes with a common terminal pathway triggered by different etiopathogenetic factors. HLH is characterised by a decreased capacity of interferon gamma production with an activated NK phenotype profile similar to other hyperinflammatory syndromes. Viruses are closely linked to the development of HLH as infectious triggers, and the break of tolerance to self-antigens is considered a critical mechanism involved in the development of immune-mediated conditions triggered by viral infections. Emerging studies in patients with COVID-19 are suggesting a key role of monocytes/macrophages in the pathogenesis of this viral infection, and there is a significant overlap between several features reported in severe COVID-19 and the features included in the HLH-2004 diagnostic criteria. Therefore, SARS-Cov-2, as other respiratory viruses, may also be considered a potential etiological trigger of HLH. The frequency of HLH in adult patients with severe COVID-19 is lower than 5%, although this figure could be underestimated considering that most reported cases lacked information about some specific criteria (mainly the histopathological criteria and the measurement of NK cell function and sCD25 levels). Because HLH is a multi-organ syndrome, the diagnostic approach in a patient with severe COVID-19 in whom HLH is suspected must be carried out in a syndromic and holistic way, and not in the light of isolated clinical or laboratory features. In COVID-19 patients presenting with persistent high fever, progressive pancytopenia, and hepatosplenic involvement, together with the characteristic triad of laboratory abnormalities (hyperferritinaemia, hypertriglyceridaemia, and hypofibrinogenaemia), the suspicion of HLH is high, and the diagnostic workup must be completed with specific immunological and histopathological studies.
2021-01-03 2021 other review-article; Review; Journal Article abstract-available 10.1007/s10067-020-05569-4 Haemophagocytic syndrome and COVID-19. Retamozo S, Brito-Zerón P, Sisó-Almirall A, Flores-Chávez A, Soto-Cárdenas MJ, Ramos-Casals M. Clin Rheumatol. 2021; 40 (4)
Severe Acute Respiratory Syndrome Coronavirus-2 Cardiovascular Complications: Implications for Cardiothoracic Anesthesiology.
Cormican DS, Winter D, McHugh S, Sonny A, [...], Ramakrishna H.
J Cardiothorac Vasc Anesth. 2021; 35 (3)
DOI: 10.1053/j.jvca.2020.05.035
2020-06-03 2020 other review-article; Review; Journal Article 10.1053/j.jvca.2020.05.035 Severe Acute Respiratory Syndrome Coronavirus-2 Cardiovascular Complications: Implications for Cardiothoracic Anesthesiology. Cormican DS, Winter D, McHugh S, Sonny A, Crowley J, Yu R, Barrack F, Núñez-Gil IJ, Ramakrishna H. J Cardiothorac Vasc Anesth. 2021; 35 (3)
In silico mutagenesis of human ACE2 with S protein and translational efficiency explain SARS-CoV-2 infectivity in different species.
Delgado Blanco J, Hernandez-Alias X, Cianferoni D, Serrano L.
PLoS Comput Biol. 2020; 16 (12)
DOI: 10.1371/journal.pcbi.1008450
The coronavirus disease COVID-19 constitutes the most severe pandemic of the last decades having caused more than 1 million deaths worldwide. The SARS-CoV-2 virus recognizes the angiotensin converting enzyme 2 (ACE2) on the surface of human cells through its spike protein. It has been reported that the coronavirus can mildly infect cats, and ferrets, and perhaps dogs while not pigs, mice, chicken and ducks. Differences in viral infectivity among different species or individuals could be due to amino acid differences at key positions of the host proteins that interact with the virus, the immune response, expression levels of host proteins and translation efficiency of the viral proteins among other factors. Here, first we have addressed the importance that sequence variants of different animal species, human individuals and virus isolates have on the interaction between the RBD domain of the SARS-CoV-2 spike S protein and human angiotensin converting enzyme 2 (ACE2). Second, we have looked at viral translation efficiency by using the tRNA adaptation index. We find that integration of both interaction energy with ACE2 and translational efficiency explains animal infectivity. Humans are the top species in which SARS-CoV-2 is both efficiently translated as well as optimally interacting with ACE2. We have found some viral mutations that increase affinity for hACE and some hACE2 variants affecting ACE2 stability and virus binding. These variants suggest that different sensitivities to coronavirus infection in humans could arise in some cases from allelic variability affecting ACE2 stability and virus binding.
2020-12-07 2020 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1371/journal.pcbi.1008450 In silico mutagenesis of human ACE2 with S protein and translational efficiency explain SARS-CoV-2 infectivity in different species. Delgado Blanco J, Hernandez-Alias X, Cianferoni D, Serrano L. PLoS Comput Biol. 2020; 16 (12)
Can Activation of NRF2 Be a Strategy against COVID-19?
Cuadrado A, Pajares M, Benito C, Jiménez-Villegas J, [...], Dinkova-Kostova AT.
Trends Pharmacol Sci. 2020; 41 (9)
DOI: 10.1016/j.tips.2020.07.003
Acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 is largely the result of a dysregulated host response, followed by damage to alveolar cells and lung fibrosis. Exacerbated proinflammatory cytokines release (cytokine storm) and loss of T lymphocytes (leukopenia) characterize the most aggressive presentation. We propose that a multifaceted anti-inflammatory strategy based on pharmacological activation of nuclear factor erythroid 2 p45-related factor 2 (NRF2) can be deployed against the virus. The strategy provides robust cytoprotection by restoring redox and protein homeostasis, promoting resolution of inflammation, and facilitating repair. NRF2 activators such as sulforaphane and bardoxolone methyl are already in clinical trials. The safety and efficacy information of these modulators in humans, together with their well-documented cytoprotective and anti-inflammatory effects in preclinical models, highlight the potential of this armamentarium for deployment to the battlefield against COVID-19.
2020-07-14 2020 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.tips.2020.07.003 Can Activation of NRF2 Be a Strategy against COVID-19? Cuadrado A, Pajares M, Benito C, Jiménez-Villegas J, Escoll M, Fernández-Ginés R, Garcia Yagüe AJ, Lastra D, Manda G, Rojo AI, Dinkova-Kostova AT. Trends Pharmacol Sci. 2020; 41 (9)
Forensic evaluation of two nucleic acid extraction systems and validation of a RT-qPCR protocol for identification of SARS-CoV-2 in post-mortem nasopharyngeal swabs
Barrio P, Fernández-Rodríguez A, Martín P, Fernández C, [...], Alonso A.
Forensic Sci Int. 2021;
DOI:
The COVID-19 outbreak has represented a challenge for the international scientific community and particularly for forensic sciences. The lack of Coronavirus post-mortem testing led the National Institute of Toxicology and Forensic Sciences (INTCF) from Spain to verify the performance and utility of a quantitative reverse transcription PCR (RT-qPCR) clinical diagnosis protocol for SARS-CoV-2 detection (TaqPath™ COVID-19 CE-IVD RT-PCR Kit), to shed light on the cause of death (COD) in potentially COVID-19 cases in judicial autopsies. Two different RNA extraction methods were also tested (EZ1® DSP Virus Kit on the EZ1® Advanced XL robot versus MagMAX™ Viral/Pathogen Nucleic Acid Isolation Kit) regarding extraction efficiency, precision and contamination. RT-qPCR was evaluated for precision, specificity, limit of detection and concordance. Both the automated and the manual RNA extraction procedures showed good efficiency, but the automated virus extraction by bio-robot produced more reproducible results than the manual extraction. The SARS-CoV-2 RT-qPCR assay showed high sensitivity with a detection limit up to 10 copies/reaction and high specificity, as no cross-reactivity was detected between any of the 12 different RNA viruses tested, including three types of coronaviruses (SARS-CoV, NL63 and 229E). Reproducibility and repeatability of the studied method as well as concordance with other SARS-CoV-2 molecular detection protocols were also demonstrated.
2021-04-02 2021 other research-article; Journal Article abstract-available Forensic evaluation of two nucleic acid extraction systems and validation of a RT-qPCR protocol for identification of SARS-CoV-2 in post-mortem nasopharyngeal swabs Barrio P, Fernández-Rodríguez A, Martín P, Fernández C, Fernández L, Alonso A. Forensic Sci Int. 2021;
Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166.
Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R.
J Steroid Biochem Mol Biol. 2020; 202
DOI: 10.1016/j.jsbmb.2020.105719
Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months.
2020-06-11 2020 other brief-report; Research Support, Non-U.S. Gov't; Review; Journal Article abstract-available 10.1016/j.jsbmb.2020.105719 Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166. Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R. J Steroid Biochem Mol Biol. 2020; 202
Sensitive detection of SARS-CoV-2 seroconversion by flow cytometry reveals the presence of nucleoprotein-reactive antibodies in unexposed individuals.
Egia-Mendikute L, Bosch A, Prieto-Fernández E, Lee SY, [...], Palazón A.
Commun Biol. 2021; 4 (1)
DOI: 10.1038/s42003-021-02011-6
There is an ongoing need of developing sensitive and specific methods for the determination of SARS-CoV-2 seroconversion. For this purpose, we have developed a multiplexed flow cytometric bead array (C19BA) that allows the identification of IgG and IgM antibodies against three immunogenic proteins simultaneously: the spike receptor-binding domain (RBD), the spike protein subunit 1 (S1) and the nucleoprotein (N). Using different cohorts of samples collected before and after the pandemic, we show that this assay is more sensitive than ELISAs performed in our laboratory. The combination of three viral antigens allows for the interrogation of full seroconversion. Importantly, we have detected N-reactive antibodies in COVID-19-negative individuals. Here we present an immunoassay that can be easily implemented and has superior potential to detect low antibody titers compared to current gold standard serology methods.
2021-04-20 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s42003-021-02011-6 Sensitive detection of SARS-CoV-2 seroconversion by flow cytometry reveals the presence of nucleoprotein-reactive antibodies in unexposed individuals. Egia-Mendikute L, Bosch A, Prieto-Fernández E, Lee SY, Jiménez-Lasheras B, García Del Río A, Antoñana-Vildosola A, Bruzzone C, Bizkarguenaga M, Embade N, Gil-Redondo R, Martínez-Chantar ML, López-Hoyos M, Abrescia NGA, Mato JM, Millet Ó, Palazón A. Commun Biol. 2021; 4 (1)
Amiodarone in the COVID-19 Era: Treatment for Symptomatic Patients Only, or Drug to Prevent Infection?
Sanchis-Gomar F, Lavie CJ, Morin DP, Perez-Quilis C, [...], Perez MV.
Am J Cardiovasc Drugs. 2020; 20 (5)
DOI: 10.1007/s40256-020-00429-7
Amiodarone, one of the most widely prescribed antiarrhythmic drugs to treat both ventricular and supraventricular arrhythmias, has been identified as a candidate drug for use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present the rationale of using amiodarone in the COVID-19 scenario, as well as whether or not amiodarone administration represents a potential strategy to prevent SARS-CoV-2 infection, rather than simply used to treat patients already symptomatic and/or with severe coronavirus disease 2019 (COVID-19), based on current evidence.
2020-10-01 2020 other research-article; Journal Article abstract-available 10.1007/s40256-020-00429-7 Amiodarone in the COVID-19 Era: Treatment for Symptomatic Patients Only, or Drug to Prevent Infection? Sanchis-Gomar F, Lavie CJ, Morin DP, Perez-Quilis C, Laukkanen JA, Perez MV. Am J Cardiovasc Drugs. 2020; 20 (5)
Re-analysis of SARS-CoV-2-infected host cell proteomics time-course data by impact pathway analysis and network analysis: a potential link with inflammatory response.
Bock JO, Ortea I.
Aging (Albany NY). 2020; 12 (12)
DOI: 10.18632/aging.103524
Coronavirus disease 2019 (COVID-19), caused by an outbreak of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in Wuhan, China, has led to an unprecedented health and economic crisis worldwide. To develop treatments that can stop or lessen the symptoms and severity of SARS-CoV-2 infection, it is critical to understand how the virus behaves inside human cells, and so far studies in this area remain scarce. A recent study investigated translatome and proteome host cell changes induced in vitro by SARS-CoV-2. Here, we use the publicly available proteomics data from this study to re-analyze the in vitro cellular consequences of SARS-CoV-2 infection by impact pathways analysis and network analysis. Notably, proteins linked to the inflammatory response, but also proteins related to chromosome segregation during mitosis, were found to be altered in response to viral infection. Upregulation of inflammatory response proteins is in line with the propagation of inflammatory reaction and lung injury that is observed in advanced stages of COVID-19 patients and which worsens with age.
2020-06-23 2020 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.18632/aging.103524 Re-analysis of SARS-CoV-2-infected host cell proteomics time-course data by impact pathway analysis and network analysis: a potential link with inflammatory response. Bock JO, Ortea I. Aging (Albany NY). 2020; 12 (12)
Risk assessment of SARS-CoV-2 in Antarctic wildlife.
Barbosa A, Varsani A, Morandini V, Grimaldi W, [...], Wille M.
Sci Total Environ. 2021; 755 (Pt 2)
DOI: 10.1016/j.scitotenv.2020.143352
The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pathogen has spread rapidly across the world, causing high numbers of deaths and significant social and economic impacts. SARS-CoV-2 is a novel coronavirus with a suggested zoonotic origin with the potential for cross-species transmission among animals. Antarctica can be considered the only continent free of SARS-CoV-2. Therefore, concerns have been expressed regarding the potential human introduction of this virus to the continent through the activities of research or tourism to minimise the effects on human health, and the potential for virus transmission to Antarctic wildlife. We assess the reverse-zoonotic transmission risk to Antarctic wildlife by considering the available information on host susceptibility, dynamics of the infection in humans, and contact interactions between humans and Antarctic wildlife. The environmental conditions in Antarctica seem to be favourable for the virus stability. Indoor spaces such as those at research stations, research vessels or tourist cruise ships could allow for more transmission among humans and depending on their movements between different locations the virus could be spread across the continent. Among Antarctic wildlife previous in silico analyses suggested that cetaceans are at greater risk of infection whereas seals and birds appear to be at a low infection risk. However, caution needed until further research is carried out and consequently, the precautionary principle should be applied. Field researchers handling animals are identified as the human group posing the highest risk of transmission to animals while tourists and other personnel pose a significant risk only when in close proximity (< 5 m) to Antarctic fauna. We highlight measures to reduce the risk as well as identify of knowledge gaps related to this issue.
2020-10-29 2020 other research-article; Journal Article abstract-available 10.1016/j.scitotenv.2020.143352 Risk assessment of SARS-CoV-2 in Antarctic wildlife. Barbosa A, Varsani A, Morandini V, Grimaldi W, Vanstreels RET, Diaz JI, Boulinier T, Dewar M, González-Acuña D, Gray R, McMahon CR, Miller G, Power M, Gamble A, Wille M. Sci Total Environ. 2021; 755 (Pt 2)
Epidemic and pandemic viral infections: impact on tuberculosis and the lung: A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC).
Ong CWM, Migliori GB, Raviglione M, MacGregor-Skinner G, [...], Goletti D.
Eur Respir J. 2020; 56 (4)
DOI: 10.1183/13993003.01727-2020
Major epidemics, including some that qualify as pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV, influenza A (H1N1)pdm/09 and most recently COVID-19, affect the lung. Tuberculosis (TB) remains the top infectious disease killer, but apart from syndemic TB/HIV little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors (excluding the ECDC PHE team) identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology and immunology of these viral infections and their interactions with TB are discussed with implications for diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.
2020-10-01 2020 other Consensus Development Conference; Research Support, Non-U.S. Gov't; research-article; Review; Journal Article abstract-available 10.1183/13993003.01727-2020 Epidemic and pandemic viral infections: impact on tuberculosis and the lung: A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC). Ong CWM, Migliori GB, Raviglione M, MacGregor-Skinner G, Sotgiu G, Alffenaar JW, Tiberi S, Adlhoch C, Alonzi T, Archuleta S, Brusin S, Cambau E, Capobianchi MR, Castilletti C, Centis R, Cirillo DM, D'Ambrosio L, Delogu G, Esposito SMR, Figueroa J, Friedland JS, Ho BCH, Ippolito G, Jankovic M, Kim HY, Rosales Klintz S, Ködmön C, Lalle E, Leo YS, Leung CC, Märtson AG, Melazzini MG, Najafi Fard S, Penttinen P, Petrone L, Petruccioli E, Pontali E, Saderi L, Santin M, Spanevello A, van Crevel R, van der Werf MJ, Visca D, Viveiros M, Zellweger JP, Zumla A, Goletti D. Eur Respir J. 2020; 56 (4)
Cutaneous Manifestations in the Context of SARS-CoV-2 Infection (COVID-19).
Carrascosa JM, Morillas V, Bielsa I, Munera-Campos M.
Actas Dermosifiliogr. 2020; 111 (9)
DOI: 10.1016/j.adengl.2020.10.001
The coronavirus 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had enormous health, economic, and social consequences. The clinical spectrum of cutaneous manifestations observed in patients with COVID-19 is both heterogeneous and complex. To date, reports have identified 5 main categories: acral lesions, vesicular rashes, urticarial rashes, maculopapular rashes, and livedoid and necrotic lesions. However, these will probably be modified as new information comes to light. Cutaneous manifestations associated with COVID-19 probably reflect the activation of pathogenic pathways by the virus or a response to inflammatory processes, vascular or systemic complications, or even treatments. Familiarity with the cutaneous manifestations of COVID-19 may enable early diagnosis or help guide prognosis.
2020-10-15 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.adengl.2020.10.001 Cutaneous Manifestations in the Context of SARS-CoV-2 Infection (COVID-19). Carrascosa JM, Morillas V, Bielsa I, Munera-Campos M. Actas Dermosifiliogr. 2020; 111 (9)
Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A.
White KM, Rosales R, Yildiz S, Kehrer T, [...], García-Sastre A.
Science. 2021; 371 (6532)
DOI: 10.1126/science.abf4058
