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: 2021-09-24
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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
Mapping the intellectual structure of the coronavirus field (2000-2020): a co-word analysis.
Pourhatami A, Kaviyani-Charati M, Kargar B, Baziyad H, [...], Olmeda-Gómez C.
Scientometrics. 2021;
DOI: 10.1007/s11192-021-04038-2
Over the two last decades, coronaviruses have affected human life in different ways, especially in terms of health and economy. Due to the profound effects of novel coronaviruses, growing tides of research are emerging in various research fields. This paper employs a co-word analysis approach to map the intellectual structure of the coronavirus literature for a better understanding of how coronavirus research and the disease itself have developed during the target timeframe. A strategic diagram has been drawn to depict the coronavirus domain's structure and development. A detailed picture of coronavirus literature has been extracted from a huge number of papers to provide a quick overview of the coronavirus literature. The main themes of past coronavirus-related publications are (a) "Antibody-Virus Interactions," (b) "Emerging Infectious Diseases," (c) "Protein Structure-based Drug Design and Antiviral Drug Discovery," (d) "Coronavirus Detection Methods," (e) "Viral Pathogenesis and Immunity," and (f) "Animal Coronaviruses." The emerging infectious diseases are mostly related to fatal diseases (such as Middle East respiratory syndrome, severe acute respiratory syndrome, and COVID-19) and animal coronaviruses (including porcine, turkey, feline, canine, equine, and bovine coronaviruses and infectious bronchitis virus), which are capable of placing animal-dependent industries such as the swine and poultry industries under strong economic pressure. Although considerable research into coronavirus has been done, this unique field has not yet matured sufficiently. Therefore, "Antibody-virus Interactions," "Emerging Infectious Diseases," and "Coronavirus Detection Methods" hold interesting, promising research gaps to be both explored and filled in the future.
2021-06-15 2021 other research-article; Journal Article abstract-available 10.1007/s11192-021-04038-2 Mapping the intellectual structure of the coronavirus field (2000-2020): a co-word analysis. Pourhatami A, Kaviyani-Charati M, Kargar B, Baziyad H, Kargar M, Olmeda-Gómez C. Scientometrics. 2021;
Clinical-Pathological Correlation of the Pathophysiology and Mechanism of Action of COVID-19 - a Primer for Clinicians.
Chee J, Loh WS, Liu Z, Mullol J, [...], Wang Y.
Curr Allergy Asthma Rep. 2021; 21 (6)
DOI: 10.1007/s11882-021-01015-w

Purpose of review

Increasing knowledge of the pathogenesis of the SARS-CoV-2 infection and the complex interaction between host and viral factors have allowed clinicians to stratify the severity of COVID-19 infection. Epidemiological data has also helped to model viral carriage and infectivity. This review presents a comprehensive summary of the pathophysiology of COVID-19, the mechanisms of action of the SARS-CoV-2 virus, and the correlation with the clinical and biochemical characteristics of the disease.

Recent findings

ACE2 and TMPRSS2 receptors have emerged as a key player in the mechanism of infection of SARS-CoV-2. Their distribution throughout the body has been shown to impact the organ-specific manifestations of COVID-19. The immune-evasive and subsequently immunoregulative properties of SARS-CoV-2 are also shown to be implicated in disease proliferation and progression. Information gleaned from the virological properties of SARS-CoV-2 is consistent with and reflects the clinical behavior of the COVID-19 infection. Further study of specific clinical phenotypes and severity classes of COVID-19 may assist in the development of targeted therapeutics to halt progression of disease from mild to moderate-severe. As the understanding of the pathophysiology and mechanism of action of SARS-CoV-2 continues to grow, it is our hope that better and more effective treatment options continue to emerge.
2021-07-14 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1007/s11882-021-01015-w Clinical-Pathological Correlation of the Pathophysiology and Mechanism of Action of COVID-19 - a Primer for Clinicians. Chee J, Loh WS, Liu Z, Mullol J, Wang Y. Curr Allergy Asthma Rep. 2021; 21 (6)
SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns.
Redondo N, Zaldívar-López S, Garrido JJ, Montoya M.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.708264
There are still many unanswered questions concerning viral SARS-CoV-2 pathogenesis in COVID-19. Accessory proteins in SARS-CoV-2 consist of eleven viral proteins whose roles during infection are still not completely understood. Here, a review on the current knowledge of SARS-CoV-2 accessory proteins is summarized updating new research that could be critical in understanding SARS-CoV-2 interaction with the host. Some accessory proteins such as ORF3b, ORF6, ORF7a and ORF8 have been shown to be important IFN-I antagonists inducing an impairment in the host immune response. In addition, ORF3a is involved in apoptosis whereas others like ORF9b and ORF9c interact with cellular organelles leading to suppression of the antiviral response in infected cells. However, possible roles of ORF7b and ORF10 are still awaiting to be described. Also, ORF3d has been reassigned. Relevant information on the knowns and the unknowns in these proteins is analyzed, which could be crucial for further understanding of SARS-CoV-2 pathogenesis and to design strategies counteracting their actions evading immune responses in COVID-19.
2021-07-07 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fimmu.2021.708264 SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns. Redondo N, Zaldívar-López S, Garrido JJ, Montoya M. Front Immunol. 2021; 12
Explorative assessment of coronavirus-like short sequences from host-associated and environmental metagenomes.
Mora M, Wicaksono WA, Egamberdieva D, Krause R, [...], Berg G.
Sci Total Environ. 2021; 793
DOI: 10.1016/j.scitotenv.2021.148494
The ongoing COVID-19 pandemic has not only globally caused a high number of causalities, but is also an unprecedented challenge for scientists. False-positive virus detection tests not only aggravate the situation in the healthcare sector, but also provide ground for speculations. Previous studies have highlighted the importance of software choice and data interpretation in virome studies. We aimed to further expand theoretical and practical knowledge in bioinformatics-driven virome studies by focusing on short, virus-like DNA sequences in metagenomic data. Analyses of datasets obtained from different sample types (terrestrial, animal and human related samples) and origins showed that coronavirus-like sequences have existed in host-associated and environmental samples before the current COVID-19 pandemic. In the analyzed datasets, various Betacoronavirus-like sequences were detected that also included SARS-CoV-2 matches. Deepening analyses indicated that the detected sequences are not of viral origin and thus should not be considered in virome profiling approaches. Our study confirms the importance of parameter selection, especially in terms of read length, for reliable virome profiling. Natural environments are an important source of coronavirus-like nucleotide sequences that should be taken into account when virome datasets are analyzed and interpreted. We therefore suggest that processing parameters are carefully selected for SARS-CoV-2 profiling in host related as well as environmental samples in order to avoid incorrect identifications.
2021-06-24 2021 other brief-report; Journal Article abstract-available 10.1016/j.scitotenv.2021.148494 Explorative assessment of coronavirus-like short sequences from host-associated and environmental metagenomes. Mora M, Wicaksono WA, Egamberdieva D, Krause R, Martinez JL, Cernava T, Berg G. Sci Total Environ. 2021; 793
Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents.
Godinho PIC, Soengas RG, Silva VLM.
Pharmaceuticals (Basel). 2021; 14 (6)
DOI: 10.3390/ph14060546
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread all over the world, creating a devastating socio-economic impact. Even though protective vaccines are starting to be administered, an effective antiviral agent for the prevention and treatment of COVID-19 is not available yet. Moreover, since new and deadly CoVs can emerge at any time with the potential of becoming pandemics, the development of therapeutic agents against potentially deadly CoVs is a research area of much current interest. In the search for anti-coronaviral drugs, researchers soon turned their heads towards glycosylated flavonoids. Glycosyl flavonoids, widespread in the plant kingdom, have received a lot of attention due to their widely recognized antioxidant, anti-inflammatory, neuroprotective, anticarcinogenic, antidiabetic, antimicrobial, and antiviral properties together with their capacity to modulate key cellular functions. The wide range of biological activities displayed by glycosyl flavonoids, along with their low toxicity, make them ideal candidates for drug development. In this review, we examine and discuss the up-to-date developments on glycosyl flavonoids as evidence-based natural sources of antivirals against coronaviruses and their potential role in the management of COVID-19.
2021-06-07 2021 other review-article; Review; Journal Article abstract-available 10.3390/ph14060546 Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents. Godinho PIC, Soengas RG, Silva VLM. Pharmaceuticals (Basel). 2021; 14 (6)
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)
Reinfection by SARS-CoV-2: The first one in a family reported in Spain.
Aguilar-Shea AL, Gutiérrez-Martín-Arroyo J, Vacas-Córdoba M, Gallardo-Mayo C.
Med Clin (Barc). 2021;
DOI: 10.1016/j.medcli.2021.04.009
2021-05-07 2021 other Letter 10.1016/j.medcli.2021.04.009 Reinfection by SARS-CoV-2: The first one in a family reported in Spain. Aguilar-Shea AL, Gutiérrez-Martín-Arroyo J, Vacas-Córdoba M, Gallardo-Mayo C. Med Clin (Barc). 2021;
Cardiopulmonary resuscitation during the COVID-19 pandemic in Spain.
Aliaño Piña M, Ruiz Villén C, Galán Serrano J, Monedero Rodríguez P.
Rev Esp Anestesiol Reanim (Engl Ed). 2021;
DOI: 10.1016/j.redare.2021.09.001

Objectives

The disease COVID-19 produces serious complications that can lead to cardiorespiratory arrest. Quality cardiopulmonary resuscitation (CPR) can improve patient prognosis. The objective of this study is to evaluate the performance of the specialty of Anesthesiology in the management of CPR during the pandemic.

Methods

A survey was carried out with Google Forms consisting of 19 questions. The access link to the questionnaire was sent by email by the Spanish Society of Anesthesia (SEDAR) to all its members.

Results

225 responses were obtained. The regions with the highest participation were: Madrid, Catalonia, Valencia and Andalusia. 68.6%% of the participants work in public hospitals. 32% of the participants habitually work in intensive care units (ICU), however, 62.1% have attended critical COVID-19 in the ICU and 72.6% have anesthetized them in the operating room. 26,3% have attended some cardiac arrest, 16,8% of the participants admitted to lead the manoeuvres, 16,8% detailed that it had been another department, and 66,2% was part of the team, but did not lead the assistance. Most of the CPR was performed in supine, only 5% was done in prone position. 54.6% of participants had not taken any course of Advance Life Support (ALS) in the last 2 years. 97.7% of respondents think that Anesthesia should lead the in-hospital CPR.

Conclusion

The specialty of Anesthesiology has actively participated in the care of the critically ill patient and in the management of CPR during the COVID-19 pandemic. However, training and/or updating in ALS is required.
2021-09-15 2021 other research-article; Journal Article abstract-available 10.1016/j.redare.2021.09.001 Cardiopulmonary resuscitation during the COVID-19 pandemic in Spain. Aliaño Piña M, Ruiz Villén C, Galán Serrano J, Monedero Rodríguez P. Rev Esp Anestesiol Reanim (Engl Ed). 2021;
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
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;
An Overview of Vaccines against SARS-CoV-2 in the COVID-19 Pandemic Era.
Pascual-Iglesias A, Canton J, Ortega-Prieto AM, Jimenez-Guardeño JM, [...], Regla-Nava JA.
Pathogens. 2021; 10 (8)
DOI: 10.3390/pathogens10081030
The emergence of SARS-CoV-2 in late 2019 led to the COVID-19 pandemic all over the world. When the virus was first isolated and its genome was sequenced in the early months of 2020, the efforts to develop a vaccine began. Based on prior well-known knowledge about coronavirus, the SARS-CoV-2 spike (S) protein was selected as the main target. Currently, more than one hundred vaccines are being investigated and several of them are already authorized by medical agencies. This review summarizes and compares the current knowledge about main approaches for vaccine development, focusing on those authorized and specifically their immunogenicity, efficacy preventing severe disease, adverse side effects, protection, and ability to cope with emergent SARS-CoV-2 variants.
2021-08-14 2021 other review-article; Review; Journal Article abstract-available 10.3390/pathogens10081030 An Overview of Vaccines against SARS-CoV-2 in the COVID-19 Pandemic Era. Pascual-Iglesias A, Canton J, Ortega-Prieto AM, Jimenez-Guardeño JM, Regla-Nava JA. Pathogens. 2021; 10 (8)
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)
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)
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
Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates.
Fakhri S, Nouri Z, Moradi SZ, Akkol EK, [...], Echeverría J.
Molecules. 2021; 26 (10)
DOI: 10.3390/molecules26102917
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.
2021-05-14 2021 other review-article; Review; Journal Article abstract-available 10.3390/molecules26102917 Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates. Fakhri S, Nouri Z, Moradi SZ, Akkol EK, Piri S, Sobarzo-Sánchez E, Farzaei MH, Echeverría J. Molecules. 2021; 26 (10)
Relevance of BET Family Proteins in SARS-CoV-2 Infection.
Lara-Ureña N, García-Domínguez M.
Biomolecules. 2021; 11 (8)
DOI: 10.3390/biom11081126
The recent pandemic we are experiencing caused by the coronavirus disease 2019 (COVID-19) has put the world's population on the rack, with more than 191 million cases and more than 4.1 million deaths confirmed to date. This disease is caused by a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A massive proteomic analysis has revealed that one of the structural proteins of the virus, the E protein, interacts with BRD2 and BRD4 proteins of the Bromodomain and Extra Terminal domain (BET) family of proteins. BETs are essential to cell cycle progression, inflammation and immune response and have also been strongly associated with infection by different types of viruses. The fundamental role BET proteins play in transcription makes them appropriate targets for the propagation strategies of some viruses. Recognition of histone acetylation by BET bromodomains is essential for transcription control. The development of drugs mimicking acetyl groups, and thereby able to displace BET proteins from chromatin, has boosted interest on BETs as attractive targets for therapeutic intervention. The success of these drugs against a variety of diseases in cellular and animal models has been recently enlarged with promising results from SARS-CoV-2 infection studies.
2021-07-30 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3390/biom11081126 Relevance of BET Family Proteins in SARS-CoV-2 Infection. Lara-Ureña N, García-Domínguez M. Biomolecules. 2021; 11 (8)
Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated?
Soldevila B, Puig-Domingo M, Marazuela M.
Rev Endocr Metab Disord. 2021;
DOI: 10.1007/s11154-021-09678-6
Although SARS-CoV-2 viral attacks starts by the interaction of spike protein (S Protein) to ACE2 receptor located at the cell surface of respiratory tract and digestive system cells, different endocrine targets, endocrine organs and metabolic conditions are of fundamental relevance for understanding disease progression and special outcomes, in particular those of fatal consequences for the patient. During pandemic, moreover, a specific phenotype of COVID-19 metabolic patient has been described, characterized by being at particular risk of worse outcomes. In the present paper we describe the mechanism of viral interaction with endocrine organs, emphasizing the specific endocrine molecules of particular relevance explaining COVID-19 disease evolution and outcomes.
2021-07-31 2021 other review-article; Review; Journal Article abstract-available 10.1007/s11154-021-09678-6 Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated? Soldevila B, Puig-Domingo M, Marazuela M. Rev Endocr Metab Disord. 2021;
Neuropilin-1: A feasible link between liver pathologies and COVID-19.
Benedicto A, García-Kamiruaga I, Arteta B.
World J Gastroenterol. 2021; 27 (24)
DOI: 10.3748/wjg.v27.i24.3516
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a tremendous impact on the health of millions of people worldwide. Unfortunately, those suffering from previous pathological conditions are more vulnerable and tend to develop more severe disease upon infection with the new SARS-CoV-2. This coronavirus interacts with the angiotensin-converting enzyme 2 receptor to invade the cells. Recently, another receptor, neuropilin-1 (NRP-1), has been reported to amplify the viral infection. Interestingly, NRP-1 is expressed in nonparenchymal liver cells and is related to and upregulated in a wide variety of liver-related pathologies. It has been observed that SARS-CoV-2 infection promotes liver injury through several pathways that may be influenced by the previous pathological status of the patient and liver expression of NRP-1. Moreover, coronavirus disease 2019 causes an inflammatory cascade called cytokine storm in patients with severe disease. This cytokine storm may influence liver sinusoidal-cell phenotype, facilitating viral invasion. In this review, the shreds of evidence linking NRP-1 with liver pathologies such as hepatocellular carcinoma, liver fibrosis, nonalcoholic fatty liver disease and inflammatory disorders are discussed in the context of SARS-CoV-2 infection. In addition, the involvement of the infection-related cytokine storm in NRP-1 overexpression and the subsequent increased risk of SARS-CoV-2 infection are also analyzed. This review aims to shed some light on the involvement of liver NRP-1 during SARS-CoV-2 infection and emphasizes the possible involvement this receptor with the observed liver damage.
2021-06-01 2021 other review-article; Review; Journal Article abstract-available 10.3748/wjg.v27.i24.3516 Neuropilin-1: A feasible link between liver pathologies and COVID-19. Benedicto A, García-Kamiruaga I, Arteta B. World J Gastroenterol. 2021; 27 (24)
In-Silico Evidence for a Two Receptor Based Strategy of SARS-CoV-2.
Milanetti E, Miotto M, Di Rienzo L, Nagaraj M, [...], Ruocco G.
Front Mol Biosci. 2021; 8
DOI: 10.3389/fmolb.2021.690655
We propose a computational investigation on the interaction mechanisms between SARS-CoV-2 spike protein and possible human cell receptors. In particular, we make use of our newly developed numerical method able to determine efficiently and effectively the relationship of complementarity between portions of protein surfaces. This innovative and general procedure, based on the representation of the molecular isoelectronic density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, which was unfeasible with previous methods. Our results indicate that SARS-CoV-2 uses a dual strategy: in addition to the known interaction with angiotensin-converting enzyme 2, the viral spike protein can also interact with sialic-acid receptors of the cells in the upper airways.
2021-06-09 2021 other research-article; Journal Article abstract-available 10.3389/fmolb.2021.690655 In-Silico Evidence for a Two Receptor Based Strategy of SARS-CoV-2. Milanetti E, Miotto M, Di Rienzo L, Nagaraj M, Monti M, Golbek TW, Gosti G, Roeters SJ, Weidner T, Otzen DE, Ruocco G. Front Mol Biosci. 2021; 8
The Positive Rhinovirus/Enterovirus Detection and SARS-CoV-2 Persistence beyond the Acute Infection Phase: An Intra-Household Surveillance Study.
Brotons P, Jordan I, Bassat Q, Henares D, [...], Muñoz-Almagro C.
Viruses. 2021; 13 (8)
DOI: 10.3390/v13081598
We aimed to assess the duration of nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA persistence in adults self-confined at home after acute infection; and to identify the associations of SARS-CoV-2 persistence with respiratory virus co-detection and infection transmission. A cross-sectional intra-household study was conducted in metropolitan Barcelona (Spain) during the time period of April to June 2020. Every adult who was the first family member reported as SARS-CoV-2-positive by reverse transcription polymerase chain reaction (RT-PCR) as well as their household child contacts had nasopharyngeal swabs tested by a targeted SARS-CoV-2 RT-PCR and a multiplex viral respiratory panel after a 15 day minimum time lag. Four-hundred and four households (404 adults and 708 children) were enrolled. SARS-CoV-2 RNA was detected in 137 (33.9%) adults and 84 (11.9%) children. Rhinovirus/Enterovirus (RV/EV) was commonly found (83.3%) in co-infection with SARS-CoV-2 in adults. The mean duration of SARS-CoV-2 RNA presence in adults' nasopharynx was 52 days (range 26-83 days). The persistence of SARS-CoV-2 was significantly associated with RV/EV co-infection (adjusted odds ratio (aOR) 9.31; 95% CI 2.57-33.80) and SARS-CoV-2 detection in child contacts (aOR 2.08; 95% CI 1.24-3.51). Prolonged nasopharyngeal SARS-CoV-2 RNA persistence beyond the acute infection phase was frequent in adults quarantined at home during the first epidemic wave; which was associated with RV/EV co-infection and could enhance intra-household infection transmission.
2021-08-12 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13081598 The Positive Rhinovirus/Enterovirus Detection and SARS-CoV-2 Persistence beyond the Acute Infection Phase: An Intra-Household Surveillance Study. Brotons P, Jordan I, Bassat Q, Henares D, Fernandez de Sevilla M, Ajanovic S, Redin A, Fumado V, Baro B, Claverol J, Varo R, Cuadras D, Hecht J, Barrabeig I, Garcia-Garcia JJ, Launes C, Muñoz-Almagro C. Viruses. 2021; 13 (8)
The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy.
Ramos E, López-Muñoz F, Gil-Martín E, Egea J, [...], Romero A.
Antioxidants (Basel). 2021; 10 (7)
DOI: 10.3390/antiox10071152
Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune response once the virus contacts the body. Melatonin is a systemic dealer that does not overlook any homeostasis disturbance, which consequently brings into play its cooperative triad, antioxidant, anti-inflammatory, and immune-stimulant backbone, to stop the infective cycle of SARS-CoV-2 or any other endogenous or exogenous threat. In COVID-19, the corporal propagation of SARS-CoV-2 involves an exacerbated oxidative activity and therefore the overproduction of great amounts of reactive oxygen and nitrogen species (RONS). The endorsement of melatonin as a possible protective agent against the current pandemic is indirectly supported by its widely demonstrated beneficial role in preclinical and clinical studies of other respiratory diseases. In addition, focusing the therapeutic action on strengthening the host protection responses in critical phases of the infective cycle makes it likely that multi-tasking melatonin will provide multi-protection, maintaining its efficacy against the virus variants that are already emerging and will emerge as long as SARS-CoV-2 continues to circulate among us.
2021-07-20 2021 other review-article; Review; Journal Article abstract-available 10.3390/antiox10071152 The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy. Ramos E, López-Muñoz F, Gil-Martín E, Egea J, Álvarez-Merz I, Painuli S, Semwal P, Martins N, Hernández-Guijo JM, Romero A. Antioxidants (Basel). 2021; 10 (7)
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 Research Support, Non-U.S. Gov't; 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)
Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update.
Anand U, Jakhmola S, Indari O, Jha HC, [...], Pérez de la Lastra JM.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.658519
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.
2021-06-30 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fimmu.2021.658519 Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update. Anand U, Jakhmola S, Indari O, Jha HC, Chen ZS, Tripathi V, Pérez de la Lastra JM. Front Immunol. 2021; 12
Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease.
Todorović-Raković N, Whitfield JR.
Cytokine. 2021; 146
DOI: 10.1016/j.cyto.2021.155637
Interferons have prominent roles in various pathophysiological conditions, mostly related to inflammation. Interferon-gamma (IFNγ) was, initially discovered as a potent antiviral agent, over 50 years ago, and has recently garnered renewed interest as a promising factor involved in both innate and adaptive immunity. When new disease epidemics appear such as SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus), IAV (Influenza A virus), and in particular the current SARS-CoV-2 pandemic, it is especially timely to review the complexity of immune system responses to viral infections. Here we consider the controversial roles of effectors like IFNγ, discussing its actions in immunomodulation and immunotolerance. We explore the possibility that modulation of IFNγ could be used to influence the course of such infections. Importantly, not only could endogenous expression of IFNγ influence the outcome, there are existing IFNγ therapeutics that can readily be applied in the clinic. However, our understanding of the molecular mechanisms controlled by IFNγ suggests that the exact timing for application of IFNγ-based therapeutics could be crucial: it should be earlier to significantly reduce the viral load and thus decrease the overall severity of the disease.
2021-07-03 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.cyto.2021.155637 Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease. Todorović-Raković N, Whitfield JR. Cytokine. 2021; 146
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)
Personal and vaccination history as factors associated with SARS-CoV-2 infection.
Fernández-Prada M, García-González P, García-Morán A, Ruiz-Álvarez I, [...], Calvo-Rodríguez C.
Med Clin (Engl Ed). 2021; 157 (5)
DOI: 10.1016/j.medcle.2021.02.007

Background and objective

SARS-CoV-2 has been and is a major global Public Health challenge. Since the beginning of the pandemic, different comorbidities have been postulated and associated with spectra of increased severity and mortality. The objectives of this research are: 1) to analyse the factors associated with SARS-CoV-2 infection (COVID-19) in a health area in northern Spain; 2) to understand the possible role of influenza vaccination and pneumococcal vaccination in the development of COVID-19.

Materials and method

A test-negative case-control study was conducted. Variables related to personal and vaccination history were considered. Although the epidemiological definition of the case varied over time, the reference definition was that corresponding to 31/01/2020 in Spain. A bivariate and multivariate analysis was performed.

Results

The sample included 188 patients, of which 63 were cases and 125 controls. The results show that obesity increases the risk 2.4-fold of suffering this infection (IC 95% 1,301-4,521) and ARA-2 increases it 2.2-fold (95% CI 1,256-6,982). On the other hand, anti-pneumococcal vaccination of 13 serotypes showed results close to statistical significance (OR = 0.4; 95% CI 0.170-1,006).

