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: 2022-05-16
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Publications 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
COVID-19: impact on Public Health and hypothesis-driven investigations on genetic susceptibility and severity.
David S, Dorado G, Duarte EL, David-Bosne S, [...], Rebelo-de-Andrade H.
Immunogenetics. 2022;
DOI: 10.1007/s00251-022-01261-w
COVID-19 is a new complex multisystem disease caused by the novel coronavirus SARS-CoV-2. In slightly over 2 years, it infected nearly 500 million and killed 6 million human beings worldwide, causing an unprecedented coronavirus pandemic. Currently, the international scientific community is engaged in elucidating the molecular mechanisms of the pathophysiology of SARS-CoV-2 infection as a basis of scientific developments for the future control of COVID-19. Global exome and genome analysis efforts work to define the human genetics of protective immunity to SARS-CoV-2 infection. Here, we review the current knowledge regarding the SARS-CoV-2 infection, the implications of COVID-19 to Public Health and discuss genotype to phenotype association approaches that could be exploited through the selection of candidate genes to identify the genetic determinants of severe COVID-19.
2022-03-29 2022 other IM; review-article; Review; Journal Article abstract-available 10.1007/s00251-022-01261-w COVID-19: impact on Public Health and hypothesis-driven investigations on genetic susceptibility and severity. David S, Dorado G, Duarte EL, David-Bosne S, Trigueiro-Louro J, Rebelo-de-Andrade H. Immunogenetics. 2022;
The Finding of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in a Wild Eurasian River Otter (Lutra lutra) Highlights the Need for Viral Surveillance in Wild Mustelids.
Padilla-Blanco M, Aguiló-Gisbert J, Rubio V, Lizana V, [...], Rubio-Guerri C.
Front Vet Sci. 2022; 9
DOI: 10.3389/fvets.2022.826991
Animals have been involved in the three known outbreaks of severe respiratory syndromes due to coronaviruses (years 2005, 2012, and 2019). The pandemic nature of the SARS-CoV-2 outbreak increases the likelihood of infection from humans of susceptible animal species that, thus, could become secondary viral hosts and even disease reservoirs. We present evidence of spillover infection of wild mustelids by reporting the presence of SARS-CoV-2 in a Eurasian river otter found near a water reservoir in the Valencian Community (Spain). We detected the virus using two different commercial RTqPCR assays on RNA extracted from the nasopharynx (swabbing) and from lung tissue and mediastinal lymph node homogenates. The corresponding samples from two additional otters from distant sites tested negative in identical assays. The diagnosis in the positive otter was confirmed by two-tube RT-PCR assay in which RNA was first retrotranscribed, and then specific regions of the spike (S), nucleocapsid (N), and ORF10 genes were separately amplified from the produced cDNA, followed by electrophoretic visualization and Sanger sequencing. The sequences of the amplified products revealed some non-synonymous changes in the N and ORF10 partial sequences, relative to the consensus sequence. These changes, identified already in human patient samples, point to human origin of the virus, although their specific combination was unique. These findings, together with our previous report of SARS-CoV-2 infection of feral American mink, highlight the need for SARS-CoV-2 surveillance of wild or feral mustelids to evaluate the risk that these animals could become SARS-CoV-2 reservoirs.
2022-03-31 2022 other brief-report; Journal Article abstract-available 10.3389/fvets.2022.826991 The Finding of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in a Wild Eurasian River Otter (<i>Lutra lutra</i>) Highlights the Need for Viral Surveillance in Wild Mustelids. Padilla-Blanco M, Aguiló-Gisbert J, Rubio V, Lizana V, Chillida-Martínez E, Cardells J, Maiques E, Rubio-Guerri C. Front Vet Sci. 2022; 9
European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis.
Task Force for the management of COVID-19 of the European Society of Cardiology, Baigent C, Windecker S, Andreini D, [...], Williams B.
Cardiovasc Res. 2022; 118 (6)
DOI: 10.1093/cvr/cvab342

Aims

Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19.

Methods and results

A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19.