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of translation have potent antiviral effects. We found that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (90% inhibitory concentration = 0.88 nM) that is more potent than remdesivir against SARS-CoV-2 in vitro by a factor of 27.5, with limited toxicity in cell culture. Through the use of a drug-resistant mutant, we show that the antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known target eEF1A (eukaryotic translation elongation factor 1A). We demonstrate the in vivo efficacy of plitidepsin treatment in two mouse models of SARS-CoV-2 infection with a reduction of viral replication in the lungs by two orders of magnitude using prophylactic treatment. Our results indicate that plitidepsin is a promising therapeutic candidate for COVID-19.
2021-01-25 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.1126/science.abf4058 Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. White KM, Rosales R, Yildiz S, Kehrer T, Miorin L, Moreno E, Jangra S, Uccellini MB, Rathnasinghe R, Coughlan L, Martinez-Romero C, Batra J, Rojc A, Bouhaddou M, Fabius JM, Obernier K, Dejosez M, Guillén MJ, Losada A, Avilés P, Schotsaert M, Zwaka T, Vignuzzi M, Shokat KM, Krogan NJ, García-Sastre A. Science. 2021; 371 (6532)
SARS-CoV-2 infection in infants aged 28 days and younger. A multicentre case series.
Velasco Rodríguez-Belvís M, Medina Benítez E, García Tirado D, Herrero Álvarez M, [...], González Jiménez D.
An Pediatr (Engl Ed). 2020;
DOI: 10.1016/j.anpede.2020.12.005
2020-12-31 2020 other Case Reports; case-report 10.1016/j.anpede.2020.12.005 SARS-CoV-2 infection in infants aged 28 days and younger. A multicentre case series. Velasco Rodríguez-Belvís M, Medina Benítez E, García Tirado D, Herrero Álvarez M, González Jiménez D. An Pediatr (Engl Ed). 2020;
COVID-19: A series of important recent clinical and laboratory reports in immunology and pathogenesis of SARS-CoV-2 infection and care of allergy patients.
Pfaar O, Torres MJ, Akdis CA.
Allergy. 2021; 76 (3)
DOI: 10.1111/all.14472
2021-03-01 2021 other Editorial 10.1111/all.14472 COVID-19: A series of important recent clinical and laboratory reports in immunology and pathogenesis of SARS-CoV-2 infection and care of allergy patients. Pfaar O, Torres MJ, Akdis CA. Allergy. 2021; 76 (3)
Platelets to surrogate lung inflammation in COVID-19 patients.
Kuchi Bhotla H, Kaul T, Balasubramanian B, Easwaran M, [...], Meyyazhagan A.
Med Hypotheses. 2020; 143
DOI: 10.1016/j.mehy.2020.110098
The neoteric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been jeopardizing the world with the symptoms of seasonal flu. The virus contagion predicted to have been originated from Wuhan, China has by far trapped 4,198,418 cases from 212 countries in the world with two international conveyances with 284,102 deaths as of 11 May 2020 (10:18 GMT). Researchers around the globe have indulged in deciphering viral mode in the body for devising a cure. Affirmations from autopsies and preliminary findings on SARS-CoV-2 hypothesized on viral pathogenesis within the host, for instance, source of inflammation in lungs and pneumonia. This hypothesis assigns the platelets as agents of infection after viral entry. Presently, curbing infection to stall the spread of SARS-CoV-2 is the prima facie intervention employed, worldwide. However, public health authorities must monitor the state of affairs scrupulously, as the deeper our understanding of this novel virus and its associated outbreak, the better we can deal with it. Knowing this idea might be far-fetched, yet this postulate would serve as the groundwork for the present situation.
2020-07-12 2020 other Letter abstract-available 10.1016/j.mehy.2020.110098 Platelets to surrogate lung inflammation in COVID-19 patients. Kuchi Bhotla H, Kaul T, Balasubramanian B, Easwaran M, Arumugam VA, Pappusamy M, Muthupandian S, Meyyazhagan A. Med Hypotheses. 2020; 143
Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review.
Alijotas-Reig J, Esteve-Valverde E, Belizna C, Selva-O'Callaghan A, [...], Miró-Mur F.
Autoimmun Rev. 2020; 19 (7)
DOI: 10.1016/j.autrev.2020.102569
Severe Acute Respiratory Syndrome related to Coronavirus-2 (SARS-CoV-2), coronavirus disease-2019 (COVID-19) may cause severe illness in 20% of patients. This may be in part due to an uncontrolled immune-response to SARS-CoV-2 infection triggering a systemic hyperinflammatory response, the so-called "cytokine storm". The reduction of this inflammatory immune-response could be considered as a potential therapeutic target against severe COVID-19. The relationship between inflammation and clot activation must also be considered. Furthermore, we must keep in mind that currently, no specific antiviral treatment is available for SARS-CoV-2. While moderate-severe forms need in-hospital surveillance plus antivirals and/or hydroxychloroquine; in severe and life-threating subsets a high intensity anti-inflammatory and immunomodulatory therapy could be a therapeutic option. However, right data on the effectiveness of different immunomodulating drugs are scarce. Herein, we discuss the pathogenesis and the possible role played by drugs such as: antimalarials, anti-IL6, anti-IL-1, calcineurin and JAK inhibitors, corticosteroids, immunoglobulins, heparins, angiotensin-converting enzyme agonists and statins in severe COVID-19.
2020-05-03 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.autrev.2020.102569 Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review. Alijotas-Reig J, Esteve-Valverde E, Belizna C, Selva-O'Callaghan A, Pardos-Gea J, Quintana A, Mekinian A, Anunciacion-Llunell A, Miró-Mur F. Autoimmun Rev. 2020; 19 (7)
The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries.
Román GC, Spencer PS, Reis J, Buguet A, [...], WFN Environmental Neurology Specialty Group.
J Neurol Sci. 2020; 414
DOI: 10.1016/j.jns.2020.116884
A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 264,679 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers. Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses. Acute hemorrhagic necrotizing encephalopathy is associated to the cytokine storm. A frontal hypoperfusion syndrome has been identified. There are isolated reports of seizures, encephalopathy, meningitis, encephalitis, and myelitis. The neurological diseases affecting the PNS and muscle in COVID-19 are less frequent and include Guillain-Barré syndrome; Miller Fisher syndrome; polyneuritis cranialis; and rare instances of viral myopathy with rhabdomyolysis. The main conclusion of this review is the pressing need to define the neurology of COVID-19, its frequency, manifestations, neuropathology and pathogenesis. On behalf of the World Federation of Neurology we invite national and regional neurological associations to create local databases to report cases with neurological manifestations observed during the on-going pandemic. International neuroepidemiological collaboration may help define the natural history of this worldwide problem.
2020-05-07 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.jns.2020.116884 The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries. Román GC, Spencer PS, Reis J, Buguet A, Faris MEA, Katrak SM, Láinez M, Medina MT, Meshram C, Mizusawa H, Öztürk S, Wasay M, WFN Environmental Neurology Specialty Group. J Neurol Sci. 2020; 414
Chronic Use Of Renin-Angiotensin-Aldosterone Inhibitors In Hypertensive Covid-19 Patients: Results From A Spanish Registry And Meta-Analysis
Aparisi Á, Catalá P, Amat-Santos I, Marcos M, [...], Alberto San Román J.
Med Clin (Barc). 2021;
DOI:
Introducción: La hipertensión es una condición prevalente entre los pacientes infectados por el SARS-CoV-2. Es controvertido si los inhibidores del sistema ren-angiotensina-aldosterona (RAAS) son beneficiosos o perjudiciales. Métodos: Hemos realizado un estudio comparativo nacional retrospectivo y no experimental de dos hospitales terciarios para evaluar el impacto del uso crónico de inhibidores del SRAA en pacientes hipertensos COVID-19. Se realizó un meta-análisis para reforzar los hallazgos. Resultados: De 849 pacientes, 422 (49,7%) eran hipertensos y 310 (73,5%) tomaban inhibidores del SRAA al inicio del estudio. Los pacientes hipertensos eran mayores, tenían más comorbilidades y una mayor incidencia de insuficiencia respiratoria (-0,151 [IC del 95%: -0,218; -0,084]). La mortalidad global en los pacientes hipertensos fue del 28,4%, pero fue menor entre los que tenían prescritos inhibidores del SRAA antes (-0,167 [IC del 95%: -0,220, -0,114]) y durante la hospitalización (0,090 [-0,008,0,188]). Se observaron hallazgos similares tras dos emparejamientos de puntuación de propensión que evaluaron el beneficio de los inhibidores de la enzima convertidora de angiotensina y los bloqueadores de los receptores de angiotensina entre los pacientes hipertensos. El análisis de regresión logística multivariante de los pacientes hipertensos reveló que la edad, la diabetes mellitus, la proteína C reactiva y la insuficiencia renal se asociaban de forma independiente con la mortalidad por todas las causas. Por el contrario, los IECAs disminuyeron el riesgo de muerte (OR 0,444 [IC del 95%: 0,224-0,881]). El meta-análisis sugirió un beneficio protector de los inhibidores del SRAA (OR 0,6 [IC del 95%: 0,42-0,8]) entre los hipertensos con COVID-19. Conclusión: Nuestros datos sugieren que los inhibidores del SRAA pueden desempeñar un papel protector en los pacientes hipertensos COVID-19. Este hallazgo fue apoyado por un meta-análisis de la evidencia actual. Su mantenimiento durante la estancia hospitalaria puede no afectar negativamente a los resultados de la COVID-19.
2021-05-06 2021 other research-article; Journal Article abstract-available Chronic Use Of Renin-Angiotensin-Aldosterone Inhibitors In Hypertensive Covid-19 Patients: Results From A Spanish Registry And Meta-Analysis Aparisi Á, Catalá P, Amat-Santos I, Marcos M, López-Otero D, Veras C, López-Pais J, Cabezón G, Antonio C, Candela J, Antúnez-Muiños P, Francisco-Gil J, Ferrero T, Rojas G, Pérez-Poza M, Uribarri A, Otero-García O, García-Granja P, Ramos V, Revilla A, Dueñas C, Gómez I, Ramón González-Juanatey J, Alberto San Román J. Med Clin (Barc). 2021;
Severe palmar hyperkeratosis and hematochezia in COVID-19.
Tammaro A, Adebanjo GAR, Chello C, Parisella FR, [...], Scarabello A.
Dermatol Ther. 2020; 33 (6)
DOI: 10.1111/dth.14423
2020-10-26 2020 other Letter; Case Reports 10.1111/dth.14423 Severe palmar hyperkeratosis and hematochezia in COVID-19. Tammaro A, Adebanjo GAR, Chello C, Parisella FR, Rello J, Del Nonno F, Scarabello A. Dermatol Ther. 2020; 33 (6)
ADAM17 inhibition may exert a protective effect on COVID-19.
Palau V, Riera M, Soler MJ.
Nephrol Dial Transplant. 2020; 35 (6)
DOI: 10.1093/ndt/gfaa093
2020-06-01 2020 other Comment; brief-report; Research Support, Non-U.S. Gov't; Journal Article 10.1093/ndt/gfaa093 ADAM17 inhibition may exert a protective effect on COVID-19. Palau V, Riera M, Soler MJ. Nephrol Dial Transplant. 2020; 35 (6)
Commentaries on Viewpoint: The interaction between SARS-CoV-2 and ACE2 may have consequences for skeletal muscle viral susceptibility and myopathies.
Tan AL, Farrow M, Biglands J, Fernandes RJ, [...], Bhandari SS.
J Appl Physiol (1985). 2020; 129 (4)
DOI: 10.1152/japplphysiol.00775.2020
2020-10-01 2020 other article-commentary; Comment; Journal Article 10.1152/japplphysiol.00775.2020 Commentaries on Viewpoint: The interaction between SARS-CoV-2 and ACE2 may have consequences for skeletal muscle viral susceptibility and myopathies. Tan AL, Farrow M, Biglands J, Fernandes RJ, Abraldes JA, de Souza Castro FA, de Souza HL, Arriel RA, Meireles A, Marocolo M, González-Rayas JM, Rayas-Gómez AL, Mobayed-Vega FN, González-Yáñez JM, Hirai DM, Belbis MD, Holmes MJ, Calvo N, Ferguson SK, Fernandes T, Oliveira EM, Pun M, Bhandari SS. J Appl Physiol (1985). 2020; 129 (4)
A Hypothesis for the Possible Role of Zinc in the Immunological Pathways Related to COVID-19 Infection.
Mayor-Ibarguren A, Busca-Arenzana C, Robles-Marhuenda Á.
Front Immunol. 2020; 11
DOI: 10.3389/fimmu.2020.01736
2020-07-10 2020 other discussion; Journal Article 10.3389/fimmu.2020.01736 A Hypothesis for the Possible Role of Zinc in the Immunological Pathways Related to COVID-19 Infection. Mayor-Ibarguren A, Busca-Arenzana C, Robles-Marhuenda Á. Front Immunol. 2020; 11
COVID-19-Related Neuropsychiatric Symptoms in Patients With Alcohol Abuse Conditions During the SARS-CoV-2 Pandemic: A Retrospective Cohort Study Using Real World Data From Electronic Health Records of a Tertiary Hospital.
Varela Rodríguez C, Arias Horcajadas F, Martín-Arriscado Arroba C, Combarro Ripoll C, [...], Rubio G.
Front Neurol. 2021; 12
DOI: 10.3389/fneur.2021.630566
Patients with an alcohol abuse disorder exhibit several medical characteristics and social determinants, which suggest a greater vulnerability to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a worse course of the coronavirus disease 2019 (COVID-19) once infected. During the first wave of the COVID-19, most of the countries have register an increase in alcohol consumption. However, studies on the impact of alcohol addiction on the risk of COVID-19 infection are very scarce and inconclusive. This research offers a descriptive observational retrospective cohort study using real world data obtained from the Electronic Health Records. We found that patients with a personal history of alcohol abuse were 8% more likely to extend their hospitalization length of stay for 1 day (95% CI = 1.04-1.12) and 15% more likely to extend their Intensive Care Unit (ICU) length of stay (95% CI = 1.01-1.30). They were also 5.47 times more at risk of needing an ICU admission (95% CI = 1.61-18.57) and 3.54 times (95% CI = 1.51-8.30) more at risk of needing a respirator. Regarding COVID-19 symptoms, patients with a personal history of alcohol abuse were 91% more likely of exhibiting dyspnea (95% CI = 1.03-3.55) and 3.15 times more at risk of showing at least one neuropsychiatric symptom (95% CI = 1.61-6.17). In addition, they showed statistically significant differences in the number of neuropsychiatric symptoms developed during the COVID-19 infection. Therefore, we strongly recommend to warn of the negative consequences of alcohol abuse over COVID-19 complications. For this purpose. Clinicians should systematically assess history of alcohol issues and drinking habits in all patients, especially for those who seek medical advice regarding COVID-19 infection, in order to predict its severity of symptoms and potential complications. Moreover, this information should be included, in a structured field, into the Electronic Health Record to facilitate the automatic extraction of data, in real time, useful to evaluate the decision-making process in a dynamic context.
2021-03-03 2021 other research-article; Journal Article abstract-available 10.3389/fneur.2021.630566 COVID-19-Related Neuropsychiatric Symptoms in Patients With Alcohol Abuse Conditions During the SARS-CoV-2 Pandemic: A Retrospective Cohort Study Using Real World Data From Electronic Health Records of a Tertiary Hospital. Varela Rodríguez C, Arias Horcajadas F, Martín-Arriscado Arroba C, Combarro Ripoll C, Juanes Gonzalez A, Esperesate Pajares M, Rodrigo Holgado I, Cadenas Manceñido Á, Sánchez Rodríguez L, Baselga Penalva B, Marín M, Rubio G. Front Neurol. 2021; 12
Exploring Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors for Organ Protection in COVID-19.
Fernandez-Fernandez B, D'Marco L, Górriz JL, Jacobs-Cachá C, [...], Ortiz A.
J Clin Med. 2020; 9 (7)
DOI: 10.3390/jcm9072030
Hospital admissions and mortality from the Coronavirus disease 2019 (COVID-19) pandemic are spreading throughout the world, and second and third waves are thought to be likely. Risk factors for severe COVID-19 include diabetes, chronic kidney disease and cardiovascular disease. Currently, there is no vaccine and no approved therapy. Therapeutic approaches are aimed at preventing viral replication and spread, limiting the impact of the inflammatory overdrive (cytokine storm), preventing thromboembolic complications and replacing or supporting organ function. However, despite organ support, mortality is currently 65% for those receiving advanced respiratory support and 78% for those requiring renal replacement therapies. Thus, efforts should be made to provide adjuvant organ protection therapy. This may imply novel therapies in clinical development (e.g., the Fas ligand trap asunercept), but uptake of repurposed drugs already in clinical use may be faster. In this regard, sodium glucose co-transporter-2 (SGLT2) inhibitors were recently shown to protect the heart and kidney both within and outside of a diabetic milieu context. Further, preclinical data support a beneficial effect for the lung. We now discuss the potential benefits and risks of SGLT2 inhibitors in COVID-19 and an ongoing clinical trial testing the impact of dapagliflozin on outcomes in COVID-19 patients with respiratory failure.
2020-06-28 2020 other review-article; Review; Journal Article abstract-available 10.3390/jcm9072030 Exploring Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors for Organ Protection in COVID-19. Fernandez-Fernandez B, D'Marco L, Górriz JL, Jacobs-Cachá C, Kanbay M, Luis-Lima S, Porrini E, Sarafidis P, Soler MJ, Ortiz A. J Clin Med. 2020; 9 (7)
Sepsis and Coronavirus Disease 2019: Common Features and Anti-Inflammatory Therapeutic Approaches.
Beltrán-García J, Osca-Verdegal R, Pallardó FV, Ferreres J, [...], García-Giménez JL.
Crit Care Med. 2020; 48 (12)
DOI: 10.1097/ccm.0000000000004625
Great efforts are being made worldwide to identify the specific clinical characteristics of infected critically ill patients that mediate the associated pathogenesis, including vascular dysfunction, thrombosis, dysregulated inflammation, and respiratory complications. Recently, coronavirus disease 2019 has been closely related to sepsis, which suggests that most deaths in ICUs in infected patients are produced by viral sepsis. Understanding the physiopathology of the disease that lead to sepsis after severe acute respiratory syndrome coronavirus 2 infection is a current clinical need to improve intensive care-applied therapies applied to critically ill patients. Although the whole representative data characterizing the immune and inflammatory status in coronavirus disease 2019 patients are not completely known, it is clear that hyperinflammation and coagulopathy contribute to disease severity. Here, we present some common features shared by severe coronavirus disease 2019 patients and sepsis and describe proposed anti-inflammatory therapies for coronavirus disease 2019 which have been previously evaluated in sepsis.
2020-12-01 2020 other article-commentary; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1097/ccm.0000000000004625 Sepsis and Coronavirus Disease 2019: Common Features and Anti-Inflammatory Therapeutic Approaches. Beltrán-García J, Osca-Verdegal R, Pallardó FV, Ferreres J, Rodríguez M, Mulet S, Ferrando-Sánchez C, Carbonell N, García-Giménez JL. Crit Care Med. 2020; 48 (12)
COVID-19 in children with underlying chronic respiratory diseases: survey results from 174 centres.
Moeller A, Thanikkel L, Duijts L, Gaillard EA, [...], Pijnenburg MWH.
ERJ Open Res. 2020; 6 (4)
DOI: 10.1183/23120541.00409-2020