Conclusion

Obesity and the use of ARA-2 increases the risk of COVID-19. Scientific knowledge about factors associated with COVID-19 should be expanded. The authors consider that the present research raises the need further investigate the role of vaccines in this infection and their possible heterologous properties.
2021-08-09 2021 other research-article; Journal Article abstract-available 10.1016/j.medcle.2021.02.007 Personal and vaccination history as factors associated with SARS-CoV-2 infection. Fernández-Prada M, García-González P, García-Morán A, Ruiz-Álvarez I, Ramas-Diez C, Calvo-Rodríguez C. Med Clin (Engl Ed). 2021; 157 (5)
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)
Perspectives on passive antibody therapy and peptide-based vaccines against emerging pathogens like SARS-CoV-2.
Palma M.
Germs. 2021; 11 (2)
DOI: 10.18683/germs.2021.1264
The current epidemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is raising awareness of the need to act faster when dealing with new pathogens. Exposure to an emerging pathogen generates an antibody response that can be used for preventing and treating the infection. These antibodies might have a high specificity to a target, few side effects, and are useful in the absence of an effective vaccine for treating immunocompromised individuals. The approved antibodies against the receptor-binding domain (RBD) of the viral spike protein of SARS-CoV-2 (e.g., regdanvimab, bamlanivimab, etesevimab, and casirivimab/imdevimab) have been selected from the antibody repertoire of B cells from convalescent patients using flow cytometry, next-generation sequencing, and phage display. This encourages use of these techniques especially phage display, because it does not require expensive types of equipment and can be performed on the lab bench, thereby making it suitable for labs with limited resources. Also, the antibodies in blood samples from convalescent patients can be used to screen pre-made peptide libraries to identify epitopes for vaccine development. Different types of vaccines against SARS-CoV-2 have been developed, including inactivated virus vaccines, mRNA-based vaccines, non-replicating vector vaccines, and protein subunits. mRNA vaccines have numerous advantages over existing vaccines, such as efficacy, ease of manufacture, safety, and cost-effectiveness. Additionally, epitope vaccination may constitute an attractive strategy to induce high levels of antibodies against a pathogen and phages might be used as immunogenic carriers of such peptides. This is a point worth considering further, as phage-based vaccines have been shown to be safe in clinical trials and phages are easy to produce and tolerate high temperatures. In conclusion, identification of the antibody repertoire of recovering patients, and the epitopes they recognize, should be an attractive alternative option for developing therapeutic and prophylactic antibodies and vaccines against emerging pathogens.
2021-06-02 2021 other review-article; Review; Journal Article abstract-available 10.18683/germs.2021.1264 Perspectives on passive antibody therapy and peptide-based vaccines against emerging pathogens like SARS-CoV-2. Palma M. Germs. 2021; 11 (2)
Decoding molnupiravir-induced mutagenesis in SARS-CoV-2.
Menéndez-Arias L.
J Biol Chem. 2021; 297 (1)
DOI: 10.1016/j.jbc.2021.100867
Molnupiravir, a prodrug of the nucleoside derivative β-D-N4-hydroxycytidine (NHC), is currently in clinical trials for COVID-19 therapy. However, the biochemical mechanisms involved in molnupiravir-induced mutagenesis had not been explored. In a recent study, Gordon et al. demonstrated that NHC can be incorporated into viral RNA and subsequently extended and used as template for RNA-dependent RNA synthesis, proposing a mutagenesis model consistent with available virological evidence. Their study uncovers molecular mechanisms by which molnupiravir drives SARS-CoV-2 into error catastrophe.
2021-06-09 2021 other Research Support, Non-U.S. Gov't; discussion; Journal Article abstract-available 10.1016/j.jbc.2021.100867 Decoding molnupiravir-induced mutagenesis in SARS-CoV-2. Menéndez-Arias L. J Biol Chem. 2021; 297 (1)
Comparative study of different SARS-CoV-2 diagnostic techniques.
Vallejo L, Martínez-Rodríguez M, Nieto-Bazán MJ, Delgado-Iribarren A, [...], Culebras E.
J Virol Methods. 2021; 298
DOI: 10.1016/j.jviromet.2021.114281
The rapid spread of SARS-CoV-2 led to the necessity of developing diagnostic tests for rapid virus detection. Many commercial platforms have appeared and have been approved for this purpose. In this study, 95 positive and 5 negative retrospective samples were analyzed by 4 different commercial RT-qPCR kits (TaqMan 2019nCoV Assay, Allplex™SARS-COV-2 Assay, FTD SARS-COV-2 Assay and qCOVID-19). The Hologic Aptima SARS-COV-2 and the Clart-COVID-19 system were also tested. serial dilutions of SARS-COV-2 standard control were included for sensitivity analysis. Among the qPCR tested qCOVID19 and Allplex™SARS-COV-2 Assay were both able to detect all the clinical samples included in the study. All four qPCR evaluated showed high sensitivity for samples with Ct<33. Clart-COVID-19 microarrays detected all samples and controls used in this study whereas Hologic Aptima Panther failed with one of the clinical samples. However, the main problem with this system was the number of invalidated samples despite avoiding the use of medium with guanidine isothiocyanate as recommended by the manufacturer. All the techniques tested were of value for SARS-CoV-2 detection.
2021-09-13 2021 other research-article; Journal Article abstract-available 10.1016/j.jviromet.2021.114281 Comparative study of different SARS-CoV-2 diagnostic techniques. Vallejo L, Martínez-Rodríguez M, Nieto-Bazán MJ, Delgado-Iribarren A, Culebras E. J Virol Methods. 2021; 298
Living evidence for SARS-CoV-2.
Santillan-Garcia A.
Med Intensiva (Engl Ed). 2021; 45 (5)
DOI: 10.1016/j.medine.2021.04.003
2021-04-30 2021 other Letter 10.1016/j.medine.2021.04.003 Living evidence for SARS-CoV-2. Santillan-Garcia A. Med Intensiva (Engl Ed). 2021; 45 (5)
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; 9 (6)
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 Research Support, Non-U.S. Gov't; 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; 9 (6)
Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients.
Chauvin M, Larsen M, Quirant B, Quentric P, [...], Sauce D.
Front Cell Infect Microbiol. 2021; 11
DOI: 10.3389/fcimb.2021.709893

Highlights

Innate immune activation during Covid-19 infection is associated with pernicious clinical outcome.

Background

Coronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity.

Methods

We measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death.

Results

Severe and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity.

Conclusion

We propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.
2021-08-23 2021 other brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.3389/fcimb.2021.709893 Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients. Chauvin M, Larsen M, Quirant B, Quentric P, Dorgham K, Royer L, Vallet H, Guihot A, Combadière B, Combadière C, Barallat J, Mayaux J, Luyt CE, Mathian A, Amoura Z, Boddaert J, Armestar F, Gorochov G, Martinez-Caceres E, Sauce D. Front Cell Infect Microbiol. 2021; 11
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.
Radiologia (Engl Ed). 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. Radiologia (Engl Ed). 2021; 63 (2)
MOV10 Helicase Interacts with Coronavirus Nucleocapsid Protein and Has Antiviral Activity.
Wang L, Sola I, Enjuanes L, Zuñiga S.
mBio. 2021;
DOI: 10.1128/mbio.01316-21
Coronaviruses (CoVs) are emergent pathogens that may cause life-threatening respiratory diseases in humans. Understanding of CoV-host interactions may help to identify novel therapeutic targets. MOV10 is an RNA helicase involved in different steps of cellular RNA metabolism. Both MOV10 antiviral and proviral activities have been described in a limited number of viruses, but this protein has not been previously associated with CoVs. We found that during Middle East respiratory syndrome coronavirus (MERS-CoV) infection, MOV10 aggregated in cytoplasmic structures colocalizing with viral nucleocapsid (N) protein. MOV10-N interaction was confirmed by endogenous MOV10 coimmunoprecipitation, and the presence of other cellular proteins was also detected in MOV10 complexes. MOV10 silencing significantly increased both N protein accumulation and virus titer, with no changes in the accumulation of viral RNAs. Moreover, MOV10 overexpression caused a 10-fold decrease in viral titers. These data indicated that MOV10 has antiviral activity during MERS-CoV infection. We postulated that this activity could be mediated by viral RNA sequestration, and in fact, RNA immunoprecipitation data showed the presence of viral RNAs in the MOV10 cytoplasmic complexes. Expression of wild-type MOV10 or of a MOV10 mutant without helicase activity in MOV10 knockout cell lines, developed by CRISPR-Cas technology, indicated that the helicase activity of MOV10 was required for its antiviral effect. Interestingly MOV10-N interaction was conserved in other mildly or highly pathogenic human CoVs, including the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although MOV10 antiviral activity was found only in highly pathogenic CoVs, suggesting a potential role of MOV10 in the modulation of human CoVs pathogenesis. IMPORTANCE Coronaviruses (CoVs) are emerging pathogens causing life-threatening diseases in humans. Knowledge of virus-host interactions and viral subversion mechanisms of host pathways is required for the development of effective countermeasures against CoVs. The interaction between cellular RNA helicase MOV10 and nucleocapsid (N) protein from several human CoVs is shown. Using MERS-CoV as a model, we demonstrate that MOV10 has antiviral function, requiring its helicase activity, most likely mediated by viral RNA sequestration in cytoplasmic ribonucleoprotein structures. Furthermore, we found that MOV10 antiviral activity may act only in highly pathogenic human CoVs, suggesting a role for MOV10 in modulating CoVs pathogenesis. The present study uncovers a complex network of viral and cellular RNAs and proteins interaction modulating the antiviral response against CoVs.
2021-09-14 2021 other Journal Article abstract-available 10.1128/mbio.01316-21 MOV10 Helicase Interacts with Coronavirus Nucleocapsid Protein and Has Antiviral Activity. Wang L, Sola I, Enjuanes L, Zuñiga S. mBio. 2021;
Single-cell RNA sequencing of SARS-CoV-2 cell entry factors in the preconceptional human endometrium.
Vilella F, Wang W, Moreno I, Roson B, [...], Simon C.
Hum Reprod. 2021; 36 (10)
DOI: 10.1093/humrep/deab183

Study question

Are SARS-CoV-2 canonical cell entry machinery, consisting of ACE2, TMPRSS2, NRP1 and LY6E, or alternative potential cell entry machinery, consisting of BSG, ANPEP, CD209, CLEC4G, TMPRSS4, TMPRSS11A, FURIN, CTSB, CTSL and IFITM1, expressed in the human endometrium across the menstrual cycle?

Summary answer

Analysis of cell entry factors for SARS-CoV-2 by single-cell RNA-sequencing (scRNAseq) in the preconceptional human endometrium reveals low risk of infection.

What is known already

Gene expression datasets from bulk endometrial tissue show no significant expression of the SARS-CoV-2 receptor ACE2 and TMPRSS2. This is in contrast to reported expression of ACE2 at the single-cell level in the decidua and trophoblast cells at the maternal-fetal interface in early pregnancy, as well as vertical transmission of SARS-CoV-2 during pregnancy.

Study design, size, duration

This analysis of SARS-CoV-2 cell entry machinery gene expression was conducted by scRNAseq in 73 181 human endometrial cells isolated from endometrial biopsies obtained from 27 donors across the menstrual cycle.

Participants/materials, setting, methods

ScRNAseq examined the expression of genes encoding cell entry machinery for SARS-CoV-2. The raw data were from a previously published dataset.

Main results and the role of chance

ScRNAseq analysis showed no significant expression of ACE2 in stromal or unciliated epithelial cells in any phase of the menstrual cycle. TMPRSS2 was expressed in epithelial cells during the early proliferative and mid-secretory phases. Interestingly, the expression of NRP1 was observed in both stromal and epithelial cells across all phases of the menstrual cycle, and LY6E was highly expressed in stromal cells. In the mid-secretory phase, coexpression of ACE2 and TMPRSS2 was detected in 0.07% of luminal epithelial cells. No cells simultaneously expressed ACE2, NRP1 and TMPRSS2 at the time of embryo implantation. Focusing on non-canonical cell entry machinery, BSG was highly expressed in all cell types across the menstrual cycle and may interact with CTSB or CTSL proteases, but viral infection using this machinery has not yet been confirmed.

Large scale data

All raw data in this study can be found at NCBI's Gene Expression Omnibus (series accession code GSE111976) and Sequence Read Archive (accession code SRP135922).

Limitations, reasons for caution

Our findings at the single-cell level imply low efficiency of SARS-CoV-2 endometrial infection using canonical receptors in a cohort of healthy reproductive-age women; however, infection of endometrial cells can only be assessed in the presence of the virus. All samples were processed for scRNAseq, so no samples are remaining to analyze protein expression or spatial transcriptomics.

Wider implications of the findings

Our results offer a useful resource to guide reproductive decisions when assessing risk of endometrial infection by SARS-CoV-2 during the preconceptional period in asymptomatic COVID-19 carriers.

Study funding/competing interest(s)

This study was jointly supported by the March of Dimes, Chan Zuckerberg Biohub and MINECO/FEDER (SAF-2015-67164-R, to C.S.) (Spanish Government), and the European Union's Horizon 2020 Framework Programme for Research and Innovation (Grant agreement 874867). W.W. was supported by the Stanford Bio-X Graduate Bowes Fellowship and Chan Zuckerberg Biohub. F.V. was supported by the Miguel Servet Program Type II of ISCIII (CPII18/00020) and the FIS project (PI18/00957). A patent disclosure has been filed for the study with the title 'Methods for assessing endometrial transformation' and the global patent number 'EP 3807648 A2' under the inventors S.R.Q., C.S., W.W. and F.V. C.S. is the Founder and Head of the Scientific Advisory Board of Igenomix SL. S.R.Q is the Director of Mirvie. I.M. is partially employed by Igenomix SL. B.R. has no interests to declare.
2021-09-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/humrep/deab183 Single-cell RNA sequencing of SARS-CoV-2 cell entry factors in the preconceptional human endometrium. Vilella F, Wang W, Moreno I, Roson B, Quake SR, Simon C. Hum Reprod. 2021; 36 (10)
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
Plasma ACE2 species are differentially altered in COVID-19 patients.
García-Ayllón MS, Moreno-Pérez O, García-Arriaza J, Ramos-Rincón JM, [...], Sáez-Valero J.
FASEB J. 2021; 35 (8)
DOI: 10.1096/fj.202100051r
Studies are needed to identify useful biomarkers to assess the severity and prognosis of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus. Here, we examine the levels of various plasma species of the SARS-CoV-2 host receptor, the angiotensin-converting enzyme 2 (ACE2), in patients at different phases of the infection. Human plasma ACE2 species were characterized by immunoprecipitation and western blotting employing antibodies against the ectodomain and the C-terminal domain, using a recombinant human ACE2 protein as control. In addition, changes in the cleaved and full-length ACE2 species were also examined in serum samples derived from humanized K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2. ACE2 immunoreactivity was present in human plasma as several molecular mass species that probably comprise truncated (70 and 75 kDa) and full-length forms (95, 100, 130, and 170 kDa). COVID-19 patients in the acute phase of infection (n = 46) had significantly decreased levels of ACE2 full-length species, while a truncated 70-kDa form was marginally higher compared with non-disease controls (n = 26). Levels of ACE2 full-length species were in the normal range in patients after a recovery period with an interval of 58-70 days (n = 29), while the 70-kDa species decreased. Levels of the truncated ACE2 species served to discriminate between individuals infected by SARS-CoV-2 and those infected with influenza A virus (n = 17). In conclusion, specific plasma ACE2 species are altered in patients with COVID-19 and these changes normalize during the recovery phase. Alterations in ACE2 species following SARS-CoV-2 infection warrant further investigation regarding their potential usefulness as biomarkers for the disease process and to asses efficacy during vaccination.
2021-08-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1096/fj.202100051r Plasma ACE2 species are differentially altered in COVID-19 patients. García-Ayllón MS, Moreno-Pérez O, García-Arriaza J, Ramos-Rincón JM, Cortés-Gómez MÁ, Brinkmalm G, Andrés M, León-Ramírez JM, Boix V, Gil J, Zetterberg H, Esteban M, Merino E, Sáez-Valero J. FASEB J. 2021; 35 (8)
Incidence and risk factors for early readmission after hospitalization for SARS-CoV-2 infection: results from a retrospective cohort study.
Kirkegaard C, Falcó-Roget A, Sánchez-Montalvá A, Valls Á, [...], Len Ò.
Infection. 2021;
DOI: 10.1007/s15010-021-01662-1

Purpose

We aim to assess risk factors related to early readmission in previous hospitalized patients with COVID-19.

Methods

We analyzed a retrospective cohort of patients with laboratory-confirmed COVID-19 admitted to Vall d'Hebron University Hospital, Barcelona, Spain. Early readmission was defined as the need for hospitalization within a period of 60 days after discharge. A descriptive analysis of the readmission was performed, including hospitalization outcome. We also performed a multivariate logistic regression to define risk factors for readmission RESULTS: A total of 629 patients were followed up during 60 days with a readmission cumulative incidence of 5.4% (34 out of 629) and an incidence rate of 0.034 person-years. Main reasons for readmission were respiratory worsening (13, 38.2%), decompensation of previous disease (12, 35.3%) or infectious complications (6, 17.6%). Median time to readmission was 12 days (interquartile range 7-33 days). Prior diagnosis of heart failure (OR 4.09; 95% CI 1.35-12.46; p = 0.013), length of stay during index admission greater than 13 days (OR 2.72; 95% CI 1.21-6.12; p = 0.015), treatment with corticosteroids (OR 2.39; 95% CI 1.01-5.70; p = 0.049) and developing pulmonary thromboembolism (OR 11.59; 95% CI 2.89-46.48; p = 0.001) were the risk factors statistically associated with early readmission.

Conclusion

Readmission cumulative incidence was 5.4%. Those patients with prior diagnosis of heart failure, length of stay greater than 13 days, treated with corticosteroids or who developed pulmonary thromboembolism might benefit from close monitoring after being discharged.
2021-07-30 2021 other research-article; Journal Article abstract-available 10.1007/s15010-021-01662-1 Incidence and risk factors for early readmission after hospitalization for SARS-CoV-2 infection: results from a retrospective cohort study. Kirkegaard C, Falcó-Roget A, Sánchez-Montalvá A, Valls Á, Clofent D, Campos-Varela I, García-García S, Leguízamo LM, Sellarès-Nadal J, Eremiev S, Villamarín M, Marzo B, Almirante B, Len Ò. Infection. 2021;
What we know and what we need to know about the origin of SARS-CoV-2.
Domingo JL.
Environ Res. 2021; 200
DOI: 10.1016/j.envres.2021.111785
Since the appearance of the first cases of COVID-19 in 2019, an unprecedented number of documents on that disease have been published in a short space of time. The current available information covers a large number of topics related with COVID-19 and/or the coronavirus (SARS-CoV-2) responsible of the disease. However, only a limited number of publications have been focused on a controversial issue: the origin of the SARS-CoV-2. In this paper, the scientific literature on the origin of SARS-CoV-2 has been reviewed. Documents published during 2020 and 2021 (January 1-July 19) in journals that are indexed in PubMed and/or Scopus has been considered. The revised studies were grouped according to these two potential origins: natural and unnatural. The analyses of the conclusions of the different documents here assessed show that even considering the zoonotic hypothesis as the most likely, with bats and pangolins being possibly in the origin of the coronavirus, today's date the intermediate source species of SARS-CoV-2 has not been confirmed yet. On the other hand, some researchers point to an unnatural origin of this coronavirus, but their conclusions are not strongly supported by a clear scientific evidence. Given the tremendous severity of the current pandemic, investigations to establish clearly and definitively the origin of SARS-CoV-2, are basic and essential in order to prevent potential future pandemics of similar nature.
2021-07-28 2021 other research-article; Journal Article abstract-available 10.1016/j.envres.2021.111785 What we know and what we need to know about the origin of SARS-CoV-2. Domingo JL. Environ Res. 2021; 200
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;
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)
Rapid and Efficient Detection of the SARS-CoV-2 Spike Protein Using an Electrochemical Aptamer-Based Sensor.
Idili A, Parolo C, Alvarez-Diduk R, Merkoçi A.
ACS Sens. 2021; 6 (8)
DOI: 10.1021/acssensors.1c01222
The availability of sensors able to rapidly detect SARS-CoV-2 directly in biological fluids in a single step would allow performing massive diagnostic testing to track in real time and contain the spread of COVID-19. Motivated by this, here, we developed an electrochemical aptamer-based (EAB) sensor able to achieve the rapid, reagentless, and quantitative measurement of the SARS-CoV-2 spike (S) protein. First, we demonstrated the ability of the selected aptamer to undergo a binding-induced conformational change in the presence of its target using fluorescence spectroscopy. Then, we engineered the aptamer to work as a bioreceptor in the EAB platform and we demonstrated its sensitivity and specificity. Finally, to demonstrate the clinical potential of the sensor, we tested it directly in biological fluids (serum and artificial saliva), achieving the rapid (minutes) and single-step detection of the S protein in its clinical range.
2021-08-10 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1021/acssensors.1c01222 Rapid and Efficient Detection of the SARS-CoV-2 Spike Protein Using an Electrochemical Aptamer-Based Sensor. Idili A, Parolo C, Alvarez-Diduk R, Merkoçi A. ACS Sens. 2021; 6 (8)
Subacute thyroiditis following COVID-19 infection.
de la Higuera López-Frías M, Perdomo CM, Galofré JC.
Rev Clin Esp (Barc). 2021; 221 (6)
DOI: 10.1016/j.rceng.2021.01.002
2021-03-26 2021 other Letter; Comment 10.1016/j.rceng.2021.01.002 Subacute thyroiditis following COVID-19 infection. de la Higuera López-Frías M, Perdomo CM, Galofré JC. Rev Clin Esp (Barc). 2021; 221 (6)
High prevalence of SARS-CoV-2 infection in patients scheduled for digestive endoscopy after the peak of the first wave of the pandemic☆ Alta prevalencia de infección por SARS-CoV-2 en pacientes programados para endoscopia digestiva después del pico de la primera onda pandémica
Pamplona J, Solano R, Ramírez M, Durandez R, [...], Sàbat M.
Gastroenterología y Hepatología (English Edition). 2021;
DOI:
Healthcare professionals in endoscopy units have a possible risk of SARS-CoV-2 infection by different routes: inhalation of airborne droplets, aerosols, conjunctival contact and faecal-oral transmission.

Objective

To describe the detection of SARS-CoV-2 in a series of patients scheduled for digestive endoscopy at the Hospital Santa Caterina, Salt, (Girona).

Methods

Descriptive study of a series of cases of patients scheduled for endoscopy during the month of May 2020, when endoscopic activity was resumed after the peak of the pandemic, following SCD, SEED, AEG and ESGE recommendations. We examined nasopharyngeal samples 48−72 h before the appointment, by RT-PCR, in all patients. RNA extraction was performed using the kits: Qiagen®-adapted, BiosSprint®96-DNA-Blood-Kit (384). For amplification-detection of SARS-CoV-2, methods recommended by the WHO and the CDC were followed.

Results

110 asymptomatic patients without close contact with a positive case in the previous 14 days were scheduled; 105 (96.4%) were negative and five (4.5%) were positive. Two patients developed respiratory symptoms after diagnosis (presymptomatic) and three remained asymptomatic. Allfive5 patients were autochthonous cases with no history of travel or residence in another city or country associated with high prevalence of infection. Four cases were women aged 60–81 years. The N gene was detected in all cases.