Conclusion

This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.
2022-05-01 2022 other research-article; Review; Journal Article abstract-available 10.1093/cvr/cvab342 European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis. Task Force for the management of COVID-19 of the European Society of Cardiology, Baigent C, Windecker S, Andreini D, Arbelo E, Barbato E, Bartorelli AL, Baumbach A, Behr ER, Berti S, Bueno H, Capodanno D, Cappato R, Chieffo A, Collet JP, Cuisset T, de Simone G, Delgado V, Dendale P, Dudek D, Edvardsen T, Elvan A, González-Juanatey JR, Gori M, Grobbee D, Guzik TJ, Halvorsen S, Haude M, Heidbuchel H, Hindricks G, Ibanez B, Karam N, Katus H, Klok FA, Konstantinides SV, Landmesser U, Leclercq C, Leonardi S, Lettino M, Marenzi G, Mauri J, Metra M, Morici N, Mueller C, Petronio AS, Polovina MM, Potpara T, Praz F, Prendergast B, Prescott E, Price S, Pruszczyk P, Rodríguez-Leor O, Roffi M, Romaguera R, Rosenkranz S, Sarkozy A, Scherrenberg M, Seferovic P, Senni M, Spera FR, Stefanini G, Thiele H, Tomasoni D, Torracca L, Touyz RM, Wilde AA, Williams B. Cardiovasc Res. 2022; 118 (6)
Excretion and viability of SARS-CoV-2 in feces and its association with the clinical outcome of COVID-19.
Cerrada-Romero C, Berastegui-Cabrera J, Camacho-Martínez P, Goikoetxea-Aguirre J, [...], Sánchez-Céspedes J.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-022-11439-7
The main objective was to evaluate the viability of the SARS-CoV-2 viral particles excreted in stools. In addition, we aimed to identify clinical factors associated with the detection of SARS-CoV-2 RNA in feces, and to determine if its presence is associated with an unfavorable clinical outcome, defined as intensive care unit (ICU) admission and/or death. A prospective multicenter cohort study of COVID-19 adult patients, with confirmed SARS-CoV-2 infection by RT-PCR assay in nasopharyngeal (NP) swabs admitted to four hospitals in Spain, from March 2020 to February 2021. Sixty-two adult COVID-19 patients had stool samples collected at admission and/or during the follow up, with a total of 79 stool samples. SARS-CoV-2 RNA was detected in stool samples from 27 (43.5%) out of the 62 patients. Replicative virus, measured by the generation of cytopathic effect in cell culture and subsequent RT-PCR confirmation of a decrease in the Ct values, was not found in any of these stool samples. Fecal virus excretion was not associated with the presence of gastrointestinal symptoms, or with differences in the evolution of COVID-19 patients. Our results suggest that SARS-CoV-2 replicative capacity is null or very limited in stool samples, and thus, the fecal-oral transmission of SARS-CoV-2 as an alternative infection route is highly unlikely. In our study, the detection of SARS-CoV-2 RNA in feces at the beginning of the disease is not associated with any clinical factor nor with an unfavorable clinical outcome.
2022-05-05 2022 fondo-covid research-article; Multicenter Study; Journal Article abstract-available 10.1038/s41598-022-11439-7 Excretion and viability of SARS-CoV-2 in feces and its association with the clinical outcome of COVID-19. Cerrada-Romero C, Berastegui-Cabrera J, Camacho-Martínez P, Goikoetxea-Aguirre J, Pérez-Palacios P, Santibáñez S, José Blanco-Vidal M, Valiente A, Alba J, Rodríguez-Álvarez R, Pascual Á, Oteo JA, Miguel Cisneros J, Pachón J, Casas-Flecha I, Cordero E, Pozo F, Sánchez-Céspedes J. Sci Rep. 2022; 12 (1)
Calcium Signaling Pathway Is Involved in the Shedding of ACE2 Catalytic Ectodomain: New Insights for Clinical and Therapeutic Applications of ACE2 for COVID-19.
García-Escobar A, Vera-Vera S, Jurado-Román A, Jiménez-Valero S, [...], Moreno R.
Biomolecules. 2022; 12 (1)
DOI: 10.3390/biom12010076
The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that exists in two forms: the first is a transmembrane protein; the second is a soluble catalytic ectodomain of ACE2. The catalytic ectodomain of ACE2 undergoes shedding by a disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), in which calmodulin mediates the calcium signaling pathway that is involved in ACE2 release, resulting in a soluble catalytic ectodomain of ACE2 that can be measured as soluble ACE2 plasma activity. The shedding of the ACE2 catalytic ectodomain plays a role in cardiac remodeling and endothelial dysfunction and is a predictor of all-cause mortality, including cardiovascular mortality. Moreover, considerable evidence supports that the ACE2 catalytic ectodomain is an essential entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Additionally, endotoxins and the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-alpha (TNFα) all enhanced soluble catalytic ectodomain ACE2 shedding from the airway epithelia, suggesting that the shedding of ACE2 may represent a mechanism by which viral entry and infection may be controlled such as some types of betacoronavirus. In this regard, ACE2 plays an important role in inflammation and thrombotic response, and its down-regulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury. Soluble forms of ACE2 have recently been shown to inhibit SARS-CoV-2 infection. Furthermore, given that vitamin D enhanced the shedding of ACE2, some studies reported that vitamin D treatment is associated with prognosis improvement in COVID-19. This is an updated review on the evidence, clinical, and therapeutic applications of ACE2 for COVID-19.
2022-01-05 2022 other IM; review-article; Review; Journal Article abstract-available 10.3390/biom12010076 Calcium Signaling Pathway Is Involved in the Shedding of ACE2 Catalytic Ectodomain: New Insights for Clinical and Therapeutic Applications of ACE2 for COVID-19. García-Escobar A, Vera-Vera S, Jurado-Román A, Jiménez-Valero S, Galeote G, Moreno R. Biomolecules. 2022; 12 (1)
Classical and Next-Generation Vaccine Platforms to SARS-CoV-2: Biotechnological Strategies and Genomic Variants.
Simões RSQ, Rodríguez-Lázaro D.
Int J Environ Res Public Health. 2022; 19 (4)
DOI: 10.3390/ijerph19042392
Several coronaviruses (CoVs) have been identified as human pathogens, including the α-CoVs strains HCoV-229E and HCoV-NL63 and the β-CoVs strains HCoV-HKU1 and HCoV-OC43. SARS-CoV, MERS-CoV, and SARS-CoV-2 are also classified as β-coronavirus. New SARS-CoV-2 spike genomic variants are responsible for human-to-human and interspecies transmissibility, consequences of adaptations of strains from animals to humans. The receptor-binding domain (RBD) of SARS-CoV-2 binds to receptor ACE2 in humans and animal species with high affinity, suggesting there have been adaptive genomic variants. New genomic variants including the incorporation, replacement, or deletion of the amino acids at a variety of positions in the S protein have been documented and are associated with the emergence of new strains adapted to different hosts. Interactions between mutated residues and RBD have been demonstrated by structural modelling of variants including D614G, B.1.1.7, B1.351, P.1, P2; other genomic variants allow escape from antibodies generated by vaccines. Epidemiological and molecular tools are being used for real-time tracking of pathogen evolution and particularly new SARS-CoV-2 variants. COVID-19 vaccines obtained from classical and next-generation vaccine production platforms have entered clinicals trials. Biotechnology strategies of the first generation (attenuated and inactivated virus-CoronaVac, CoVaxin; BBIBP-CorV), second generation (replicating-incompetent vector vaccines-ChAdOx-1; Ad5-nCoV; Sputnik V; JNJ-78436735 vaccine-replicating-competent vector, protein subunits, virus-like particles-NVX-CoV2373 vaccine), and third generation (nucleic-acid vaccines-INO-4800 (DNA); mRNA-1273 and BNT 162b (RNA vaccines) have been used. Additionally, dendritic cells (LV-SMENP-DC) and artificial antigen-presenting (aAPC) cells modified with lentiviral vector have also been developed to inhibit viral activity. Recombinant vaccines against COVID-19 are continuously being applied, and new clinical trials have been tested by interchangeability studies of viral vaccines developed by classical and next-generation platforms.
2022-02-18 2022 other IM; review-article; Review; Journal Article abstract-available 10.3390/ijerph19042392 Classical and Next-Generation Vaccine Platforms to SARS-CoV-2: Biotechnological Strategies and Genomic Variants. Simões RSQ, Rodríguez-Lázaro D. Int J Environ Res Public Health. 2022; 19 (4)
Persistent COVID-19 syndrome. A narrative review.
López-Sampalo A, Bernal-López MR, Gómez-Huelgas R.
Rev Clin Esp (Barc). 2022; 222 (4)
DOI: 10.1016/j.rceng.2021.10.001
As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.
2022-02-28 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.rceng.2021.10.001 Persistent COVID-19 syndrome. A narrative review. López-Sampalo A, Bernal-López MR, Gómez-Huelgas R. Rev Clin Esp (Barc). 2022; 222 (4)
ACE2 Serum Levels as Predictor of Infectability and Outcome in COVID-19.
Maza MDC, Úbeda M, Delgado P, Horndler L, [...], Fresno M.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.836516

Background

COVID-19 can generate a broad spectrum of severity and symptoms. Many studies analysed the determinants of severity but not among some types of symptoms. More importantly, very few studies analysed patients highly exposed to the virus that nonetheless remain uninfected.