Background

Early reports suggest that most children infected with severe acute respiratory syndrome coronavirus 2 ("SARS-CoV-2") have mild symptoms. What is not known is whether children with chronic respiratory illnesses have exacerbations associated with SARS-CoV-2 virus.

Methods

An expert panel created a survey, which was circulated twice (in April and May 2020) to members of the Paediatric Assembly of the European Respiratory Society (ERS) and via the social media of the ERS. The survey stratified patients by the following conditions: asthma, cystic fibrosis (CF), bronchopulmonary dysplasia (BPD) and other respiratory conditions.

Results

In total 174 centres responded to at least one survey. 80 centres reported no cases, whereas 94 entered data from 945 children with coronavirus disease 2019 (COVID-19). SARS-CoV-2 was isolated from 49 children with asthma of whom 29 required no treatment, 19 needed supplemental oxygen and four children required mechanical ventilation. Of the 14 children with CF and COVID-19, 10 required no treatment and four had only minor symptoms. Among the nine children with BPD and COVID-19, two required no treatment, five required inpatient care and oxygen and two were admitted to a paediatric intensive care unit (PICU) requiring invasive ventilation. Data were available from 33 children with other conditions and SARS-CoV-2 of whom 20 required supplemental oxygen and 11 needed noninvasive or invasive ventilation.

Conclusions

Within the participating centres, in children with asthma and CF, infection with SARS-CoV-2 was well tolerated, but a substantial minority of children with BPD and other conditions required ventilatory support indicating that these latter groups are at risk from SARS-CoV-2 infection.
2020-10-26 2020 other research-article; Journal Article abstract-available 10.1183/23120541.00409-2020 COVID-19 in children with underlying chronic respiratory diseases: survey results from 174 centres. Moeller A, Thanikkel L, Duijts L, Gaillard EA, Garcia-Marcos L, Kantar A, Tabin N, Turner S, Zacharasiewicz A, Pijnenburg MWH. ERJ Open Res. 2020; 6 (4)
Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial.
Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, [...], Metcovid Team.
Clin Infect Dis. 2021; 72 (9)
DOI: 10.1093/cid/ciaa1177

Background

Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19.

Methods

A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality.

Results

From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7.

Conclusions

The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population.

Clinical trials registration

NCT04343729.
2021-05-01 2021 other Research Support, Non-U.S. Gov't; research-article; Randomized Controlled Trial; Journal Article abstract-available 10.1093/cid/ciaa1177 Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial. Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, Safe IP, Borba MGS, Netto RLA, Maciel ABS, Neto JRS, Oliveira LB, Figueiredo EFG, Oliveira Dinelly KM, de Almeida Rodrigues MG, Brito M, Mourão MPG, Pivoto João GA, Hajjar LA, Bassat Q, Romero GAS, Naveca FG, Vasconcelos HL, de Araújo Tavares M, Brito-Sousa JD, Costa FTM, Nogueira ML, Baía-da-Silva DC, Xavier MS, Monteiro WM, Lacerda MVG, Metcovid Team. Clin Infect Dis. 2021; 72 (9)
Ocular manifestations of SARS-CoV-2: Literature review☆ Manifestaciones oftalmológicas del SARS-CoV-2: Revisión de la literatura
Pérez-Bartolomé F, Sánchez-Quirós J.
Arch Soc Esp Oftalmol (Engl Ed). 2020; 96 (1)
DOI:
In this review, a summary is presented of the main reports regarding the potential ocular manifestations of the new coronavirus disease (COVID-19). Scientific evidence is based on letters to the editor, clinical cases and case series, cross-sectional, and a few longitudinal studies. To date, it includes viral conjunctivitis, immune conjunctivitis, and oculomotor palsies (OCP) due to the novel coronavirus. Retinopathy is discussed, but no cases have been published yet. A viral conjunctivitis outbreak can be isolated or associated with the systemic picture, mainly pulmonary, before or after the onset of respiratory symptoms. It can be both unilateral and bilateral, follicles are typical, and duration is variable between 5 and 21 days. Immune-mediated conjunctivitis consists of eye redness, together with erythroderma and fever. It appears more frequently in children, and has been associated with a “Kawasaki-like” disease and toxic shock syndrome. OCP can present on its own, or as part of Miller-Fisher syndrome, along with ataxia, and hyporeflexia. Ophthalmologists have a considerable risk of developing COVID-19 due to close contact with the patient, exposure to tears and eye secretions, and the use of various pieces of equipment and devices susceptible to contamination.
2020-10-19 2020 other review-article; Review; Journal Article abstract-available Ocular manifestations of SARS-CoV-2: Literature review☆ Manifestaciones oftalmológicas del SARS-CoV-2: Revisión de la literatura Pérez-Bartolomé F, Sánchez-Quirós J. Arch Soc Esp Oftalmol (Engl Ed). 2020; 96 (1)
Experimental data using candesartan and captopril indicate no double-edged sword effect in COVID-19.
Pedrosa MA, Valenzuela R, Garrido-Gil P, Labandeira CM, [...], Rodriguez-Perez AI.
Clin Sci (Lond). 2021; 135 (3)
DOI: 10.1042/cs20201511
The key link between renin-angiotensin system (RAS) and COVID-19 is ACE2 (angiotensin-converting enzyme 2), which acts as a double-edged sword, because ACE2 increases the tissue anti-inflammatory response but it is also the entry receptor for the virus. There is an important controversy on several drugs that regulate RAS activity and possibly ACE2, and are widely used, particularly by patients most vulnerable to severe COVID-19. In the lung of healthy rats, we observed that candesartan (an angiotensin type-1, AT1, receptor blocker; ARB) and captopril (an ACE inhibitor; ACEI) up-regulated expression of tissue ACE2 and RAS anti-inflammatory axis receptors (AT2 and Mas receptors). This effect was particularly pronounced in rats with metabolic syndrome (obesity, increased blood pressure and hyperglycemia) and aged rats. Treatment of cultures of human type-II pneumocytes with candesartan or captopril induced up-regulation of ACE2 expression in cells. Treatment with viral spike protein induced a decrease in full-length (i.e. transmembrane) ACE2, an increase in levels of a short intracellular ACE2 polypeptide and an increase in ADAM17 activity in cells, together with an increase in levels of soluble ACE2 and major proinflammatory cytokines in the culture medium. Spike protein-induced changes and levels of spike protein internalization in cells were inhibited by pretreatment with the above-mentioned drugs. The results suggest that these drugs increase ACE2 levels and promote the anti-inflammatory RAS axis in the lung. Furthermore, possible up-regulation of viral entry by the drug-induced increase in expression of transmembrane ACE2 is counteracted by additional mechanisms, particularly by drug-induced inhibition of ADAM17 activity.
2021-02-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1042/cs20201511 Experimental data using candesartan and captopril indicate no double-edged sword effect in COVID-19. Pedrosa MA, Valenzuela R, Garrido-Gil P, Labandeira CM, Navarro G, Franco R, Labandeira-Garcia JL, Rodriguez-Perez AI. Clin Sci (Lond). 2021; 135 (3)
Differentiating characteristics of patients with asthma in the severe acute respiratory syndrome coronavirus 2 infection.
Lemus Calderon JA, Beneyto Martin P, Guzmán Rodriguez R, Caligaris Cataldi HS, [...], Senent Sánchez CJ.
Ann Allergy Asthma Immunol. 2021; 126 (1)
DOI: 10.1016/j.anai.2020.09.004
2020-09-07 2020 other Letter; brief-report 10.1016/j.anai.2020.09.004 Differentiating characteristics of patients with asthma in the severe acute respiratory syndrome coronavirus 2 infection. Lemus Calderon JA, Beneyto Martin P, Guzmán Rodriguez R, Caligaris Cataldi HS, Senent Sánchez CJ. Ann Allergy Asthma Immunol. 2021; 126 (1)
Are Oral Mucosal Changes a Sign of COVID-19? A Cross-Sectional Study at a Field Hospital.
Nuño González A, Magaletskyy K, Martín Carrillo P, Lozano Masdemont B, [...], Herranz Pinto P.
Actas Dermosifiliogr (Engl Ed). 2021;
DOI: 10.1016/j.adengl.2021.05.010

Background

Coronavirus disease 19 (COVID-19) has many manifestations, including respiratory, thrombotic, neurologic, digestive, and cutaneous ones. Cutaneous manifestations have been classified into 5 clinical patterns: acro-ischemic (pseudo-chilblain), vesicular, urticarial, maculopapular, and livedoid. Oral manifestations have also been reported, but much less frequently.

Patients and methods

We performed a cross-sectional study in which we examined the oral mucosa of 666 patients with COVID-19 at the IFEMA field hospital in Madrid in April 2020.

Results

Seventy-eight patients (11.7%) had changes involving the oral mucosa. The most common were transient anterior U-shaped lingual papillitis (11.5%) accompanied or not by tongue swelling (6.6%), aphthous stomatitis (6.9%), a burning sensation in the mouth (5.3%), mucositis (3.9%), glossitis with patchy depapillation (3.9%), white tongue (1.6%), and enanthema (0.5%). Most of the patients also reported taste disturbances.

Conclusions

COVID-19 also manifests in the oral cavity. The most common manifestations are transient U-shaped lingual papillitis, glossitis with patchy depapillation, and burning mouth syndrome. Mucositis with or without aphthous ulcers or enanthema may also be observed. Any these findings may be key clues to a diagnosis of COVID-19.
2021-05-12 2021 other research-article; Journal Article abstract-available 10.1016/j.adengl.2021.05.010 Are Oral Mucosal Changes a Sign of COVID-19? A Cross-Sectional Study at a Field Hospital. Nuño González A, Magaletskyy K, Martín Carrillo P, Lozano Masdemont B, Mayor Ibarguren A, Feito Rodríguez M, Herranz Pinto P. Actas Dermosifiliogr (Engl Ed). 2021;
Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists.
Calabrese F, Pezzuto F, Fortarezza F, Hofman P, [...], Lunardi F.
Virchows Arch. 2020; 477 (3)
DOI: 10.1007/s00428-020-02886-6
Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.
2020-07-09 2020 other review-article; Review; Journal Article abstract-available 10.1007/s00428-020-02886-6 Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists. Calabrese F, Pezzuto F, Fortarezza F, Hofman P, Kern I, Panizo A, von der Thüsen J, Timofeev S, Gorkiewicz G, Lunardi F. Virchows Arch. 2020; 477 (3)
Canonical and Noncanonical Autophagy as Potential Targets for COVID-19.
Bello-Perez M, Sola I, Novoa B, Klionsky DJ, [...], Falco A.
Cells. 2020; 9 (7)
DOI: 10.3390/cells9071619
The SARS-CoV-2 pandemic necessitates a review of the molecular mechanisms underlying cellular infection by coronaviruses, in order to identify potential therapeutic targets against the associated new disease (COVID-19). Previous studies on its counterparts prove a complex and concomitant interaction between coronaviruses and autophagy. The precise manipulation of this pathway allows these viruses to exploit the autophagy molecular machinery while avoiding its protective apoptotic drift and cellular innate immune responses. In turn, the maneuverability margins of such hijacking appear to be so narrow that the modulation of the autophagy, regardless of whether using inducers or inhibitors (many of which are FDA-approved for the treatment of other diseases), is usually detrimental to viral replication, including SARS-CoV-2. Recent discoveries indicate that these interactions stretch into the still poorly explored noncanonical autophagy pathway, which might play a substantial role in coronavirus replication. Still, some potential therapeutic targets within this pathway, such as RAB9 and its interacting proteins, look promising considering current knowledge. Thus, the combinatory treatment of COVID-19 with drugs affecting both canonical and noncanonical autophagy pathways may be a turning point in the fight against this and other viral infections, which may also imply beneficial prospects of long-term protection.
2020-07-05 2020 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.3390/cells9071619 Canonical and Noncanonical Autophagy as Potential Targets for COVID-19. Bello-Perez M, Sola I, Novoa B, Klionsky DJ, Falco A. Cells. 2020; 9 (7)
Use of Anti-Cytokine Therapy in Kidney Transplant Recipients with COVID-19.
Bodro M, Cofan F, Ríos J, Herrera S, [...], Diekmann F.
J Clin Med. 2021; 10 (8)
DOI: 10.3390/jcm10081551
In the context of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to evaluate the impact of anti-cytokine therapies (AT) in kidney transplant recipients requiring hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is an observational retrospective study, which included patients from March to May 2020. An inverse probability of treatment weighting from a propensity score to receive AT was used in all statistical analyses, and we applied a bootstrap procedure in order to calculate an estimation of the 2.5th and 97.5th percentiles of odds ratio (OR). outcomes were measured using an ordinal scale determination (OSD). A total of 33 kidney recipients required hospitalization and 54% of them received at least one AT, mainly tocilizumab (42%), followed by anakinra (12%). There was no statistical effect in terms of intensive care unit (ICU) admission, respiratory secondary infections (35% vs. 7%) or mortality (16% vs. 13%) comparing patients that received AT with those who did not. Nevertheless, patients who received AT presented better outcomes during hospitalization in terms of OSD ≥5 ((OR 0.31; 2.5th, 97.5th percentiles (0.10; 0.72)). These analyses indicate, as a plausible hypothesis, that the use of AT in kidney transplant recipients presenting with COVID-19 could be beneficial, even though multicenter randomized control trials using these therapies in transplanted patients are needed.
2021-04-07 2021 other research-article; Journal Article abstract-available 10.3390/jcm10081551 Use of Anti-Cytokine Therapy in Kidney Transplant Recipients with COVID-19. Bodro M, Cofan F, Ríos J, Herrera S, Linares L, Marcos MA, Soriano A, Moreno A, Diekmann F. J Clin Med. 2021; 10 (8)
A Systematic Review and Meta-Analysis of Hospitalised Current Smokers and COVID-19.
González-Rubio J, Navarro-López C, López-Nájera E, López-Nájera A, [...], Nájera A.
Int J Environ Res Public Health. 2020; 17 (20)
DOI: 10.3390/ijerph17207394
SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It produces severe acute respiratory disease (COVID-19), which is fatal in many cases, characterised by the cytokine release syndrome (CRS). According to the World Health Organization, those who smoke are likely to be more vulnerable to infection. Here, in order to clarify the epidemiologic relationship between smoking and COVID-19, we present a systematic literature review until 28th April 2020 and a meta-analysis. We included 18 recent COVID-19 clinical and epidemiological studies based on smoking patient status from 720 initial studies in China, the USA, and Italy. The percentage of hospitalised current smokers was 7.7% (95% CI: 6.9-8.4) in China, 2.3% (95% CI: 1.7-2.9) in the USA and 7.6% (95% CI: 4.2-11.0) in Italy. These percentages were compared to the smoking prevalence of each country and statistically significant differences were found in them all (p < 0.0001). By means of the meta-analysis, we offer epidemiological evidence showing that smokers were statistically less likely to be hospitalised (OR = 0.18, 95% CI: 0.14-0.23, p < 0.01). In conclusion, the analysis of data from 18 studies shows a much lower percentage of hospitalised current smokers than expected. As more studies become available, this trend should be checked to obtain conclusive results and to explore, where appropriate, the underlying mechanism of the severe progression and adverse outcomes of COVID-19.
2020-10-11 2020 other Meta-Analysis; Research Support, Non-U.S. Gov't; research-article; Systematic Review; Journal Article abstract-available 10.3390/ijerph17207394 A Systematic Review and Meta-Analysis of Hospitalised Current Smokers and COVID-19. González-Rubio J, Navarro-López C, López-Nájera E, López-Nájera A, Jiménez-Díaz L, Navarro-López JD, Nájera A. Int J Environ Res Public Health. 2020; 17 (20)
Fractional diffusion on the human proteome as an alternative to the multi-organ damage of SARS-CoV-2.
Estrada E.
Chaos. 2020; 30 (8)
DOI: 10.1063/5.0015626
The coronavirus 2019 (COVID-19) respiratory disease is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which uses the enzyme ACE2 to enter human cells. This disease is characterized by important damage at a multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. However, not every organ in which ACE2 is abundant is affected by SARS-CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus. We consider here diffusive processes through the protein-protein interaction (PPI) network of proteins targeted by SARS-CoV-2 as an alternative route. We found a subdiffusive regime that allows the propagation of virus perturbations through the PPI network at a significant rate. By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19.
2020-08-01 2020 other other; Journal Article abstract-available 10.1063/5.0015626 Fractional diffusion on the human proteome as an alternative to the multi-organ damage of SARS-CoV-2. Estrada E. Chaos. 2020; 30 (8)
Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing.
Kern C, Schöning V, Chaccour C, Hammann F.
Front Pharmacol. 2021; 12
DOI: 10.3389/fphar.2021.625678
Several repurposed drugs are currently under investigation in the fight against coronavirus disease 2019 (COVID-19). Candidates are often selected solely by their effective concentrations in vitro, an approach that has largely not lived up to expectations in COVID-19. Cell lines used in in vitro experiments are not necessarily representative of lung tissue. Yet, even if the proposed mode of action is indeed true, viral dynamics in vivo, host response, and concentration-time profiles must also be considered. Here we address the latter issue and describe a model of human SARS-CoV-2 viral kinetics with acquired immune response to investigate the dynamic impact of timing and dosing regimens of hydroxychloroquine, lopinavir/ritonavir, ivermectin, artemisinin, and nitazoxanide. We observed greatest benefits when treatments were given immediately at the time of diagnosis. Even interventions with minor antiviral effect may reduce host exposure if timed correctly. Ivermectin seems to be at least partially effective: given on positivity, peak viral load dropped by 0.3-0.6 log units and exposure by 8.8-22.3%. The other drugs had little to no appreciable effect. Given how well previous clinical trial results for hydroxychloroquine and lopinavir/ritonavir are explained by the models presented here, similar strategies should be considered in future drug candidate prioritization efforts.
2021-03-10 2021 other review-article; Review; Journal Article abstract-available 10.3389/fphar.2021.625678 Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing. Kern C, Schöning V, Chaccour C, Hammann F. Front Pharmacol. 2021; 12
Same pollution sources for climate change might be hyperactivating the NLRP3 inflammasome and exacerbating neuroinflammation and SARS mortality.
Macias-Verde D, Lara PC, Burgos-Burgos J.
Med Hypotheses. 2021; 146
DOI: 10.1016/j.mehy.2020.110396
We have reviewed a considerable amount of recent scientific papers relating inflammation caused by air pollution with chronic and severe medical conditions. Furthermore, there are evidences relating organ inflammation caused by not only outdoor long-term but also short-term inhaled radioisotopes contained in high polluted air or in household natural radioactive background aerosols, in addition to SARS-COV-2 attached to bioaerosols, which are related with a worst evolution of severe acute respiratory syndrome patients. Reactive oxygen species (ROS) production induced by the interaction with environmental ionizing radiation contained in pollution is pointed out as a critical mechanism that predispose mainly to elder population, but not excluding young subjects, presenting previous chronic conditions of lung inflammation or neuroinflammation, which can lead to the most serious consequences.
2020-11-17 2020 other research-article; Review; Journal Article abstract-available 10.1016/j.mehy.2020.110396 Same pollution sources for climate change might be hyperactivating the NLRP3 inflammasome and exacerbating neuroinflammation and SARS mortality. Macias-Verde D, Lara PC, Burgos-Burgos J. Med Hypotheses. 2021; 146
COVID-19-induced endotheliitis: emerging evidence and possible therapeutic strategies.
Calabretta E, Moraleda JM, Iacobelli M, Jara R, [...], Richardson P.
Br J Haematol. 2021; 193 (1)
DOI: 10.1111/bjh.17240
2021-02-04 2021 other article-commentary; Research Support, Non-U.S. Gov't; Journal Article 10.1111/bjh.17240 COVID-19-induced endotheliitis: emerging evidence and possible therapeutic strategies. Calabretta E, Moraleda JM, Iacobelli M, Jara R, Vlodavsky I, O'Gorman P, Pagliuca A, Mo C, Baron RM, Aghemo A, Soiffer R, Fareed J, Carlo-Stella C, Richardson P. Br J Haematol. 2021; 193 (1)
High rates of severe disease and death due to SARS-CoV-2 infection in rheumatic disease patients treated with rituximab: a descriptive study.
Loarce-Martos J, García-Fernández A, López-Gutiérrez F, García-García V, [...], Vázquez-Díaz M.
Rheumatol Int. 2020; 40 (12)
DOI: 10.1007/s00296-020-04699-x
The objective of this study is to describe the characteristics and outcomes of rheumatic and musculoskeletal disease (RMD) patients who were treated with rituximab and had suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this descriptive study, RMD patients who were treated with rituximab in the last 12 months at the Rheumatology Department of our hospital were screened for SARS-CoV-2 infection via telephone interview and a comprehensive review of clinical health records (01/02/2020-26/05/2020). Those with probable or confirmed SARS-CoV-2 infection were included. In total, 76 patients were screened. Of these, 13 (17.1%) had suspected or confirmed SARS-CoV-2 infection. With regard to these 13 patients, the median age at coronavirus disease (COVID-19) diagnosis was 68 years (range 28-76 years) and 8 (61.5%) were female. Five patients had rheumatoid arthritis, three had systemic vasculitis, two had Sjögren syndrome, and two had systemic lupus erythematosus. Additionally, seven patients (53.8%) had pulmonary involvement secondary to RMD. Eight patients (61.5%) developed severe disease leading to hospitalization, and seven developed bilateral pneumonia and respiratory insufficiency. Of the eight hospitalized patients, five (62.5%) fulfilled the acute respiratory distress syndrome criteria and three developed a critical disease and died. Our cohort had a high rate of severe disease requiring hospitalization (61.5%), with bilateral pneumonia and hyperinflammation leading to a high mortality rate (23.1%). Treatment with rituximab should be considered a possible risk factor for unfavorable outcomes in COVID-19 patients with RMD. However, further study is required to confirm this association.
2020-09-18 2020 other brief-report; Journal Article; Observational Study abstract-available 10.1007/s00296-020-04699-x High rates of severe disease and death due to SARS-CoV-2 infection in rheumatic disease patients treated with rituximab: a descriptive study. Loarce-Martos J, García-Fernández A, López-Gutiérrez F, García-García V, Calvo-Sanz L, Del Bosque-Granero I, Terán-Tinedo MA, Boteanu A, Bachiller-Corral J, Vázquez-Díaz M. Rheumatol Int. 2020; 40 (12)
The SARS-CoV-2 Pandemic in Latin America: the Need for Multidisciplinary Approaches.
Callejas D, Echevarría JM, Carrero Y, Rodríguez-Morales AJ, [...], Moreira R.
Curr Trop Med Rep. 2020;
DOI: 10.1007/s40475-020-00219-w