Conclusions

A high prevalence of SARS-CoV-2 infection was detected in patients scheduled for digestive endoscopy. Given the risk of transmission to professionals, we consider it advisable to perform SARS-CoV-2 RT-PCR 48−72 h before the examination in situations of high incidence in the population.
2021-09-14 2021 other research-article; Journal Article abstract-available High prevalence of SARS-CoV-2 infection in patients scheduled for digestive endoscopy after the peak of the first wave of the pandemic☆ Alta prevalencia de infección por SARS-CoV-2 en pacientes programados para endoscopia digestiva después del pico de la primera onda pandémica Pamplona J, Solano R, Ramírez M, Durandez R, Mohamed F, Pardo L, Sàbat M. Gastroenterología y Hepatología (English Edition). 2021;
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)
SARS-CoV-2, Zika viruses and mycoplasma: Structure, pathogenesis and some treatment options in these emerging viral and bacterial infectious diseases.
Ferreira G, Santander A, Savio F, Guirado M, [...], Nicolson GL.
Biochim Biophys Acta Mol Basis Dis. 2021; 1867 (12)
DOI: 10.1016/j.bbadis.2021.166264
The molecular evolution of life on earth along with changing environmental, conditions has rendered mankind susceptible to endemic and pandemic emerging infectious diseases. The effects of certain systemic viral and bacterial infections on morbidity and mortality are considered as examples of recent emerging infections. Here we will focus on three examples of infections that are important in pregnancy and early childhood: SARS-CoV-2 virus, Zika virus, and Mycoplasma species. The basic structural characteristics of these infectious agents will be examined, along with their general pathogenic mechanisms. Coronavirus infections, such as caused by the SARS-CoV-2 virus, likely evolved from zoonotic bat viruses to infect humans and cause a pandemic that has been the biggest challenge for humanity since the Spanish Flu pandemic of the early 20th century. In contrast, Zika Virus infections represent an expanding infectious threat in the context of global climate change. The relationship of these infections to pregnancy, the vertical transmission and neurological sequels make these viruses highly relevant to the topics of this special issue. Finally, mycoplasmal infections have been present before mankind evolved, but they were rarely identified as human pathogens until recently, and they are now recognized as important coinfections that are able to modify the course and prognosis of various infectious diseases and other chronic illnesses. The infectious processes caused by these intracellular microorganisms are examined as well as some general aspects of their pathogeneses, clinical presentations, and diagnoses. We will finally consider examples of treatments that have been used to reduce morbidity and mortality of these infections and discuss briefly the current status of vaccines, in particular, against the SARS-CoV-2 virus. It is important to understand some of the basic features of these emerging infectious diseases and the pathogens involved in order to better appreciate the contributions of this special issue on how infectious diseases can affect human pregnancy, fetuses and neonates.
2021-09-03 2021 other research-article; Journal Article abstract-available 10.1016/j.bbadis.2021.166264 SARS-CoV-2, Zika viruses and mycoplasma: Structure, pathogenesis and some treatment options in these emerging viral and bacterial infectious diseases. Ferreira G, Santander A, Savio F, Guirado M, Sobrevia L, Nicolson GL. Biochim Biophys Acta Mol Basis Dis. 2021; 1867 (12)
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)
A Pandemic within Other Pandemics. When a Multiple Infection of a Host Occurs: SARS-CoV-2, HIV and Mycobacterium tuberculosis.
González-Domenech CM, Pérez-Hernández I, Gómez-Ayerbe C, Viciana Ramos I, [...], Santos J.
Viruses. 2021; 13 (5)
DOI: 10.3390/v13050931
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.
2021-05-17 2021 other review-article; Review; Journal Article abstract-available 10.3390/v13050931 A Pandemic within Other Pandemics. When a Multiple Infection of a Host Occurs: SARS-CoV-2, HIV and <i>Mycobacterium tuberculosis</i>. González-Domenech CM, Pérez-Hernández I, Gómez-Ayerbe C, Viciana Ramos I, Palacios-Muñoz R, Santos J. Viruses. 2021; 13 (5)
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
Longitudinal study of a SARS-CoV-2 infection in an immunocompromised patient with X-linked agammaglobulinemia.
Ciuffreda L, Lorenzo-Salazar JM, Alcoba-Florez J, Rodriguez-Pérez H, [...], Flores C.
J Infect. 2021;
DOI: 10.1016/j.jinf.2021.07.028
2021-07-28 2021 other Letter 10.1016/j.jinf.2021.07.028 Longitudinal study of a SARS-CoV-2 infection in an immunocompromised patient with X-linked agammaglobulinemia. Ciuffreda L, Lorenzo-Salazar JM, Alcoba-Florez J, Rodriguez-Pérez H, Gil-Campesino H, Íñigo-Campos A, García-Martínez de Artola D, Valenzuela-Fernández A, Hayek-Peraza M, Rojo-Alba S, Alvarez-Argüelles ME, Díez-Gil O, González-Montelongo R, Flores C. J Infect. 2021;
Immunological imprinting of the antibody response in COVID-19 patients.
Aydillo T, Rombauts A, Stadlbauer D, Aslam S, [...], García-Sastre A.
Nat Commun. 2021; 12 (1)
DOI: 10.1038/s41467-021-23977-1
In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.
2021-06-18 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.1038/s41467-021-23977-1 Immunological imprinting of the antibody response in COVID-19 patients. Aydillo T, Rombauts A, Stadlbauer D, Aslam S, Abelenda-Alonso G, Escalera A, Amanat F, Jiang K, Krammer F, Carratala J, García-Sastre A. Nat Commun. 2021; 12 (1)
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)
COVID-19, A new challenge in the dental practice.
Silvestre FJ, Martinez-Herrera M, Márquez-Arrico CF, Silvestre-Rangil J.
J Clin Exp Dent. 2021; 13 (7)
DOI: 10.4317/jced.57362

Background

This review was conducted in order to learn the latest information about how to prevent cross-infection of COVID-19 in dentistry. The aim of this study is offer a clinical protocol to reduce the risk of infection of COVID-19 in dental settings.

Material and methods

We carried out a review based on the PRISMA guide (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We used the following three databases: PubMed, Embase and Scopus. The search strategy was performed in the three databases applying the search terms "COVID-19 AND dental", "COVID-19 AND dentistry", selecting human studies published from November 2019 to May 2020. English publications regarding COVID-19 as the central topic of the research were eligible for inclusion, regardless of study design. There are very few published studies on the association between COVID-19 and dentistry, for that reason we also included the English abstract of two studies written in Chinese. The following exclusion criteria were established: animal studies and in vitro studies.

Results

The search identified a total of 212 articles, of which 54 were preselected, and 23 were finally included in the review on the basis of the inclusion and exclusion criteria. We collected all the information about routes of general and oral infection, dental patient evaluation and cross-infection control in Dental Clinic in the selected studies.

Conclusions

Cross infection in the dental clinic involve a very important risk due to the return to dental settings after periods of social isolation of the population after the epidemic outbreak of SARS-CoV-2. Therefore, we must take adequate and sufficient security measures to protect the patients and the dental clinic staff. Key words:COVID-19, COVID-19 cross infection risk, COVID-19 prevention in Dentistry, COVID-19 in Dental Clinic.
2021-07-01 2021 other review-article; Review; Journal Article abstract-available 10.4317/jced.57362 COVID-19, A new challenge in the dental practice. Silvestre FJ, Martinez-Herrera M, Márquez-Arrico CF, Silvestre-Rangil J. J Clin Exp Dent. 2021; 13 (7)
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
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)
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
The Role of Dysbiosis in Critically Ill Patients With COVID-19 and Acute Respiratory Distress Syndrome.
Battaglini D, Robba C, Fedele A, Trancǎ S, [...], Pelosi P.
Front Med (Lausanne). 2021; 8
DOI: 10.3389/fmed.2021.671714
In late December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) quickly spread worldwide, and the syndrome it causes, coronavirus disease 2019 (COVID-19), has reached pandemic proportions. Around 30% of patients with COVID-19 experience severe respiratory distress and are admitted to the intensive care unit for comprehensive critical care. Patients with COVID-19 often present an enhanced immune response with a hyperinflammatory state characterized by a "cytokine storm," which may reflect changes in the microbiota composition. Moreover, the evolution to acute respiratory distress syndrome (ARDS) may increase the severity of COVID-19 and related dysbiosis. During critical illness, the multitude of therapies administered, including antibiotics, sedatives, analgesics, body position, invasive mechanical ventilation, and nutritional support, may enhance the inflammatory response and alter the balance of patients' microbiota. This status of dysbiosis may lead to hyper vulnerability in patients and an inappropriate response to critical circumstances. In this context, the aim of our narrative review is to provide an overview of possible interaction between patients' microbiota dysbiosis and clinical status of severe COVID-19 with ARDS, taking into consideration the characteristic hyperinflammatory state of this condition, respiratory distress, and provide an overview on possible nutritional strategies for critically ill patients with COVID-19-ARDS.
2021-06-04 2021 other review-article; Review; Journal Article abstract-available 10.3389/fmed.2021.671714 The Role of Dysbiosis in Critically Ill Patients With COVID-19 and Acute Respiratory Distress Syndrome. Battaglini D, Robba C, Fedele A, Trancǎ S, Sukkar SG, Di Pilato V, Bassetti M, Giacobbe DR, Vena A, Patroniti N, Ball L, Brunetti I, Torres Martí A, Rocco PRM, Pelosi P. Front Med (Lausanne). 2021; 8
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; Review; 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)
Pathogenesis and Management of COVID-19.
Alfarouk KO, AlHoufie STS, Ahmed SBM, Shabana M, [...], Reshkin SJ.
J Xenobiot. 2021; 11 (2)
DOI: 10.3390/jox11020006
COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19.
2021-05-21 2021 other review-article; Review; Journal Article abstract-available 10.3390/jox11020006 Pathogenesis and Management of COVID-19. Alfarouk KO, AlHoufie STS, Ahmed SBM, Shabana M, Ahmed A, Alqahtani SS, Alqahtani AS, Alqahtani AM, Ramadan AM, Ahmed ME, Ali HS, Bashir A, Devesa J, Cardone RA, Ibrahim ME, Schwartz L, Reshkin SJ. J Xenobiot. 2021; 11 (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
Chest CT abnormalities in COVID-19: a systematic review.
Ghayda RA, Lee KH, Kim JS, Lee S, [...], Shin JI.
Int J Med Sci. 2021; 18 (15)
DOI: 10.7150/ijms.50568
Computed tomography (CT) of the chest is one of the main diagnositic tools for coronavirus disease 2019 (COVID-19) infection. To document the chest CT findings in patients with confirmed COVID-19 and their association with the clinical severity, we searched related literatures through PubMed, MEDLINE, Embase, Web of Science (inception to May 4, 2020) and reviewed reference lists of previous systematic reviews. A total of 31 case reports (3768 patients) on CT findings of COVID-19 were included. The most common comorbid conditions were hypertension (18.4%) and diabetes mellitus (8.3%). The most common symptom was fever (78.7%), followed by cough (60.2%). It took an average of 5.6 days from symptom onset to admission. The most common chest CT finding was vascular enlargement (84.8%), followed by ground-glass opacity (GGO) (60.1%), air-bronchogram (47.8%), and consolidation (41.4%). Most lung lesions were located in the lung periphery (72.2%) and involved bilateral lung (76%). Most patients showed normal range of laboratory findings such as white blood cell count (96.4%) and lymphocyte (87.2%). Compared to previous published meta-analyses, our study is the first to summarize the different radiologic characteristics of chest CT in a total of 3768 COVID-19 patients by compiling case series studies. A comprehensive diagnostic approach should be adopted for patients with known COVID-19, suspected cases, and for exposed individuals.
2021-08-01 2021 other research-article; Journal Article abstract-available 10.7150/ijms.50568 Chest CT abnormalities in COVID-19: a systematic review. Ghayda RA, Lee KH, Kim JS, Lee S, Hong SH, Kim KS, Kim KE, Seok J, Kim H, Seo J, Lee S, Koyanagi A, Jacob L, Smith L, Li H, Kronbichler A, Shin JI. Int J Med Sci. 2021; 18 (15)
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)
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)
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)
Critical Presentation of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection: A Case Report.
Massanella M, Martin-Urda A, Mateu L, Marín T, [...], Paredes R.
Open Forum Infect Dis. 2021; 8 (7)
DOI: 10.1093/ofid/ofab329

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections have been reported; however, most cases are milder than the primary infection. We report the first case of a life-threatening critical presentation of a SARS-CoV-2 reinfection.

Methods

A 62-year-old man from Palamós (Spain) suffered a first mild coronavirus disease 2019 (COVID-19) episode in March 2020, confirmed by 2 independent SARS-CoV-2 nasopharyngeal polymerase chain reaction (PCR) assays and a normal radiograph. He recovered completely and tested negative on 2 consecutive PCRs. In August 2020, the patient developed a second SARS-CoV-2 infection with life-threatening bilateral pneumonia and Acute respiratory distress syndrome criteria, requiring COVID-19-specific treatment (remdesivir + dexamethasone) plus high-flow oxygen therapy. Nasopharyngeal swabs from the second episode were obtained for virus quantification by real-time PCR, for virus outgrowth and sequencing. In addition, plasma and peripheral blood mononuclear cells during the hospitalization period were used to determine SARS-CoV-2-specific humoral and T-cell responses.

Results

Genomic analysis of SARS-CoV-2 showed that the virus had probably originated shortly before symptom onset. When the reinfection occurred, the subject showed a weak immune response, with marginal humoral and specific T-cell responses against SARS-CoV-2. All antibody isotypes tested as well as SARS-CoV-2 neutralizing antibodies increased sharply after day 8 postsymptoms. A slight increase of T-cell responses was observed at day 19 after symptom onset.

Conclusions

The reinfection was firmly documented and occurred in the absence of robust preexisting humoral and cellular immunity. SARS-CoV-2 immunity in some subjects is unprotective and/or short-lived; therefore, SARS-CoV-2 vaccine schedules inducing long-term immunity will be required to bring the pandemic under control.
2021-06-23 2021 other Case Reports; case-report abstract-available 10.1093/ofid/ofab329 Critical Presentation of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection: A Case Report. Massanella M, Martin-Urda A, Mateu L, Marín T, Aldas I, Riveira-Muñoz E, Kipelainen A, Jiménez-Moyano E, Rodriguez de la Concepción ML, Avila-Nieto C, Trinité B, Pradenas E, Rodon J, Marfil S, Parera M, Carrillo J, Blanco J, Prado JG, Ballana E, Vergara-Alert J, Segalés J, Noguera-Julian M, Masabeu À, Clotet B, Toda MR, Paredes R. Open Forum Infect Dis. 2021; 8 (7)
Gastrointestinal Perspective of Coronavirus Disease 2019 in Children-An Updated Review.
Assa A, Benninga MA, Borrelli O, Broekaert I, [...], Gastrointestinal Committee of ESPGHAN.
J Pediatr Gastroenterol Nutr. 2021; 73 (3)
DOI: 10.1097/mpg.0000000000003204

Abstract

Gastrointestinal symptoms are common findings in children with severe acute respiratory syndrome coronavirus 2 infection, including vomiting, diarrhoea, abdominal pain, and difficulty in feeding, although these symptoms tend to be mild. The hepato-biliary system and the pancreas may also be involved, usually with a mild elevation of transaminases and, rarely, pancreatitis. In contrast, a late hyper-inflammatory phenomenon, termed multisystem inflammatory syndrome (MIS-C), is characterized by more frequent gastrointestinal manifestations with greater severity, sometimes presenting as peritonitis. Gastrointestinal and hepato-biliary manifestations are probably related to a loss in enterocyte absorption capability and microscopic mucosal damage caused by a viral infection of intestinal epithelial cells, hepatocytes and other cells through the angiotensin conversion enzyme 2 receptor resulting in immune cells activation with subsequent release of inflammatory cytokines. Specific conditions such as inflammatory bowel disease (IBD) and liver transplantation may pose a risk for the more severe presentation of coronavirus disease 2019 (COVID-19) but as adult data accumulate, paediatric data is still limited. The aim of this review is to summarize the current evidence about the effect of COVID-19 on the gastrointestinal system in children, with emphasis on the emerging MIS-C and specific considerations such as patients with IBD and liver transplant recipients.
2021-09-01 2021 other review-article; Review; Journal Article abstract-available 10.1097/mpg.0000000000003204 Gastrointestinal Perspective of Coronavirus Disease 2019 in Children-An Updated Review. Assa A, Benninga MA, Borrelli O, Broekaert I, de Carpi JM, Saccomani MD, Dolinsek J, Mas E, Miele E, Thomson M, Tzivinikos C, Gastrointestinal Committee of ESPGHAN. J Pediatr Gastroenterol Nutr. 2021; 73 (3)
First Detection of SARS-CoV-2 B.1.1.7 Variant of Concern in an Asymptomatic Dog in Spain.
Barroso-Arévalo S, Rivera B, Domínguez L, Sánchez-Vizcaíno JM.
Viruses. 2021; 13 (7)
DOI: 10.3390/v13071379
Natural SARS-CoV-2 infection in pets has been widely documented during the last year. Although the majority of reports suggested that dogs' susceptibility to the infection is low, little is known about viral pathogenicity and transmissibility in the case of variants of concern, such as B.1.1.7 in this species. Here, as part of a large-scale study on SARS-CoV-2 prevalence in pets in Spain, we have detected the B.1.1.7 variant of concern (VOC) in a dog whose owners were infected with SARS-CoV-2. The animal did not present any symptoms, but viral loads were high in the nasal and rectal swabs. In addition, viral isolation was possible from both swabs, demonstrating that the dog was shedding infectious virus. Seroconversion occurred 23 days after the first sampling. This study documents the first detection of B.1.1.7 VOC in a dog in Spain and emphasizes the importance of performing active surveillance and genomic investigation on infected animals.
2021-07-15 2021 fondo-covid Research Support, Non-U.S. Gov't; Case Reports; case-report abstract-available 10.3390/v13071379 First Detection of SARS-CoV-2 B.1.1.7 Variant of Concern in an Asymptomatic Dog in Spain. Barroso-Arévalo S, Rivera B, Domínguez L, Sánchez-Vizcaíno JM. Viruses. 2021; 13 (7)
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 Research Support, Non-U.S. Gov't; 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
Volcanic Ash as a Precursor for SARS-CoV-2 Infection Among Susceptible Populations in Ecuador: A Satellite Imaging and Excess Mortality-Based Analysis.
Toulkeridis T, Seqqat R, Torres Arias M, Salazar-Martinez R, [...], Debut A.
Disaster Med Public Health Prep. 2021;
DOI: 10.1017/dmp.2021.154
The global coronavirus disease 2019 (COVID-19) pandemic has altered entire nations and their health systems. The greatest impact of the pandemic has been seen among vulnerable populations, such as those with comorbidities like heart diseases, kidney failure, obesity, or those with worse health determinants such as unemployment and poverty. In the current study, we are proposing previous exposure to fine-grained volcanic ashes as a risk factor for developing COVID-19. Based on several previous studies it has been known since the mid 1980s of the past century that volcanic ash is most likely an accelerating factor to suffer from different types of cancer, including lung or thyroid cancer. Our study postulates, that people who are most likely to be infected during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) widespread wave will be those with comorbidities that are related to previous exposure to volcanic ashes. We have explored 8703 satellite images from the past 21 y of available data from the National Oceanic and Atmospheric Administration (NOAA) database and correlated them with the data from the national institute of health statistics in Ecuador. Additionally, we provide more realistic numbers of fatalities due to the virus based on excess mortality data of 2020-2021, when compared with previous years. This study would be a very first of its kind combining social and spatial distribution of COVID-19 infections and volcanic ash distribution. The results and implications of our study will also help countries to identify such aforementioned vulnerable parts of the society, if the given geodynamic and volcanic settings are similar.
2021-05-19 2021 other research-article; Journal Article abstract-available 10.1017/dmp.2021.154 Volcanic Ash as a Precursor for SARS-CoV-2 Infection Among Susceptible Populations in Ecuador: A Satellite Imaging and Excess Mortality-Based Analysis. Toulkeridis T, Seqqat R, Torres Arias M, Salazar-Martinez R, Ortiz-Prado E, Chunga S, Vizuete K, Heredia-R M, Debut A. Disaster Med Public Health Prep. 2021;
The Relevance of Monoclonal Antibodies in the Treatment of COVID-19.
Torrente-López A, Hermosilla J, Navas N, Cuadros-Rodríguez L, [...], Salmerón-García A.
Vaccines (Basel). 2021; 9 (6)
DOI: 10.3390/vaccines9060557
Major efforts have been made in the search for effective treatments since the outbreak of the COVID-19 infection in December 2019. Extensive research has been conducted on drugs that are already available and new treatments are also under development. Within this context, therapeutic monoclonal antibodies (mAbs) have been the subject of widespread investigation focusing on two target-based groups, i.e., non-SARS-CoV-2 specific mAbs, that target immune system responses, and SARS-CoV-2 specific mAbs, designed to neutralize the virus protein structure. Here we review the latest literature about the use of mAbs in order to describe the state of the art of the clinical trials and the benefits of using these biotherapeutics in the treatment of COVID-19. The clinical trials considered in the present review include both observational and randomized studies. We begin by presenting the studies conducted using non-SARS-CoV-2 specific mAbs for treating different immune disorders that were already on the market. Within this group of mAbs, we focus particularly on anti-IL-6/IL-6R. This is followed by a discussion of the studies on SARS-CoV-2 specific mAbs. Our findings indicate that SARS-CoV-2 specific mAbs are significantly more effective than non-specific ones.
2021-05-26 2021 other review-article; Review; Journal Article abstract-available 10.3390/vaccines9060557 The Relevance of Monoclonal Antibodies in the Treatment of COVID-19. Torrente-López A, Hermosilla J, Navas N, Cuadros-Rodríguez L, Cabeza J, Salmerón-García A. Vaccines (Basel). 2021; 9 (6)
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)
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)
Insights into the potential role of alpha1-antitrypsin in COVID-19 patients: Mechanisms, current update, and future perspectives.
Marzouk S, Attia N, Mashal M.
Clin Respir J. 2021; 15 (9)
DOI: 10.1111/crj.13406
In this work, we provide an up-to-date summary of the available molecular- and cell-related mechanisms by which alpha1-antitrypsin (AAT) protein could be of benefit in treating COVID-19 patients. As well, we demonstrate the current status in terms of the ongoing clinical trials using AAT in COVID-19 patients. Finally, we touch on the potential role gene therapy and stem cell-based gene therapy could have in such emerging and serious condition caused by the SARS-CoV-2 virus.
2021-07-12 2021 other article-commentary; Journal Article abstract-available 10.1111/crj.13406 Insights into the potential role of alpha1-antitrypsin in COVID-19 patients: Mechanisms, current update, and future perspectives. Marzouk S, Attia N, Mashal M. Clin Respir J. 2021; 15 (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)
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)
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)
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. 2021; 68 (4)
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).
2020-10-23 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. 2021; 68 (4)
Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications?
Castro P, Palomo M, Moreno-Castaño AB, Fernández S, [...], Diaz-Ricart M.
Cardiovasc Drugs Ther. 2021;
DOI: 10.1007/s10557-021-07207-w
Patients with COVID-19 present a wide spectrum of disease severity, from asymptomatic cases in the majority to serious disease leading to critical care and even death. Clinically, four different scenarios occur within the typical disease timeline: first, an incubation and asymptomatic period; second, a stage with mild symptoms due mainly to the virus itself; third, in up to 20% of the patients, a stage with severe symptoms where a hyperinflammatory response with a cytokine storm driven by host immunity induces acute respiratory distress syndrome; and finally, a post-acute sequelae (PASC) phase, which present symptoms that can range from mild or annoying to actually quite incapacitating. Although the most common manifestation is acute respiratory failure of the lungs, other organs are also frequently involved. The clinical manifestations of the COVID-19 infection support a key role for endothelial dysfunction in the pathobiology of this condition. The virus enters into the organism via its interaction with angiotensin-converting enzyme 2-receptor that is present prominently in the alveoli, but also in endothelial cells, which can be directly infected by the virus. Cytokine release syndrome can also drive endothelial damage independently. Consequently, a distinctive feature of SARS-CoV-2 infection is vascular harm, with severe endothelial injury, widespread thrombosis, microangiopathy, and neo-angiogenesis in response to endothelial damage. Therefore, endothelial dysfunction seems to be the pathophysiological substrate for severe COVID-19 complications. Biomarkers of endothelial injury could constitute strong indicators of disease progression and severity. In addition, the endothelium could represent a very attractive target to both prevent and treat these complications. To establish an adequate therapy, the underlying pathophysiology and corresponding clinical stage should be clearly identified. In this review, the clinical features of COVID-19, the central role of the endothelium in COVID-19 and in other pathologies, and the potential of specific therapies aimed at protecting the endothelium in COVID-19 patients are addressed.
2021-06-07 2021 other review-article; Review; Journal Article abstract-available 10.1007/s10557-021-07207-w Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications? Castro P, Palomo M, Moreno-Castaño AB, Fernández S, Torramadé-Moix S, Pascual G, Martinez-Sanchez J, Richardson E, Téllez A, Nicolas JM, Carreras E, Richardson PG, Badimon JJ, Escolar G, Diaz-Ricart M. Cardiovasc Drugs Ther. 2021;
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)
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; 76 (8)
DOI: 10.1093/gerona/glab074

Background

The most susceptible population group to critical and fatal coronavirus disease 2019 (COVID-19) is older adults. In severe acute respiratory syndrome coronavirus 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 analyze 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 3-month period (March 1-May 31, 2020). A total of 143 patients were included in the study cohort. From 2 April, 2020, in accordance with World Health Organization 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

In total, 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 (interquartile range: 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 noncorticosteroid group (81.8%). Treatment with corticosteroids was an independent survival factor (hazard ratio: 0.61; 95% CI: 0.41-0.93; p = .006).