Methods

We analysed serum levels of ACE2, Angiotensin II and anti-Spike antibodies in 2 different cohorts at high risk of viral exposure, highly exposed but uninfected subjects, either high risk health care workers or persons cohabiting with infected close relatives and seropositive patients with symptoms. We tested the ability of the sera of these subjects to neutralize lentivirus pseudotyped with the Spike-protein.

Results

We found that the serum levels of ACE2 are significantly higher in highly exposed but uninfected subjects. Moreover, sera from this seronegative persons can neutralize SARS-CoV-2 infection in cellular assays more strongly that sera from non-exposed negative controls eventhough they do not have anti-CoV-2 IgG antibodies suggesting that high levels of ACE2 in serum may somewhat protect against an active infection without generating a conventional antibody response. Finally, we show that among patients with symptoms, ACE2 levels were significantly higher in infected patients who developed cutaneous as compared with respiratory symptoms and ACE2 was also higher in those with milder symptoms.

Conclusions

These findings suggest that soluble ACE2 could be used as a potential biomarker to predict SARS-CoV-2 infection risk and to discriminate COVID-19 disease subtypes.
2022-03-23 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.836516 ACE2 Serum Levels as Predictor of Infectability and Outcome in COVID-19. Maza MDC, Úbeda M, Delgado P, Horndler L, Llamas MA, van Santen HM, Alarcón B, Abia D, García-Bermejo L, Serrano-Villar S, Bastolla U, Fresno M. Front Immunol. 2022; 13
Genomic Diversity of SARS-CoV-2 in Algeria and North African Countries: What We Know So Far and What We Expect?
Menasria T, Aguilera M.
Microorganisms. 2022; 10 (2)
DOI: 10.3390/microorganisms10020467
Here, we report a first comprehensive genomic analysis of SARS-CoV-2 variants circulating in North African countries, including Algeria, Egypt, Libya, Morocco, Sudan and Tunisia, with respect to genomic clades and mutational patterns. As of December 2021, a total of 1669 high-coverage whole-genome sequences submitted to EpiCoV GISAID database were analyzed to infer clades and mutation annotation compared with the wild-type variant Wuhan-Hu-1. Phylogenetic analysis of SARS-CoV-2 genomes revealed the existence of eleven GISAID clades with GR (variant of the spike protein S-D614G and nucleocapsid protein N-G204R), GH (variant of the ORF3a coding protein ORF3a-Q57H) and GK (variant S-T478K) being the most common with 25.9%, 19.9%, and 19.6%, respectively, followed by their parent clade G (variant S-D614G) (10.3%). Lower prevalence was noted for GRY (variant S-N501Y) (5.1%), S (variant ORF8-L84S) (3.1%) and GV (variant of the ORF3a coding protein NS3-G251V) (2.0%). Interestingly, 1.5% of total genomes were assigned as GRA (Omicron), the newly emerged clade. Across the North African countries, 108 SARS-CoV-2 lineages using the Pangolin assignment were identified, whereby most genomes fell within six major lineages and variants of concern (VOC) including B.1, the Delta variants (AY.X, B.1.617.2), C.36, B.1.1.7 and B.1.1. The effect of mutations in SAR-CoV-2 genomes highlighted similar profiles with D614G spike (S) and ORF1b-P314L variants as the most changes found in 95.3% and 87.9% of total sequences, respectively. In addition, mutations affecting other viral proteins appeared frequently including; N:RG203KR, N:G212V, NSP3:T428I, ORF3a:Q57H, S:N501Y, M:I82T and E:V5F. These findings highlight the importance of genomic surveillance for understanding the SARS-CoV-2 genetic diversity and its spread patterns, leading to a better guiding of public health intervention measures. The know-how analysis of the present work could be implemented worldwide in order to overcome this health crisis through harmonized approaches.
2022-02-18 2022 other research-article; Journal Article abstract-available 10.3390/microorganisms10020467 Genomic Diversity of SARS-CoV-2 in Algeria and North African Countries: What We Know So Far and What We Expect? Menasria T, Aguilera M. Microorganisms. 2022; 10 (2)
Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis.
Schmid B, Griesel M, Fischer AL, Romero CS, [...], Fichtner F.
J Clin Med. 2022; 11 (2)
DOI: 10.3390/jcm11020391
Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65-1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03-1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71-0.96) but may have little or no effect on mortality (RR: 1.08, 0.51-2.31). Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.
2022-01-13 2022 other review-article; Review; Journal Article abstract-available 10.3390/jcm11020391 Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis. Schmid B, Griesel M, Fischer AL, Romero CS, Metzendorf MI, Weibel S, Fichtner F. J Clin Med. 2022; 11 (2)
Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Hyperimmune Immunoglobulin Demonstrates Potent Neutralization and Antibody-Dependent Cellular Cytotoxicity and Phagocytosis Through N and S Proteins.
Díez JM, Romero C, Cruz M, Vandeberg P, [...], Gajardo R.
J Infect Dis. 2022; 225 (6)
DOI: 10.1093/infdis/jiab540

Background

Although coronavirus disease 2019 (COVID-19) vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need.

Methods

Functional characterization of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus-induced cytotoxicity, median tissue culture infectious dose [TCID50] reduction, and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA [1], Italy [1], and Spain [2]; 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1, and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated.

Results

All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all 4 methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. The hIG (IgG type) induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25-100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins.