Purpose of review

Acute respiratory infections of viral etiology (ARIVE) constitute one of the most frequent infectious processes among humans. They cause significant morbidity and mortality every year in all age groups and regions of the world. Their etiology is diverse, and seasonal viruses began their journey, at some point, with an episode of expansion before their annual circulation as seasonal agents. The coronavirus disease 2019 (COVID-19) pandemic is a challenge for Latin America. Understanding dynamics is essential for decision making, to reduce the health, economic, and social impacts of the pandemic.

Recent findings

Currently, governments in Latin America have taken measures to mitigate the spread of COVID-19 primarily based on World Health Organization recommendations. However, the potential impact of the virus in Latin America is still unknown. Given the urgency, governments need more accurate estimates of what could happen in Latin America in order to make informed decisions, At the September 20, 2020, cumulative cases 2295 of COVID-19 per 1 million population has been registered in Latin America and the Caribbean. Brazil, Peru, and Chile are the most countries affected by this pandemic, registering a total of cumulative cases per million inhabitants of 21,148, 22,941, and 23,262 respectively. Peru has shown the highest death numbers with 949 per million inhabitants.

Summary

The Latin American health authorities should make the most beneficial decisions based in scientific facts for the health and life of citizens, both understood in the broadest and most inclusive sense.Once the epidemic is over, Latin America should begin a profound health reform, at a single and universal health system, integrated and coordinated, where the leading role of the Ministry of Health is resumed, to have a national network of modern, integrated, and excellent quality laboratories for the benefit of the entire society.
2020-11-03 2020 other review-article; Review; Journal Article abstract-available 10.1007/s40475-020-00219-w The SARS-CoV-2 Pandemic in Latin America: the Need for Multidisciplinary Approaches. Callejas D, Echevarría JM, Carrero Y, Rodríguez-Morales AJ, Moreira R. Curr Trop Med Rep. 2020;
Ozone (O3) and SARS-CoV-2: Physiological Bases and Their Therapeutic Possibilities According to COVID-19 Evolutionary Stage.
Fernández-Cuadros ME, Albaladejo-Florín MJ, Peña-Lora D, Álava-Rabasa S, [...], Pérez-Moro OS.
SN Compr Clin Med. 2020;
DOI: 10.1007/s42399-020-00328-7
To date, there is no definitive treatment for the new SARS-CoV-2 pandemic. Three evolutionary stages in SARS-CoV-2 infection are recognized (early infection, pulmonary phase, and systemic hyper inflammation), with characteristic clinical signs and symptoms. There are 80 international experimental trials underway seeking effective treatment for the COVID-19 pandemic. Of these, there are only three that consider ozone therapy (major auto hemotherapy) as an alternative option. There is no study that evaluates rectal ozone insufflation, despite being a safe, cheap, risk-free technique. That technique is a systemic route of ozone administration (95-96%) and that could be extrapolated to the use of SARS-CoV-2, given the excellent results observed in the management of Ebola. Ozone has four proven biological properties that could allow its use as an alternative therapy in the different phases of SARS-CoV-2 infection. Ozone could inactivate the virus by direct (O3) or indirect oxidation (ROS and LOPs) and could stimulate the cellular and humoral immune systems, being useful in the early COVID-19 infection phase (stages 1 and 2a). Ozone improves gas exchange, reduces inflammation, and modulates the antioxidant system, so it would be useful in the hyper inflammation or "cytokine storm" phase, and in the hypoxemia and/or multi-organ failure phase (stage 2b and stage 3). Given the current pandemic, it is urgent to carry out an experimental study that confirms or rules out the biological properties of ozone and thus allows it to be an alternative or compassionate therapy for the effective management of SARS-Cov-2 infection. The Ethical Committee at our Hospital has authorized the use of this technique for compassionate management of SARS-CoV-2 infection, considering the four biological Ozone properties exposed previously.
2020-07-07 2020 other review-article; Review; Journal Article abstract-available 10.1007/s42399-020-00328-7 Ozone (O3) and SARS-CoV-2: Physiological Bases and Their Therapeutic Possibilities According to COVID-19 Evolutionary Stage. Fernández-Cuadros ME, Albaladejo-Florín MJ, Peña-Lora D, Álava-Rabasa S, Pérez-Moro OS. SN Compr Clin Med. 2020;
Disease-modifying therapies and SARS-CoV-2 vaccination in multiple sclerosis: an expert consensus.
Centonze D, Rocca MA, Gasperini C, Kappos L, [...], Filippi M.
J Neurol. 2021;
DOI: 10.1007/s00415-021-10545-2
Coronavirus disease (COVID-19) appeared in December 2019 in the Chinese city of Wuhan and has quickly become a global pandemic. The disease is caused by the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), an RNA beta coronavirus phylogenetically similar to SARS coronavirus. To date, more than 132 million cases of COVID19 have been recorded in the world, of which over 2.8 million were fatal ( https://coronavirus.jhu.edu/map.html ). A huge vaccination campaign has started around the world since the end of 2020. The availability of vaccines has raised some concerns among neurologists regarding the safety and efficacy of vaccination in patients with multiple sclerosis (MS) taking immunomodulatory or immunosuppressive therapies.
2021-04-12 2021 other research-article; Journal Article abstract-available 10.1007/s00415-021-10545-2 Disease-modifying therapies and SARS-CoV-2 vaccination in multiple sclerosis: an expert consensus. Centonze D, Rocca MA, Gasperini C, Kappos L, Hartung HP, Magyari M, Oreja-Guevara C, Trojano M, Wiendl H, Filippi M. J Neurol. 2021;
Climatological and social fallacies about COVID-19 pandemic
Farooq A, Kumar U, Uddin J, Rashid M, [...], Ahmad M.
Environmental Sustainability. 2021;
DOI:
Coronavirus disease (COVID-19) has emerged as a major global challenge since 2019. With the fast rise in the infected cases and deaths worldwide, many environmental and climate-related myths and fallacies spreaded fast. These fallacies include virus cannot spread in hot and humid conditions, cold weather can inhibit the virus, drinking hot water and sunlight can help cure the COVID-19, ultraviolet (UV) disinfectant lamps and UV rays from sunlight can kill the virus, use of hairdryers and hot showers for virus prevention, etc. Social norms and mindset of the people in the world towards a pandemic are quite similar. The primary purpose of this article is to enlighten the readers regarding these climatological misconceptions and social fallacies, helping spread proper knowledge and manage the outbreak of this deadly pandemic.
2021-05-20 2021 other brief-report; Brief Report abstract-available Climatological and social fallacies about COVID-19 pandemic Farooq A, Kumar U, Uddin J, Rashid M, Gilani M, Farooq T, Shakoor A, Ahmad M. Environmental Sustainability. 2021;
A systematic review of neurological manifestations of SARS-CoV-2 infection: the devil is hidden in the details.
Romoli M, Jelcic I, Bernard-Valnet R, García Azorín D, [...], Infectious Disease Panel of the European Academy of Neurology.
Eur J Neurol. 2020; 27 (9)
DOI: 10.1111/ene.14382

Background and purpose

We systematically reviewed available evidence for reports of neurological signs and symptoms in patients with COVID-19 to identify cases with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection or immune-mediated reaction in the nervous system.

Methods

We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for articles on COVID-19 and nervous system involvement that were published from 1 January to 24 April 2020. Data on design, sample size, neurological assessment and related work-up were extracted. Biases were assessed with the Newcastle-Ottawa scale.

Results

We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID-19. The reports focused on smell and taste (n = 5) and evaluation of neurological symptoms and signs in cohorts (n = 5). There were cases of Guillain-Barré syndrome/Miller-Fisher syndrome/cranial neuropathy (seven cases), meningitis/encephalitis (nine cases) and various other conditions (five cases). The number of patients with examination of cerebrospinal fluid and, in particular, SARS-CoV-2 polymerase chain reaction was negligible. Two had a positive SARS-CoV-2 polymerase chain reaction examination of cerebrospinal fluid specimen. Study of potential parenchymal involvement with magnetic resonance imaging was rare. Only four reports received a rating of the highest quality standards.

Conclusions

This systematic review failed to establish comprehensive insights into nervous system manifestations of COVID-19 beyond immune-mediated complications in the aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS-CoV-2 on behalf of the Infectious Disease Panel of the European Academy of Neurology.
2020-06-30 2020 other research-article; Systematic Review; Journal Article abstract-available 10.1111/ene.14382 A systematic review of neurological manifestations of SARS-CoV-2 infection: the devil is hidden in the details. Romoli M, Jelcic I, Bernard-Valnet R, García Azorín D, Mancinelli L, Akhvlediani T, Monaco S, Taba P, Taba P, Sellner J, Infectious Disease Panel of the European Academy of Neurology. Eur J Neurol. 2020; 27 (9)
Increased CSF levels of IL-1β, IL-6, and ACE in SARS-CoV-2-associated encephalitis.
Bodro M, Compta Y, Llansó L, Esteller D, [...], “Hospital Clínic Infecto-COVID-19” and “Hospital Clínic Neuro-COVID-19” groups.
Neurol Neuroimmunol Neuroinflamm. 2020; 7 (5)
DOI: 10.1212/nxi.0000000000000821
2020-07-01 2020 other brief-report; Journal Article; Case Reports 10.1212/nxi.0000000000000821 Increased CSF levels of IL-1β, IL-6, and ACE in SARS-CoV-2-associated encephalitis. Bodro M, Compta Y, Llansó L, Esteller D, Doncel-Moriano A, Mesa A, Rodríguez A, Sarto J, Martínez-Hernandez E, Vlagea A, Egri N, Filella X, Morales-Ruiz M, Yagüe J, Soriano Á, Graus F, García F, “Hospital Clínic Infecto-COVID-19” and “Hospital Clínic Neuro-COVID-19” groups. Neurol Neuroimmunol Neuroinflamm. 2020; 7 (5)
A sensitive and affordable multiplex RT-qPCR assay for SARS-CoV-2 detection.
Reijns MAM, Thompson L, Acosta JC, Black HA, [...], Jackson AP.
PLoS Biol. 2020; 18 (12)
DOI: 10.1371/journal.pbio.3001030
With the ongoing COVID-19 (Coronavirus Disease 2019) pandemic, caused by the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), there is a need for sensitive, specific, and affordable diagnostic tests to identify infected individuals, not all of whom are symptomatic. The most sensitive test involves the detection of viral RNA using RT-qPCR (quantitative reverse transcription PCR), with many commercial kits now available for this purpose. However, these are expensive, and supply of such kits in sufficient numbers cannot always be guaranteed. We therefore developed a multiplex assay using well-established SARS-CoV-2 targets alongside a human cellular control (RPP30) and a viral spike-in control (Phocine Herpes Virus 1 [PhHV-1]), which monitor sample quality and nucleic acid extraction efficiency, respectively. Here, we establish that this test performs as well as widely used commercial assays, but at substantially reduced cost. Furthermore, we demonstrate >1,000-fold variability in material routinely collected by combined nose and throat swabbing and establish a statistically significant correlation between the detected level of human and SARS-CoV-2 nucleic acids. The inclusion of the human control probe in our assay therefore provides a quantitative measure of sample quality that could help reduce false-negative rates. We demonstrate the feasibility of establishing a robust RT-qPCR assay at approximately 10% of the cost of equivalent commercial assays, which could benefit low-resource environments and make high-volume testing affordable.
2020-12-15 2020 other Controlled Clinical Trial; Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1371/journal.pbio.3001030 A sensitive and affordable multiplex RT-qPCR assay for SARS-CoV-2 detection. Reijns MAM, Thompson L, Acosta JC, Black HA, Sanchez-Luque FJ, Diamond A, Parry DA, Daniels A, O'Shea M, Uggenti C, Sanchez MC, O'Callaghan A, McNab MLL, Adamowicz M, Friman ET, Hurd T, Jarman EJ, Chee FLM, Rainger JK, Walker M, Drake C, Longman D, Mordstein C, Warlow SJ, McKay S, Slater L, Ansari M, Tomlinson IPM, Moore D, Wilkinson N, Shepherd J, Templeton K, Johannessen I, Tait-Burkard C, Haas JG, Gilbert N, Adams IR, Jackson AP. PLoS Biol. 2020; 18 (12)
SARS-CoV-2 viability under different meteorological conditions, surfaces, fluids and transmission between animals.
Fernández-Raga M, Díaz-Marugán L, García Escolano M, Bort C, [...], Fanjul V.
Environ Res. 2021; 192
DOI: 10.1016/j.envres.2020.110293
Since the COVID-19 outbreak, researchers have tried to characterise the novel coronavirus SARS-CoV-2 to better understand the pathogenic mechanisms of the virus and prevent further dissemination. As a consequence, there has been a bloom in scientific research papers focused on the behaviour of the virus in different environmental contexts. Nevertheless, despite these efforts and due to its novelty, available information about this coronavirus is limited, as several research studies are still ongoing. This review aims to shed light on this issue. To that end, we have examined the scientific literature to date regarding the viability of SARS-CoV-2 on surfaces and fluids or under different environmental conditions (temperature, precipitation and UV radiation). We have also addressed the role of animals in the transmission of this coronavirus.
2020-10-02 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.envres.2020.110293 SARS-CoV-2 viability under different meteorological conditions, surfaces, fluids and transmission between animals. Fernández-Raga M, Díaz-Marugán L, García Escolano M, Bort C, Fanjul V. Environ Res. 2021; 192
COVID-19: unravelling the clinical progression of nature's virtually perfect biological weapon.
Lippi G, Sanchis-Gomar F, Henry BM.
Ann Transl Med. 2020; 8 (11)
DOI: 10.21037/atm-20-3989
Coronavirus disease 2019 (COVID-19) pandemic has shocked the world and caused morbidity and mortality on an unprecedented level in the era of modern medicine. Evidence generated to-date on the virulence and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that COVID-19 may be considered a perfect storm, caused by a nature's virtually perfect biological weapon. This conclusion is supported by an updated analysis of pathogenesis and clinical progression of this infectious disease. It is now readily apparent that COVID-19 is not a clear-cut disorder, but is instead a gradually evolving pathology, characterized by a series of stages sustained by different molecular and biological mechanisms. The disease can hence be divided in at least five different phases (incubation, respiratory, pro-inflammatory, pro-thrombotic, and death or remission). Whilst the virus triggers direct cytopathic injury during the initial stage of illness, in the following evolving phases, it is the host itself that undergoes an almost suicidal reaction, sustained, amplified and maintained by the immune, complement and hemostatic systems. Another peculiar property making SARS-CoV-2 a devious and vicious pathogen is the biophysical structure of its receptor biding domain, which needs to be primed by human proteases, thus being less efficiently targetable by the host immune system. The unique pathophysiology of COVID-19 requires the customization of therapy by individual patient characteristics and according to the phase-specific, evolving derangement of the multiple biological pathways.
2020-06-01 2020 other review-article; Review; Journal Article abstract-available 10.21037/atm-20-3989 COVID-19: unravelling the clinical progression of nature's virtually perfect biological weapon. Lippi G, Sanchis-Gomar F, Henry BM. Ann Transl Med. 2020; 8 (11)
Simultaneous Detection and Mutation Surveillance of SARS-CoV-2 and co-infections of multiple respiratory viruses by Rapid field-deployable sequencing.
Bi C, Ramos-Mandujano G, Tian Y, Hala S, [...], Li M.
Med (N Y). 2021;
DOI: 10.1016/j.medj.2021.03.015