Conclusions

In critically ill older adults with COVID-19 pneumonia, the use of corticosteroid treatment resulted in lower mortality without severe adverse events.
2021-07-01 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; 76 (8)
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)
Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol.
Arévalos V, Ortega-Paz L, Fernandez-Rodríguez D, Alfonso Jiménez-Díaz V, [...], CV COVID-19 Registry Investigators.
PLoS One. 2021; 16 (7)
DOI: 10.1371/journal.pone.0255263

Background

Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes.

Study and design

This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee.

Conclusion

The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.
2021-07-29 2021 other Clinical Trial; Research Support, Non-U.S. Gov't; research-article; Multicenter Study; Journal Article; Observational Study abstract-available 10.1371/journal.pone.0255263 Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol. Arévalos V, Ortega-Paz L, Fernandez-Rodríguez D, Alfonso Jiménez-Díaz V, Rius JB, Campo G, Rodríguez-Santamarta M, de Prado AP, Gómez-Menchero A, Díaz Fernández JF, Scardino C, Gonzalo N, Pernigotti A, Alfonso F, Jesús Amat-Santos I, Silvestro A, Ielasi A, María de la Torre J, Bastidas G, Gómez-Lara J, Sabaté M, Brugaletta S, CV COVID-19 Registry Investigators. PLoS One. 2021; 16 (7)
SARS-CoV-2, a Threat to Marine Mammals? A Study from Italian Seawaters.
Audino T, Grattarola C, Centelleghe C, Peletto S, [...], Casalone C.
Animals (Basel). 2021; 11 (6)
DOI: 10.3390/ani11061663
Zoonotically transmitted coronaviruses were responsible for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing the dramatic Coronavirus Disease-2019 (CoViD-19) pandemic, which affected public health, the economy, and society on a global scale. The impact of the SARS-CoV-2 pandemic permeated into our environment and wildlife as well; in particular, concern has been raised about the viral occurrence and persistence in aquatic and marine ecosystems. The discharge of untreated wastewaters carrying infectious SARS-CoV-2 into natural water systems that are home to sea mammals may have dramatic consequences on vulnerable species. The efficient transmission of coronaviruses raises questions regarding the contributions of virus-receptor interactions. The main receptor of SARS-CoV-2 is Angiotensin Converting Enzyme-2 (ACE-2), serving as a functional receptor for the viral spike (S) protein. This study aimed, through the comparative analysis of the ACE-2 receptor with the human one, at assessing susceptibility to SARS-CoV-2 for different species of marine mammals living in Italian waters. We also determined, by means of immunohistochemistry, ACE-2 receptor localization in the lung tissue from different cetacean species, in order to provide a preliminary characterization of ACE-2 expression in the marine mammal respiratory tracts. Furthermore, to evaluate if and how Italian wastewater management and coastal exposition to extreme weather events may led to susceptible marine mammal populations being exposed to SARS-CoV-2, geomapping data were carried out and overlapped. The results showed the potential SARS-CoV-2 exposure for marine mammals inhabiting Italian coastal waters, putting them at risk when swimming and feeding in specific risk areas. Thus, we highlighted the potential hazard of the reverse zoonotic transmission of SARS-CoV-2 infection, along with its impact on marine mammals regularly inhabiting the Mediterranean Sea, while also stressing the need for appropriate action in order to prevent further damage to specific vulnerable populations.
2021-06-03 2021 other research-article; Journal Article abstract-available 10.3390/ani11061663 SARS-CoV-2, a Threat to Marine Mammals? A Study from Italian Seawaters. Audino T, Grattarola C, Centelleghe C, Peletto S, Giorda F, Florio CL, Caramelli M, Bozzetta E, Mazzariol S, Di Guardo G, Lauriano G, Casalone C. Animals (Basel). 2021; 11 (6)
Neurological manifestations of COVID-19 in patients: from path physiology to therapy.
Merino JJ, Macho-González A, Benedi J, González MP.
Neurol Sci. 2021;
DOI: 10.1007/s10072-021-05505-7
Coronavirus is a family of ARN positive single-stranded belonging to the family of Coronaviridae. There are several families of coronavirus that transmit more or less serious diseases. However, the so-called coronavirus-19 (SARS-CoV2) is the one that is currently causing most of the problems; in fact, biological dysfunctions that this virus causes provoke damage in various organs, from the lung to the heart, the kidney, the circulatory system, and even the brain. The neurological manifestations caused by viral infection, as well as the hypercoagulopathy and systemic inflammation, have been reported in several studies. In this review, we update the neurological mechanisms by which coronavirus-19 causes neurological manifestation in patients such as encephalomyelitis, Guillain-Barré syndrome, lacunars infarcts, neuropsychiatry disorders such as anxiety and depression, and vascular alterations. This review explains (a) the possible pathways by which coronavirus-19 can induce the different neurological manifestations, (b) the strategies used by the virus to cross the barrier system, (c) how the immune system responds to the infection, and (d) the treatment than can be administered to the COVID-19 patients.
2021-08-21 2021 other review-article; Review; Journal Article abstract-available 10.1007/s10072-021-05505-7 Neurological manifestations of COVID-19 in patients: from path physiology to therapy. Merino JJ, Macho-González A, Benedi J, González MP. Neurol Sci. 2021;
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
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)
Long-term impact of COVID-19 associated acute respiratory distress syndrome.
Aranda J, Oriol I, Martín M, Feria L, [...], Carratalà J.
J Infect. 2021;
DOI: 10.1016/j.jinf.2021.08.018

Objectives

To determine the health status, exercise capacity, and health related quality of life (HRQoL) of COVID-19 associated acute respiratory distress syndrome (ARDS) survivors, 8 months after diagnosis.

Methods

All eligible patients were interviewed and underwent a physical examination, chest X-ray, and 6 min walk test (6MWT). Scales to evaluate post-traumatic stress disorder, depression, anxiety, and HRQoL were applied.

Results

Of 1295 patients, 365 suffered ARDS and 166 survived to hospital discharge. Five died after discharge and 48 were lost to follow-up. Of the 113 remaining patients, 81% had persistent symptoms. More than 50% of patients completed less than 80% of the theoretical distance on the 6MWT, 50% had an abnormal X-ray and 93% of patients developed psychiatric disorders. Mean SF-36 scores were worse than in the general population. After multivariate regression analysis, female sex, non-Caucasian race, and Charlson index>2 were independent risk factors for a worse mental health component summary score on the SF-36, and age was associated with a better prognosis. Female sex and chronic obstructive pulmonary disease were independently associated with a worse physical component summary score.

Conclusion

COVID-19 associated ARDS survivors have long-term consequences in health status, exercise capacity, and HRQoL. Strategies addressed to prevent these sequelae are needed.
2021-08-13 2021 other research-article; Journal Article abstract-available 10.1016/j.jinf.2021.08.018 Long-term impact of COVID-19 associated acute respiratory distress syndrome. Aranda J, Oriol I, Martín M, Feria L, Vázquez N, Rhyman N, Vall-Llosera E, Pallarés N, Coloma A, Pestaña M, Loureiro J, Güell E, Borjabad B, León E, Franz E, Domènech A, Pintado S, Contra A, Cortés MDS, Chivite I, Clivillé R, Vacas M, Ceresuela LM, Carratalà J. J Infect. 2021;
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)
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
[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)
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)
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
Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission.
Sánchez-Rovira P, Pérez-Chica G, Ortega-Granados AL, Aguilar-García J, [...], Herrero-Rodríguez C.
Medicine (Baltimore). 2021; 100 (29)
DOI: 10.1097/md.0000000000026533

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (-108.19; CI 95% -140.15, -75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.
2021-07-01 2021 other research-article; Journal Article; Observational Study abstract-available 10.1097/md.0000000000026533 Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission. Sánchez-Rovira P, Pérez-Chica G, Ortega-Granados AL, Aguilar-García J, Díaz-Beltrán L, Gálvez-Montosa F, García-Verdejo F, Luque-Caro N, Quero-Blanco C, Fernández-Navarro M, Rodríguez-Sánchez A, Ruiz-Bailén M, Yaguez-Mateos L, Marín-Pozo JF, Sierra-Torres MI, Lacárcel-Bautista C, Duro-Ruiz GJ, Duro-Fernández MÁ, García-Alegría J, Herrero-Rodríguez C. Medicine (Baltimore). 2021; 100 (29)
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)
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)
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
Identification of Niemann-Pick C1 protein as a potential novel SARS-CoV-2 intracellular target.
García-Dorival I, Cuesta-Geijo MÁ, Barrado-Gil L, Galindo I, [...], Alonso C.
Antiviral Res. 2021; 194
DOI: 10.1016/j.antiviral.2021.105167
Niemann-Pick type C1 (NPC1) receptor is an endosomal membrane protein that regulates intracellular cholesterol traffic. This protein has been shown to play an important role for several viruses. It has been reported that SARS-CoV-2 enters the cell through plasma membrane fusion and/or endosomal entry upon availability of proteases. However, the whole process is not fully understood yet and additional viral/host factors might be required for viral fusion and subsequent viral replication. Here, we report a novel interaction between the SARS-CoV-2 nucleoprotein (N) and the cholesterol transporter NPC1. Furthermore, we have found that some compounds reported to interact with NPC1, carbazole SC816 and sulfides SC198 and SC073, were able to reduce SARS-CoV-2 viral infection with a good selectivity index in human cell infection models. These findings suggest the importance of NPC1 for SARS-CoV-2 viral infection and a new possible potential therapeutic target to fight against COVID-19.
2021-08-24 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1016/j.antiviral.2021.105167 Identification of Niemann-Pick C1 protein as a potential novel SARS-CoV-2 intracellular target. García-Dorival I, Cuesta-Geijo MÁ, Barrado-Gil L, Galindo I, Garaigorta U, Urquiza J, Puerto AD, Campillo NE, Martínez A, Gastaminza P, Gil C, Alonso C. Antiviral Res. 2021; 194
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)
Emergence and Spread of B.1.1.7 Lineage in Primary Care and Clinical Impact in the Morbi-Mortality among Hospitalized Patients in Madrid, Spain.
Martínez-García L, Espinel MA, Abreu M, González-Alba JM, [...], Aranaz J.
Microorganisms. 2021; 9 (7)
DOI: 10.3390/microorganisms9071517
In December 2020, UK authorities warned of the rapid spread of a new SARS-CoV-2 variant, belonging to the B.1.1.7 lineage, known as the Alpha variant. This variant is characterized by 17 mutations and 3 deletions. The deletion 69-70 in the spike protein can be detected by commercial platforms, allowing its real-time spread to be known. From the last days of December 2020 and over 4 months, all respiratory samples with a positive result for SARS-CoV-2 from patients treated in primary care and the emergency department were screened to detect this variant based on the strategy S gene target failure (SGTF). The first cases were detected during week 53 (2020) and reached >90% of all cases during weeks 15-16 (2021). During this period, the B.1.1.7/SGTF variant spread at a rapid and constant replacement rate of around 30-36%. The probability of intensive care unit admission was twice higher among patients infected by the B.1.1.7/SGTF variant, but there were no differences in death rate. During the peak of the third pandemic wave, this variant was not the most prevalent, and it became dominant when this wave was declining. Our results confirm that the B.1.1.7/SGTF variant displaced other SARS-CoV-2 variants in our healthcare area in 4 months. This displacement has led to an increase in the burden of disease.
2021-07-15 2021 other research-article; Journal Article abstract-available 10.3390/microorganisms9071517 Emergence and Spread of B.1.1.7 Lineage in Primary Care and Clinical Impact in the Morbi-Mortality among Hospitalized Patients in Madrid, Spain. Martínez-García L, Espinel MA, Abreu M, González-Alba JM, Gijón D, McGee A, Cantón R, Galán JC, Aranaz J. Microorganisms. 2021; 9 (7)
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)
Acute transverse myelitis following SARS-CoV-2 infection.
Jauregui-Larrañaga C, Ostolaza-Ibáñez A, Martín-Bujanda M.
Neurologia (Engl Ed). 2021; 36 (7)
DOI: 10.1016/j.nrleng.2021.05.003
2021-07-22 2021 other Letter 10.1016/j.nrleng.2021.05.003 Acute transverse myelitis following SARS-CoV-2 infection. Jauregui-Larrañaga C, Ostolaza-Ibáñez A, Martín-Bujanda M. Neurologia (Engl Ed). 2021; 36 (7)
Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram.
Attia ZI, Kapa S, Dugan J, Pereira N, [...], Discover Consortium (Digital and Noninvasive Screening for COVID-19 with AI ECG Repository).
Mayo Clin Proc. 2021; 96 (8)
DOI: 10.1016/j.mayocp.2021.05.027

Objective

To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG).

Methods

A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site.

Results

The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%.

Conclusion

Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control.
2021-08-01 2021 other Research Support, Non-U.S. Gov't; research-article; Multicenter Study; Journal Article abstract-available 10.1016/j.mayocp.2021.05.027 Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram. Attia ZI, Kapa S, Dugan J, Pereira N, Noseworthy PA, Jimenez FL, Cruz J, Carter RE, DeSimone DC, Signorino J, Halamka J, Chennaiah Gari NR, Madathala RS, Platonov PG, Gul F, Janssens SP, Narayan S, Upadhyay GA, Alenghat FJ, Lahiri MK, Dujardin K, Hermel M, Dominic P, Turk-Adawi K, Asaad N, Svensson A, Fernandez-Aviles F, Esakof DD, Bartunek J, Noheria A, Sridhar AR, Lanza GA, Cohoon K, Padmanabhan D, Pardo Gutierrez JA, Sinagra G, Merlo M, Zagari D, Rodriguez Escenaro BD, Pahlajani DB, Loncar G, Vukomanovic V, Jensen HK, Farkouh ME, Luescher TF, Su Ping CL, Peters NS, Friedman PA, Discover Consortium (Digital and Noninvasive Screening for COVID-19 with AI ECG Repository). Mayo Clin Proc. 2021; 96 (8)
COVID Obesity: A One-Year Narrative Review.
Ovalle DLP, Rodrigo-Cano S, González A, Soler C, [...], Soriano JM.
Nutrients. 2021; 13 (6)
DOI: 10.3390/nu13062060
On 11 March 2020, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO). This study focuses on a narrative review about the illness during the first year of the pandemic in relation to obesity. Databases were used to search studies published up to 8 December 2020. In total, 4430 articles and other scientific literature were found, and 24 articles were included in this one-year narrative review. The mean BMI value of severe COVID-19 patients ranged from 24.5 to 33.4 kg/m2, versus <18.5 to 24.3 kg/m2 for non-severe patients. Articles using the terms obesity or overweight without indicating the BMI value in these patients were common, but this is not useful, as the anthropometric parameters, when not defined by this index, are confusing due to the classification being different in the West compared to among Asian and Korean criteria-based adults. We proposed a new term, called COVID obesity, to define the importance of this anthropometric parameter, among others, in relation with this pandemic.
2021-06-16 2021 other review-article; Review; Journal Article abstract-available 10.3390/nu13062060 COVID Obesity: A One-Year Narrative Review. Ovalle DLP, Rodrigo-Cano S, González A, Soler C, Catalá-Gregori AI, Merino-Torres JF, Soriano JM. Nutrients. 2021; 13 (6)
Platinum chloride-based viability RT-qPCR for SARS-CoV-2 detection in complex samples.
Cuevas-Ferrando E, Randazzo W, Pérez-Cataluña A, Falcó I, [...], Sánchez G.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-97700-x
Isolation, contact tracing and restrictions on social movement are being globally implemented to prevent and control onward spread of SARS-CoV-2, even though the infection risk modelled on RNA detection by RT-qPCR remains biased as viral shedding and infectivity are not discerned. Thus, we aimed to develop a rapid viability RT-qPCR procedure to infer SARS-CoV-2 infectivity in clinical specimens and environmental samples. We screened monoazide dyes and platinum compounds as viability molecular markers on five SARS-CoV-2 RNA targets. A platinum chloride-based viability RT-qPCR was then optimized using genomic RNA, and inactivated SARS-CoV-2 particles inoculated in buffer, stool, and urine. Our results were finally validated in nasopharyngeal swabs from persons who tested positive for COVID-19 and in wastewater samples positive for SARS-CoV-2 RNA. We established a rapid viability RT-qPCR that selectively detects potentially infectious SARS-CoV-2 particles in complex matrices. In particular, the confirmed positivity of nasopharyngeal swabs following the viability procedure suggests their potential infectivity, while the complete prevention of amplification in wastewater indicated either non-infectious particles or free RNA. The viability RT-qPCR approach provides a more accurate ascertainment of the infectious viruses detection and it may complement analyses to foster risk-based investigations for the prevention and control of new or re-occurring outbreaks with a broad application spectrum.
2021-09-13 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-021-97700-x Platinum chloride-based viability RT-qPCR for SARS-CoV-2 detection in complex samples. Cuevas-Ferrando E, Randazzo W, Pérez-Cataluña A, Falcó I, Navarro D, Martin-Latil S, Díaz-Reolid A, Girón-Guzmán I, Allende A, Sánchez G. Sci Rep. 2021; 11 (1)
Superspreading in the emergence of COVID-19 variants
Gómez-Carballa A, Pardo-Seco J, Bello X, Martinón-Torres F, [...], Salas A.
Trends Genet. 2021;
DOI:
Superspreading and variants of concern (VOC) of the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the main catalyzers of the coronavirus disease 2019 (COVID-19) pandemic. However, measuring their individual impact is challenging. By examining the largest database of SARS-CoV-2 genomes The Global Initiative on Sharing Avian Influenza Data [GISAID; n >1.2 million high-quality (HQ) sequences], we present evidence suggesting that superspreading has had a key role in the epidemiological predominance of VOC. There are clear signatures in the database compatible with large superspreading events (SSEs) coinciding chronologically with the worst epidemiological scenarios triggered by VOC. The data suggest that, without the randomness effect of the genetic drift facilitated by superspreading, new VOC of SARS-CoV-2 would have had more limited chance of success.
2021-09-08 2021 other review-article; Review; Journal Article abstract-available Superspreading in the emergence of COVID-19 variants Gómez-Carballa A, Pardo-Seco J, Bello X, Martinón-Torres F, Salas A. Trends Genet. 2021;
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
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
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)
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)
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)
Positive association between outdoor air pollution and the incidence and severity of COVID-19. A review of the recent scientific evidences.
Marquès M, Domingo JL.
Environ Res. 2021;
DOI: 10.1016/j.envres.2021.111930
In June 2020, we published a review focused on assessing the influence of various air pollutants on the transmission of SARS-CoV-2, and the severity of COVID-19 in patients infected by the coronavirus. The results of most of those reviewed studies suggested that chronic exposure to certain air pollutants might lead to more severe and lethal forms of COVID-19, as well as delays/complications in the recovery of the patients. Since then, a notable number of studies on this topic have been published, including also various reviews. Given the importance of this issue, we have updated the information published since our previous review. Taking together the previous results and those of most investigations now reviewed, we have concluded that there is a significant association between chronic exposure to various outdoor air pollutants: PM2.5, PM10, O3, NO2, SO2 and CO, and the incidence/risk of COVID-19 cases, as well as the severity/mortality of the disease. Unfortunately, studies on the potential influence of other important air pollutants such as VOCs, dioxins and furans, or metals, are not available in the scientific literature. In relation to the influence of outdoor air pollutants on the transmission of SARS-CoV-2, although the scientific evidence is much more limited, some studies point to PM2.5 and PM10 as potential airborne transmitters of the virus. Anyhow, it is clear that environmental air pollution plays an important negative role in COVID-19, increasing its incidence and mortality.
2021-08-20 2021 other research-article; Journal Article abstract-available 10.1016/j.envres.2021.111930 Positive association between outdoor air pollution and the incidence and severity of COVID-19. A review of the recent scientific evidences. Marquès M, Domingo JL. Environ Res. 2021;
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)
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
Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19.
Bannerman BP, Júlvez J, Oarga A, Blundell TL, [...], Floto RA.
Life Sci Alliance. 2021; 4 (10)
DOI: 10.26508/lsa.202000954
The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for more than 3 million deaths in 219 countries across the world and with more than 140 million cases. The absence of FDA-approved drugs against SARS-CoV-2 has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and SARS-CoV-2 to provide insight into the virus' pathogenic mechanism and support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, first, in its healthy state. We then demonstrate how the entry of SARS-CoV-2 into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. A new computational method that predicts 20 unique reactions as drug targets from our models and provides a platform for future studies on viral entry inhibition, immune regulation, and drug optimisation strategies. The model is available in BioModels (https://www.ebi.ac.uk/biomodels/MODEL2007210001) and the software tool, findCPcli, that implements the computational method is available at https://github.com/findCP/findCPcli.
2021-08-05 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.26508/lsa.202000954 Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19. Bannerman BP, Júlvez J, Oarga A, Blundell TL, Moreno P, Floto RA. Life Sci Alliance. 2021; 4 (10)
Polyphenols and their potential role to fight viral diseases: An overview.
Montenegro-Landívar MF, Tapia-Quirós P, Vecino X, Reig M, [...], Saurina J.
Sci Total Environ. 2021; 801
DOI: 10.1016/j.scitotenv.2021.149719
Fruits, vegetables, spices, and herbs are a potential source of phenolic acids and polyphenols. These compounds are known as natural by-products or secondary metabolites of plants, which are present in the daily diet and provide important benefits to the human body such as antioxidant, anti-inflammatory, anticancer, anti-allergic, antihypertensive and antiviral properties, among others. Plentiful evidence has been provided on the great potential of polyphenols against different viruses that cause widespread health problems. As a result, this review focuses on the potential antiviral properties of some polyphenols and their action mechanism against various types of viruses such as coronaviruses, influenza, herpes simplex, dengue fever, and rotavirus, among others. Also, it is important to highlight the relationship between antiviral and antioxidant activities that can contribute to the protection of cells and tissues of the human body. The wide variety of action mechanisms of antiviral agents, such as polyphenols, against viral infections could be applied as a treatment or prevention strategy; but at the same time, antiviral polyphenols could be used to produce natural antiviral drugs. A recent example of an antiviral polyphenol application deals with the use of hesperidin extracted from Citrus sinensis. The action mechanism of hesperidin relies on its binding to the key entry or spike protein of SARS-CoV-2. Finally, the extraction, purification and recovery of polyphenols with potential antiviral activity, which are essential for virus replication and infection without side-effects, have been critically reviewed.
2021-08-19 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.scitotenv.2021.149719 Polyphenols and their potential role to fight viral diseases: An overview. Montenegro-Landívar MF, Tapia-Quirós P, Vecino X, Reig M, Valderrama C, Granados M, Cortina JL, Saurina J. Sci Total Environ. 2021; 801
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)
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
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)
Guillain Barré syndrome associated with COVID-19- lessons learned about its pathogenesis during the first year of the pandemic, a systematic review.
Freire M, Andrade A, Sopeña B, Lopez-Rodriguez M, [...], González-Quintela A.
Autoimmun Rev. 2021; 20 (8)
DOI: 10.1016/j.autrev.2021.102875
2021-06-10 2021 other Letter; Systematic Review 10.1016/j.autrev.2021.102875 Guillain Barré syndrome associated with COVID-19- lessons learned about its pathogenesis during the first year of the pandemic, a systematic review. Freire M, Andrade A, Sopeña B, Lopez-Rodriguez M, Varela P, Cacabelos P, Esteban H, González-Quintela A. Autoimmun Rev. 2021; 20 (8)
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)
The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data.
Malato J, Sotzny F, Bauer S, Freitag H, [...], Sepúlveda N.
Heliyon. 2021; 7 (8)
DOI: 10.1016/j.heliyon.2021.e07665
People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report a high frequency of viral infections and flu-like symptoms during their disease course. Given that this reporting agrees with different immunological abnormalities and altered gene expression profiles observed in the disease, we aimed at answering whether the expression of the human angiotensin-converting enzyme 2 (ACE2), the major cell entry receptor for SARS-CoV-2, is also altered in these patients. In particular, a low expression of ACE2 could be indicative of a high risk of developing COVID-19. We then performed a meta-analysis of public data on CpG DNA methylation and gene expression of this enzyme and its homologous ACE protein in peripheral blood mononuclear cells and related subsets. We found that patients with ME/CFS have decreased methylation levels of four CpG probes in the ACE locus (cg09920557, cg19802564, cg21094739, and cg10468385) and of another probe in the promoter region of the ACE2 gene (cg08559914). We also found a decreased expression of ACE2 but not of ACE in patients when compared to healthy controls. Accordingly, in newly collected data, there was evidence for a significant higher proportion of samples with an ACE2 expression below the limit of detection in patients than healthy controls. Altogether, patients with ME/CFS can be at a higher COVID-19 risk and, if so, they should be considered a priority group for vaccination by public health authorities. To further support this conclusion, similar research is recommended for other human cell entry receptors and cell types, namely, those cells targeted by the virus.
2021-07-29 2021 other research-article; Journal Article abstract-available 10.1016/j.heliyon.2021.e07665 The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data. Malato J, Sotzny F, Bauer S, Freitag H, Fonseca A, Grabowska AD, Graça L, Cordeiro C, Nacul L, Lacerda EM, Castro-Marrero J, Scheibenbogen C, Westermeier F, Sepúlveda N. Heliyon. 2021; 7 (8)
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
COVID-19 pandemic as a risk factor for the reactivation of herpes viruses.
Maldonado MD, Romero-Aibar J, Pérez-San-Gregorio MA.
Epidemiol Infect. 2021; 149
DOI: 10.1017/s0950268821001333
The appearance on the skin of herpes virus lesions, concomitantly with the coronavirus disease 2019 (COVID-19) pandemic, leads us to suspect an underlying infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Diagnostic reverse transcriptase polymerase chain reaction tests and immunoglobulin M (IgM) and IgG seroconversion studies have therefore been carried out. We present three cases of herpes virus infections in immunocompetent patients: one of the infections was herpes simplex 1 in a 40-year-old woman, and the other two were herpes varicella-zoster infections in a 62-year-old man and a 25-year-old woman. The patients were in the care of the southern health district of Seville of the SAS (Andalusian Health Service) during the Spanish state of alarm over the COVID-19 pandemic. The SARS-CoV-2 infection was confirmed in only one of the three cases. In this study, we briefly review the etiopathogenic role of the COVID-19 pandemic situation, whereby immunodeficiencies are generated that favour the appearance of other viral infections, such as herpes virus infections.
2021-06-16 2021 other Research Support, Non-U.S. Gov't; review-article; Journal Article; Case Reports abstract-available 10.1017/s0950268821001333 COVID-19 pandemic as a risk factor for the reactivation of herpes viruses. Maldonado MD, Romero-Aibar J, Pérez-San-Gregorio MA. Epidemiol Infect. 2021; 149
An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity.
Gómez-Zorita S, Milton-Laskibar I, García-Arellano L, González M, [...], Portillo MP.
Int J Mol Sci. 2021; 22 (15)
DOI: 10.3390/ijms22157975
The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.
2021-07-26 2021 other review-article; Review; Journal Article abstract-available 10.3390/ijms22157975 An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity. Gómez-Zorita S, Milton-Laskibar I, García-Arellano L, González M, Portillo MP. Int J Mol Sci. 2021; 22 (15)
Elimination of SARS-CoV-2 along wastewater and sludge treatment processes.
Serra-Compte A, González S, Arnaldos M, Berlendis S, [...], Litrico X.
Water Res. 2021; 202
DOI: 10.1016/j.watres.2021.117435
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is shed in the feces of infected people. As a consequence, genomic RNA of the virus can be detected in wastewater. Although the presence of viral RNA does not inform on the infectivity of the virus, this presence of genetic material raised the question of the effectiveness of treatment processes in reducing the virus in wastewater and sludge. In this work, treatment lines of 16 wastewater treatment plants were monitored to evaluate the removal of SARS-CoV-2 RNA in raw, processed waters and sludge, from March to May 2020. Viral RNA copies were enumerated using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in 5 different laboratories. These laboratories participated in proficiency testing scheme and their results demonstrated the reliability and comparability of the results obtained for each one. SARS-CoV-2 RNA was found in 50.5% of the 101 influent wastewater samples characterized. Positive results were detected more frequently in those regions with a COVID-19 incidence higher than 100 cases per 100,000 inhabitants. Wastewater treatment plants (WWTPs) significantly reduced the occurrence of virus RNA along the water treatment lines. Secondary treatment effluents showed an occurrence of SARS-CoV-2 RNA in 23.3% of the samples and no positive results were found after MBR and chlorination. Non-treated sludge (from primary and secondary treatments) presented a higher occurrence of SARS-CoV-2 RNA than the corresponding water samples, demonstrating the affinity of virus particles for solids. Furthermore, SARS-CoV-2 RNA was detected in treated sludge after thickening and anaerobic digestion, whereas viral RNA was completely eliminated from sludge only when thermal hydrolysis was applied. Finally, co-analysis of SARS-CoV-2 and F-specific RNA bacteriophages was done in the same water and sludge samples in order to investigate the potential use of these bacteriophages as indicators of SARS-CoV-2 fate and reduction along the wastewater treatment.
2021-07-15 2021 other research-article; Journal Article abstract-available 10.1016/j.watres.2021.117435 Elimination of SARS-CoV-2 along wastewater and sludge treatment processes. Serra-Compte A, González S, Arnaldos M, Berlendis S, Courtois S, Loret JF, Schlosser O, Yáñez AM, Soria-Soria E, Fittipaldi M, Saucedo G, Pinar-Méndez A, Paraira M, Galofré B, Lema JM, Balboa S, Mauricio-Iglesias M, Bosch A, Pintó RM, Bertrand I, Gantzer C, Montero C, Litrico X. Water Res. 2021; 202
COVID-19 and short and medium-term outcomes in liver transplant patients: A spanish single-center case series.
Tejedor-Tejada J, Fuentes-Valenzuela E, Alonso-Martin C, Almohalla-Alvarez C, [...], Garcia-Pajares F.
J Clin Exp Hepatol. 2021;
DOI: 10.1016/j.jceh.2021.05.009