Conclusions

Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.
2022-03-01 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/infdis/jiab540 Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Hyperimmune Immunoglobulin Demonstrates Potent Neutralization and Antibody-Dependent Cellular Cytotoxicity and Phagocytosis Through N and S Proteins. Díez JM, Romero C, Cruz M, Vandeberg P, Merritt WK, Pradenas E, Trinité B, Blanco J, Clotet B, Willis T, Gajardo R. J Infect Dis. 2022; 225 (6)
What Should Be Learned From Repurposed Antivirals Against SARS-CoV-2?
Martinez MA.
Front Microbiol. 2022; 13
DOI: 10.3389/fmicb.2022.843587
2022-02-16 2022 other discussion; Journal Article 10.3389/fmicb.2022.843587 What Should Be Learned From Repurposed Antivirals Against SARS-CoV-2? Martinez MA. Front Microbiol. 2022; 13
Entrectinib-A SARS-CoV-2 Inhibitor in Human Lung Tissue (HLT) Cells.
Peralta-Garcia A, Torrens-Fontanals M, Stepniewski TM, Grau-Expósito J, [...], Selent J.
Int J Mol Sci. 2021; 22 (24)
DOI: 10.3390/ijms222413592
Since the start of the COVID-19 outbreak, pharmaceutical companies and research groups have focused on the development of vaccines and antiviral drugs against SARS-CoV-2. Here, we apply a drug repurposing strategy to identify drug candidates that are able to block the entrance of the virus into human cells. By combining virtual screening with in vitro pseudovirus assays and antiviral assays in Human Lung Tissue (HLT) cells, we identify entrectinib as a potential antiviral drug.
2021-12-18 2021 other IM; research-article; Journal Article abstract-available 10.3390/ijms222413592 Entrectinib-A SARS-CoV-2 Inhibitor in Human Lung Tissue (HLT) Cells. Peralta-Garcia A, Torrens-Fontanals M, Stepniewski TM, Grau-Expósito J, Perea D, Ayinampudi V, Waldhoer M, Zimmermann M, Buzón MJ, Genescà M, Selent J. Int J Mol Sci. 2021; 22 (24)
Decreased and Heterogeneous Neutralizing Antibody Responses Against RBD of SARS-CoV-2 Variants After mRNA Vaccination.
Hernández-Luis P, Aguilar R, Pelegrin-Pérez J, Ruiz-Olalla G, [...], Engel P.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.816389
The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerging variants raises concerns about their capacity to evade immune protection provided by natural infection or vaccination. The receptor-binding domain (RBD) of the viral spike protein is the major target of neutralizing antibodies, and viral variants accumulate mutations in this region. In this study, we determined the antibody neutralization capacity against the RBD of SARS-CoV-2 variants Alpha (B.1.1.7), Gamma (P.1), Epsilon (B.1.427), Kappa (B.1.617.1), and Delta (B.1.617.2) in a cohort of healthcare workers naturally infected or receiving COVID-19 mRNA vaccines from Moderna or Pfizer-BioNTech. We show that the five RBD variants displayed an augmented binding to ACE2 compared to the original Wuhan strain. The most significant increase was observed in variants Epsilon and Delta, containing mutation L452R. Using a flow cytometry cell-based assay, we found that SARS-CoV-2-infected subjects presented low levels of RBD-specific neutralizing antibodies against all variants analyzed, except Alpha. However, the neutralizing activity incremented considerably after a subsequent mRNA-vaccine dose, to levels significantly higher than those in naïve individuals receiving two vaccine doses. Importantly, we observed partially impaired neutralizing responses against most variants in fully vaccinated individuals. Variants Gamma and Kappa encompassing RBD E484K/Q mutations presented the highest neutralizing resistance. Furthermore, a wide heterogeneity in the magnitude of RBD-specific neutralizing responses against all tested SARS-CoV-2 variants following both mRNA vaccines was detected. Altogether, our findings provide important knowledge regarding SARS-CoV-2 vaccine-induced immunity, and should be very useful to guide future vaccination regimens and personalized vaccine approaches.
2022-04-06 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.816389 Decreased and Heterogeneous Neutralizing Antibody Responses Against RBD of SARS-CoV-2 Variants After mRNA Vaccination. Hernández-Luis P, Aguilar R, Pelegrin-Pérez J, Ruiz-Olalla G, García-Basteiro AL, Tortajada M, Moncunill G, Dobaño C, Angulo A, Engel P. Front Immunol. 2022; 13
Advances and gaps in SARS-CoV-2 infection models.
Muñoz-Fontela C, Widerspick L, Albrecht RA, Beer M, [...], Barouch DH.
PLoS Pathog. 2022; 18 (1)
DOI: 10.1371/journal.ppat.1010161
The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age.
2022-01-13 2022 other review-article; Review; Journal Article abstract-available 10.1371/journal.ppat.1010161 Advances and gaps in SARS-CoV-2 infection models. Muñoz-Fontela C, Widerspick L, Albrecht RA, Beer M, Carroll MW, de Wit E, Diamond MS, Dowling WE, Funnell SGP, García-Sastre A, Gerhards NM, de Jong R, Munster VJ, Neyts J, Perlman S, Reed DS, Richt JA, Riveros-Balta X, Roy CJ, Salguero FJ, Schotsaert M, Schwartz LM, Seder RA, Segalés J, Vasan SS, Henao-Restrepo AM, Barouch DH. PLoS Pathog. 2022; 18 (1)
Editorial: A Compendium of Recent Research on Stem Cell-Based Therapy for Covid-19.
Hmadcha A, Soria B, Zhao RC, Smani T, [...], Valverde I.
Front Cell Dev Biol. 2021; 9
DOI: 10.3389/fcell.2021.813384
2021-12-14 2021 other Editorial 10.3389/fcell.2021.813384 Editorial: A Compendium of Recent Research on Stem Cell-Based Therapy for Covid-19. Hmadcha A, Soria B, Zhao RC, Smani T, Valverde I. Front Cell Dev Biol. 2021; 9
Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges.
Masterson CH, Ceccato A, Artigas A, Dos Santos C, [...], Laffey JG.
Intensive Care Med Exp. 2021; 9 (1)
DOI: 10.1186/s40635-021-00424-5
Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to 'licence' or 'pre-activate' these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.
2021-12-31 2021 other review-article; Review; Journal Article abstract-available 10.1186/s40635-021-00424-5 Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges. Masterson CH, Ceccato A, Artigas A, Dos Santos C, Rocco PR, Rolandsson Enes S, Weiss DJ, McAuley D, Matthay MA, English K, Curley GF, Laffey JG. Intensive Care Med Exp. 2021; 9 (1)
ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points.
Tamayo-Velasco Á, Peñarrubia-Ponce MJ, Álvarez FJ, de la Fuente I, [...], Andaluz-Ojeda D.
Front Med (Lausanne). 2022; 9
DOI: 10.3389/fmed.2022.882477
The implication of the ABO blood group in COVID-19 disease was formulated early, at the beginning of the COVID-19 pandemic more than 2 years ago. It has now been established that the A blood group is associated with more susceptibility and severe symptoms of COVID-19, while the O blood group shows protection against viral infection. In this review, we summarize the underlying pathophysiology of ABO blood groups and COVID-19 to explain the molecular aspects behind the protective mechanism in the O blood group. A or B antigens are not associated with a different risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than that of other antigens. In this case, the cornerstone is natural anti-A and anti-B antibodies from the ABO system. They are capable of interfering with the S protein (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2; host cell receptor), thereby conferring protection to patients with sufficient antibodies (O blood group). Indeed, the titers of natural antibodies and the IgG isotype (specific to the O blood group) may be determinants of susceptibility and severity. Moreover, older adults are associated with a higher risk of bad outcomes due to the lack of antibodies and the upregulation of ACE2 expression during senescence. A better understanding of the role of the molecular mechanism of ABO blood groups in COVID-19 facilitates better prognostic stratification of the disease. Furthermore, it could represent an opportunity for new therapeutic strategies.
2022-04-25 2022 other review-article; Review; Journal Article abstract-available 10.3389/fmed.2022.882477 ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points. Tamayo-Velasco Á, Peñarrubia-Ponce MJ, Álvarez FJ, de la Fuente I, Pérez-González S, Andaluz-Ojeda D. Front Med (Lausanne). 2022; 9
Chronic Rhinosinusitis and COVID-19.
Marin C, Hummel T, Liu Z, Mullol J.
J Allergy Clin Immunol Pract. 2022;
DOI: 10.1016/j.jaip.2022.03.003