Background

Strategies for monitoring the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are crucial for combating the pandemic. Detection and mutation surveillance of SARS-CoV-2 and other respiratory viruses require separate and complex workflows that rely on highly-specialized facilities, personnel, and reagents. To date, no method can rapidly diagnose multiple viral infections and determine variants in a high-throughput manner.

Methods

We describe a method for multiplex isothermal amplification-based sequencing and real-time analysis of multiple viral genomes, termed NIRVANA. It can simultaneously detect SARS-CoV-2, influenza A, human adenovirus, and human coronavirus, and monitor mutations for up to 96 samples in real-time.

Findings

NIRVANA showed high sensitivity and specificity for SARS-CoV-2 in 70 clinical samples with a detection limit of 20 viral RNA copies per μl of extracted nucleic acid. It also detected the influenza A co-infection in two samples. The variant analysis results of SARS-CoV-2 positive samples mirror the epidemiology of COVID-19. Additionally, NIRVANA could simultaneously detect SARS-CoV-2 and PMMoV (an omnipresent virus and water quality indicator) in municipal wastewater samples.

Conclusions

NIRVANA provides high-confidence detection of both SARS-CoV-2 and other respiratory viruses and mutation surveillance of SARS-CoV-2 on the fly. We expect it to offer a promising solution for rapid field-deployable detection and mutational surveillance of pandemic viruses.

Funding

M.L. is supported by KAUST Office of Sponsored Research (BAS/1/1080-01). This work is supported by KAUST Competitive Research Grant (URF/1/3412-01-01, M.L. and J.C.I.B.) and Universidad Catolica San Antonio de Murcia (J.C.I.B.). A.M.H. is supported by Saudi Ministry of Education (project 436).
2021-03-31 2021 other research-article; Journal Article abstract-available 10.1016/j.medj.2021.03.015 Simultaneous Detection and Mutation Surveillance of SARS-CoV-2 and co-infections of multiple respiratory viruses by Rapid field-deployable sequencing. Bi C, Ramos-Mandujano G, Tian Y, Hala S, Xu J, Mfarrej S, Esteban CR, Delicado EN, Alofi FS, Khogeer A, Hashem AM, Almontashiri NAM, Pain A, Izpisua Belmonte JC, Li M. Med (N Y). 2021;
Cardiac magnetic resonance characterization of COVID-19 myocarditis.
Caballeros Lam M, de la Fuente Villena A, Hernández Hernández A, García de Yébenes M, [...], Bastarrika Alemañ G.
Rev Esp Cardiol (Engl Ed). 2020; 73 (10)
DOI: 10.1016/j.rec.2020.06.018
2020-07-04 2020 other Letter; Case Reports; case-report 10.1016/j.rec.2020.06.018 Cardiac magnetic resonance characterization of COVID-19 myocarditis. Caballeros Lam M, de la Fuente Villena A, Hernández Hernández A, García de Yébenes M, Bastarrika Alemañ G. Rev Esp Cardiol (Engl Ed). 2020; 73 (10)
The Covid-19 pandemic seen from the frontline.
Carmona LEO, Nielfa MDCC, Alvarado ALD.
Int Braz J Urol. 2020; 46 (suppl.1)
DOI: 10.1590/s1677-5538.ibju.2020.s123
COVID-19 disease caused by infection with the SARS-CoV-2 virus produces respiratory symptoms, predominantly of the upper airways, which can progress to pneumonia after 7 days with persistent fever, cough and dyspnea, and even develop a syndrome of acute respiratory distress (ARDS), multi-organ failure and death. Since COVID-19 disease was declared by the WHO there has been a redistribution of the healthcare system for these types of patients, especially in the front line, which is, in primary care, emergencies and in intensive care units (ICU). In primary care, the fundamental role is the diagnosis of the suspected patients, follow-up mainly by telemedicine (specially telephone calls) to detect warning signs in case of worsening and subsequent referral to the emergency department; as well as explaining home isolation measures. In the emergency department, it is included the management of suspicious cases and, if it any risk factor is found, complementary tests are carried out for precise diagnosis and admission assessment; In case of oxygen saturation <95% and poor general condition, valuation is requested for admission to the ICU. Depending on the severity of the patient, he/she would be or not a candidate for invasive mechanical ventilation, which must be performed by trained personnel to prevent the spread of the infection minimizing the risk of contagion. ARDS's treatment strategies include pulmonary protection ventilation, prone position, recruitment maneuvers and, less frequently, oxygenation by extracorporeal membrane. Among the specific treatments for COVID-19 stand out mainly drugs to reduce viral load, although sometimes specific drugs will be needed to treat hyperinflammation, hypercoagulability and concomitant infections. One of the goals to be achieved is for patients to recover and be able to successfully return to work; for this purpose, an adequate physical and psychological rehabilitation program is essential, as about 50% have symptoms of anxiety and depression.
2020-07-01 2020 other research-article; Journal Article abstract-available 10.1590/s1677-5538.ibju.2020.s123 The Covid-19 pandemic seen from the frontline. Carmona LEO, Nielfa MDCC, Alvarado ALD. Int Braz J Urol. 2020; 46 (suppl.1)
Are Animals a Neglected Transmission Route of SARS-CoV-2?
Hernández M, Abad D, Eiros JM, Rodríguez-Lázaro D.
Pathogens. 2020; 9 (6)
DOI: 10.3390/pathogens9060480
Little information on the SARS-CoV-2 virus in animals is available to date. Whereas no one husbandry animal case has been reported to date, which would have significant implications in food safety, companion animals play a role in COVID-19 epidemiology that opens up new questions. There is evidence that SARS-CoV-2 can infect felines, dogs and minks, and there is evidence of human-to-animal infection. Likewise, the S protein nucleotide sequence of the SARS-CoV-2 virus isolated in domestic animals and humans is identical, and the replication of the SARS-CoV-2 in cats is efficient. Besides, the epidemiological evidence for this current pandemic indicates that the spillover to humans was associated with close contact between man and exotic animals, very probably in Chinese wet markets, thus there is a growing general consensus that the exotic animal markets, should be strictly regulated. The examination of these findings and the particular role of animals in COVID-19 should be carefully analyzed in order to establish preparation and containment measures. Animal management and epidemiological surveillance must be also considered for COVID-19 control, and it can open up new questions regarding COVID-19 epidemiology and the role that animals play in it.
2020-06-18 2020 other discussion; Journal Article abstract-available 10.3390/pathogens9060480 Are Animals a Neglected Transmission Route of SARS-CoV-2? Hernández M, Abad D, Eiros JM, Rodríguez-Lázaro D. Pathogens. 2020; 9 (6)
Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019.
Sanchis-Gomar F, Lavie CJ, Perez-Quilis C, Henry BM, [...], Lippi G.
Mayo Clin Proc. 2020; 95 (6)
DOI: 10.1016/j.mayocp.2020.03.026
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.
2020-04-04 2020 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.mayocp.2020.03.026 Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019. Sanchis-Gomar F, Lavie CJ, Perez-Quilis C, Henry BM, Lippi G. Mayo Clin Proc. 2020; 95 (6)
Artificial Intelligence-Aided Precision Medicine for COVID-19: Strategic Areas of Research and Development.
Santus E, Marino N, Cirillo D, Chersoni E, [...], Lindvall C.
J Med Internet Res. 2021; 23 (3)
DOI: 10.2196/22453
Artificial intelligence (AI) technologies can play a key role in preventing, detecting, and monitoring epidemics. In this paper, we provide an overview of the recently published literature on the COVID-19 pandemic in four strategic areas: (1) triage, diagnosis, and risk prediction; (2) drug repurposing and development; (3) pharmacogenomics and vaccines; and (4) mining of the medical literature. We highlight how AI-powered health care can enable public health systems to efficiently handle future outbreaks and improve patient outcomes.
2021-03-12 2021 other research-article; Journal Article abstract-available 10.2196/22453 Artificial Intelligence-Aided Precision Medicine for COVID-19: Strategic Areas of Research and Development. Santus E, Marino N, Cirillo D, Chersoni E, Montagud A, Santuccione Chadha A, Valencia A, Hughes K, Lindvall C. J Med Internet Res. 2021; 23 (3)
Bovine Coronavirus Immune Milk Against COVID-19.
Arenas A, Borge C, Carbonero A, Garcia-Bocanegra I, [...], Arenas-Montes A.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.637152
After a year of evolution of the SARS-CoV-2 epidemic, there is still no specific effective treatment for the disease. Although the majority of infected people experience mild disease, some patients develop a serious disease, especially when other pathologies concur. For this reason, it would be very convenient to find pharmacological and immunological mechanisms that help control SARS-CoV-2 infection. Since the COVID-19 and BCoV viruses are very close phylogenetically, different studies demonstrate the existence of cross-immunity as they retain shared epitopes in their structure. As a possible control measure against COVID-19, we propose the use of cow's milk immune to BCoV. Thus, the antigenic recognition of some highly conserved structures of viral proteins, particularly M and S2, by anti-BCoV antibodies present in milk would cause a total or partial inactivation of SARS-COV-2 (acting as a particular vaccine) and be addressed more easily by GALT's highly specialized antigen-presenting cells, thus helping the specific immune response.
2021-03-23 2021 other research-article; Review; Journal Article abstract-available 10.3389/fimmu.2021.637152 Bovine Coronavirus Immune Milk Against COVID-19. Arenas A, Borge C, Carbonero A, Garcia-Bocanegra I, Cano-Terriza D, Caballero J, Arenas-Montes A. Front Immunol. 2021; 12
Protecting older patients with cardiovascular diseases from COVID-19 complications using current medications.
Alves M, Fernandes MA, Bahat G, Benetos A, [...], EuGMS Special Interest Group in Cardiovascular Medicine (Chairpersons A. Ungar and A. Benetos).
Eur Geriatr Med. 2021;
DOI: 10.1007/s41999-021-00504-5

Purpose

In the pathogenesis of severe COVID-19 complications, derangements of renin-angiotensin-aldosterone system (RAAS), vascular endothelial dysfunction leading to inflammation and coagulopathy, and arrhythmias play an important role. Therefore, it is worth considering the use of currently available drugs to protect COVID-19 patients with cardiovascular diseases.

Methods

We review the current experience of conventional cardiovascular drugs [angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, anticoagulants, acetosalicylic acid, antiarrhythmic drugs, statins] as well as some other drug classes (antidiabetic drugs, vitamin D and NSAIDs) frequently used by older patients with cardiovascular diseases. Data were sought from clinical databases for COVID-19 and appropriate key words. Conclusions and recommendations are based on a consensus among all authors.

Results

Several cardiovascular drugs have a potential to protect patients with COVID-19, although evidence is largely based on retrospective, observational studies. Despite propensity score adjustments used in many analyses observational studies are not equivalent to randomised controlled trials (RCTs). Ongoing RCTs include treatment with antithrombotics, pulmonary vasodilators, RAAS-related drugs, and colchicine. RCTs in the acute phase of COVID-19 may not, however, recognise the benefits of long term anti-atherogenic therapies, such as statins.

Conclusions

Most current cardiovascular drugs can be safely continued during COVID-19. Some drug classes may even be protective. Age-specific data are scarce, though, and conditions which are common in older patients (frailty, comorbidities, polypharmacy) must be individually considered for each drug group.
2021-05-25 2021 other research-article; Journal Article abstract-available 10.1007/s41999-021-00504-5 Protecting older patients with cardiovascular diseases from COVID-19 complications using current medications. Alves M, Fernandes MA, Bahat G, Benetos A, Clemente H, Grodzicki T, Martínez-Sellés M, Mattace-Raso F, Rajkumar C, Ungar A, Werner N, Strandberg TE, EuGMS Special Interest Group in Cardiovascular Medicine (Chairpersons A. Ungar and A. Benetos). Eur Geriatr Med. 2021;
Nonlinear science against the COVID-19 pandemic.
Pérez-García VM.
Physica D. 2021; 424
DOI: 10.1016/j.physd.2021.132946
This special issue showcases recent uses of mathematical and nonlinear science methods in the study of different problems arising in the context of the COVID-19 pandemic. The sixteen original research papers included in this collection span a wide spectrum of studies including classical epidemiological models, new models accounting for COVID-19 specificities, non-pharmaceutical control measures, network models and other problems related to the pandemic.
2021-04-30 2021 other research-article; Journal Article abstract-available 10.1016/j.physd.2021.132946 Nonlinear science against the COVID-19 pandemic. Pérez-García VM. Physica D. 2021; 424
The Coronavirus Pandemic (SARS-CoV-2): New Problems Demand New Solutions, the Alternative of Mesenchymal (Stem) Stromal Cells.
Eiro N, Cabrera JR, Fraile M, Costa L, [...], Vizoso FJ.
Front Cell Dev Biol. 2020; 8
DOI: 10.3389/fcell.2020.00645
Mesenchymal (stem) stromal cells (MSC) can be a therapeutic alternative for COVID-19 considering their anti-inflammatory, regenerative, angiogenic, and even antimicrobial capacity. Preliminary data point to therapeutic interest of MSC for patients with COVID-19, and their effect seems based on the MSC's ability to curb the cytokine storm caused by COVID-19. In fact, promising clinical studies using MSC to treat COVID-19, are currently underway. For this reason, now is the time to firmly consider new approaches to MSC research that addresses key issues, like selecting the most optimal type of MSC for each indication, assuming the heterogeneity of the donor-dependent MSC and the biological niche where MSC are located.
2020-07-16 2020 other review-article; Review; Journal Article abstract-available 10.3389/fcell.2020.00645 The Coronavirus Pandemic (SARS-CoV-2): New Problems Demand New Solutions, the Alternative of Mesenchymal (Stem) Stromal Cells. Eiro N, Cabrera JR, Fraile M, Costa L, Vizoso FJ. Front Cell Dev Biol. 2020; 8
Miller-Fisher syndrome after SARS-CoV-2 infection.
Reyes-Bueno JA, García-Trujillo L, Urbaneja P, Ciano-Petersen NL, [...], Serrano-Castro PJ.
Eur J Neurol. 2020; 27 (9)
DOI: 10.1111/ene.14383

Introduction

On March 11th, 2020, the WHO declared the SARS-Cov-2 pandemic. Syndromes have been detected in relation to COVID-19 such as encephalitis, acute necrotizing hemorrhagic encephalopathy and cerebrovascular complications. There are also cases of peripheral nervous system involvement.

Methods

Our case would be the 3rd patient with MFS associated with COVID-19 as far as we know.