Background & aims

The evidence suggests that most vulnerable subjects to COVID-19 infection suffer from patients with comorbidities or immunosuppression, including liver transplant recipients. Liver graft dysfunction may be a rare complication. Some patients complain about the post-COVID-19 syndrome. The aim of this study was to assess medium and short-term outcomes in liver transplant patients.

Patients and methods

A retrospective case series was performed at a tertiary referral center. We screened 845 patients who had liver transplant (LT) in our center. All consecutive LT patients with COVID-19 during the Spanish outbreak from March 2020 to April 2021, were included. Demographics, pre-existing comorbidities, clinical and radiological data of COVID-19 infection, complications and liver graft function were assessed at diagnosis and 3-month follow-up.

Results

Overall, 20 LT patients were diagnosed with confirmed COVID-19. We included 16 patients that met the inclusion criteria, 8 nonhospitalised (50%) and 8 (50%) hospitalised patients were analyzed. The median follow-up was 5.33 months (IQR 3.06-8.26). One patient died during the follow-up. All patients presented some grade of respiratory or functional symptoms. Dyspnoea and fatigue were the most prevalent symptoms during the 3-months follow-up. No Liver graft dysfunction were reported despite of partial immunosuppression withdrawal in 4 patients (25%). One patient had cardiovascular complications.

Conclusions

Our results suggest the presence of post-COVID-19 syndrome with mild residual physical and psychological dysfunction in this subgroup of patients at 3-month after COVID-19. However, no cases of loss or liver graft dysfunction were reported.
2021-05-31 2021 other Case Reports; case-report abstract-available 10.1016/j.jceh.2021.05.009 COVID-19 and short and medium-term outcomes in liver transplant patients: A spanish single-center case series. Tejedor-Tejada J, Fuentes-Valenzuela E, Alonso-Martin C, Almohalla-Alvarez C, Garcia-Pajares F. J Clin Exp Hepatol. 2021;
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;
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
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;
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)
SARS-CoV-2 identified by transmission electron microscopy in lymphoproliferative and ischaemic intestinal lesions of COVID-19 patients with acute abdominal pain: two case reports.
Martin-Cardona A, Lloreta Trull J, Albero-González R, Paraira Beser M, [...], Esteve M.
BMC Gastroenterol. 2021; 21 (1)
DOI: 10.1186/s12876-021-01905-3

Background

SARS-CoV-2 may produce intestinal symptoms that are generally mild, with a small percentage of patients developing more severe symptoms. The involvement of SARS-CoV-2 in the physiopathology of bowel damage is poorly known. Transmission electron microscopy (TEM) is a useful tool that provides an understanding of SARS-CoV-2 invasiveness, replication and dissemination in body cells but information outside the respiratory tract is very limited. We report two cases of severe intestinal complications (intestinal lymphoma and ischaemic colitis) in which the presence of SARS-CoV-2 in intestinal tissue was confirmed by TEM. These are the first two cases reported in the literature of persistence of SARS-CoV-2 demonstrated by TEM in intestinal tissue after COVID 19 recovery and SARS-CoV-2 nasopharyngeal clearance.

Case presentation

During the first pandemic peak (1st March-30th April 2020) 932 patients were admitted in Hospital Universitari Mútua Terrassa due to COVID-19, 41 (4.4%) required cross-sectional imaging techniques to assess severe abdominal pain and six of them (0.64%) required surgical resection. SARS-CoV-2 in bowel tissue was demonstrated by TEM in two of these patients. The first case presented as an ileocaecal inflammatory mass which turned to be a B-cell lymphoma. Viral particles were found in the cytoplasm of endothelial cells of damaged mucosa. In situ hybridization was negative in tumour cells, thus ruling out an oncogenic role for the virus. SARS-CoV-2 remained in intestinal tissue 6 months after nasopharyngeal clearance, suggesting latent infection. The second patient had a severe ischaemic colitis with perforation and SARS-CoV-2 was also identified in endothelial cells.

Conclusions

Severe intestinal complications associated with COVID-19 are uncommon. SARS-CoV-2 was identified by TEM in two cases, suggesting a causal role in bowel damage.
2021-08-26 2021 other Journal Article; Case Reports; case-report abstract-available 10.1186/s12876-021-01905-3 SARS-CoV-2 identified by transmission electron microscopy in lymphoproliferative and ischaemic intestinal lesions of COVID-19 patients with acute abdominal pain: two case reports. Martin-Cardona A, Lloreta Trull J, Albero-González R, Paraira Beser M, Andújar X, Ruiz-Ramirez P, Tur-Martínez J, Ferrer C, De Marcos Izquierdo JA, Pérez-Madrigal A, Goiburú González L, Espinós Perez J, Esteve M. BMC Gastroenterol. 2021; 21 (1)
Infrared Based Saliva Screening Test for COVID-19.
Wood BR, Kochan K, Bedolla DE, Salazar-Quiroz N, [...], Heraud P.
Angew Chem Int Ed Engl. 2021; 60 (31)
DOI: 10.1002/anie.202104453
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented need for diagnostic testing that is critical in controlling the spread of COVID-19. We propose a portable infrared spectrometer with purpose-built transflection accessory for rapid point-of-care detection of COVID-19 markers in saliva. Initially, purified virion particles were characterized with Raman spectroscopy, synchrotron infrared (IR) and AFM-IR. A data set comprising 171 transflection infrared spectra from 29 subjects testing positive for SARS-CoV-2 by RT-qPCR and 28 testing negative, was modeled using Monte Carlo Double Cross Validation with 50 randomized test and model sets. The testing sensitivity was 93 % (27/29) with a specificity of 82 % (23/28) that included positive samples on the limit of detection for RT-qPCR. Herein, we demonstrate a proof-of-concept high throughput infrared COVID-19 test that is rapid, inexpensive, portable and utilizes sample self-collection thus minimizing the risk to healthcare workers and ideally suited to mass screening.
2021-06-29 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1002/anie.202104453 Infrared Based Saliva Screening Test for COVID-19. Wood BR, Kochan K, Bedolla DE, Salazar-Quiroz N, Grimley SL, Perez-Guaita D, Baker MJ, Vongsvivut J, Tobin MJ, Bambery KR, Christensen D, Pasricha S, Eden AK, Mclean A, Roy S, Roberts JA, Druce J, Williamson DA, McAuley J, Catton M, Purcell DFJ, Godfrey DI, Heraud P. Angew Chem Int Ed Engl. 2021; 60 (31)
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
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)
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
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)
Serological evidence of SARS-CoV-2 and co-infections in stray cats in Spain.
Villanueva-Saz S, Giner J, Tobajas AP, Pérez MD, [...], Fernández A.
Transbound Emerg Dis. 2021;
DOI: 10.1111/tbed.14062
A new coronavirus known as SARS-CoV-2 emerged in Wuhan in 2019 and spread rapidly to the rest of the world causing the pandemic disease named coronavirus disease of 2019 (COVID-19). Little information is known about the impact this virus can cause upon domestic and stray animals. The potential impact of SARS-CoV-2 has become of great interest in cats due to transmission among domestic cats and the severe phenotypes described recently in a domestic cat. In this context, there is a public health warning that needs to be investigated in relation with the epidemiological role of this virus in stray cats. Consequently, in order to know the impact of the possible transmission chain, blood samples were obtained from 114 stray cats in the city of Zaragoza (Spain) and tested for SARS-CoV-2 and other selected pathogens susceptible to immunosuppression including Toxoplasma gondii, Leishmania infantum, feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) from January to October 2020. Four cats (3.51%), based on enzyme-linked immunosorbent assay (ELISA) using the receptor binding domain (RBD) of Spike antigen, were seroreactive to SARS-CoV-2. T. gondii, L. infantum, FeLV and FIV seroprevalence was 12.28%, 16.67%, 4.39% and 19.30%, respectively. Among seropositive cats to SARS-CoV-2, three cats were also seropositive to other pathogens including antibodies detected against T. gondii and FIV (n = 1); T. gondii (n = 1); and FIV and L. infantum (n = 1). The subjects giving positive for SARS-CoV-2 were captured in urban areas of the city in different months: January 2020 (2/4), February 2020 (1/4) and July 2020 (1/4). This study revealed, for the first time, the exposure of stray cats to SARS-CoV-2 in Spain and the existence of concomitant infections with other pathogens including T. gondii, L. infantum and FIV, suggesting that immunosuppressed animals might be especially susceptible to SARS-CoV-2 infection.
2021-03-09 2021 other research-article; Journal Article abstract-available 10.1111/tbed.14062 Serological evidence of SARS-CoV-2 and co-infections in stray cats in Spain. Villanueva-Saz S, Giner J, Tobajas AP, Pérez MD, González-Ramírez AM, Macías-León J, González A, Verde M, Yzuel A, Hurtado-Guerrero R, Pardo J, Santiago L, Paño-Pardo JR, Ruíz H, Lacasta DM, Sánchez L, Marteles D, Gracia AP, Fernández A. Transbound Emerg Dis. 2021;
Importance of Lung Ultrasound Follow-Up in Patients Who Had Recovered from Coronavirus Disease 2019: Results from a Prospective Study.
Hernández-Píriz A, Tung-Chen Y, Jiménez-Virumbrales D, Ayala-Larrañaga I, [...], Casasola-Sánchez GG.
J Clin Med. 2021; 10 (14)
DOI: 10.3390/jcm10143196
There is growing evidence regarding the imaging findings of coronavirus disease 2019 (COVID-19) in lung ultrasounds, however, their role in predicting the prognosis has yet to be explored. Our objective was to assess the usefulness of lung ultrasound in the short-term follow-up (1 and 3 months) of patients with SARS-CoV-2 pneumonia, and to describe the progression of the most relevant lung ultrasound findings. We conducted a prospective, longitudinal and observational study performed in patients with confirmed COVID-19 who underwent a lung ultrasound examination during hospitalization and repeated it 1 and 3 months after hospital discharge. A total of 96 patients were enrolled. In the initial ultrasound, bilateral involvement was present in 100% of the patients with mild, moderate or severe ARDS. The most affected lung area was the posteroinferior (93.8%) followed by the lateral (88.7%). Subpleural consolidations were present in 68% of the patients and consolidations larger than 1 cm in 24%. One month after the initial study, only 20.8% had complete resolution on lung ultrasound. This percentage rose to 68.7% at 3 months. Residual lesions were observed in a significant percentage of patients who recovered from moderate or severe ARDS (32.4% and 61.5%, respectively). In conclusion, lung injury associated with COVID-19 might take time to resolve. The findings in this report support the use of lung ultrasound in the short-term follow-up of patients recovered from COVID-19, as a radiation-sparing, easy to use, novel care path worth exploring.
2021-07-20 2021 other research-article; Journal Article abstract-available 10.3390/jcm10143196 Importance of Lung Ultrasound Follow-Up in Patients Who Had Recovered from Coronavirus Disease 2019: Results from a Prospective Study. Hernández-Píriz A, Tung-Chen Y, Jiménez-Virumbrales D, Ayala-Larrañaga I, Barba-Martín R, Canora-Lebrato J, Zapatero-Gaviria A, Casasola-Sánchez GG. J Clin Med. 2021; 10 (14)
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)
Evaluation of silver nanoparticles for the prevention of SARS-CoV-2 infection in health workers: In vitro and in vivo.
Almanza-Reyes H, Moreno S, Plascencia-López I, Alvarado-Vera M, [...], Bogdanchikova N.
PLoS One. 2021; 16 (8)
DOI: 10.1371/journal.pone.0256401
SARS-CoV-2 infection in hospital areas is of a particular concern, since the close interaction between health care personnel and patients diagnosed with COVID-19, which allows virus to be easily spread between them and subsequently to their families and communities. Preventing SARS-CoV-2 infection among healthcare personnel is essential to reduce the frequency of infections and outbreaks during the pandemic considering that they work in high-risk areas. In this research, silver nanoparticles (AgNPs) were tested in vitro and shown to have an inhibitory effect on SARS-CoV-2 infection in cultured cells. Subsequently, we assess the effects of mouthwash and nose rinse with ARGOVIT® silver nanoparticles (AgNPs), in the prevention of SARS-CoV-2 contagion in health workers consider as high-risk group of acquiring the infection in the General Tijuana Hospital, Mexico, a hospital for the exclusive recruitment of patients diagnosed with COVID-19. We present a prospective randomized study of 231 participants that was carried out for 9 weeks (during the declaration of a pandemic). The "experimental" group was instructed to do mouthwash and nose rinse with the AgNPs solution; the "control" group was instructed to do mouthwashes and nose rinse in a conventional way. The incidence of SARS-CoV-2 infection was significantly lower in the "experimental" group (two participants of 114, 1.8%) compared to the "control" group (thirty-three participants of 117, 28.2%), with an 84.8% efficiency. We conclude that the mouth and nasal rinse with AgNPs helps in the prevention of SARS-CoV-2 infection in health personnel who are exposed to patients diagnosed with COVID-19.
2021-08-19 2021 other Clinical Trial; Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1371/journal.pone.0256401 Evaluation of silver nanoparticles for the prevention of SARS-CoV-2 infection in health workers: In vitro and in vivo. Almanza-Reyes H, Moreno S, Plascencia-López I, Alvarado-Vera M, Patrón-Romero L, Borrego B, Reyes-Escamilla A, Valencia-Manzo D, Brun A, Pestryakov A, Bogdanchikova N. PLoS One. 2021; 16 (8)
Atrial fibrillation in patients with SARS-CoV-2 infection.
García-Granja PE, Veras C, Aparisi Á, Amat-Santos IJ, [...], San Román JA.
Med Clin (Engl Ed). 2021; 157 (2)
DOI: 10.1016/j.medcle.2021.01.010

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 39.9 mm, 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 > 1.5 mg/dL at admission, LDH > 250 UI/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.
2021-07-19 2021 other research-article; Journal Article abstract-available 10.1016/j.medcle.2021.01.010 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 (Engl Ed). 2021; 157 (2)
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)
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)
Prevalence of and factors associated with COVID-19 diagnosis in symptomatic patients followed in general practices in Germany between March 2020 and March 2021.
Jacob L, Koyanagi A, Smith L, Haro JM, [...], Kostev K.
Int J Infect Dis. 2021; 111
DOI: 10.1016/j.ijid.2021.08.010

Aims

This study aimed to investigate the prevalence of and the factors associated with the diagnosis of coronavirus disease 2019 (COVID-19) in symptomatic patients followed in general practices in Germany between March 2020 and March 2021.

Methods

Symptomatic patients tested for COVID-19 and followed in one of 962 general practices in Germany from March 2020 to March 2021 were included in this study. Covariates included sex, age, and comorbidities present in at least 3% of the population. The association between these factors and the diagnosis of COVID-19 was analyzed using an adjusted logistic regression model.

Results

A total of 301,290 patients tested for COVID-19 were included in this study (54.7% women; mean [SD] age 44.6 [18.5] years). The prevalence of COVID-19 was 13.8% in this sample. Male sex and older age were positively and significantly associated with COVID-19. In terms of comorbidities, the strongest positive associations with COVID-19 were observed for cardiac arrhythmias, depression, and obesity. There was also a negative relationship between the odds of being diagnosed with COVID-19 and several conditions such as chronic sinusitis, asthma, and anxiety disorders.