The COVID-19 pandemic has raised awareness about olfactory dysfunction, although a loss of smell was present in the general population before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease that is also one of the most common causes of olfactory dysfunction. It can be classified into different phenotypes (ie, with and without nasal polyps) and endotypes (ie, type 2 and non-type 2 inflammation). However, scientific information regarding CRS within the context of COVID-19 is still scarce. This review focuses on (1) the potential effects of severe acute respiratory syndrome coronavirus 2 infection on CRS symptoms, including a loss of smell, and comorbidities; (2) the pathophysiologic mechanisms involved in the olfactory dysfunction; (3) CRS diagnosis in the context of COVID-19, including telemedicine; (4) the protective hypothesis of CRS in COVID-19; and (5) the efficacy and safety of therapeutic options for CRS within the context of COVID-19.
2022-03-17 2022 other IM; research-article; Journal Article abstract-available 10.1016/j.jaip.2022.03.003 Chronic Rhinosinusitis and COVID-19. Marin C, Hummel T, Liu Z, Mullol J. J Allergy Clin Immunol Pract. 2022;
Impact of COVID-19 on liver disease: From the experimental to the clinic perspective.
Gato S, Lucena-Valera A, Muñoz-Hernández R, Sousa JM, [...], Ampuero J.
World J Virol. 2021; 10 (6)
DOI: 10.5501/wjv.v10.i6.301
Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a predominantly respiratory infection, various degrees of liver function abnormalities have been reported. Pre-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies, but it can critically compromise survival and trigger hepatic decompensation. The collapse of the healthcare services has negatively impacted the diagnosis, monitoring, and treatment of liver diseases in non-COVID-19 patients. In this review, we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.
2021-11-01 2021 other review-article; Review; Journal Article abstract-available 10.5501/wjv.v10.i6.301 Impact of COVID-19 on liver disease: From the experimental to the clinic perspective. Gato S, Lucena-Valera A, Muñoz-Hernández R, Sousa JM, Romero-Gómez M, Ampuero J. World J Virol. 2021; 10 (6)
Experimental and natural infections of severe acute respiratory syndrome-related coronavirus 2 in pets and wild and farm animals.
Mastutik G, Rohman A, I'tishom R, Ruiz-Arrondo I, [...], de Blas I.
Vet World. 2022; 15 (3)
DOI: 10.14202/vetworld.2022.565-589
The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has spread globally and has led to extremely high mortality rates. In addition to infecting humans, this virus also has infected animals. Experimental studies and natural infections showed that dogs have a low susceptibility to SARS-CoV-2 infection, whereas domesticated cats and other animals in the family Felidae, such as lions, tigers, snow leopards, and cougars, have a high susceptibility to viral infections. In addition, wild white-tailed deer, gorillas, and otters have been found to be infected by SARS-CoV-2. Furry farm animals, such as minks, have a high susceptibility to SARS-CoV-2 infection. The virus appears to spread among minks and generate several new mutations, resulting in increased viral virulence. Furthermore, livestock animals, such as cattle, sheep, and pigs, were found to have low susceptibility to the virus, whereas chicken, ducks, turkeys, quail, and geese did not show susceptibility to SARS-CoV-2 infection. This knowledge can provide insights for the development of SARS-CoV-2 mitigation strategies in animals and humans. Therefore, this review focuses on experimental (both replication and transmission) in vitro, ex vivo, and in vivo studies of SARS-CoV-2 infections in pets and in wild and farm animals, and to provide details on the mechanism associated with natural infection.
2022-03-10 2022 other review-article; Review; Journal Article abstract-available 10.14202/vetworld.2022.565-589 Experimental and natural infections of severe acute respiratory syndrome-related coronavirus 2 in pets and wild and farm animals. Mastutik G, Rohman A, I'tishom R, Ruiz-Arrondo I, de Blas I. Vet World. 2022; 15 (3)
SARS-CoV-2 in animals: potential for unknown reservoir hosts and public health implications.
Sharun K, Dhama K, Pawde AM, Gortázar C, [...], Attia YA.
Vet Q. 2021; 41 (1)
DOI: 10.1080/01652176.2021.1921311
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously 2019-nCoV) is suspected of having originated in 2019 in China from a coronavirus infected bat of the genus Rhinolophus. Following the initial emergence, possibly facilitated by a mammalian bridge host, SARS-CoV-2 is currently transmitted across the globe via efficient human-to-human transmission. Results obtained from experimental studies indicate that animal species such as cats, ferrets, raccoon dogs, cynomolgus macaques, rhesus macaques, white-tailed deer, rabbits, Egyptian fruit bats, and Syrian hamsters are susceptible to SARS-CoV-2 infection, and that cat-to-cat and ferret-to-ferret transmission can take place via contact and air. However, natural infections of SARS-CoV-2 have been reported only in pet dogs and cats, tigers, lions, snow leopards, pumas, and gorillas at zoos, and farmed mink and ferrets. Even though human-to-animal spillover has been reported at several instances, SARS-CoV-2 transmission from animals-to-humans has only been reported from mink-to-humans in mink farms. Following the rapid transmission of SARS-CoV-2 within the mink population, a new mink-associated SARS-CoV-2 variant emerged that was identified in both humans and mink. The increasing reports of SARS-CoV-2 in carnivores indicate the higher susceptibility of animal species belonging to this order. The sporadic reports of SARS-CoV-2 infection in domestic and wild animal species require further investigation to determine if SARS-CoV-2 or related Betacoronaviruses can get established in kept, feral or wild animal populations, which may eventually act as viral reservoirs. This review analyzes the current evidence of SARS-CoV-2 natural infection in domestic and wild animal species and their possible implications on public health.
2021-12-01 2021 other review-article; Review; Journal Article abstract-available 10.1080/01652176.2021.1921311 SARS-CoV-2 in animals: potential for unknown reservoir hosts and public health implications. Sharun K, Dhama K, Pawde AM, Gortázar C, Tiwari R, Tiwari R, Bonilla-Aldana DK, Rodriguez-Morales AJ, de la Fuente J, Michalak I, Michalak I, Attia YA. Vet Q. 2021; 41 (1)
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 (Engl Ed). 2021; 157 (9)
DOI: 10.1016/j.medcle.2021.04.010
2021-11-05 2021 other letter; Journal Article 10.1016/j.medcle.2021.04.010 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 (Engl Ed). 2021; 157 (9)
SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients.
Gutiérrez-Chamorro L, Riveira-Muñoz E, Barrios C, Palau V, [...], Ballana E.
Viruses. 2021; 13 (9)
DOI: 10.3390/v13091715
Angiotensin converting enzyme 2 (ACE2) is a host ectopeptidase and the receptor for the SARS-CoV-2 virus, albeit virus-ACE2 interaction goes far beyond viral entry into target cells. Controversial data exists linking viral infection to changes in ACE2 expression and function, which might influence the subsequent induction of an inflammatory response. Here, we tested the significance of soluble ACE2 enzymatic activity longitudinally in nasopharyngeal swabs and plasma samples of SARS-CoV-2 infected patients, along with the induction of inflammatory cytokines. Release of soluble functional ACE2 increases upon SARS-CoV-2 infection in swabs and plasma of infected patients, albeit rapidly decreasing during infection course in parallel with ACE2 gene expression. Similarly, SARS-CoV-2 infection also induced the expression of inflammatory cytokines. These changes positively correlated with the viral load. Overall, our results demonstrate the existence of mechanisms by which SARS-CoV-2 modulates ACE2 expression and function, intracellular viral sensing and subsequent inflammatory response, offering new insights into ACE2 dynamics in the human upper respiratory tract and pointing towards soluble ACE2 levels as a putative early biomarker of infection severity.
2021-08-28 2021 other IM; Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13091715 SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients. Gutiérrez-Chamorro L, Riveira-Muñoz E, Barrios C, Palau V, Nevot M, Pedreño-López S, Senserrich J, Massanella M, Clotet B, Cabrera C, Mitjà O, Crespo M, Pascual J, Riera M, Ballana E. Viruses. 2021; 13 (9)
Headache as a Symptom of COVID-19: Narrative Review of 1-Year Research.
Caronna E, Pozo-Rosich P.
Curr Pain Headache Rep. 2021; 25 (11)
DOI: 10.1007/s11916-021-00987-8