Results

We present a 51 years old female diagnosed with MFS two weeks after COVID-19. RTPCR to SARS-CoV-2 was negative but IgG was positive.

Conclusion

Most of the cases were mild or moderate with typical signs and symptoms. All were treated with IV immunoglobulin with good response in most cases. Despite the short evolution time of the cases surviving the current pandemic, the description of cases of post-infectious neurological syndromes suggests that this is probably not an infrequent complication in the subacute stage of Covid-19 disease.
2020-09-01 2020 other Case Reports; case-report abstract-available 10.1111/ene.14383 Miller-Fisher syndrome after SARS-CoV-2 infection. Reyes-Bueno JA, García-Trujillo L, Urbaneja P, Ciano-Petersen NL, Postigo-Pozo MJ, Martínez-Tomás C, Serrano-Castro PJ. Eur J Neurol. 2020; 27 (9)
Vacunas Frente A Sars-Cov-2 Y Piel
Galván-Casas C, Català A, Muñoz-Santos C.
Actas Dermosifiliogr (Engl Ed). 2021;
DOI:
Las vacunas contra el SARS-CoV-2 son las primeras vacunas que han sido usadas en humanos contra coronavirus y su desarrollo se ha producido en un tiempo récord. En los análisis de seguridad de los ensayos clínicos previos a su aprobación y en la fase post-autorización en la población, se han descrito efectos secundarios dermatológicos. La descripción y categorización de las manifestaciones cutáneas de la COVID-19 fueron importantes para el conocimiento de la enfermedad y de la misma forma pueden serlo las generadas por las vacunas. En este artículo hacemos un repaso a las características de los diferentes tipos de vacunas disponibles y en desarrollo, su modo de interacción con el sistema inmune, las consecuentes manifestaciones clínicas que pueden generar, con especial interés en los efectos secundarios dermatológicos hasta el momento descritos y las actitudes terapéuticas recomendadas ante cada una de estas reacciones.
2021-05-27 2021 other review-article; Review; Journal Article abstract-available Vacunas Frente A Sars-Cov-2 Y Piel Galván-Casas C, Català A, Muñoz-Santos C. Actas Dermosifiliogr (Engl Ed). 2021;
Genetically Engineered Live-Attenuated Middle East Respiratory Syndrome Coronavirus Viruses Confer Full Protection against Lethal Infection.
Gutiérrez-Álvarez J, Honrubia JM, Fernández-Delgado R, Wang L, [...], Enjuanes L.
mBio. 2021; 12 (2)
DOI: 10.1128/mbio.00103-21
There are no approved vaccines against the life-threatening Middle East respiratory syndrome coronavirus (MERS-CoV). Attenuated vaccines have proven their potential to induce strong and long-lasting immune responses. We have previously described that severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a virulence factor. Based on this knowledge, a collection of mutants carrying partial deletions spanning the C-terminal domain of the E protein (rMERS-CoV-E*) has been generated using a reverse genetics system. One of these mutants, MERS-CoV-E*Δ2in, was attenuated and provided full protection in a challenge with virulent MERS-CoV after a single immunization dose. The MERS-CoV-E*Δ2in mutant was stable as it maintained its attenuation after 16 passages in cell cultures and has been selected as a promising vaccine candidate.IMPORTANCE The emergence of the new highly pathogenic human coronavirus SARS-CoV-2 that has already infected more than 80 million persons, killing nearly two million of them, clearly indicates the need to design efficient and safe vaccines protecting from these coronaviruses. Modern vaccines can be derived from virus-host interaction research directed to the identification of signaling pathways essential for virus replication and for virus-induced pathogenesis, in order to learn how to attenuate these viruses and design vaccines. Using a reverse genetics system developed in our laboratory, an infectious cDNA clone of MERS-CoV was engineered. Using this cDNA, we sequentially deleted several predicted and conserved motifs within the envelope (E) protein of MERS-CoV, previously associated with the presence of virulence factors. The in vitro and in vivo evaluation of these deletion mutants highlighted the relevance of predicted linear motifs in viral pathogenesis. Two of them, an Atg8 protein binding motif (Atg8-BM), and a forkhead-associated binding motif (FHA-BM), when deleted, rendered an attenuated virus that was evaluated as a vaccine candidate, leading to full protection against challenge with a lethal dose of MERS-CoV. This approach can be extended to the engineering of vaccines protecting against the new pandemic SARS-CoV-2.
2021-03-02 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1128/mbio.00103-21 Genetically Engineered Live-Attenuated Middle East Respiratory Syndrome Coronavirus Viruses Confer Full Protection against Lethal Infection. Gutiérrez-Álvarez J, Honrubia JM, Fernández-Delgado R, Wang L, Castaño-Rodríguez C, Zúñiga S, Sola I, Enjuanes L. mBio. 2021; 12 (2)
Pathology of Coronavirus Infections: A Review of Lesions in Animals in the One-Health Perspective.
Zappulli V, Ferro S, Bonsembiante F, Brocca G, [...], Castagnaro M.
Animals (Basel). 2020; 10 (12)
DOI: 10.3390/ani10122377
Coronaviruses (CoVs) are worldwide distributed RNA-viruses affecting several species, including humans, and causing a broad spectrum of diseases. Historically, they have not been considered a severe threat to public health until two outbreaks of COVs-related atypical human pneumonia derived from animal hosts appeared in 2002 and in 2012. The concern related to CoVs infection dramatically rose after the COVID-19 global outbreak, for which a spill-over from wild animals is also most likely. In light of this CoV zoonotic risk, and their ability to adapt to new species and dramatically spread, it appears pivotal to understand the pathophysiology and mechanisms of tissue injury of known CoVs within the "One-Health" concept. This review specifically describes all CoVs diseases in animals, schematically representing the tissue damage and summarizing the major lesions in an attempt to compare and put them in relation, also with human infections. Some information on pathogenesis and genetic diversity is also included. Investigating the lesions and distribution of CoVs can be crucial to understand and monitor the evolution of these viruses as well as of other pathogens and to further deepen the pathogenesis and transmission of this disease to help public health preventive measures and therapies.
2020-12-11 2020 other review-article; Review; Journal Article abstract-available 10.3390/ani10122377 Pathology of Coronavirus Infections: A Review of Lesions in Animals in the One-Health Perspective. Zappulli V, Ferro S, Bonsembiante F, Brocca G, Calore A, Cavicchioli L, Centelleghe C, Corazzola G, De Vreese S, Gelain ME, Mazzariol S, Moccia V, Rensi N, Sammarco A, Torrigiani F, Verin R, Castagnaro M. Animals (Basel). 2020; 10 (12)
Atrial fibrillation in patients with SARS-CoV-2 infection.
García-Granja PE, Veras C, Aparisi Á, Amat-Santos IJ, [...], San Román JA.
Med Clin (Barc). 2021;
DOI: 10.1016/j.medcli.2021.01.003

Introduction and objective

the SARS-CoV-2 infection ranges from asymptomatic to critical forms and several prognostic factors have been described. Atrial fibrillation (AF) is common in acute situations where it is linked with more complications and mortality. We aimed to evaluate the prognostic information of AF in this population.

Methods

retrospective analysis of a cohort of 517 patients consecutively admitted in a tertiary hospital due to SARS-CoV-2 infection. We divided the patients in two groups according the development of AF and compared the main features of both groups. An univariable and multivariable analysis of mortality were also performed.

Results

among 517 patients with SARS-CoV-2 infection admitted in a tertiary center, 54 (10.4%) developed AF. These patients are older (81.6 vs 66.5 years old, p<0.001) and present more hypertension (74% vs 47%, p<0.001), cardiomyopathy (9% vs 1%, p=0.002), previous heart failure admission (9% vs 0.4%, p<0.001), previous episodes of AF (83% vs 1%, p<0.001) and bigger left atrium (47.8 vs 39.9mm, p<0.001). AF COVID-19 patients present more acute respiratory failure (72% vs 40%, p<0.001) and higher in-hospital mortality (50% vs 22%, p<0.001). Predictors of AF development are age and previous AF. AF is not an independent predictor of in-hospital mortality. Predictors are age, creatinine>1.5mg/dL at admission, LDH>250UI/L at admission and acute respiratory failure.

Conclusion

Atrial fibrillation appears in 10% of hospitalized patients with SARS-CoV-2 infection. These patients present more comorbidities and two-fold increase in hospital mortality. Atrial fibrillation is not an independent prognostic factor.
2021-01-28 2021 other research-article; Journal Article abstract-available 10.1016/j.medcli.2021.01.003 Atrial fibrillation in patients with SARS-CoV-2 infection. García-Granja PE, Veras C, Aparisi Á, Amat-Santos IJ, Catalá P, Marcos M, Cabezón G, Candela J, Gil JF, Uribarri A, Revilla A, Carrasco M, Gómez I, San Román JA. Med Clin (Barc). 2021;
Protective Face Mask Filter Capable of Inactivating SARS-CoV-2, and Methicillin-Resistant Staphylococcus aureus and Staphylococcus epidermidis.
Martí M, Tuñón-Molina A, Aachmann FL, Muramoto Y, [...], Serrano-Aroca Á.
Polymers (Basel). 2021; 13 (2)
DOI: 10.3390/polym13020207
Face masks have globally been accepted to be an effective protective tool to prevent bacterial and viral transmission, especially against indoor aerosol transmission. However, commercial face masks contain filters that are made of materials that are not capable of inactivating either SARS-CoV-2 or multidrug-resistant bacteria. Therefore, symptomatic and asymptomatic individuals can infect other people even if they wear them because some viable viral or bacterial loads can escape from the masks. Furthermore, viral or bacterial contact transmission can occur after touching the mask, which constitutes an increasing source of contaminated biological waste. Additionally, bacterial pathogens contribute to the SARS-CoV-2-mediated pneumonia disease complex, and their resistance to antibiotics in pneumonia treatment is increasing at an alarming rate. In this regard, herein, we report the development of a non-woven face mask filter fabricated with a biofunctional coating of benzalkonium chloride that is capable of inactivating more than 99% of SARS-CoV-2 particles in one minute of contact, and the life-threatening methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis (normalized antibacterial halos of 0.52 ± 0.04 and 0.72 ± 0.04, respectively). Nonetheless, despite the results obtained, further studies are needed to ensure the safety and correct use of this technology for the mass production and commercialization of this broad-spectrum antimicrobial face mask filter. Our novel protective non-woven face mask filter would be useful for many healthcare workers and researchers working in this urgent and challenging field.
2021-01-08 2021 other research-article; Journal Article abstract-available 10.3390/polym13020207 Protective Face Mask Filter Capable of Inactivating SARS-CoV-2, and Methicillin-Resistant <i>Staphylococcus aureus</i> and <i>Staphylococcus epidermidis</i>. Martí M, Tuñón-Molina A, Aachmann FL, Muramoto Y, Noda T, Takayama K, Serrano-Aroca Á. Polymers (Basel). 2021; 13 (2)
Cascading from SARS-CoV-2 to Parkinson’s Disease through Protein-Protein Interactions
Estrada E.
Viruses. 2021; 13 (5)
DOI:
Extensive extrapulmonary damages in a dozen of organs/systems, including the central nervous system (CNS), are reported in patients of the coronavirus disease 2019 (COVID-19). Three cases of Parkinson’s disease (PD) have been reported as a direct consequence of COVID-19. In spite of the scarce data for establishing a definitive link between COVID-19 and PD, some hypotheses have been proposed to explain the cases reported. They, however, do not fit well with the clinical findings reported for COVID-19 patients, in general, and for the PD cases reported, in particular. Given the importance of this potential connection, we present here a molecular-level mechanistic hypothesis that explains well these findings and will serve to explore the potential CNS damage in COVID-19 patients. The model explaining the cascade effects from COVID-19 to CNS is developed by using bioinformatic tools. It includes the post-translational modification of host proteins in the lungs by viral proteins, the transport of modified host proteins via exosomes out the lungs, and the disruption of protein-protein interaction in the CNS by these modified host proteins. Our hypothesis is supported by finding 44 proteins significantly expressed in the CNS which are associated with PD and whose interactions can be perturbed by 24 host proteins significantly expressed in the lungs. These 24 perturbators are found to interact with viral proteins and to form part of the cargoes of exosomes in human tissues. The joint set of perturbators and PD-vulnerable proteins form a tightly connected network with significantly more connections than expected by selecting a random cluster of proteins of similar size from the human proteome. The molecular-level mechanistic hypothesis presented here provides several routes for the cascading of effects from the lungs of COVID-19 patients to PD. In particular, the disruption of autophagy/ubiquitination processes appears as an important mechanism that triggers the generation of large amounts of exosomes containing perturbators in their cargo, which would insult several PD-vulnerable proteins, potentially triggering Parkinsonism in COVID-19 patients.
2021-05-01 2021 other research-article; Journal Article abstract-available Cascading from SARS-CoV-2 to Parkinson’s Disease through Protein-Protein Interactions Estrada E. Viruses. 2021; 13 (5)
Symptomatology in head and neck district in coronavirus disease (COVID-19): A possible neuroinvasive action of SARS-CoV-2.
Freni F, Meduri A, Gazia F, Nicastro V, [...], Galletti F.
Am J Otolaryngol. 2020; 41 (5)
DOI: 10.1016/j.amjoto.2020.102612

Objective

The aim of this manuscript is to investigate transversally Ear Nose Throat (ENT) symptoms COVID-19 infection correlated and to study the neurotropism and neuroinvasiveness of the virus in the head-neck district through the investigation of the sense of smell, taste, tearing, salivation and hearing.

Methods

A total of 50 patients with laboratory-confirmed COVID-19 infection were included in our study. For each patient we evaluated the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS), the Summated Xerostomia Inventory-Dutch Version (SXI-DV), The Standardized Patient Evaluation of Eye Dryness (SPEED), Schirmer test I, the Hearing Handicap Inventory For Adults (HHIA) and the Tinnitus Handicap Inventory (THI). All the tests we carried out were performed during the active phase of the symptomatology from COVID-19 (Condition A) and 15 after SARS-COV-2 RT-PCR test negative (Condition B).

Results

A total of 46 patients (92%) had olfactory dysfunction related to the infection. The 70% of patients reported gustatory disorders. Cough, fever, headache and asthenia were the most prevalent symptoms. There was a statistically significant difference (p < 0,001) in sQOD-NS, SXI-DV, SPEED, Schirmer test, HHIA and THI between Condition A and Condition B.

Conclusions

In our population there was an alteration of the sense of taste, of the sense of smell, dry eyes and of the oral cavity and an auditory discomfort, symptoms probably linked to the neurotropism of the virus. Furthermore, anosmia, dysgeusia and xerostomia are early symptoms of COVID-19, which can be exploited for an early quarantine and a limitation of viral contagion.
2020-06-18 2020 other review-article; Review; Journal Article abstract-available 10.1016/j.amjoto.2020.102612 Symptomatology in head and neck district in coronavirus disease (COVID-19): A possible neuroinvasive action of SARS-CoV-2. Freni F, Meduri A, Gazia F, Nicastro V, Galletti C, Aragona P, Galletti C, Galletti B, Galletti F. Am J Otolaryngol. 2020; 41 (5)
COVID-19: from epidemiology to treatment.
Pericàs JM, Hernandez-Meneses M, Sheahan TP, Quintana E, [...], Hospital Clínic Cardiovascular Infections Study Group.
Eur Heart J. 2020; 41 (22)
DOI: 10.1093/eurheartj/ehaa462
The COVID-19 pandemic has greatly impacted the daily clinical practice of cardiologists and cardiovascular surgeons. Preparedness of health workers and health services is crucial to tackle the enormous challenge posed by SARS-CoV-2 in wards, operating theatres, intensive care units, and interventionist laboratories. This Clinical Review provides an overview of COVID-19 and focuses on relevant aspects on prevention and management for specialists within the cardiovascular field.
2020-06-01 2020 other review-article; Journal Article; Case Reports abstract-available 10.1093/eurheartj/ehaa462 COVID-19: from epidemiology to treatment. Pericàs JM, Hernandez-Meneses M, Sheahan TP, Quintana E, Ambrosioni J, Sandoval E, Falces C, Marcos MA, Tuset M, Vilella A, Moreno A, Miro JM, Hospital Clínic Cardiovascular Infections Study Group. Eur Heart J. 2020; 41 (22)
Fetal Transient Skin Edema in Two Pregnant Women With Coronavirus Disease 2019 (COVID-19).
Garcia-Manau P, Garcia-Ruiz I, Rodo C, Sulleiro E, [...], Suy A.
Obstet Gynecol. 2020; 136 (5)
DOI: 10.1097/aog.0000000000004059

Background

The risk of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Positive reverse-transcription polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 infection in neonates and placental tissue have been reported, and immunoglobulin M antibodies have been detected in neonates born to mothers with infection.

Cases

The first case is a woman at 22 3/7 weeks of gestation with coronavirus disease 2019 (COVID-19) who was admitted to the intensive care unit. In the second case, the patient remained at home with mild symptoms, starting at 20 weeks of gestation. In both cases, fetal skin edema was observed on ultrasound examination while maternal SARS-COV-2 RT-PCR test results were positive and resolved when maternal SARS-COV-2 RT-PCR test results became negative. The RT-PCR test result for SARS-CoV-2 in amniotic fluid was negative in both cases. The two pregnancies are ongoing and uneventful.