Conclusions

Approximately 14% of symptomatic patients tested for COVID-19 were diagnosed with COVID-19 in German general practices from March 2020 to March 2021.
2021-08-09 2021 other research-article; Journal Article abstract-available 10.1016/j.ijid.2021.08.010 Prevalence of and factors associated with COVID-19 diagnosis in symptomatic patients followed in general practices in Germany between March 2020 and March 2021. Jacob L, Koyanagi A, Smith L, Haro JM, Rohe AM, Kostev K. Int J Infect Dis. 2021; 111
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)
In Silico and In Vitro Analyses Validate Human MicroRNAs Targeting the SARS-CoV-2 3'-UTR.
Barreda-Manso MA, Nieto-Díaz M, Soto A, Muñoz-Galdeano T, [...], Maza RM.
Int J Mol Sci. 2021; 22 (11)
DOI: 10.3390/ijms22116094
COVID-19 pandemic is caused by betacoronavirus SARS-CoV-2. The genome of this virus is composed of a single strand of RNA with 5' and 3'-UTR flanking a region of protein-coding ORFs closely resembling cells' mRNAs. MicroRNAs are endogenous post-transcriptional regulators that target mRNA to modulate protein expression and mediate cellular functions, including antiviral defense. In the present study, we carried out a bioinformatics screening to search for endogenous human microRNAs targeting the 3'-UTR of SARS-CoV-2. Results from the computational techniques allowed us to identify 10 potential candidates. The capacity of 3 of them, together with hsa-miR-138-5p, to target the SARS-CoV-2 3'-UTR was validated in vitro by gene reporter assays. Available information indicates that two of these microRNAs, namely, hsa-miR-3941 and hsa-miR-138-5p, combine effective targeting of SARS-CoV-2 genome with complementary antiviral or protective effects in the host cells that make them potential candidates for therapeutic treatment of most, if not all, COVID-19 variants known to date. All information obtained while conducting the present analysis is available at Open Science Framework repository.
2021-06-05 2021 other research-article; Journal Article abstract-available 10.3390/ijms22116094 In Silico and In Vitro Analyses Validate Human MicroRNAs Targeting the SARS-CoV-2 3'-UTR. Barreda-Manso MA, Nieto-Díaz M, Soto A, Muñoz-Galdeano T, Reigada D, Maza RM. Int J Mol Sci. 2021; 22 (11)
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)
Mathematical Model of SARS-Cov-2 Propagation Versus ACE2 Fits COVID-19 Lethality Across Age and Sex and Predicts That of SARS.
Bastolla U.
Front Mol Biosci. 2021; 8
DOI: 10.3389/fmolb.2021.706122
The fatality rate of Covid-19 escalates with age and is larger in men than women. I show that these variations correlate strongly with the level of the viral receptor protein ACE2 in rat lungs, which is consistent with the still limited data on human ACE2. Surprisingly, lower receptor levels correlate with higher fatality. I propose two possible explanations of this negative correlation: First, a previous mathematical model predicts that the velocity of viral progression in the organism as a function of the receptor level has a maximum and declines for abundant receptor. Secondly, degradation of ACE2 by the virus may cause the runaway inflammatory response that characterizes severe CoViD-19. I present here a mathematical model that predicts the lethality as a function of ACE2 protein level based on the two above hypothesis. The model fits Covid-19 fatality rate across age and sex in three countries with high accuracy ( r2>0.9 ) under the hypothesis that the speed of viral progression in the infected organism is a decreasing function of the ACE2 level. Moreover, rescaling the fitted parameters by the ratio of the binding rates of the spike proteins of SARS-CoV and SARS-CoV-2 allows predicting the fatality rate of SARS-CoV across age and sex, thus linking the molecular and epidemiological levels.
2021-07-12 2021 other research-article; Journal Article abstract-available 10.3389/fmolb.2021.706122 Mathematical Model of SARS-Cov-2 Propagation Versus ACE2 Fits COVID-19 Lethality Across Age and Sex and Predicts That of SARS. Bastolla U. Front Mol Biosci. 2021; 8
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)
Intravenous immunoglobulins for the treatment of the hyper-inflammatory response in COVID-19. Another failure of immunomodulatory therapy?
López-Medrano F, Aguado JM.
Clin Microbiol Infect. 2021;
DOI: 10.1016/j.cmi.2021.07.012
2021-07-26 2021 other discussion; Journal Article 10.1016/j.cmi.2021.07.012 Intravenous immunoglobulins for the treatment of the hyper-inflammatory response in COVID-19. Another failure of immunomodulatory therapy? López-Medrano F, Aguado JM. Clin Microbiol Infect. 2021;
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)
Clinical utility of novel biosensing platform: Diagnosis of coronavirus SARS-CoV-2 at point of care.
Aljabali AAA, Pal K, Serrano-Aroca A, Takayama K, [...], Tambuwala MM.
Mater Lett. 2021; 304
DOI: 10.1016/j.matlet.2021.130612
Early detection is the first step in the fight against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, an efficient, rapid, selective, specific, and inexpensive SARS-CoV-2 diagnostic method is the need of the hour. The reverse transcription-polymerase chain reaction (RT-PCR) technology is massively utilized to detect infection with SARS-CoV-2. However, scientists continue to strive to create enhanced technology while continually developing nanomaterial-enabled biosensing methods that can provide new methodologies, potentially fulfilling the present demand for rapid and early identification of coronavirus disease 2019 (COVID-19) patients. Our review presents a summary of the recent diagnosis of SARS-CoV-2 of COVID-19 pandemic and nanomaterial-available biosensing methods. Although limited research on nanomaterials-based nanosensors has been published, allowing for biosensing approaches for diagnosing SARS-CoV-2, this study highlights nanomaterials that provide an enhanced biosensing strategy and potential processes that lead to COVID-19 diagnosis.
2021-08-06 2021 other brief-report; Journal Article abstract-available 10.1016/j.matlet.2021.130612 Clinical utility of novel biosensing platform: Diagnosis of coronavirus SARS-CoV-2 at point of care. Aljabali AAA, Pal K, Serrano-Aroca A, Takayama K, Dua K, Tambuwala MM. Mater Lett. 2021; 304
A case study of 2019-nCOV cases in Argentina with the real data based on daily cases from March 03, 2020 to March 29, 2021 using classical and fractional derivatives.
Kumar P, Erturk VS, Murillo-Arcila M, Banerjee R, [...], Manickam A.
Adv Differ Equ. 2021; 2021 (1)
DOI: 10.1186/s13662-021-03499-2
In this study, our aim is to explore the dynamics of COVID-19 or 2019-nCOV in Argentina considering the parameter values based on the real data of this virus from March 03, 2020 to March 29, 2021 which is a data range of more than one complete year. We propose a Atangana-Baleanu type fractional-order model and simulate it by using predictor-corrector (P-C) method. First we introduce the biological nature of this virus in theoretical way and then formulate a mathematical model to define its dynamics. We use a well-known effective optimization scheme based on the renowned trust-region-reflective (TRR) method to perform the model calibration. We have plotted the real cases of COVID-19 and compared our integer-order model with the simulated data along with the calculation of basic reproductive number. Concerning fractional-order simulations, first we prove the existence and uniqueness of solution and then write the solution along with the stability of the given P-C method. A number of graphs at various fractional-order values are simulated to predict the future dynamics of the virus in Argentina which is the main contribution of this paper.
2021-07-20 2021 other research-article; Journal Article abstract-available 10.1186/s13662-021-03499-2 A case study of 2019-nCOV cases in Argentina with the real data based on daily cases from March 03, 2020 to March 29, 2021 using classical and fractional derivatives. Kumar P, Erturk VS, Murillo-Arcila M, Banerjee R, Manickam A. Adv Differ Equ. 2021; 2021 (1)
Plant-Based Phytochemical Screening by Targeting Main Protease of SARS-CoV-2 to Design Effective Potent Inhibitors.
Mahmud S, Biswas S, Paul GK, Mita MA, [...], Simal-Gandara J.
Biology (Basel). 2021; 10 (7)
DOI: 10.3390/biology10070589
Currently, a worldwide pandemic has been declared in response to the spread of coronavirus disease 2019 (COVID-19), a fatal and fast-spreading viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The low availability of efficient vaccines and treatment options has resulted in a high mortality rate, bringing the world economy to its knees. Thus, mechanistic investigations of drugs capable of counteracting this disease are in high demand. The main protease (Mpro) expressed by SARS-CoV-2 has been targeted for the development of potential drug candidates due to the crucial role played by Mpro in viral replication and transcription. We generated a phytochemical library containing 1672 phytochemicals derived from 56 plants, which have been reported as having antiviral, antibacterial, and antifungal activity. A molecular docking program was used to screen the top three candidate compounds: epicatechin-3-O-gallate, psi-taraxasterol, and catechin gallate, which had respective binding affinities of -8.4, -8.5, and -8.8 kcal/mol. Several active sites in the targeted protein, including Cys145, His41, Met49, Glu66, and Met165, were found to interact with the top three candidate compounds. The multiple simulation profile, root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and solvent-accessible surface area values supported the inflexible nature of the docked protein-compound complexes. The toxicity and carcinogenicity profiles were assessed, which showed that epicatechin-3-O-gallate, psi-taraxasterol, and catechin gallate had favorable pharmacological properties with no adverse effects. These findings suggest that these compounds could be developed as part of an effective drug development pathway to treat COVID-19.
2021-06-26 2021 other research-article; Journal Article abstract-available 10.3390/biology10070589 Plant-Based Phytochemical Screening by Targeting Main Protease of SARS-CoV-2 to Design Effective Potent Inhibitors. Mahmud S, Biswas S, Paul GK, Mita MA, Promi MM, Afrose S, Hasan MR, Zaman S, Uddin MS, Dhama K, Emran TB, Saleh MA, Simal-Gandara J. Biology (Basel). 2021; 10 (7)
Obesity - A Risk Factor for Psoriasis and COVID-19.
Llamas-Velasco M, Ovejero-Merino E, Salgado-Boquete L.
Actas Dermosifiliogr. 2021; 112 (6)
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; 112 (6)
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Setting-specific Transmission Rates: A Systematic Review and Meta-analysis.
Thompson HA, Mousa A, Dighe A, Fu H, [...], Ferguson NM.
Clin Infect Dis. 2021; 73 (3)
DOI: 10.1093/cid/ciab100

Background

Understanding the drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is crucial for control policies, but evidence of transmission rates in different settings remains limited.

Methods

We conducted a systematic review to estimate secondary attack rates (SARs) and observed reproduction numbers (Robs) in different settings exploring differences by age, symptom status, and duration of exposure. To account for additional study heterogeneity, we employed a beta-binomial model to pool SARs across studies and a negative-binomial model to estimate Robs.

Results

Households showed the highest transmission rates, with a pooled SAR of 21.1% (95% confidence interval [CI]:17.4-24.8). SARs were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of ≤5 days. SARs related to contacts at social events with family and friends were higher than those for low-risk casual contacts (5.9% vs 1.2%). Estimates of SARs and Robs for asymptomatic index cases were approximately one-seventh, and for presymptomatic two-thirds of those for symptomatic index cases. We found some evidence for reduced transmission potential both from and to individuals younger than 20 years of age in the household context, which is more limited when examining all settings.

Conclusions

Our results suggest that exposure in settings with familiar contacts increases SARS-CoV-2 transmission potential. Additionally, the differences observed in transmissibility by index case symptom status and duration of exposure have important implications for control strategies, such as contact tracing, testing, and rapid isolation of cases. There were limited data to explore transmission patterns in workplaces, schools, and care homes, highlighting the need for further research in such settings.
2021-08-01 2021 other Meta-Analysis; Research Support, Non-U.S. Gov't; research-article; Systematic Review; Journal Article abstract-available 10.1093/cid/ciab100 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Setting-specific Transmission Rates: A Systematic Review and Meta-analysis. Thompson HA, Mousa A, Dighe A, Fu H, Arnedo-Pena A, Barrett P, Bellido-Blasco J, Bi Q, Caputi A, Chaw L, De Maria L, Hoffmann M, Mahapure K, Ng K, Raghuram J, Singh G, Soman B, Soriano V, Valent F, Vimercati L, Wee LE, Wong J, Ghani AC, Ferguson NM. Clin Infect Dis. 2021; 73 (3)
Aerosol transmission of human pathogens: From miasmata to modern viral pandemics and their preservation potential in the Anthropocene record
Moreno T, Gibbons W.
Geoscience Frontiers. 2021;
DOI:
Graphical abstract Ongoing uncertainty over the relative importance of aerosol transmission of COVID-19 is in part rooted in the history of medical science and our understanding of how epidemic diseases can spread through human populations. Ancient Greek medical theory held that such illnesses are transmitted by airborne pathogenic emanations containing particulate matter (“miasmata”). Notable Roman and medieval scholars such as Varro, Ibn al-Khatib and Fracastoro developed these ideas, combining them with early germ theory and the concept of contagion. A widely held but vaguely defined belief in toxic miasmatic mists as a dominant causative agent in disease propagation was overtaken by the science of 19th century microbiology and epidemiology, especially in the study of cholera, which was proven to be mainly transmitted by contaminated water. Airborne disease transmission came to be viewed as burdened by a dubious historical reputation and difficult to demonstrate convincingly. A breakthrough came with the classic mid-20th century work of Wells, Riley and Mills who proved how expiratory aerosols (their “droplet nuclei”) could transport still-infectious tuberculosis bacteria through ventilation systems. The topic of aerosol transmission of pathogenic respiratory diseases assumed a new dimension with the mid-late 20th century “Great Acceleration” of an increasingly hypermobile human population repeatedly infected by different strains of zoonotic viruses, and has taken centre stage this century in response to outbreaks of new respiratory infections that include coronaviruses. From a geoscience perspective, the consequences of pandemic-status diseases such as COVID-19, produced by viral pathogens utilising aerosols to infect a human population currently approaching 8 billion, are far-reaching and unprecedented. The obvious and sudden impacts on for example waste plastic production, water and air quality and atmospheric chemistry are accelerating human awareness of current environmental challenges. As such, the “anthropause” lockdown enforced by COVID-19 may come to be seen as a harbinger of change great enough to be preserved in the Anthropocene stratal record.
2021-08-11 2021 other research-article; Journal Article abstract-available Aerosol transmission of human pathogens: From miasmata to modern viral pandemics and their preservation potential in the Anthropocene record Moreno T, Gibbons W. Geoscience Frontiers. 2021;
SARS-CoV-2 Vaccines and the Skin.
Galván-Casas C, Català A, Muñoz-Santos C.
Actas Dermosifiliogr. 2021;
DOI: 10.1016/j.adengl.2021.07.028
Vaccines against the severe acute respiratory coronavirus 2, which are the first to be used in humans against any coronavirus, were developed and produced in record time. Dermatologic adverse effects appeared during clinical trials and have also been described in the population since approval. Just as descriptions and categorization of skin manifestations of the coronavirus disease 2019 proved important for understanding the disease itself, characterizing the effects of vaccines may also further that goal. This paper reviews the properties of the different types of vaccines currently available and under development and describes how they interact with the immune system and the clinical signs they may cause. We focus on dermatologic adverse effects reported to date and recommendations for managing them.
2021-08-28 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.adengl.2021.07.028 SARS-CoV-2 Vaccines and the Skin. Galván-Casas C, Català A, Muñoz-Santos C. Actas Dermosifiliogr. 2021;
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)
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)
Surface contamination with SARS-CoV-2: A systematic review.
Gonçalves J, da Silva PG, Reis L, Nascimento MSJ, [...], Mesquita JR.
Sci Total Environ. 2021; 798
DOI: 10.1016/j.scitotenv.2021.149231
Little is known about contaminated surfaces as a route of transmission for SARS-CoV- 2 and a systematic review is missing and urgently needed to provide guidelines for future research studies. As such, the aim of the present study was to review the current scientific knowledge and to summarize the existing studies in which SARS-CoV-2 has been detected in inanimate surfaces. This systematic review includes studies since the emergence of SARS-CoV-2, available in PubMed/MEDLINE and Scopus. Duplicate publications were removed, and exclusion criteria was applied to eliminate unrelated studies, resulting in 37 eligible publications. The present study provides the first overview of SARS-CoV-2 detection in surfaces. The highest detection rates occurred in hospitals and healthcare facilities with COVID-19 patients. Contamination with SARS-CoV-2 on surfaces was detected in a wide range of facilities and surfaces. There is a lack of studies performing viability testing for SARS-CoV-2 recovered from surfaces, and consequently it is not yet possible to assess the potential for transmission via surfaces.
2021-07-24 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.scitotenv.2021.149231 Surface contamination with SARS-CoV-2: A systematic review. Gonçalves J, da Silva PG, Reis L, Nascimento MSJ, Koritnik T, Paragi M, Mesquita JR. Sci Total Environ. 2021; 798
Severe Epistaxis after Tissue Plasminogen Activator administration for Acute Ischemic Stroke in SARS-COV-2 Infection.
Khandelwal P, Martínez-Pías E, Bach I, Prakash T, [...], Arenillas JF.
Brain Circ. 2021; 7 (2)
DOI: 10.4103/bc.bc_17_21
Patients with COVID-19 may suffer from hemorrhagic complications. Our article highlights two cases of COVID-19-infected patients, who suffered severe epistaxis after initiation of intravenous recombinant tissue plasminogen activator (IV-rtPA) for acute ischemic stroke, followed by a sudden decline in their clinical status and ultimately leading to death within days. Given the global impact and mortality of COVID-19, it is essential to be aware of its unusual presentation and improve therapeutic strategies. We present two cases of individuals who suffered from a large vessel occlusion of and were candidates for both IV-rtPA and mechanical thrombectomy. They received IV-rtPA but had epistaxis so severe that they were not able to receive MT and died within the next few days. There are many potential mechanisms by which epistaxis can happen in an individual with COVID-19 who received IV-rtPA including invasion of the nasal mucosa and endothelium through angiotensin-converting enzyme 2 receptors by the virus. We also hypothesize that the coagulation abnormality seen in COVID-19 patients can be potentiated by the use of treatments such as IV-rtPA. We review these issues with a diagram illustrating the possible mechanisms.
2021-04-01 2021 other Case Reports; case-report abstract-available 10.4103/bc.bc_17_21 Severe Epistaxis after Tissue Plasminogen Activator administration for Acute Ischemic Stroke in SARS-COV-2 Infection. Khandelwal P, Martínez-Pías E, Bach I, Prakash T, Hillen ME, Martínez-Galdámez M, Arenillas JF. Brain Circ. 2021; 7 (2)
Impact of COVID-19 in Liver Disease Progression.
Martinez MA, Franco S.
Hepatol Commun. 2021; 5 (7)
DOI: 10.1002/hep4.1745
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus disease 19 (COVID-19), which has infected millions of people worldwide in only a few months. A minority, but significant number, of infected individuals require hospitalization and intensive care. From the start of this new virus pandemic, it was apparent that obese and/or diabetic individuals had a bad prognosis for COVID-19 progression, strongly suggesting an association between liver disease and severe COVID-19. Because chronic liver disease (CLD) is associated with immune dysregulation and inflammation, it is unsurprising that patients with CLD may carry a greater risk of adverse outcomes following SARS-CoV-2 infection. Initial COVID-19 data have also indicated that healthy infected individuals display abnormal liver function tests, suggesting a possible direct implication of SARS-CoV-2 in liver damage. Here we show that COVID-19 affects the liver metabolism and increases the morbidity and mortality of individuals with underlying CLD.
2021-05-31 2021 other review-article; Review; Journal Article abstract-available 10.1002/hep4.1745 Impact of COVID-19 in Liver Disease Progression. Martinez MA, Franco S. Hepatol Commun. 2021; 5 (7)
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)
Rapid antigen tests for the detection of SARS-CoV-2: A narrative review.
Aguilar-Shea AL, Vera-García M, Güerri-Fernández R.
Aten Primaria. 2021; 53 (9)
DOI: 10.1016/j.aprim.2021.102127
The rapid identificationand isolation of COVID-19 patients has become the cornerstone for the control of the recent outbreak. Real-time quantitative polymerase chain reaction is routinely used to confirm COVID-19 diagnosis and is considered the gold standard due to high sensitivity and specificity. Nevertheless, it usually takes several days and a relatively higher cost. Antigen tests based have emerged to cope with such disadvantages, by offering rapid results, an easy-to-use procedure, and low costs. The objective of the narrative review was to provide up-to-date data about CE-marked rapid antigen tests (RATs) for COVID-19. Given their large number, the study only focused on representative and widely used in Spain (Standard Q, Nadal, Panbio, CerTest, and Wondfo). RATs have become a very useful and validated tool for controlling the spread of COVID-19 allowing the rapid identification of active infection and isolation of positive patients. The present revision of the literature has demonstrated that sensitivity and specificity of all available RATs in Spain are high and accomplish European regulations and WHO recommendations.
2021-05-28 2021 other research-article; Journal Article abstract-available 10.1016/j.aprim.2021.102127 Rapid antigen tests for the detection of SARS-CoV-2: A narrative review. Aguilar-Shea AL, Vera-García M, Güerri-Fernández R. Aten Primaria. 2021; 53 (9)
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
Optic Nerve Head Vessel Density Assessment in Recovered COVID-19 Patients: A Prospective Study Using Optical Coherence Tomography Angiography.
Burgos-Blasco B, Güemes-Villahoz N, Vidal-Villegas B, Garcia-Feijoo J, [...], Mendez-Hernandez CD.
J Glaucoma. 2021; 30 (8)
DOI: 10.1097/ijg.0000000000001858

Precis

Vascular diseases have been linked to alterations in optic nerve head perfusion.

Purpose

The main objective was to investigate the changes in peripapillary vessel density (VD) in post coronavirus disease (COVID-19) patients.

Methods

In this prospective pilot exploratory study, patients with COVID-19 that were attended in the Emergency Department of Hospital Clinico San Carlos (Madrid) were included. All patients underwent optic nerve head optical coherence tomography angiography using the Cirrus HD-OCT 500 with AngioPlex OCTA (Zeiss, Dublin, CA) 4 and 12 weeks after diagnosis by positive reverse transcriptase-polymerase chain reaction test from nasopharyngeal swab at the Emergency Department. Sociodemographic data, medical history, disease severity, and laboratory work-up were collected.

Results

One hundred and eighty eyes of 90 patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection were included. None of the patients reported visual changes. Severe patients were older, more frequently hispanic, dyslipidemic, and presented lower lymphocytes counts, as well as increased ferritin, D-dimer, fibrinogen, and international normalized ratio levels. No changes in optic nerve head vascularization were observed when both visits were compared. No correlation was found between VD and clinical parameters, disease severity and laboratory work-up.

Conclusions

Changes to peripapillary VD were not observed in patients with COVID-19 in the early months following diagnosis.
2021-08-01 2021 other research-article; Journal Article abstract-available 10.1097/ijg.0000000000001858 Optic Nerve Head Vessel Density Assessment in Recovered COVID-19 Patients: A Prospective Study Using Optical Coherence Tomography Angiography. Burgos-Blasco B, Güemes-Villahoz N, Vidal-Villegas B, Garcia-Feijoo J, Donate-Lopez J, Martin-Sanchez FJ, Gonzalez-Armengol JJ, Mendez-Hernandez CD. J Glaucoma. 2021; 30 (8)
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;
Optimization and Clinical Evaluation of a Multi-Target Loop-Mediated Isothermal Amplification Assay for the Detection of SARS-CoV-2 in Nasopharyngeal Samples.
Roumani F, Azinheiro S, Sousa H, Sousa A, [...], Garrido-Maestu A.
Viruses. 2021; 13 (5)
DOI: 10.3390/v13050940
SARS-CoV-2 is the coronavirus responsible for COVID-19, which has spread worldwide, affecting more than 200 countries, infecting over 140 million people in one year. The gold standard to identify infected people is RT-qPCR, which is highly sensitive, but needs specialized equipment and trained personnel. The demand for these reagents has caused shortages in certain countries. Isothermal nucleic acid techniques, such as loop-mediated isothermal amplification (LAMP) have emerged as an alternative or as a complement to RT-qPCR. In this study, we developed and evaluated a multi-target RT-LAMP for the detection of SARS-CoV-2. The method was evaluated against an RT-qPCR in 152 clinical nasopharyngeal swab samples. The results obtained indicated that both assays presented a "good concordance" (Cohen's k of 0.69), the RT-LAMP was highly specific (99%) but had lower sensitivity compared to the gold standard (63.3%). The calculated low sensitivity was associated with samples with very low viral load (RT-qPCR Cq values higher than 35) which may be associated with non-infectious individuals. If an internal Cq threshold below 35 was set, the sensitivity and Cohen's k increased to 90.9% and 0.92, respectively. The interpretation of the Cohen's k for this was "very good concordance". The RT-LAMP is an attractive approach for frequent individual testing in decentralized setups.
2021-05-19 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13050940 Optimization and Clinical Evaluation of a Multi-Target Loop-Mediated Isothermal Amplification Assay for the Detection of SARS-CoV-2 in Nasopharyngeal Samples. Roumani F, Azinheiro S, Sousa H, Sousa A, Timóteo M, Varandas T, Fonseca-Silva D, Baldaque I, Carvalho J, Prado M, Garrido-Maestu A. Viruses. 2021; 13 (5)
Cardiac magnetic resonance in recovering COVID-19 patients. Feature tracking and mapping analysis to detect persistent myocardial involvement.
Urmeneta Ulloa J, Martínez de Vega V, Salvador Montañés O, Álvarez Vázquez A, [...], Ángel Cabrera J.
Int J Cardiol Heart Vasc. 2021; 36
DOI: 10.1016/j.ijcha.2021.100854

Background

Post-COVID-19 patients may incur myocardial involvement secondary to systemic inflammation. Our aim was to detect possible oedema/diffuse fibrosis using cardiac magnetic resonance imaging (CMR) mapping and to study myocardial deformation of the left ventricle (LV) using feature tracking (FT).

Methods

Prospective analysis of consecutively recruited post-COVID-19 patients undergoing CMR. T1 and T2 mapping sequences were acquired and FT analysis was performed using 2D steady-state free precession cine sequences. Statistical significance was set to p < 0.05.

Results

Included were 57 post-COVID-19 patients and 20 healthy controls, mean age 59 ± 15 years, men 80.7%. The most frequent risk factors were hypertension (33.3%) and dyslipidaemia (36.8%). The contact-to-CMR interval was 81 ± 27 days. LV ejection fraction (LVEF) was 61 ± 10%. Late gadolinium enhancement (LGE) was evident in 26.3% of patients (19.3%, non-ischaemic). T2 mapping values (suggestive of oedema) were higher in the study patients than in the controls (50.9 ± 4.3 ms vs 48 ± 1.9 ms, p < 0.01). No between-group differences were observed for native T1 nor for circumferential strain (CS) or radial strain (RS) values (18.6 ± 3.3% vs 19.2 ± 2.1% (p = 0.52) and 32.3 ± 8.1% vs 33.6 ± 7.1% (p = 0.9), respectively). A sub-group analysis for the contact-to-CMR interval (<8 weeks vs ≥ 8 weeks) showed that FT-CS (15.6 ± 2.2% vs 18.9 ± 2.6%, p < 0.01) and FT-RS (24.9 ± 5.8 vs 33.5 ± 7.2%, p < 0.01) values were lower for the shorter interval.