Purpose of review

Headache is a common symptom of COVID-19 with emerging literature being published on the subject. Although it may seem unspecific, scientific evidence has allowed a better definition of this headache type, revealing relevant associations with other COVID-19 symptoms and prognoses. We therefore sought to highlight the most remarkable findings concerning headache secondary to COVID-19, specifically focusing on epidemiology, characteristics, pathophysiology, and treatments.

Recent findings

The real prevalence of headache as a symptom of COVID-19 is still unclear ranging from 10 to 70%. Headache mainly has a tension-type-like phenotype, although 25% of individuals present with migraine-like features that also occur in patients without personal migraine history. This finding suggests that a likely pathophysiological mechanism is the activation of the trigeminovascular system. SARS-CoV-2 neurotropism can occur by trans-synaptic invasion through the olfactory route from the nasal cavity, leading to anosmia which has been associated with headache. SARS-CoV-2 protein has been found not only in olfactory mucosa and bulbs but also in trigeminal branches and the trigeminal ganglion, supporting this hypothesis. However, other mechanisms such as brain vessels inflammation due to SARS-CoV-2 damage to the endothelium or systemic inflammation in the context of cytokine storm cannot be ruled out. Interestingly, headache has been associated with lower COVID-19 mortality. No specific treatment for COVID-19 headache is available at present. Studies show that investigating COVID-19 headache represents an opportunity not only to better understand COVID-19 in general but also to advance in the knowledge of both secondary and primary headaches. Future research is therefore warranted.
2021-11-11 2021 other review-article; Review; Journal Article abstract-available 10.1007/s11916-021-00987-8 Headache as a Symptom of COVID-19: Narrative Review of 1-Year Research. Caronna E, Pozo-Rosich P. Curr Pain Headache Rep. 2021; 25 (11)
Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19.
Tejerina F, Catalan P, Rodriguez-Grande C, Adan J, [...], Gregorio Marañon Microbiology ID COVID 19 Study Group.
BMC Infect Dis. 2022; 22 (1)
DOI: 10.1186/s12879-022-07153-4

Background

There is a paucity of knowledge on the long-term outcome in patients diagnosed with COVID-19. We describe a cohort of patients with a constellation of symptoms occurring four weeks after diagnosis causing different degrees of reduced functional capacity. Although different hypothesis have been proposed to explain this condition like persistent immune activation or immunological dysfunction, to date, no physiopathological mechanism has been identified. Consequently, there are no therapeutic options besides symptomatic treatment and rehabilitation.

Methods

We evaluated patients with symptoms that persisted for at least 4 weeks after COVID-19. Epidemiological and clinical data were collected. Blood tests, including inflammatory markers, were conducted, and imaging studies made if deemed necessary. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) in plasma, stool, and urine were performed. Patients were offered antiviral treatment (compassionate use).