Conclusion

Transient fetal skin edema noted in these two patients with COVID-19 in the second trimester may represent results of fetal infection or altered fetal physiology due to maternal disease or may be unrelated to the maternal illness.
2020-11-01 2020 other Research Support, Non-U.S. Gov't; Journal Article; Case Reports; case-report abstract-available 10.1097/aog.0000000000004059 Fetal Transient Skin Edema in Two Pregnant Women With Coronavirus Disease 2019 (COVID-19). Garcia-Manau P, Garcia-Ruiz I, Rodo C, Sulleiro E, Maiz N, Catalan M, Fernández-Hidalgo N, Balcells J, Antón A, Carreras E, Suy A. Obstet Gynecol. 2020; 136 (5)
A multiplex antigen microarray for simultaneous IgG and IgM detection against SARS-CoV-2 reveals higher seroprevalence than reported.
Ruano-Gallego D, García-Villadangos M, Moreno-Paz M, Gómez-Elvira J, [...], Parro V.
Microb Biotechnol. 2021; 14 (3)
DOI: 10.1111/1751-7915.13801
The surge of SARS-CoV-2 has challenged health systems worldwide and efficient tests to detect viral particles, as well as antibodies generated against them, are needed. Specificity, sensitivity, promptness or scalability are the main parameters to estimate the final performance, but rarely all of them match in a single test. We have developed SCOVAM, a protein microarray with several viral antigens (spike, nucleocapsid, main protease Nsp5) as capturing probes in a fluorescence immunoassay for COVID-19 serological testing. SCOVAM depicts IgG and IgM antibody responses against each of these proteins of 22 individuals in a single microscope slide. It detects specific IgM (0.094 μg ml-1 ) and IgG (~0.017 μg ml-1 ) and is scalable and cost-effective. We validated SCOVAM by comparing with a widely used chemiluminescent commercial serological test (n = 742). SCOVAM showed twice the sensitivity and allowed following seroconversion in a single assay. By analysing the prevalence 4 months later in a subset of 76 positive sera, we still detected 93.42% of positives, almost doubling the detection of the commercial assay. The higher sensitivity of SCOVAM is especially relevant to screen sera for convalescent plasma-based treatments, high-throughput antibody response monitoring after vaccination or evaluation of vaccine efficiency.
2021-05-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1111/1751-7915.13801 A multiplex antigen microarray for simultaneous IgG and IgM detection against SARS-CoV-2 reveals higher seroprevalence than reported. Ruano-Gallego D, García-Villadangos M, Moreno-Paz M, Gómez-Elvira J, Postigo M, Simón-Sacristán M, Reyburn HT, Carolis C, Rodrigo N, Codeseira YB, Rueda P, Zúñiga S, Enjuanes L, Parro V. Microb Biotechnol. 2021; 14 (3)
Forensic evaluation of two nucleic acid extraction systems and validation of a RT-qPCR protocol for identification of SARS-CoV-2 in post-mortem nasopharyngeal swabs.
Barrio PA, Fernández-Rodríguez A, Martín P, Fernández C, [...], Alonso A.
Forensic Sci Int. 2021; 323
DOI: 10.1016/j.forsciint.2021.110775
The COVID-19 outbreak has represented a challenge for the international scientific community and particularly for forensic sciences. The lack of Coronavirus post-mortem testing led the National Institute of Toxicology and Forensic Sciences (INTCF) from Spain to verify the performance and utility of a quantitative reverse transcription PCR (RT-qPCR) clinical diagnosis protocol for SARS-CoV-2 detection (TaqPath™ COVID-19 CE-IVD RT-PCR Kit), to shed light on the cause of death (COD) in potentially COVID-19 cases in judicial autopsies. Two different RNA extraction methods were also tested (EZ1® DSP Virus Kit on the EZ1® Advanced XL robot versus MagMAX™ Viral/Pathogen Nucleic Acid Isolation Kit) regarding extraction efficiency, precision and contamination. RT-qPCR was evaluated for precision, specificity, limit of detection and concordance. Both the automated and the manual RNA extraction procedures showed good efficiency, but the automated virus extraction by bio-robot produced more reproducible results than the manual extraction. The SARS-CoV-2 RT-qPCR assay showed high sensitivity with a detection limit up to 10 copies/reaction and high specificity, as no cross-reactivity was detected between any of the 12 different RNA viruses tested, including three types of coronaviruses (SARS-CoV, NL63 and 229E). Reproducibility and repeatability of the studied method as well as concordance with other SARS-CoV-2 molecular detection protocols were also demonstrated.
2021-04-02 2021 other Journal Article abstract-available 10.1016/j.forsciint.2021.110775 Forensic evaluation of two nucleic acid extraction systems and validation of a RT-qPCR protocol for identification of SARS-CoV-2 in post-mortem nasopharyngeal swabs. Barrio PA, Fernández-Rodríguez A, Martín P, Fernández C, Fernández L, Alonso A. Forensic Sci Int. 2021; 323
Innate and Adaptive Immunity Alterations in Metabolic Associated Fatty Liver Disease and Its Implication in COVID-19 Severity.
Lamadrid P, Alonso-Peña M, San Segundo D, Arias-Loste M, [...], Lopez-Hoyos M.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.651728
The coronavirus infectious disease 2019 (COVID-19) pandemic has hit the world, affecting health, medical care, economies and our society as a whole. Furthermore, COVID-19 pandemic joins the increasing prevalence of metabolic syndrome in western countries. Patients suffering from obesity, type II diabetes mellitus, cardiac involvement and metabolic associated fatty liver disease (MAFLD) have enhanced risk of suffering severe COVID-19 and mortality. Importantly, up to 25% of the population in western countries is susceptible of suffering from both MAFLD and COVID-19, while none approved treatment is currently available for any of them. Moreover, it is well known that exacerbated innate immune responses are key in the development of the most severe stages of MAFLD and COVID-19. In this review, we focus on the role of the immune system in the establishment and progression of MAFLD and discuss its potential implication in the development of severe COVID-19 in MAFLD patients. As a result, we hope to clarify their common pathology, but also uncover new potential therapeutic targets and prognostic biomarkers for further research.
2021-03-30 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fimmu.2021.651728 Innate and Adaptive Immunity Alterations in Metabolic Associated Fatty Liver Disease and Its Implication in COVID-19 Severity. Lamadrid P, Alonso-Peña M, San Segundo D, Arias-Loste M, Crespo J, Lopez-Hoyos M. Front Immunol. 2021; 12
ATTR amyloidosis during the COVID-19 pandemic: insights from a global medical roundtable.
Brannagan TH, Auer-Grumbach M, Berk JL, Briani C, [...], Ruberg FL.
Orphanet J Rare Dis. 2021; 16 (1)
DOI: 10.1186/s13023-021-01834-0

Background

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing the ongoing coronavirus disease 2019 (COVID-19) pandemic has raised serious concern for patients with chronic disease. A correlation has been identified between the severity of COVID-19 and a patient's preexisting comorbidities. Although COVID-19 primarily involves the respiratory system, dysfunction in multiple organ systems is common, particularly in the cardiovascular, gastrointestinal, immune, renal, and nervous systems. Patients with amyloid transthyretin (ATTR) amyloidosis represent a population particularly vulnerable to COVID-19 morbidity due to the multisystem nature of ATTR amyloidosis.

Main body

ATTR amyloidosis is a clinically heterogeneous progressive disease, resulting from the accumulation of amyloid fibrils in various organs and tissues. Amyloid deposition causes multisystem clinical manifestations, including cardiomyopathy and polyneuropathy, along with gastrointestinal symptoms and renal dysfunction. Given the potential for exacerbation of organ dysfunction, physicians note possible unique challenges in the management of patients with ATTR amyloidosis who develop multiorgan complications from COVID-19. While the interplay between COVID-19 and ATTR amyloidosis is still being evaluated, physicians should consider that the heightened susceptibility of patients with ATTR amyloidosis to multiorgan complications might increase their risk for poor outcomes with COVID-19.

Conclusion

Patients with ATTR amyloidosis are suspected to have a higher risk of morbidity and mortality due to age and underlying ATTR amyloidosis-related organ dysfunction. While further research is needed to characterize this risk and management implications, ATTR amyloidosis patients might require specialized management if they develop COVID-19. The risks of delaying diagnosis or interrupting treatment for patients with ATTR amyloidosis should be balanced with the risk of exposure in the health care setting. Both physicians and patients must adapt to a new construct for care during and possibly after the pandemic to ensure optimal health for patients with ATTR amyloidosis, minimizing treatment interruptions.
2021-05-06 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1186/s13023-021-01834-0 ATTR amyloidosis during the COVID-19 pandemic: insights from a global medical roundtable. Brannagan TH, Auer-Grumbach M, Berk JL, Briani C, Bril V, Coelho T, Damy T, Dispenzieri A, Drachman BM, Fine N, Gaggin HK, Gertz M, Gillmore JD, Gonzalez E, Hanna M, Hurwitz DR, Khella SL, Maurer MS, Nativi-Nicolau J, Olugemo K, Quintana LF, Rosen AM, Schmidt HH, Shehata J, Waddington-Cruz M, Whelan C, Ruberg FL. Orphanet J Rare Dis. 2021; 16 (1)
Nebulized CLODOS Technology Shows Clear Virucidal Properties against the Human Coronavirus HCoV-229E at Non-Cytotoxic Doses.
Andreu S, Ripa I, Bello-Morales R, López-Guerrero JA.
Viruses. 2021; 13 (3)
DOI: 10.3390/v13030531
The emergent human coronavirus SARS-CoV-2 and its high infectivity rate has highlighted the strong need for new disinfection systems. Evidence has proven that airborne transmission is an important route of spreading for this virus. Therefore, this short communication introduces CLODOS Technology®, a novel strategy to disinfect contaminated surfaces. It is a product based on stable and 99% pure chlorine dioxide, already certified as a bactericide, fungicide and virucide against different pathogens. In this study, CLODOS Technology®, by direct contact or thermonebulization, showed virucidal activity against the human coronavirus HCoV-229E at non-cytotoxic doses. Different conditions such as nebulization, exposure time and product concentration have been tested to standardize and optimize this new feasible method for disinfection.
2021-03-23 2021 other Research Support, Non-U.S. Gov't; research-article; Evaluation Study; Journal Article abstract-available 10.3390/v13030531 Nebulized CLODOS Technology Shows Clear Virucidal Properties against the Human Coronavirus HCoV-229E at Non-Cytotoxic Doses. Andreu S, Ripa I, Bello-Morales R, López-Guerrero JA. Viruses. 2021; 13 (3)
Asthma and the Coronavirus Disease 2019 Pandemic: A Literature Review.
Morais-Almeida M, Pité H, Aguiar R, Ansotegui I, [...], Bousquet J.
Int Arch Allergy Immunol. 2020; 181 (9)
DOI: 10.1159/000509057
Even though respiratory viruses are one of the most common triggers for asthma exacerbations, not all of these viruses affect patients equally. There is no strong evidence supporting that patients with asthma have a higher risk of becoming seriously ill from coronavirus disease 2019 (CO-VID-19), although recent reports from the USA and the UK suggest that asthma is much more common in children and adults with mild to severe COVID-19 than has previously been reported in Asia and in Europe. As in previous severe acute respiratory syndrome (SARS) outbreaks, patients with asthma, especially children, appear to be less susceptible to the coronavirus with a low rate of asthma exacerbations. A different expression of viral receptors and T2 inflammation can be responsible for different outcomes. Future studies focused on asthma and on other allergic disorders are needed to provide a greater understanding of the impact of underlying asthma and allergic inflammation on COVID-19 susceptibility and disease severity. However, for the moment, it is crucial that asthmatic patients maintain their controller medication, from inhaled corticosteroids to biologics, without making any dose adjustments on their own or stopping the medication. New data are emerging daily, rapidly updating our understanding of this novel coronavirus.
2020-06-09 2020 other review-article; Review; Journal Article abstract-available 10.1159/000509057 Asthma and the Coronavirus Disease 2019 Pandemic: A Literature Review. Morais-Almeida M, Pité H, Aguiar R, Ansotegui I, Bousquet J. Int Arch Allergy Immunol. 2020; 181 (9)
New-onset psychosis in COVID-19 pandemic: a case series in Madrid.
Rentero D, Juanes A, Losada CP, Álvarez S, [...], Urricelqui J.
Psychiatry Res. 2020; 290
DOI: 10.1016/j.psychres.2020.113097
2020-05-13 2020 other Letter; Comment 10.1016/j.psychres.2020.113097 New-onset psychosis in COVID-19 pandemic: a case series in Madrid. Rentero D, Juanes A, Losada CP, Álvarez S, Parra A, Santana V, Martí I, Urricelqui J. Psychiatry Res. 2020; 290
Real-time measurement of the uncertain epidemiological appearances of COVID-19 infections.
Gupta M, Jain R, Taneja S, Chaudhary G, [...], Verdú E.
Appl Soft Comput. 2021; 101
DOI: 10.1016/j.asoc.2020.107039
Virus diseases are a continued threat to human health in both community and healthcare settings. The current virus disease COVID-19 outbreak raises an unparalleled public health issue for the world at large. Wuhan is the city in China from where this virus came first and, after some time the whole world was affected by this severe disease. It is a challenge for every country's people and higher authorities to fight with this battle due to the insufficient number of resources. On-going assessment of the epidemiological features and future impacts of the COVID-19 disease is required to stay up-to-date of any changes to its spread dynamics and foresee needed resources and consequences in different aspects as social or economic ones. This paper proposes a prediction model of confirmed and death cases of COVID-19. The model is based on a deep learning algorithm with two long short-term memory (LSTM) layers. We consider the available infection cases of COVID-19 in India from January 22, 2020, till October 9, 2020, and parameterize the model. The proposed model is an inference to obtain predicted coronavirus cases and deaths for the next 30 days, taking the data of the previous 260 days of duration of the pandemic. The proposed deep learning model has been compared with other popular prediction methods (Support Vector Machine, Decision Tree and Random Forest) showing a lower normalized RMSE. This work also compares COVID-19 with other previous diseases (SARS, MERS, h1n1, Ebola, and 2019-nCoV). Based on the mortality rate and virus spread, this study concludes that the novel coronavirus (COVID-19) is more dangerous than other diseases.
2020-12-25 2020 other research-article; Journal Article abstract-available 10.1016/j.asoc.2020.107039 Real-time measurement of the uncertain epidemiological appearances of COVID-19 infections. Gupta M, Jain R, Taneja S, Chaudhary G, Khari M, Verdú E. Appl Soft Comput. 2021; 101
Clinical course of coronavirus disease-2019 in pregnancy.
Pereira A, Cruz-Melguizo S, Adrien M, Fuentes L, [...], Perez-Medina T.
Acta Obstet Gynecol Scand. 2020; 99 (7)
DOI: 10.1111/aogs.13921
INTRODUCTION:The aim of this study is to report our clinical experience in the management of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first 30 days of the coronavirus disease (COVID-19) pandemic. MATERIAL AND METHODS:We reviewed clinical data from the first 60 pregnant women with COVID-19 whose care was managed at Puerta de Hierro University Hospital, Madrid, Spain from 14 March to 14 April 2020. Demographic data, clinical findings, laboratory test results, imaging findings, treatment received, and outcomes were collected. An analysis of variance (Kruskal-Wallis test) was performed to compare the medians of laboratory parameters. Fisher's exact test was used to evaluate categorical variables. A correspondence analysis was used to explore associations between variables. RESULTS:A total of 60 pregnant women were diagnosed with COVID-19. The most common symptoms were fever and cough (75.5% each) followed by dyspnea (37.8%). Forty-one women (68.6%) required hospital admission (18 because of disease worsening and 23 for delivery) of whom 21 women (35%) underwent pharmacological treatment, including hydroxychloroquine, antivirals, antibiotics, and tocilizumab. No renal or cardiac failures or maternal deaths were reported. Lymphopenia (50%), thrombocytopenia (25%), and elevated C-reactive protein (CRP) (59%) were observed in the early stages of the disease. Median CRP, D-dimer, and the neutrophil/lymphocyte ratio were elevated. High CRP and D-dimer levels were the parameters most frequently associated with severe pneumonia. The neutrophil/lymphocyte ratio was found to be the most sensitive marker for disease improvement (relative risk 6.65; 95% CI 4.1-5.9). During the study period, 18 of the women (78%) delivered vaginally. All newborns tested negative for SARS-CoV-2 and none of them were infected during breastfeeding. No SARS-CoV-2 was detected in placental tissue. CONCLUSIONS:Most of the pregnant women with COVID-19 had a favorable clinical course. However, one-third of them developed pneumonia, of whom 5% presented a critical clinical status. CRP and D-dimer levels positively correlated with severe pneumonia and the neutrophil/lymphocyte ratio decreased as the patients improved clinically. Seventy-eight percent of the women had a vaginal delivery. No vertical or horizontal transmissions were diagnosed in the neonates during labor or breastfeeding.
2020-06-10 2020 other research-article; Journal Article abstract-available 10.1111/aogs.13921 Clinical course of coronavirus disease-2019 in pregnancy. Pereira A, Cruz-Melguizo S, Adrien M, Fuentes L, Marin E, Perez-Medina T. Acta Obstet Gynecol Scand. 2020; 99 (7)
Minimally Invasive Autopsy Practice in COVID-19 Cases: Biosafety and Findings.
Rakislova N, Marimon L, Ismail MR, Carrilho C, [...], Ordi J.
Pathogens. 2021; 10 (4)
DOI: 10.3390/pathogens10040412
Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening the body, which may be a valid alternative in these cases. We aimed to: (a) provide biosafety guidelines for conducting MIAs in COVID-19 cases, (b) compare the performance of MIA versus complete autopsy, and (c) evaluate the safety of the procedure. Between October and December 2020, MIAs were conducted in six deceased patients with PCR-confirmed COVID-19, in a basic autopsy room, with reinforced personal protective equipment. Samples from the lungs and key organs were successfully obtained in all cases. A complete autopsy was performed on the same body immediately after the MIA. The diagnoses of the MIA matched those of the complete autopsy. In four patients, COVID-19 was the main cause of death, being responsible for the different stages of diffuse alveolar damage. No COVID-19 infection was detected in the personnel performing the MIAs or complete autopsies. In conclusion, MIA might be a feasible, adequate and safe alternative for cause of death investigation in COVID-19 cases.
2021-04-01 2021 other research-article; Journal Article abstract-available 10.3390/pathogens10040412 Minimally Invasive Autopsy Practice in COVID-19 Cases: Biosafety and Findings. Rakislova N, Marimon L, Ismail MR, Carrilho C, Fernandes F, Ferrando M, Castillo P, Rodrigo-Calvo MT, Guerrero J, Ortiz E, Muñoz-Beatove A, Martinez MJ, Hurtado JC, Navarro M, Bassat Q, Maixenchs M, Delgado V, Wallong E, Aceituno A, Kim J, Paganelli C, Goco NJ, Aldecoa I, Martinez-Pozo A, Martinez D, Ramírez-Ruz J, Cathomas G, Haab M, Menéndez C, Ordi J. Pathogens. 2021; 10 (4)
Prognostic Implications of Chronic Heart Failure and Utility of NT-proBNP Levels in Heart Failure Patients with SARS-CoV-2 Infection.
Belarte-Tornero LC, Valdivielso-Moré S, Vicente Elcano M, Solé-González E, [...], Farré N.
J Clin Med. 2021; 10 (2)
DOI: 10.3390/jcm10020323

Background

The prevalence and prognostic value of chronic heart failure (CHF) in the setting of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has seldom been studied. The aim of this study was to analyze the prevalence and prognosis of CHF in this setting.