Conclusions

Post-COVID-19 patients compared to heathy controls had raised T2 values (related to oedema), but similar native T1, FT-CS and FT-RS values. FT-CS and FT-RS values were lower in post-COVID-19 patients undergoing CMR after < 8 weeks compared to ≥ 8 weeks.
2021-08-03 2021 other research-article; Journal Article abstract-available 10.1016/j.ijcha.2021.100854 Cardiac magnetic resonance in recovering COVID-19 patients. Feature tracking and mapping analysis to detect persistent myocardial involvement. Urmeneta Ulloa J, Martínez de Vega V, Salvador Montañés O, Álvarez Vázquez A, Sánchez-Enrique C, Hernández Jiménez S, Sancho García FD, López Ruiz L, Recio Rodríguez M, Pizarro G, Carnevali Ruiz D, Ángel Cabrera J. Int J Cardiol Heart Vasc. 2021; 36
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
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)
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
The structural basis of accelerated host cell entry by SARS-CoV-2†.
Seyran M, Takayama K, Uversky VN, Lundstrom K, [...], Uhal BD.
FEBS J. 2021; 288 (17)
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.
2020-12-14 2020 other article-commentary; Research Support, Non-U.S. Gov't; 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. 2021; 288 (17)
Vaccinations in Patients Receiving Systemic Drugs for Skin Disorders: What Can We Learn for SARS-Cov-2 Vaccination Strategies?
Speeckaert R, Lambert J, Puig L, Speeckaert M, [...], van Geel N.
Drugs R D. 2021; 21 (3)
DOI: 10.1007/s40268-021-00349-0
Large-scale vaccination strategies are currently being deployed against severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2). Whether systemic medication for skin diseases affects the efficacy of vaccination and whether temporary interruption or extension of the dosing interval is necessary is under debate. Most immunomodulating/immunosuppressive drugs only affect vaccine-induced immune responses to a limited or moderate extent, preserving sufficient immunity in most patients. Mycophenolate mofetil, Janus kinase inhibitors, and rituximab require a more cautious approach, and judicious timing of vaccination might be appropriate in patients receiving these treatments. It should be noted that, for most drugs except methotrexate, data on the length of the interruption period to restore vaccine-induced immune responses to normal levels are either very limited or absent. In these cases, only the drug half-life can be used as a practical guideline. In most patients, systemic medication can be continued through the vaccination process, although case-by-case decisions can be considered.
2021-06-09 2021 other research-article; Review; Journal Article abstract-available 10.1007/s40268-021-00349-0 Vaccinations in Patients Receiving Systemic Drugs for Skin Disorders: What Can We Learn for SARS-Cov-2 Vaccination Strategies? Speeckaert R, Lambert J, Puig L, Speeckaert M, Lapeere H, De Schepper S, van Geel N. Drugs R D. 2021; 21 (3)
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. 2021; 296
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 the 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.
2020-12-06 2020 other Research Support, Non-U.S. Gov't; 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. 2021; 296
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)
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)
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)
Upper respiratory tract SARS-CoV-2 RNA loads in symptomatic and asymptomatic children and adults.
Costa R, Bueno F, Albert E, Torres I, [...], Navarro D.
Clin Microbiol Infect. 2021;
DOI: 10.1016/j.cmi.2021.08.001

Objectives

Studies comparing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA load in the upper respiratory tract (URT) between children and adults-who either presented with coronavirus disease 2019 (COVID-19) or were asymptomatic-have yielded inconsistent results. Here, we conducted a retrospective, single-centre study to address this issue.

Patients and methods

Included were 1184 consecutive subjects (256 children and 928 adults) testing positive for SARS-CoV-2 RNA in nasopharyngeal exudates (NPs); of these, 424 (121 children and 303 adults) had COVID-19 and 760 (135 children and 625 adults) were asymptomatic close contacts of COVID-19 patients. SARS-CoV-2 RNA testing was carried out using the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, MS, USA). The AMPLIRUN® TOTAL SARS-CoV-2 RNA Control (Vircell SA, Granada, Spain) was used for estimating SARS-CoV-2 RNA loads (in copies/mL). SARS-CoV-2 RNA loads at the time of laboratory diagnosis (single specimen/patient) were used for comparison purposes.

Results

Median initial SARS-CoV-2 RNA load was lower (p 0.094) in children (6.98 log10 copies/mL, range 3.0-11.7) than in adults (7.14 log10 copies/mL, range 2.2-13.4) with COVID-19. As for asymptomatic individuals, median SARS-CoV-2 RNA load was comparable (p 0.97) in children (6.20 log10 copies/mL, range 1.8-11.6) and adults (6.48 log10 copies/mL, range 1.9-11.8). Children with COVID-19 symptoms displayed SARS-CoV-2 RNA loads (6.98 log10 copies/mL, range 3.0-11.7) comparable to those of their asymptomatic counterparts (6.20 log10 copies/mL, range 1.8-11.6) (p 0.61). Meanwhile in adults, median SARS-CoV-2 RNA load was significantly higher in symptomatic (7.14 log10 copies/mL, range 2.2-13.4) than in asymptomatic subjects (6.48 log10 copies/mL, range 1.9-11.8) (p < 0.001). Overall, the observed URT SARS-CoV-2 RNA clearance rate was faster in children than in adults.

Conclusions

Based on viral load data at the time of diagnosis, our results suggest that SARS-CoV-2-infected children, with or without COVID-19, may display NP viral loads of comparable magnitude to those found in their adult counterparts. However, children may have shorter viral shedding than adults.
2021-08-09 2021 other research-article; Journal Article abstract-available 10.1016/j.cmi.2021.08.001 Upper respiratory tract SARS-CoV-2 RNA loads in symptomatic and asymptomatic children and adults. Costa R, Bueno F, Albert E, Torres I, Carbonell-Sahuquillo S, Barrés-Fernández A, Sánchez D, Padrón C, Colomina J, Lázaro Carreño MI, Bretón-Martínez JR, Martínez-Costa C, Navarro D. Clin Microbiol Infect. 2021;
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)
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)
Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses.
Ortega N, Ribes M, Vidal M, Rubio R, [...], Dobaño C.
Nat Commun. 2021; 12 (1)
DOI: 10.1038/s41467-021-24979-9
Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
2021-08-06 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41467-021-24979-9 Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses. Ortega N, Ribes M, Vidal M, Rubio R, Aguilar R, Williams S, Barrios D, Alonso S, Hernández-Luis P, Mitchell RA, Jairoce C, Cruz A, Jimenez A, Santano R, Méndez S, Lamoglia M, Rosell N, Llupià A, Puyol L, Chi J, Melero NR, Parras D, Serra P, Pradenas E, Trinité B, Blanco J, Mayor A, Barroso S, Varela P, Vilella A, Trilla A, Santamaria P, Carolis C, Tortajada M, Izquierdo L, Angulo A, Engel P, García-Basteiro AL, Moncunill G, Dobaño C. Nat Commun. 2021; 12 (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
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)
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)
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)
Acute Lung Injury Biomarkers in the Prediction of COVID-19 Severity: Total Thiol, Ferritin and Lactate Dehydrogenase.
Martinez Mesa A, Cabrera César E, Martín-Montañez E, Sanchez Alvarez E, [...], Velasco Garrido JL.
Antioxidants (Basel). 2021; 10 (8)
DOI: 10.3390/antiox10081221
SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in COVID-19 pathogenesis; we therefore conceived a study of the potential discriminative ability of serum biomarkers in patients with ARDS and those with mild to moderate disease (non-ARDS). 60 subjects were enrolled in a single-centre, prospective cohort study of consecutively admitted patients: 29 ARDS/31 non-ARDS. Blood samples were drawn and marker levels analysed by spectrophotometry and immunoassay techniques. C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin were significantly higher in ARDS versus non-ARDS cases at hospital admission. Leukocytes, LDH, ferritin, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were also significantly elevated in ARDS compared to non-ARDS patients during the hospital stay. Total thiol (TT) was found to be significantly lower in ARDS. Conversely, D-dimer, matrix metalloproteinase-9 (MMP-9) and advanced glycosylated end products (AGE) were elevated. Leukocytes, LDH, CRP, ferritin and IL-6 were found to be significantly higher in non-survivors. However, lymphocyte, tumour necrosis factor beta (TGF-β), and TT were lower. In summary, our results support the potential value of TT, ferritin and LDH as prognostic biomarkers for ARDS development in COVID-19 patients, distinguishing non-ARDS from ARDS (AUCs = 0.92; 0.91; 0.89) in a fast and cost-effective manner. These oxidative/inflammatory parameters appear to play an important role in COVID-19 monitoring and can be used in the clinical management of patients.
2021-07-29 2021 other research-article; Journal Article abstract-available 10.3390/antiox10081221 Acute Lung Injury Biomarkers in the Prediction of COVID-19 Severity: Total Thiol, Ferritin and Lactate Dehydrogenase. Martinez Mesa A, Cabrera César E, Martín-Montañez E, Sanchez Alvarez E, Lopez PM, Romero-Zerbo Y, Garcia-Fernandez M, Velasco Garrido JL. Antioxidants (Basel). 2021; 10 (8)
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)
Antiviral Therapeutic Approaches for SARS-CoV-2 Infection: A Systematic Review.
Gil Martínez V, Avedillo Salas A, Santander Ballestín S.
Pharmaceuticals (Basel). 2021; 14 (8)
DOI: 10.3390/ph14080736
Due to the lack of an etiologic treatment for SARS-CoV-2 and the difficulties involved in developing new drugs, some drugs already approved for other diseases or with efficacy against SARS and MERS, have been used in patients with COVID-19. This systematic review aims to summarize evidence on the efficacy and safety of five antivirals applied to patients with COVID-19, that have proven to be effective either in vitro studies or in studies on SARS-CoV and MERS.; An intensive search of different databases (Pub Med, WoS, MEDLINE and Cochrane COVID-19 Study Register) has been carried out until the end of April 2021. This systematic review has been conducted according to the PRISMA statement. From each of the included studies, the characteristics of the intervention and comparison groups, demographic data and results were extracted independently; Remdesivir is well tolerated and helps to accelerate clinical improvement but is ineffective in reducing mortality. Favipiravir is safe and shows promising results regarding symptom resolution but does not improve viral clearance. The use of lopinavir/ritonavir has been associated with an increased risk of gastrointestinal adverse events and it has not proven to be effective. No significant differences were observed between patients treated with ribavirin or umifenovir and their respective control groups; Remdesivir and favipiravir are well tolerated and effective in accelerating clinical improvement. This systematic review does not support the use of lopinavir/ritonavir, ribavirin and umifenovir in hospitalized patients with COVID-19.
2021-07-28 2021 other review-article; Review; Journal Article abstract-available 10.3390/ph14080736 Antiviral Therapeutic Approaches for SARS-CoV-2 Infection: A Systematic Review. Gil Martínez V, Avedillo Salas A, Santander Ballestín S. Pharmaceuticals (Basel). 2021; 14 (8)
Surviving older patients show preserved cellular and humoral immunological memory several months after SARS-CoV-2 infection.
García-Torre A, Bueno-García E, López-Martínez R, Rioseras B, [...], Alonso-Arias R.
J Gerontol A Biol Sci Med Sci. 2021;
DOI: 10.1093/gerona/glab206
Understanding how older people respond to SARS-CoV-2 is critical if we are to confront the COVID-19 pandemic and establish effective vaccination strategies. Immunosenescence reduces the ability to respond to neoantigens and may compromise the life of infected individuals. Here, we analysed the immunological memory to SARS-CoV-2 in 102 recovered patients aged over 60 years several months after the infection had been resolved. Specific memory T lymphocytes against the virus were measured by IFN-γ and granzyme B release by ELISpot; memory B lymphocyte responses were quantified by detection of anti-S IgG1 producer cells by ELISpot and anti-S and anti-N antibodies were determined by ELISA. Memory T lymphocytes were found in peripheral blood of most of the studied donors, more than seven months after the infection in some of them. Fewer patients maintained memory B lymphocytes, but antibodies, mainly anti-S, were highly durable and positively correlated with T responses. More robust humoral responses were found in patients who had more severe symptoms and had been admitted to hospital. We concluded that specific immunity against SARS-CoV-2 is effectively preserved regardless of age, despite the great heterogeneity of their immune responses, and that memory T lymphocytes and anti-S IgG might be more durable than memory B cells and anti-N IgG.
2021-07-12 2021 other research-article; Journal Article abstract-available 10.1093/gerona/glab206 Surviving older patients show preserved cellular and humoral immunological memory several months after SARS-CoV-2 infection. García-Torre A, Bueno-García E, López-Martínez R, Rioseras B, Moro-García MA, Alonso-Alvarez S, Lluna-González A, Sousa-Fernández A, Fernández-Gudin M, Campos-Riopedre L, Castro-Del Cueto C, Pérez-Fernéndez AB, Alonso-Rodríguez A, Menéndez-Peña C, Menéndez-Peña L, García-Arnaldo N, Feito-Díaz E, Fernández-Lorences A, Fraile-Manzano A, Fernández-Iglesias C, Rivera JA, Pérez-Fonseca C, Urdiales-Ruano E, Debán-Fernández M, Mendes-Moreira H, Herrero-Puente P, Alonso-Arias R. J Gerontol A Biol Sci Med Sci. 2021;
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)
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)
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)
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)
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
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
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)
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)
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)
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
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. 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. 2020; 13 (4)
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 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)
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)
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)
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)
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
Association of ABO and Rh blood groups with obstetric outcomes in SARS-CoV-2 infected pregnancies: A prospective study with a multivariate analysis.
Sainz Bueno JA, Cerrillos González L, Abascal-Saiz A, Rodríguez Gallego MV, [...], Spanish Obstetric Emergency Group.
Eur J Obstet Gynecol Reprod Biol. 2021; 264
DOI: 10.1016/j.ejogrb.2021.07.008

Objective

To evaluate the influence of ABO and Rh blood groups on morbidity among SARS-CoV-2 infected pregnancies.

Design

Prospective observational study.

Setting

78 centers of the Spanish Obstetric Emergency Group.

Population

Pregnant women with SARS-CoV-2 tested with polymerase-chain-reaction between 26-February and 5-November 2020. A cohort of 1278 SARS-CoV-2(+) pregnant women was analyzed and a concurrent comparison group of 1453 SARS-COV-2(-) patients was established.

Methods

Data were collected from medical charts. SARS-COV-2(+) was compared with SARS-COV-2(-) for differences in distribution of blood groups. We performed multivariate analysis, controlling for maternal age and ethnicity, to evaluate association of ABO and Rh blood groups with maternal and perinatal outcomes in SARS-CoV-2(+) patients with adjusted odds ratios (aOR) and 95% confidence intervals (CI).

Main outcomes measures

Medical morbidity: Symptomatic COVID-19 and medical complications. Obstetric outcomes: caesarean delivery, preterm deliveries, preterm premature rupture of membranes (PPROM), hemorrhagic events, pre-eclampsia, maternal and neonatal mortality, stillbirth.

Results

Differences were noted between blood types and Rh for age and ethnicity comparing SARS-CoV-2(+) and SARS-CoV-2(-) groups (p < 0.05). Among the SARS-CoV-2(+) cohort, the odds of symptomatic COVID-19 and obstetric hemorrhagic event were higher in Rh+ vs Rh- mothers (aOR 1.48, 95% CI 1.02-2.14, p = 0.037, and aOR 8.72, 95% CI 1.20-63.57, p = 0.033, respectively), and PPROM were higher among blood type A vs non-A mothers (aOR 2.06, 95% CI 1.01-4.18, p = 0.046).

Conclusions

In SARS-CoV-2(+) pregnant women, Rh- status was associated with a lower risk of symptomatic COVID-19, while Rh+ and blood group A were associated with obstetric hemorrhage and PPROM, respectively.
2021-07-07 2021 other research-article; Journal Article; Observational Study abstract-available 10.1016/j.ejogrb.2021.07.008 Association of ABO and Rh blood groups with obstetric outcomes in SARS-CoV-2 infected pregnancies: A prospective study with a multivariate analysis. Sainz Bueno JA, Cerrillos González L, Abascal-Saiz A, Rodríguez Gallego MV, López Pérez R, Fernández Alonso AM, de la Cruz Conty ML, Alonso Saiz R, Molina Oller M, Santamaría Ortiz A, Martínez-Pérez Ó, Spanish Obstetric Emergency Group. Eur J Obstet Gynecol Reprod Biol. 2021; 264
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)
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)
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)
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
A Multicenter Analysis of the Outcome of Cancer Patients with Neutropenia and COVID-19 Optionally Treated with Granulocyte-Colony Stimulating Factor (G-CSF): A Comparative Analysis.
Sereno M, Jimenez-Gordo AM, Baena-Espinar J, Aguado C, [...], Colmenarejo G.
Cancers (Basel). 2021; 13 (16)
DOI: 10.3390/cancers13164205

Background

Approximately 15% of patients infected by SARS-CoV-2 develop a distress syndrome secondary to a host hyperinflammatory response induced by a cytokine storm. Myelosuppression is associated with a higher risk of infections and mortality. There are data to support methods of management for neutropenia and COVID-19. We present a multicenter experience during the first COVID-19 outbreak in neutropenic cancer patients infected by SARS-CoV-2.

Methods

Clinical retrospective data were collected from neutropenic cancer patients with COVID-19. Comorbidities, tumor type, stage, treatment, neutropenia severity, G-CSF, COVID-19 parameters, and mortality were analyzed. A bivariate analysis of the impact on mortality was carried out. Additionally, we performed a multivariable logistic regression to predict respiratory failure and death.

Results

Among the 943 cancer patients screened, 83 patients (11.3%) simultaneously had neutropenia and an infection with COVID-19. The lungs (26%) and breasts (22%) were the primary locations affected, and most patients had advanced disease (67%). In the logistic model, as adjusted covariates, sex, age, treatment (palliative vs. curative), tumor type, and the lowest level of neutrophils were used. A significant effect was obtained for the number of days of G-CSF treatment (OR = 1.4, 95% CI [1,1,03,92], p-value = 0.01).

Conclusions

Our findings suggest that a prolonged G-CSF treatment could be disadvantageous for these cancer patients with infections by COVID-19, with a higher probability of worse outcome.
2021-08-20 2021 other research-article; Journal Article abstract-available 10.3390/cancers13164205 A Multicenter Analysis of the Outcome of Cancer Patients with Neutropenia and COVID-19 Optionally Treated with Granulocyte-Colony Stimulating Factor (G-CSF): A Comparative Analysis. Sereno M, Jimenez-Gordo AM, Baena-Espinar J, Aguado C, Mielgo X, Pertejo A, Álvarez-Álvarez R, Sánchez A, López JL, Molina R, López-Alfonso A, Hernández B, Chiara LE, Martín AM, López-Martín A, Dorta M, Collazo-Lorduy A, Casado E, de Molina AR, Colmenarejo G. Cancers (Basel). 2021; 13 (16)
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.
Neurologia (Engl Ed). 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. Neurologia (Engl Ed). 2020; 35 (4)
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
Pulmonary immuno-thrombosis in COVID-19 ARDS pathogenesis.
O'Donnell JS, Peyvandi F, Martin-Loeches I.
Intensive Care Med. 2021; 47 (8)
DOI: 10.1007/s00134-021-06419-w
2021-05-30 2021 other brief-report; Research Support, Non-U.S. Gov't; Journal Article 10.1007/s00134-021-06419-w Pulmonary immuno-thrombosis in COVID-19 ARDS pathogenesis. O'Donnell JS, Peyvandi F, Martin-Loeches I. Intensive Care Med. 2021; 47 (8)
Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients.
Andrés C, Garcia-Cehic D, Gregori J, Piñana M, [...], Quer J.
Emerg Microbes Infect. 2020; 9 (1)
DOI: 10.1080/22221751.2020.1806735
The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site (PRRAR/S), generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We suggest that natural selection has favoured a "Don't burn down the house" strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability.
2020-12-01 2020 other research-article; Journal Article abstract-available 10.1080/22221751.2020.1806735 Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients. Andrés C, Garcia-Cehic D, Gregori J, Piñana M, Rodriguez-Frias F, Guerrero-Murillo M, Esperalba J, Rando A, Goterris L, Codina MG, Quer S, Martín MC, Campins M, Ferrer R, Almirante B, Esteban JI, Pumarola T, Antón A, Quer J. Emerg Microbes Infect. 2020; 9 (1)
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)
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)
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)
SARS-CoV-2 normalized viral loads and subgenomic RNA detection as tools for improving clinical decision-making and work reincorporation.
Santos Bravo M, Nicolás D, Berengua C, Fernandez M, [...], Marcos MA.
J Infect Dis. 2021;
DOI: 10.1093/infdis/jiab394

Background

SARS-CoV-2 RT-PCR provides a highly variable cycle-threshold (Ct) value that cannot distinguish viral infectivity. Subgenomic RNA (sgRNA) has been used to monitor active replication. Given the importance of long RT-PCR positivity and the need for work reincorporation and discontinuing isolation, we studied the functionality of normalized viral loads (NVL) for patient monitoring and sgRNA for viral infectivity detection.

Methods

NVL measured through the Nucleocapsid and RNA-dependent-RNA-polymerase genes and sgRNA RT-PCRs were performed in 2 consecutive swabs from 84 health-care workers.

Results

NVL provided similar and accurate quantities of both genes of SARS-CoV-2 at two different time-points of infection, overcoming Ct-value and swab collection variability. Among SARS-CoV-2-positive samples, 51.19% were sgRNA-positive in the 1 stRT-PCR and 5.95% in the 2 ndRT-PCR. All sgRNA-positive samples had >4log10RNAcopies/1000cells, while samples with ≤1log10 NVL were sgRNA-negative. Although NVL were positive until 29 days after symptom onset, 84.1% of sgRNA-positive samples were from the first 7 days, which correlated with viral culture viability. Multivariate analyses showed that sgRNA, NVL and days of symptoms were significantly associated (p<0.001).

Conclusions

NVL and sgRNA are two rapid accessible techniques that could be easily implemented in routine hospital practice providing a useful proxy for viral infectivity and COVID-19 patient follow-up.
2021-07-30 2021 other research-article; Journal Article abstract-available 10.1093/infdis/jiab394 SARS-CoV-2 normalized viral loads and subgenomic RNA detection as tools for improving clinical decision-making and work reincorporation. Santos Bravo M, Nicolás D, Berengua C, Fernandez M, Hurtado JC, Tortajada M, Barroso S, Vilella A, Mosquera M, Vila J, Marcos MA. J Infect Dis. 2021;
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
Discrimination of non-infectious SARS-CoV-2 particles from fomites by viability RT-qPCR.
Cuevas-Ferrando E, Girón-Guzmán I, Falcó I, Pérez-Cataluña A, [...], Sánchez G.
Environ Res. 2021; 203
DOI: 10.1016/j.envres.2021.111831
The ongoing coronavirus 2019 (COVID-19) pandemic constitutes a concerning global threat to public health and economy. In the midst of this pandemic scenario, the role of environment-to-human COVID-19 spread is still a matter of debate because mixed results have been reported concerning SARS-CoV-2 stability on high-touch surfaces in real-life scenarios. Up to now, no alternative and accessible procedures for cell culture have been applied to evaluate SARS-CoV-2 infectivity on fomites. Several strategies based on viral capsid integrity have latterly been developed using viability markers to selectively remove false-positive qPCR signals resulting from free nucleic acids and damaged viruses. These have finally allowed an estimation of viral infectivity. The present study aims to provide a rapid molecular-based protocol for detection and quantification of viable SARS-CoV-2 from fomites based on the discrimination of non-infectious SARS-CoV-2 particles by platinum chloride (IV) (PtCl4) viability RT-qPCR. An initial assessment compared two different swabbing procedures to recover inactivated SARS-CoV-2 particles from fomites coupled with two RNA extraction methods. Procedures were validated with human (E229) and porcine (PEDV) coronavirus surrogates, and compared with inactivated SARS-CoV-2 suspensions on glass, steel and plastic surfaces. The viability RT-qPCR efficiently removed the PCR amplification signals from heat and gamma-irradiated inactivated SARS-CoV-2 suspensions that had been collected from specified surfaces. This study proposes a rapid viability RT-qPCR that discriminates non-infectious SARS-CoV-2 particles on surfaces thus helping researchers to better understand the risk of contracting COVID-19 through contact with fomites and to develop more efficient epidemiological measures.
2021-08-02 2021 other research-article; Journal Article abstract-available 10.1016/j.envres.2021.111831 Discrimination of non-infectious SARS-CoV-2 particles from fomites by viability RT-qPCR. Cuevas-Ferrando E, Girón-Guzmán I, Falcó I, Pérez-Cataluña A, Díaz-Reolid A, Aznar R, Randazzo W, Sánchez G. Environ Res. 2021; 203
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)
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)
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; 22 (9)
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; 22 (9)
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)
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
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)
Absence of SARS-CoV-2 Antibodies in Natural Environment Exposure in Sheep in Close Contact with Humans.
Villanueva-Saz S, Giner J, Fernández A, Lacasta D, [...], Ruíz H.
Animals (Basel). 2021; 11 (7)
DOI: 10.3390/ani11071984
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the zoonotic causative agent of coronavirus disease 2019 (COVID-19) that has caused a pandemic situation with millions of infected humans worldwide. Among domestic animals, there have been limited studies regarding the transmissibility and exposure to the infection in natural conditions. Some animals are exposed and/or susceptible to SARS-CoV-2 infection, such as cats, ferrets and dogs. By contrast, there is no information about the susceptibility of ruminants to SARS-CoV-2. This study tested the antibody response in 90 ovine pre-pandemic serum samples and 336 sheep serum samples from the pandemic period (June 2020 to March 2021). In both cases, the animals were in close contact with a veterinary student community composed of more than 700 members. None of the serum samples analyzed was seroreactive based on an enzyme-linked immunosorbent assay (ELISA) using the receptor-binding domain (RBD) of the spike antigen. In this sense, no statistical difference was observed compared to the pre-pandemic sheep. Our results suggest that it seems unlikely that sheep could play a relevant role in the epidemiology of SARS-CoV-2 infection. This is the first study to report the absence of evidence of sheep exposure to SARS-CoV-2 in natural conditions.
2021-07-02 2021 other research-article; Journal Article abstract-available 10.3390/ani11071984 Absence of SARS-CoV-2 Antibodies in Natural Environment Exposure in Sheep in Close Contact with Humans. Villanueva-Saz S, Giner J, Fernández A, Lacasta D, Ortín A, Ramos JJ, Ferrer LM, Ruiz de Arcaute M, Tobajas AP, Pérez MD, Verde M, Marteles D, Hurtado-Guerrero R, Pardo J, Santiago L, González-Ramírez AM, Macías-León J, García-García A, Taleb V, Lira-Navarrete E, Paño-Pardo JR, Ruíz H. Animals (Basel). 2021; 11 (7)
Self-collected mid-nasal swabs and saliva specimens, compared with nasopharyngeal swabs, for SARS-CoV-2 detection in mild COVID-19 patients.
Alemany A, Millat-Martinez P, Ouchi D, Corbacho-Monné M, [...], Mitjà O.
J Infect. 2021;
DOI: 10.1016/j.jinf.2021.09.012
2021-09-16 2021 other Letter 10.1016/j.jinf.2021.09.012 Self-collected mid-nasal swabs and saliva specimens, compared with nasopharyngeal swabs, for SARS-CoV-2 detection in mild COVID-19 patients. Alemany A, Millat-Martinez P, Ouchi D, Corbacho-Monné M, Bordoy AE, Esteban C, Hernández Á, Casañ C, Gonzalez V, Costes G, Capdevila-Jáuregui M, Torrano-Soler P, José AS, Ara J, Prat N, Clotet B, Bassat Q, Gimenez M, Blanco I, Baro B, Mitjà O. J Infect. 2021;
Lack of evidence for infectious SARS-CoV-2 in feces and sewage.
Albert S, Ruíz A, Pemán J, Salavert M, [...], Domingo-Calap P.
Eur J Clin Microbiol Infect Dis. 2021;
DOI: 10.1007/s10096-021-04304-4
The SARS-CoV-2 can be excreted in feces and can reach sewage systems. Determining the presence of infective viral particles in feces and sewage is necessary to take adequate control measures and to elucidate new routes of transmission. Here, we have developed a sample concentration methodology that allows us to maintain viral infectivity. Feces of COVID-19 patients and wastewater samples have been analyzed both by molecular methods and cell culture. Our results show no evidence of infective viral particles, suggesting that fecal-oral transmission is not a primary route. However, larger-scale efforts are needed, especially with the emergence of new viral variants.
2021-07-09 2021 fondo-covid brief-report; Journal Article abstract-available 10.1007/s10096-021-04304-4 Lack of evidence for infectious SARS-CoV-2 in feces and sewage. Albert S, Ruíz A, Pemán J, Salavert M, Domingo-Calap P. Eur J Clin Microbiol Infect Dis. 2021;
The attributes of the images representing the SARS-CoV-2 coronavirus affect people's perception of the virus.
Andreu-Sánchez C, Martín-Pascual MÁ.
PLoS One. 2021; 16 (8)
DOI: 10.1371/journal.pone.0253738

Background

The recent COVID-19 pandemic has seen an explosion of coronavirus-related information. In many cases, this information was supported by images representing the SARS-CoV-2.