Results

We evaluated 29 patients who reported fatigue, muscle pain, dyspnea, inappropriate tachycardia, and low-grade fever. Median number of days from COVID-19 to positive RT-PCR in extra-respiratory samples was 55 (39-67). Previous COVID-19 was mild in 55% of the cases. Thirteen patients (45%) had positive plasma RT-PCR results and 51% were positive in at least one RT-PCR sample (plasma, urine, or stool). Functional status was severely reduced in 48% of the subjects. Eighteen patients (62%) received antiviral treatment. Improvement was seen in most patients (p = 0.000) and patients in the treatment group achieved better outcomes with significant differences (p = 0.01).

Conclusions

In a cohort of COVID-19 patients with persistent symptoms, 45% of them have detectable plasma SARS-CoV-2 RNA. Our results indicate possible systemic viral persistence in these patients, who may benefit of antiviral treatment strategies.
2022-03-03 2022 other research-article; Journal Article abstract-available 10.1186/s12879-022-07153-4 Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19. Tejerina F, Catalan P, Rodriguez-Grande C, Adan J, Rodriguez-Gonzalez C, Muñoz P, Aldamiz T, Diez C, Perez L, Fanciulli C, Garcia de Viedma D, Gregorio Marañon Microbiology ID COVID 19 Study Group. BMC Infect Dis. 2022; 22 (1)
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; 126 (8)
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; 126 (8)
A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2.
Devi KP, Pourkarim MR, Thijssen M, Sureda A, [...], Khayat Kashani HR.
Pharmacol Rep. 2022; 74 (2)
DOI: 10.1007/s43440-021-00344-x
Currently, the world is facing a pandemic of the new coronavirus SARS-CoV-2 that causes COVID-19. Identifying key targets in the viral infection lifecycle is urgently needed for designing therapeutic strategies to combat the virus. Furin is a subtilisin-like proprotein convertase with diverse cellular functions. Emerging evidence suggests that furin plays a critical role in the activation and/or infectivity of SARS-CoV-2. In this perspective, we discuss the potential role of furin in the entry SARS-CoV-2 into host cells. Furthermore, we evaluate available peptide and non-peptide furin inhibitors and potential outcomes, including immune responses.
2022-01-15 2022 other brief-report; Journal Article abstract-available 10.1007/s43440-021-00344-x A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2. Devi KP, Pourkarim MR, Thijssen M, Sureda A, Khayatkashani M, Cismaru CA, Neagoe IB, Habtemariam S, Razmjouei S, Khayat Kashani HR. Pharmacol Rep. 2022; 74 (2)
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)
The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo.
Beltrán-Camacho L, Eslava-Alcón S, Rojas-Torres M, Sánchez-Morillo D, [...], Durán-Ruiz MC.
Mol Med. 2022; 28 (1)
DOI: 10.1186/s10020-022-00465-w

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 million deaths worldwide. While asymptomatic individuals are responsible of many potential transmissions, the difficulty to identify and isolate them at the high peak of infection constitutes still a real challenge. Moreover, SARS-CoV-2 provokes severe vascular damage and thromboembolic events in critical COVID-19 patients, deriving in many related deaths and long-hauler symptoms. Understanding how these processes are triggered as well as the potential long-term sequelae, even in asymptomatic individuals, becomes essential.

Methods

We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum from COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Healthy CACs were incubated ex-vivo with the serum of either COVID-19 negative (PCR -/IgG -, n:8) or COVID-19 positive asymptomatic donors, at different infective stages: PCR +/IgG - (n:8) and PCR -/IgG + (n:8). Also, a label free quantitative approach was applied to identify and quantify protein differences between these serums. Finally, machine learning algorithms were applied to validate the differential protein patterns in CACs.

Results

Our results confirmed that SARS-CoV-2 promotes changes at the protein level in the serum of infected asymptomatic individuals, mainly correlated with altered coagulation and inflammatory processes (Fibrinogen, Von Willebrand Factor, Thrombospondin-1). At the cellular level, proteins like ICAM-1, TLR2 or Ezrin/Radixin were only up-regulated in CACs treated with the serum of asymptomatic patients at the highest peak of infection (PCR + /IgG -), but not with the serum of PCR -/IgG + individuals. Several proteins stood out as significantly discriminating markers in CACs in response to PCR or IgG + serums. Many of these proteins particiArticle title: Kindly check and confirm the edit made in the article title.pate in the initial endothelial response against the virus.