Methods

This single-center study included 829 consecutive patients with SARS-CoV-2 infection from February to April 2020. Patients with a previous history of CHF were matched 1:2 for age and sex. We analyze the prognostic value of pre-existing CHF. Prognostic implications of N terminal pro brain natriuretic peptide (NT-proBNP) levels on admission in the CHF cohort were explored.

Results

A total of 129 patients (43 CHF and 86 non-CHF) where finally included. All-cause mortality was higher in CHF patients compared to non-CHF patients (51.2% vs. 29.1%, p = 0.014). CHF was independently associated with 30-day mortality (hazard ratio (HR) 2.3, confidence interval (CI) 95%: 1.26-2.4). Patients with CHF and high-sensitivity troponin T < 14 ng/L showed excellent prognosis. An NT-proBNP level > 2598 pg/mL on admission was associated with higher 30-day mortality in patients with CHF.

Conclusions

All-cause mortality in CHF patients hospitalized due to SARS-CoV-2 infection was 51.2%. CHF was independently associated with all-cause mortality (HR 2.3, CI 95% 1.26-4.2). NT-proBNP levels could be used for stratification risk purposes to guide medical decisions if larger studies confirm this finding.
2021-01-17 2021 other research-article; Journal Article abstract-available 10.3390/jcm10020323 Prognostic Implications of Chronic Heart Failure and Utility of NT-proBNP Levels in Heart Failure Patients with SARS-CoV-2 Infection. Belarte-Tornero LC, Valdivielso-Moré S, Vicente Elcano M, Solé-González E, Ruíz-Bustillo S, Calvo-Fernández A, Subinara I, Cabero P, Soler C, Cubero-Gallego H, Vaquerizo B, Farré N. J Clin Med. 2021; 10 (2)
A Simple, Affordable, Rapid, Stabilized, Colorimetric, Versatile RT-LAMP Assay to Detect SARS-CoV-2.
García-Bernalt Diego J, Fernández-Soto P, Domínguez-Gil M, Belhassen-García M, [...], Muro A.
Diagnostics (Basel). 2021; 11 (3)
DOI: 10.3390/diagnostics11030438
The SARS-CoV-2 pandemic has forced all countries worldwide to rapidly develop and implement widespread testing to control and manage the Coronavirus Disease 2019 (COVID-19). reverse-transcription (RT)-qPCR is the gold standard molecular diagnostic method for COVID-19, mostly in automated testing platforms. These systems are accurate and effective, but also costly, time-consuming, high-technological, infrastructure-dependent, and currently suffer from commercial reagent supply shortages. The reverse-transcription loop-mediated isothermal amplification (RT-LAMP) can be used as an alternative testing method. Here, we present a novel versatile (real-time and colorimetric) RT-LAMP for the simple (one-step), affordable (~1.7 €/sample), and rapid detection of SARS-CoV-2 targeting both ORF1ab and N genes of the novel virus genome. We demonstrate the assay on RT-qPCR-positive clinical samples, obtaining most positive results under 25 min. In addition, a novel 30-min one-step drying protocol has been developed to stabilize the RT-LAMP reaction mixtures, allowing them to be stored at room temperature functionally for up to two months, as predicted by the Q10. This Dry-RT-LAMP methodology is suitable for potentially ready-to-use COVID-19 diagnosis. After further testing and validation, it could be easily applied both in developed and in low-income countries yielding rapid and reliable results.
2021-03-04 2021 other research-article; Journal Article abstract-available 10.3390/diagnostics11030438 A <u>S</u>imple, <u>A</u>ffordable, <u>R</u>apid, <u>S</u>tabilized, <u>Co</u>lorimetric, <u>V</u>ersatile RT-LAMP Assay to Detect SARS-CoV-2. García-Bernalt Diego J, Fernández-Soto P, Domínguez-Gil M, Belhassen-García M, Bellido JLM, Muro A. Diagnostics (Basel). 2021; 11 (3)
ECMO use in COVID-19: lessons from past respiratory virus outbreaks-a narrative review.
Cho HJ, Heinsar S, Jeong IS, Shekar K, [...], Fraser JF.
Crit Care. 2020; 24 (1)
DOI: 10.1186/s13054-020-02979-3
The spread of coronavirus disease 2019 (COVID-19) continues to grow exponentially in most countries, posing an unprecedented burden on the healthcare sector and the world economy. Previous respiratory virus outbreaks, such as severe acute respiratory syndrome (SARS), pandemic H1N1 and Middle East respiratory syndrome (MERS), have provided significant insights into preparation and provision of intensive care support including extracorporeal membrane oxygenation (ECMO). Many patients have already been supported with ECMO during the current COVID-19 pandemic, and it is likely that many more may receive ECMO support, although, at this point, the role of ECMO in COVID-19-related cardiopulmonary failure is unclear. Here, we review the experience with the use of ECMO in the past respiratory virus outbreaks and discuss potential role for ECMO in COVID-19.
2020-06-06 2020 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1186/s13054-020-02979-3 ECMO use in COVID-19: lessons from past respiratory virus outbreaks-a narrative review. Cho HJ, Heinsar S, Jeong IS, Shekar K, Li Bassi G, Jung JS, Suen JY, Fraser JF. Crit Care. 2020; 24 (1)
Are the Portable Air Cleaners (PAC) really effective to terminate airborne SARS-CoV-2?
Rodríguez M, Palop ML, Seseña S, Rodríguez A.
Sci Total Environ. 2021; 785
DOI: 10.1016/j.scitotenv.2021.147300
The transmission of SARS-CoV-2 virus through aerosols has become an outstanding issue, where plenty of spread aspects are being analyzed. Portable Air Cleaners (PAC) with high-efficiency particulate air (HEPA) filters have been discussed as an adjunctive means for indoor environments coronavirus decontamination. This study evaluates, first, the air and surfaces SARS-COV-2 RNA contamination due to positive patients in households, and second, the efficiency of a PAC with HEPA filter to eliminate virus. A total of 29 air and surface samples were collected inside 9 households, by using an air portable collector with gelatin filters and swabs. SARS-CoV-2 RNA detection was performed using real-time reverse transcription polymerase chain reaction (RT-PCR). Overall, all the air samples collected before using PAC and 75% of swab samples were positive for SARS-CoV-2. After the PAC usage, all samples except one were negative, displaying a 80% device effectiveness. Portable HEPA cleaners usage allowed the removal of SARS CoV-2 and, therefore, they could be recommended for places with inadequate ventilation, considering the limitations and functionality of the device.
2021-04-29 2021 other brief-report; Journal Article abstract-available 10.1016/j.scitotenv.2021.147300 Are the Portable Air Cleaners (PAC) really effective to terminate airborne SARS-CoV-2? Rodríguez M, Palop ML, Seseña S, Rodríguez A. Sci Total Environ. 2021; 785
Rescue of SARS-CoV-2 from a Single Bacterial Artificial Chromosome.
Ye C, Chiem K, Park JG, Oladunni F, [...], Martinez-Sobrido L.
mBio. 2020; 11 (5)
DOI: 10.1128/mbio.02168-20
Infectious coronavirus (CoV) disease 2019 (COVID-19) emerged in the city of Wuhan (China) in December 2019, causing a pandemic that has dramatically impacted public health and socioeconomic activities worldwide. A previously unknown coronavirus, severe acute respiratory syndrome CoV-2 (SARS-CoV-2), has been identified as the causative agent of COVID-19. To date, there are no U.S. Food and Drug Administration (FDA)-approved vaccines or therapeutics available for the prevention or treatment of SARS-CoV-2 infection and/or associated COVID-19 disease, which has triggered a large influx of scientific efforts to develop countermeasures to control SARS-CoV-2 spread. To contribute to these efforts, we have developed an infectious cDNA clone of the SARS-CoV-2 USA-WA1/2020 strain based on the use of a bacterial artificial chromosome (BAC). Recombinant SARS-CoV-2 (rSARS-CoV-2) was readily rescued by transfection of the BAC into Vero E6 cells. Importantly, BAC-derived rSARS-CoV-2 exhibited growth properties and plaque sizes in cultured cells comparable to those of the natural SARS-CoV-2 isolate. Likewise, rSARS-CoV-2 showed levels of replication similar to those of the natural isolate in nasal turbinates and lungs of infected golden Syrian hamsters. This is, to our knowledge, the first BAC-based reverse genetics system for the generation of infectious rSARS-CoV-2 that displays features in vivo similar to those of a natural viral isolate. This SARS-CoV-2 BAC-based reverse genetics will facilitate studies addressing several important questions in the biology of SARS-CoV-2, as well as the identification of antivirals and development of vaccines for the treatment of SARS-CoV-2 infection and associated COVID-19 disease.IMPORTANCE The pandemic coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is a major threat to global human health. To date, there are no approved prophylactics or therapeutics available for COVID-19. Reverse genetics is a powerful approach to understand factors involved in viral pathogenesis, antiviral screening, and vaccine development. In this study, we describe the feasibility of generating recombinant SARS-CoV-2 (rSARS-CoV-2) by transfection of a single bacterial artificial chromosome (BAC). Importantly, rSARS-CoV-2 possesses the same phenotype as the natural isolate in vitro and in vivo This is the first description of a BAC-based reverse genetics system for SARS-CoV-2 and the first time that an rSARS-CoV-2 isolate has been shown to be phenotypically identical to a natural isolate in a validated animal model of SARS-CoV-2 infection. The BAC-based reverse genetics approach will facilitate the study of SARS-CoV-2 and the development of prophylactics and therapeutics for the treatment of COVID-19.
2020-09-25 2020 other research-article; Journal Article abstract-available 10.1128/mbio.02168-20 Rescue of SARS-CoV-2 from a Single Bacterial Artificial Chromosome. Ye C, Chiem K, Park JG, Oladunni F, Platt RN, Anderson T, Almazan F, de la Torre JC, Martinez-Sobrido L. mBio. 2020; 11 (5)
Incidence, Clinical Characteristics, and Evolution of SARS-CoV-2 Infection in Patients With Inflammatory Bowel Disease: A Single-Center Study in Madrid, Spain.
Guerra I, Algaba A, Jiménez L, Mar Aller M, [...], Bermejo F.
Inflamm Bowel Dis. 2021; 27 (1)
DOI: 10.1093/ibd/izaa221

Background

There are scarce data about SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD). Our aim was to analyze the incidence, clinical presentation, and severity of SARS-CoV-2 infection in patients with IBD.

Methods

This is a cross-sectional, observational study. We contacted all the patients being treated at our IBD unit to identify those patients with suspected or confirmed SARS-CoV-2 infection, following the World Health Organization case definition. Data were obtained by patient electronical medical records and by phone interview.

Results

Eighty-two of 805 patients with IBD (10.2%; 95% confidence interval [CI], 8.3-12.5) were diagnosed as having confirmed (28 patients, 3.5%; 95% CI, 2.4-5.0) or suspected (54 patients, 6.7%) infection. Patient age was 46 ± 14 years, 44 patients were female (53.7%), 17.3% were smokers, 51.2% had Crohn disease (CD), and 39.0% had comorbidities. Digestive symptoms were reported in 41 patients (50.0%), with diarrhea as the most common (42.7%). One patient (1.2%) was diagnosed with IBD flare-up during SARS-CoV-2 infection. Twenty-two patients (26.8%) temporarily withdrew from their IBD treatment because of COVID-19. Most of the patients had mild disease (79.3%), and 1 patient died (1.2%). In the multivariate analysis, the presence of dyspnea was associated with moderate to severe infection (odds ratio, 5.3; 95% CI, 1.6-17.7; P = 0.01) and myalgias (odds ratio, 4.8; 95% CI, 1.3-17.9; P = 0.02) were related to a milder clinical course. Immunosuppression was not related to severity.

Conclusions

SARS-CoV-2 infection in patients with IBD is not rare. Dyspnea is associated with a more severe infection. Therapy for IBD, including immunomodulators and biologic therapy, is not related to a greater severity of COVID-19, and SARS-CoV-2 infections do not appear to be related to IBD flare-ups.
2021-01-01 2021 other research-article; Journal Article; Observational Study abstract-available 10.1093/ibd/izaa221 Incidence, Clinical Characteristics, and Evolution of SARS-CoV-2 Infection in Patients With Inflammatory Bowel Disease: A Single-Center Study in Madrid, Spain. Guerra I, Algaba A, Jiménez L, Mar Aller M, Garza D, Bonillo D, Molina Esteban LM, Bermejo F. Inflamm Bowel Dis. 2021; 27 (1)
Acute myelitis and SARS-CoV-2 infection. A new etiology of myelitis?
Águila-Gordo D, Manuel Flores-Barragán J, Ferragut-Lloret F, Portela-Gutierrez J, [...], Carlos Villa Guzmán J.
J Clin Neurosci. 2020; 80
DOI: 10.1016/j.jocn.2020.07.074
The etiological agent of coronavirus disease-19 (COVID-19), SARS-coronavirus-2 (SARS-CoV-2), emerged in Wuhan, China, and quickly spread worldwide leading the World Health Organization (WHO) to recognize it not only as a pandemic but also as an important thread to public health. Beyond respiratory symptoms, new neurological manifestations are being identified such as headache, ageusia, anosmia, encephalitis or acute cerebrovascular disease. Here we report the case of an acute transverse myelitis (TM) in a patient with SARS-CoV-2 infection detected by the nasopharyngeal swab technique but not in cerebrospinal fluid (CSF) analysis. Anti-herpes simplex virus (HSV) 1 and varicella-zoster IgM antibodies were not detected in serum samples and spinal and brain magnetic resonance imaging (MRI) showed no abnormal findings. This case remarks that COVID-19 nervous system damage could be caused by immune-mediated mechanisms.
2020-09-30 2020 other Case Reports; case-report abstract-available 10.1016/j.jocn.2020.07.074 Acute myelitis and SARS-CoV-2 infection. A new etiology of myelitis? Águila-Gordo D, Manuel Flores-Barragán J, Ferragut-Lloret F, Portela-Gutierrez J, LaRosa-Salas B, Porras-Leal L, Carlos Villa Guzmán J. J Clin Neurosci. 2020; 80
Letter: Hemorrhagic Conditions Affecting the Central Nervous System in COVID-19 Patients.
García-García S, Cepeda S, Arrese I, Sarabia R.
Neurosurgery. 2020; 87 (3)
DOI: 10.1093/neuros/nyaa253
2020-09-01 2020 other letter; Journal Article 10.1093/neuros/nyaa253 Letter: Hemorrhagic Conditions Affecting the Central Nervous System in COVID-19 Patients. García-García S, Cepeda S, Arrese I, Sarabia R. Neurosurgery. 2020; 87 (3)
ACE2 activators for the treatment of COVID 19 patients.
Rodríguez-Puertas R.
J Med Virol. 2020; 92 (10)
DOI: 10.1002/jmv.25992
2020-06-02 2020 other Research Support, Non-U.S. Gov't; letter; Journal Article 10.1002/jmv.25992 ACE2 activators for the treatment of COVID 19 patients. Rodríguez-Puertas R. J Med Virol. 2020; 92 (10)
Statins and other drugs: Facing COVID-19 as a vascular disease.
Sanchis-Gomar F, Perez-Quilis C, Favaloro EJ, Lippi G.
Pharmacol Res. 2020; 159
DOI: 10.1016/j.phrs.2020.105033
2020-06-17 2020 other Letter; Comment 10.1016/j.phrs.2020.105033 Statins and other drugs: Facing COVID-19 as a vascular disease. Sanchis-Gomar F, Perez-Quilis C, Favaloro EJ, Lippi G. Pharmacol Res. 2020; 159
Employing bioactive compounds derived from Ipomoea obscura (L.) to evaluate potential inhibitor for SARS-CoV-2 main protease and ACE2 protein.
Poochi SP, Easwaran M, Balasubramanian B, Anbuselvam M, [...], Kaul T.
Food Front. 2020;
DOI: 10.1002/fft2.29
Angiotensin converting enzyme 2 (ACE2) and main protease (MPro) are significant target proteins, mainly involved in the attachment of viral genome to host cells and aid in replication of severe acute respiratory syndrome-coronaviruses or SARS-CoV genome. In the present study, we identified 11 potent bioactive compounds from ethanolic leaf extract of Ipomoea obscura (L.) by using GC-MS analysis. These potential bioactive compounds were considered for molecular docking studies against ACE2 and MPro target proteins to determine the antiviral effects against SARS-COV. Results exhibits that among 11 compounds from I. obscura (L.), urso-deoxycholic acid, demeclocycline, tetracycline, chlorotetracycline, and ethyl iso-allocholate had potential viral inhibitory activity. Hence, the present findings suggested that chemical constitution present in I. obscura (L.) will address inhibition of corona viral replication in host cells.
2020-07-06 2020 other research-article; Journal Article abstract-available 10.1002/fft2.29 Employing bioactive compounds derived from <i>Ipomoea obscura</i> (L.) to evaluate potential inhibitor for SARS-CoV-2 main protease and ACE2 protein.