Aim

To evaluate how attributes of images representing the SARS-CoV-2 coronavirus that were used in the initial phase of the coronavirus crisis in 2020 influenced the public's perceptions.

Methods

We have carried out an in-depth survey using 46 coronavirus images, asking individuals how beautiful, scientific, realistic, infectious, scary and didactic they appeared to be.

Results

We collected 91,908 responses, obtaining 15,315 associations for each category. While the reference image of SARS-CoV-2 used in the media is a three-dimensional, colour, illustration, we found that illustrations of the coronavirus were perceived as beautiful but not very realistic, scientific or didactic. By contrast, black and white coronavirus images are thought to be the opposite. The beauty of coronavirus images was negatively correlated with the perception of scientific realism and didactic value.

Conclusion

Given these effects and the consequences on the individual's perception, it is important to evaluate the influence that different images of SARS-CoV-2 may have on the population.
2021-08-25 2021 other research-article; Journal Article abstract-available 10.1371/journal.pone.0253738 The attributes of the images representing the SARS-CoV-2 coronavirus affect people's perception of the virus. Andreu-Sánchez C, Martín-Pascual MÁ. PLoS One. 2021; 16 (8)
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)
Household Severe Acute Respiratory Syndrome Coronavirus 2 Transmission and Children: A Network Prospective Study.
Soriano-Arandes A, Gatell A, Serrano P, Biosca M, [...], COVID-19 Pediatric Disease in Catalonia Research Group.
Clin Infect Dis. 2021; 73 (6)
DOI: 10.1093/cid/ciab228

Background

The role of children in household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. We describe the epidemiological and clinical characteristics of children with coronavirus disease 2019 (COVID-19) in Catalonia, Spain, and investigate the household transmission dynamics.

Methods

A prospective, observational, multicenter study was performed during summer and school periods (1 July 2020-31 October 2020) to analyze epidemiological and clinical features and viral household transmission dynamics in COVID-19 patients aged <16 years. A pediatric index case was established when a child was the first individual infected. Secondary cases were defined when another household member tested positive for SARS-CoV-2 before the child. The secondary attack rate (SAR) was calculated, and logistic regression was used to assess associations between transmission risk factors and SARS-CoV-2 infection.

Results

The study included 1040 COVID-19 patients. Almost half (47.2%) were asymptomatic, 10.8% had comorbidities, and 2.6% required hospitalization. No deaths were reported. Viral transmission was common among household members (62.3%). More than 70% (756/1040) of pediatric cases were secondary to an adult, whereas 7.7% (80/1040) were index cases. The SAR was significantly lower in households with COVID-19 pediatric index cases during the school period relative to summer (P = .02) and compared to adults (P = .006). No individual or environmental risk factors associated with the SAR.

Conclusions

Children are unlikely to cause household COVID-19 clusters or be major drivers of the pandemic, even if attending school. Interventions aimed at children are expected to have a small impact on reducing SARS-CoV-2 transmission.
2021-09-01 2021 other research-article; Journal Article abstract-available 10.1093/cid/ciab228 Household Severe Acute Respiratory Syndrome Coronavirus 2 Transmission and Children: A Network Prospective Study. Soriano-Arandes A, Gatell A, Serrano P, Biosca M, Campillo F, Capdevila R, Fàbrega A, Lobato Z, López N, Moreno AM, Poblet M, Riera-Bosch MT, Rius N, Ruiz M, Sánchez A, Valldepérez C, Vilà M, Pineda V, Lazcano U, Díaz Y, Reyes-Urueña J, Soler-Palacín P, COVID-19 Pediatric Disease in Catalonia Research Group. Clin Infect Dis. 2021; 73 (6)
Mesenchymal Stem Cell-Based Therapy as an Alternative to the Treatment of Acute Respiratory Distress Syndrome: Current Evidence and Future Perspectives.
Fernández-Francos S, Eiro N, González-Galiano N, Vizoso FJ.
Int J Mol Sci. 2021; 22 (15)
DOI: 10.3390/ijms22157850
Acute respiratory distress syndrome (ARDS) represents a current challenge for medicine due to its incidence, morbidity and mortality and, also, the absence of an optimal treatment. The COVID-19 outbreak only increased the urgent demand for an affordable, safe and effective treatment for this process. Early clinical trials suggest the therapeutic usefulness of mesenchymal stem cells (MSCs) in acute lung injury (ALI) and ARDS. MSC-based therapies show antimicrobial, anti-inflammatory, regenerative, angiogenic, antifibrotic, anti-oxidative stress and anti-apoptotic actions, which can thwart the physiopathological mechanisms engaged in ARDS. In addition, MSC secretome and their derived products, especially exosomes, may reproduce the therapeutic effects of MSC in lung injury. This last strategy of treatment could avoid several safety issues potentially associated with the transplantation of living and proliferative cell populations and may be formulated in different forms. However, the following diverse limitations must be addressed: (i) selection of the optimal MSC, bearing in mind both the heterogeneity among donors and across different histological origins, (ii) massive obtention of these biological products through genetic manipulations of the most appropriate MSC, (iii) bioreactors that allow their growth in 3D, (iv) ideal culture conditions and (v) adequate functional testing of these obtaining biological products before their clinical application.
2021-07-22 2021 other review-article; Review; Journal Article abstract-available 10.3390/ijms22157850 Mesenchymal Stem Cell-Based Therapy as an Alternative to the Treatment of Acute Respiratory Distress Syndrome: Current Evidence and Future Perspectives. Fernández-Francos S, Eiro N, González-Galiano N, Vizoso FJ. Int J Mol Sci. 2021; 22 (15)
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)
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; 13 (5)
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; 13 (5)
Periodontal health and the initiation and progression of COVID-19.
Sanz M.
J Periodontal Implant Sci. 2021; 51 (3)
DOI: 10.5051/jpis.215103edi01
2021-06-01 2021 other Editorial 10.5051/jpis.215103edi01 Periodontal health and the initiation and progression of COVID-19. Sanz M. J Periodontal Implant Sci. 2021; 51 (3)
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)
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)
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;
Challenges at the host-arthropod-coronavirus interface and COVID-19: a One Health approach.
Fuente J, Mera IGF, Gortázar C.
Front Biosci (Landmark Ed). 2021; 26 (8)
DOI: 10.52586/4951
Background: The world faces the challenge posed by the interaction between hosts and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) with potential role for arthropod vectors, and the effect of SARS-CoV-2 variants on acquired immunity, vaccine efficacy and coronavirus disease-19 (COVID-19) pandemic control. Proposal: The characterization of the role played by animal hosts and host-virus interactions is essential to address this challenge. Zoonotic (animal-to-human) and reverse zoonotic (human-to-animal) routes may be involved in virus transmission with a possible still unconfirmed role for arthropod vectors. Herein we propose to consider the risks posed by the possible role of arthropod vectors in COVID-19 and that immunity against SARS-CoV-2 may increase the risk for zoonotic virus transmission. These risks should be considered when evaluating vaccine efficacy and monitoring animal SARS-CoV-2 variants. Conclusion: Virus surveillance, epidemiology, sequencing and evaluation of susceptibility to antibodies and other protective immune mechanisms from vaccinated individuals should be improved. A One Health approach such as the one applied by our group SaBio is necessary for a more effective control of COVID-19 and prevention of future pandemics.
2021-08-01 2021 other Journal Article abstract-available 10.52586/4951 Challenges at the host-arthropod-coronavirus interface and COVID-19: a One Health approach. Fuente J, Mera IGF, Gortázar C. Front Biosci (Landmark Ed). 2021; 26 (8)
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)
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)
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
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)
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; Case Reports 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
Autoimmune diseases and vaccines against COVID-19. Decision making in uncertain scenarios.
Cairoli E, Espinosa G.
Med Clin (Engl Ed). 2021; 157 (5)
DOI: 10.1016/j.medcle.2021.05.003
2021-08-07 2021 other brief-report; Journal Article 10.1016/j.medcle.2021.05.003 Autoimmune diseases and vaccines against COVID-19. Decision making in uncertain scenarios. Cairoli E, Espinosa G. Med Clin (Engl Ed). 2021; 157 (5)
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)
Science, not speculation, is essential to determine how SARS-CoV-2 reached humans.
Calisher CH, Carroll D, Colwell R, Corley RB, [...], Turner M.
Lancet. 2021; 398 (10296)
DOI: 10.1016/s0140-6736(21)01419-7
2021-07-05 2021 other Letter; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural 10.1016/s0140-6736(21)01419-7 Science, not speculation, is essential to determine how SARS-CoV-2 reached humans. Calisher CH, Carroll D, Colwell R, Corley RB, Daszak P, Drosten C, Enjuanes L, Farrar J, Field H, Golding J, Gorbalenya AE, Haagmans B, Hughes JM, Keusch GT, Lam SK, Lubroth J, Mackenzie JS, Madoff L, Mazet JK, Perlman SM, Poon L, Saif L, Subbarao K, Turner M. Lancet. 2021; 398 (10296)
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)
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)
De Novo Movement Disorders and COVID-19: Exploring the Interface.
Ghosh R, Biswas U, Roy D, Pandit A, [...], Benito-León J.
Mov Disord Clin Pract. 2021;
DOI: 10.1002/mdc3.13224

Background

Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being widely documented. However, movement disorders in the setting of 2019 coronavirus infectious disease (COVID-19) have been a strikingly less discussed topic.

Objectives

To summarize available pieces of evidence documenting de novo movement disorders in COVID-19.

Methods

We used the existing PRISMA consensus statement. Data were collected from PubMed, EMBASE, Web of Science, and Scopus databases up to the 29th January, 2021, using pre-specified searching strategies.

Results

Twenty-two articles were selected for the qualitative synthesis. Among these, a total of 52 patients with de novo movement disorders were reported. Most of these had myoclonus, ataxia, tremor or a combination of these, while three had parkinsonism and one a functional disorder. In general, they were managed successfully by intravenous immunoglobulin or steroids. Some cases, primarily with myoclonus, could be ascribed to medication exposures, metabolic disturbances or severe hypoxia, meanwhile others to a post-or para-infectious immune-mediated mechanism. SARS-CoV-2 could also invade the central nervous system, through vascular or retrograde axonal pathways, and cause movement disorders by two primary mechanisms. Firstly, through the downregulation of angiotensin-converting enzyme 2 receptors, resulting in the imbalance of dopamine and norepinephrine; and secondly, the virus could cause cellular vacuolation, demyelination and gliosis, leading to encephalitis and associated movement disorders.

Conclusion

De novo movement disorders are scantly reported in COVID-19. The links between SARS-CoV-2 and movement disorders are not yet established. However, we should closely monitor COVID-19 survivors for the possibility of post-COVID movement disorders.
2021-04-28 2021 other review-article; Review; Journal Article abstract-available 10.1002/mdc3.13224 De Novo Movement Disorders and COVID-19: Exploring the Interface. Ghosh R, Biswas U, Roy D, Pandit A, Lahiri D, Ray BK, Benito-León J. Mov Disord Clin Pract. 2021;
The sound of host-SARS-CoV-2 molecular interactions.
de la Fuente J, Pastor Comín JJ, Gortázar C.
Innovation (N Y). 2021; 2 (3)
DOI: 10.1016/j.xinn.2021.100126
2021-06-08 2021 other News 10.1016/j.xinn.2021.100126 The sound of host-SARS-CoV-2 molecular interactions. de la Fuente J, Pastor Comín JJ, Gortázar C. Innovation (N Y). 2021; 2 (3)
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
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
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)
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
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;
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
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)
Neurological Manifestations of Coronavirus Disease 2019: A Comprehensive Review and Meta-Analysis of the First 6 Months of Pandemic Reporting.
Huth SF, Cho SM, Robba C, Highton D, [...], Fanning JP.
Front Neurol. 2021; 12
DOI: 10.3389/fneur.2021.664599
Background: There is growing evidence that SARS-Cov-2 infection is associated with severe neurological complications. Understanding the nature and prevalence of these neurologic manifestations is essential for identifying higher-risk patients and projecting demand for ongoing resource utilisation. This review and meta-analysis report the neurologic manifestations identified in hospitalised COVID-19 patients and provide a preliminary estimate of disease prevalence. Methods: MEDLINE, Embase and Scopus were searched for studies reporting the occurrence of neurological complications in hospitalised COVID-19 patients. Results: A total of 2,207 unique entries were identified and screened, among which 14 cohort studies and 53 case reports were included, reporting on a total of 8,577 patients. Central nervous system manifestations included ischemic stroke (n = 226), delirium (n = 79), intracranial haemorrhage (ICH, n = 57), meningoencephalitis (n = 13), seizures (n = 3), and acute demyelinating encephalitis (n = 2). Peripheral nervous system manifestations included Guillain-Barrè Syndrome (n = 21) and other peripheral neuropathies (n = 3). The pooled period prevalence of ischemic stroke from identified studies was 1.3% [95%CI: 0.9-1.8%, 102/7,715] in all hospitalised COVID-19 patients, and 2.8% [95%CI: 1.0-4.6%, 9/318] among COVID-19 patients admitted to ICU. The pooled prevalence of ICH was estimated at 0.4% [95%CI: 0-0.8%, 6/1,006]. Conclusions: The COVID-19 pandemic exerts a substantial neurologic burden which may have residual effects on patients and healthcare systems for years. Low quality evidence impedes the ability to accurately predict the magnitude of this burden. Robust studies with standardised screening and case definitions are required to improve understanding of this disease and optimise treatment of individuals at higher risk for neurologic sequelae.
2021-08-12 2021 other Systematic Review; systematic-review abstract-available 10.3389/fneur.2021.664599 Neurological Manifestations of Coronavirus Disease 2019: A Comprehensive Review and Meta-Analysis of the First 6 Months of Pandemic Reporting. Huth SF, Cho SM, Robba C, Highton D, Battaglini D, Bellapart J, Suen JY, Li Bassi G, Taccone FS, Arora RC, Whitman G, Fraser JF, Fanning JP. Front Neurol. 2021; 12
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: 10.1016/j.msard.2021.102917

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; Systematic Review; Journal Article abstract-available 10.1016/j.msard.2021.102917 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
Viewpoint of a WHO Advisory Group Tasked to Consider Establishing a Closely-monitored Challenge Model of Coronavirus Disease 2019 (COVID-19) in Healthy Volunteers.
Levine MM, Abdullah S, Arabi YM, Darko DM, [...], Restrepo AMH.
Clin Infect Dis. 2021; 72 (11)
DOI: 10.1093/cid/ciaa1290
WHO convened an Advisory Group (AG) to consider the feasibility, potential value, and limitations of establishing a closely-monitored challenge model of experimental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) in healthy adult volunteers. The AG included experts in design, establishment, and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (the potential of SARS-CoV-2 to cause severe/fatal illness, its high transmissibility, and lack of a "rescue treatment" to prevent progression from mild/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household/community contacts. A COVID-19 model could demonstrate protection against virus shedding and/or illness induced by prior SARS-CoV-2 challenge or vaccination. A limitation of the model is that vaccine efficacy in experimentally challenged healthy young adults cannot per se be extrapolated to predict efficacy in elderly/high-risk adults.
2021-06-01 2021 other review-article; Journal Article abstract-available 10.1093/cid/ciaa1290 Viewpoint of a WHO Advisory Group Tasked to Consider Establishing a Closely-monitored Challenge Model of Coronavirus Disease 2019 (COVID-19) in Healthy Volunteers. Levine MM, Abdullah S, Arabi YM, Darko DM, Durbin AP, Estrada V, Jamrozik E, Kremsner PG, Lagos R, Pitisuttithum P, Plotkin SA, Sauerwein R, Shi SL, Sommerfelt H, Subbarao K, Treanor JJ, Vrati S, King D, Balasingam S, Weller C, Aguilar AO, Cassetti MC, Krause PR, Restrepo AMH. Clin Infect Dis. 2021; 72 (11)
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)
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
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)
Increased Blood Monocytic Myeloid Derived Suppressor Cells but Low Regulatory T Lymphocytes in Patients with Mild COVID-19.
Jiménez-Cortegana C, Liró J, Palazón-Carrión N, Salamanca E, [...], Sánchez-Margalet V.
Viral Immunol. 2021;
DOI: 10.1089/vim.2021.0044
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may produce a systemic disease, the coronavirus disease-19 (COVID-19), with high morbidity and mortality. Even though we do not fully understand the interaction of innate and adaptive immunity in the control and complications of the viral infection, it is well recognized that SARS-CoV-2 induces an immunodepression that impairs the elimination of the virus and favors its rapid dissemination in the organism. Even less is known about the possible participation of inhibitory cells of the innate immune system, such as the myeloid-derived suppressor cells (MDSCs), or the adaptive immune system, such as the T regulatory cells (Tregs). That is why we aimed to study blood levels of MDSCs, as well as lymphocyte subpopulations, including Tregs, and activated (OX-40+) and inhibited (PD-1) T lymphocytes in patients with mild COVID-19 in comparison with data obtained from control donors. We have found that 20 hospitalized patients with COVID-19 and no health history of immunosuppression had a significant increase in the number of peripheral monocytic MDSCs (M-MDSC), but a decrease in Tregs, as well as an increase in the number of inhibited or exhausted T cells, whereas the number of activated T cells was significantly decreased compared with that from 20 healthy controls. Moreover, there was a significant negative correlation (r = 0.496) between the number of M-MDSC and the number of activated T cells. Therefore, M-MDSC rather than Tregs may contribute to the immunosuppression observed in patients with COVID-19.
2021-09-16 2021 other Journal Article abstract-available 10.1089/vim.2021.0044 Increased Blood Monocytic Myeloid Derived Suppressor Cells but Low Regulatory T Lymphocytes in Patients with Mild COVID-19. Jiménez-Cortegana C, Liró J, Palazón-Carrión N, Salamanca E, Sojo-Dorado J, de la Cruz-Merino L, Pascual Á, Rodríguez-Baño J, Sánchez-Margalet V. Viral Immunol. 2021;
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)
Nutrition in the Actual COVID-19 Pandemic. A Narrative Review.
Clemente-Suárez VJ, Ramos-Campo DJ, Mielgo-Ayuso J, Dalamitros AA, [...], Tornero-Aguilera JF.
Nutrients. 2021; 13 (6)
DOI: 10.3390/nu13061924
The pandemic of Coronavirus Disease 2019 (COVID-19) has shocked world health authorities generating a global health crisis. The present study discusses the main finding in nutrition sciences associated with COVID-19 in the literature. We conducted a consensus critical review using primary sources, scientific articles, and secondary bibliographic indexes, databases, and web pages. The method was a narrative literature review of the available literature regarding nutrition interventions and nutrition-related factors during the COVID-19 pandemic. The main search engines used in the present research were PubMed, SciELO, and Google Scholar. We found how the COVID-19 lockdown promoted unhealthy dietary changes and increases in body weight of the population, showing obesity and low physical activity levels as increased risk factors of COVID-19 affection and physiopathology. In addition, hospitalized COVID-19 patients presented malnutrition and deficiencies in vitamin C, D, B12 selenium, iron, omega-3, and medium and long-chain fatty acids highlighting the potential health effect of vitamin C and D interventions. Further investigations are needed to show the complete role and implications of nutrition both in the prevention and in the treatment of patients with COVID-19.
2021-06-03 2021 other review-article; Review; Journal Article abstract-available 10.3390/nu13061924 Nutrition in the Actual COVID-19 Pandemic. A Narrative Review. Clemente-Suárez VJ, Ramos-Campo DJ, Mielgo-Ayuso J, Dalamitros AA, Nikolaidis PA, Hormeño-Holgado A, Tornero-Aguilera JF. Nutrients. 2021; 13 (6)
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)
The New Generation hDHODH Inhibitor MEDS433 Hinders the In Vitro Replication of SARS-CoV-2 and Other Human Coronaviruses.
Calistri A, Luganini A, Mognetti B, Elder E, [...], Parolin C.
Microorganisms. 2021; 9 (8)
DOI: 10.3390/microorganisms9081731
Although coronaviruses (CoVs) have long been predicted to cause zoonotic diseases and pandemics with high probability, the lack of effective anti-pan-CoVs drugs rapidly usable against the emerging SARS-CoV-2 actually prevented a promptly therapeutic intervention for COVID-19. Development of host-targeting antivirals could be an alternative strategy for the control of emerging CoVs infections, as they could be quickly repositioned from one pandemic event to another. To contribute to these pandemic preparedness efforts, here we report on the broad-spectrum CoVs antiviral activity of MEDS433, a new inhibitor of the human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of the de novo pyrimidine biosynthesis pathway. MEDS433 inhibited the in vitro replication of hCoV-OC43 and hCoV-229E, as well as of SARS-CoV-2, at low nanomolar range. Notably, the anti-SARS-CoV-2 activity of MEDS433 against SARS-CoV-2 was also observed in kidney organoids generated from human embryonic stem cells. Then, the antiviral activity of MEDS433 was reversed by the addition of exogenous uridine or the product of hDHODH, the orotate, thus confirming hDHODH as the specific target of MEDS433 in hCoVs-infected cells. Taken together, these findings suggest MEDS433 as a potential candidate to develop novel drugs for COVID-19, as well as broad-spectrum antiviral agents exploitable for future CoVs threats.
2021-08-14 2021 other research-article; Journal Article abstract-available 10.3390/microorganisms9081731 The New Generation <i>h</i>DHODH Inhibitor MEDS433 Hinders the In Vitro Replication of SARS-CoV-2 and Other Human Coronaviruses. Calistri A, Luganini A, Mognetti B, Elder E, Sibille G, Conciatori V, Del Vecchio C, Sainas S, Boschi D, Montserrat N, Mirazimi A, Lolli ML, Gribaudo G, Parolin C. Microorganisms. 2021; 9 (8)
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)
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)
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; 11 (4)
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; 11 (4)
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