Conclusions

The ex vivo incubation of CACs with the serum of asymptomatic COVID-19 donors at different stages of infection promoted protein changes representative of the endothelial dysfunction and inflammatory response after viral infection, together with activation of the coagulation process. The current approach constitutes an optimal model to study the response of vascular cells to SARS-CoV-2 infection, and an alternative platform to test potential inhibitors targeting either the virus entry pathway or the immune responses following SARS-CoV-2 infection.
2022-04-09 2022 other research-article; Journal Article abstract-available 10.1186/s10020-022-00465-w The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo. Beltrán-Camacho L, Eslava-Alcón S, Rojas-Torres M, Sánchez-Morillo D, Martinez-Nicolás MP, Martín-Bermejo V, de la Torre IG, Berrocoso E, Moreno JA, Moreno-Luna R, Durán-Ruiz MC. Mol Med. 2022; 28 (1)
Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins.
Tajuelo A, López-Siles M, Más V, Pérez-Romero P, [...], López D.
Int J Mol Sci. 2022; 23 (6)
DOI: 10.3390/ijms23062977
The B and T lymphocytes of the adaptive immune system are important for the control of most viral infections, including COVID-19. Identification of epitopes recognized by these cells is fundamental for understanding how the immune system detects and removes pathogens, and for antiviral vaccine design. Intriguingly, several cross-reactive T lymphocyte epitopes from SARS-CoV-2 with other betacoronaviruses responsible for the common cold have been identified. In addition, antibodies that cross-recognize the spike protein, but not the nucleoprotein (N protein), from different betacoronavirus have also been reported. Using a consensus of eight bioinformatic methods for predicting B-cell epitopes and the collection of experimentally detected epitopes for SARS-CoV and SARS-CoV-2, we identified four surface-exposed, conserved, and hypothetical antigenic regions that are exclusive of the N protein. These regions were analyzed using ELISA assays with two cohorts: SARS-CoV-2 infected patients and pre-COVID-19 samples. Here we describe four epitopes from SARS-CoV-2 N protein that are recognized by the humoral response from multiple individuals infected with COVID-19, and are conserved in other human coronaviruses. Three of these linear surface-exposed sequences and their peptide homologs in SARS-CoV-2 and HCoV-OC43 were also recognized by antibodies from pre-COVID-19 serum samples, indicating cross-reactivity of antibodies against coronavirus N proteins. Different conserved human coronaviruses (HCoVs) cross-reactive B epitopes against SARS-CoV-2 N protein are detected in a significant fraction of individuals not exposed to this pandemic virus. These results have potential clinical implications.
2022-03-10 2022 other IM; research-article; Journal Article abstract-available 10.3390/ijms23062977 Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins. Tajuelo A, López-Siles M, Más V, Pérez-Romero P, Aguado JM, Briz V, McConnell MJ, Martín-Galiano AJ, López D. Int J Mol Sci. 2022; 23 (6)
Dental Healthcare Amid the COVID-19 Pandemic.
Butt RT, Janjua OS, Qureshi SM, Shaikh MS, [...], Zafar MS.
Int J Environ Res Public Health. 2021; 18 (21)
DOI: 10.3390/ijerph182111008
The hustle and bustle of the planet Earth have come to a halt thanks to the novel coronavirus. The virus has affected approximately 219 million people globally; taken the lives of 4.55 million patients as of September 2021; and created an ambiance of fear, social distancing, and economic instability. The purpose of this review article is to trace the historical origin and evolution of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). The virus is highly contagious with a unique feature of rapid mutations-the scientific research is paving the way for discoveries regarding novel coronavirus disease (COVID-19) diagnosis, features, prevention, and vaccination. The connections between the coronavirus pandemic and dental practices are essential because COVID-19 is transmitted by aerosols, fomites, and respiratory droplets, which are also produced during dental procedures, putting both the patient and the dentist at risk. The main emphasis of this paper is to highlight the psychological, economic, and social impact of this pandemic on dental practices throughout the world and under what circumstances and guidelines can dental health care be provided. In the current situation of the pandemic, an appropriate screening tool must be established either by using rapid molecular testing or saliva point-of-care technology, which will be effective in identifying as well as isolating the potential contacts and carriers in hopes to contain and mitigate infection. The blessing in disguise is that this virus has united the leaders, scientists, health care providers, and people of all professions from all around the world to fight against a common enemy.
2021-10-20 2021 other IM; review-article; Review; Journal Article abstract-available 10.3390/ijerph182111008 Dental Healthcare Amid the COVID-19 Pandemic. Butt RT, Janjua OS, Qureshi SM, Shaikh MS, Guerrero-Gironés J, Rodríguez-Lozano FJ, Zafar MS. Int J Environ Res Public Health. 2021; 18 (21)
Is There Less Alteration of Smell Sensation in Patients With Omicron SARS-CoV-2 Variant Infection?
Rodriguez-Sevilla JJ, Güerri-Fernádez R, Bertran Recasens B.
Front Med (Lausanne). 2022; 9
DOI: 10.3389/fmed.2022.852998
The ongoing pandemic Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern in terms of public health Within the symptoms secondary to SARS-CoV-2 infection, hyposmia and anosmia have emerged as characteristic symptoms during the onset of the pandemic. Although many researchers have investigated the etiopathogenesis of this phenomenon, the main cause is not clear. The appearance of the new variant of concern Omicron has meant a breakthrough in the chronology of this pandemic, presenting greater transmissibility and less severity, according to the first reports. We have been impressed by the decrease in anosmia reported with this new variant and in patients reinfected or who had received vaccination before becoming infected. Based on the literature published to date, this review proposes different hypotheses to explain this possible lesser affectation of smell. On the one hand, modifications in the SARS-CoV-2 spike protein could produce changes in cell tropism and interaction with proteins that promote virus uptake (ACE-2, TMPRSS2, and TMEM16F). These proteins can be found in the sustentacular cells and glandular cells of the olfactory epithelium. Second, due to the characteristics of the virus or previous immunity (infection or vaccination), there could be less systemic or local inflammation that would generate less cell damage in the olfactory epithelium and/or in the central nervous system.
2022-04-12 2022 other research-article; Journal Article abstract-available 10.3389/fmed.2022.852998 Is There Less Alteration of Smell Sensation in Patients With Omicron SARS-CoV-2 Variant Infection? Rodriguez-Sevilla JJ, Güerri-Fernádez R, Bertran Recasens B. Front Med (Lausanne). 2022; 9
Narrative review on clinical considerations for patients with diabetes and COVID-19: More questions than answers.
Katsiki N, Gómez-Huelgas R, Mikhailidis DP, Pérez-Martínez P.
Int J Clin Pract. 2021; 75 (11)
DOI: 10.1111/ijcp.14833

Background-aim

Diabetes, obesity and hypertension are common comorbidities associated with increased severity and mortality rates from Corona Virus Disease (COVID)-19.

Methods

In this narrative review (using the PubMed database), we discuss epidemiological data and pathophysiological links between diabetes and COVID-19. The potential effects of glycaemic control and antidiabetic drugs on the prevalence and outcomes of COVID-19 are also reviewed, as well as the role of telemedicine and diabetes self-management in the post-COVID-19 era.

Results

Diabetes has been linked to COVID-19 morbidity and mortality, although further research is needed to elucidate this association. In the meantime, physicians should be aware of the potential rise in the prevalence of diabetes (due to unhealthy lifestyle changes during the pandemic), its severity and complications and focus on achieving optimal diabetes prevention and management. Telemedicine and diabetes self-management may help towards this direction. Dipeptidyl-peptidase 4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors may affect viral entry and infection, and thus COVID-19 outcomes, as shown in observational studies.

Conclusion

Diabetes has been associated with COVID-19 development and progression. Certain antidiabetic drugs may influence COVID-19 prevention and management. The results of ongoing randomized clinical trials will shed more light on this field.
2021-09-21 2021 other review-article; Review; Journal Article abstract-available 10.1111/ijcp.14833 Narrative review on clinical considerations for patients with diabetes and COVID-19: More questions than answers. Katsiki N, Gómez-Huelgas R, Mikhailidis DP, Pérez-Martínez P. Int J Clin Pract. 2021; 75 (11)
Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19.
Muskiet FAJ, Carrera-Bastos P, Pruimboom L, Lucia A, [...], Furman D.
Nutrients. 2022; 14 (7)
DOI: 10.3390/nu14071388
Obesity, and obesity-associated conditions such as hypertension, chronic kidney disease, type 2 diabetes, and cardiovascular disease, are important risk factors for severe Coronavirus disease-2019 (COVID-19). The common denominator is metaflammation, a portmanteau of metabolism and inflammation, which is characterized by chronically elevated levels of leptin and pro-inflammatory cytokines. These induce the "Suppressor Of Cytokine Signaling 1 and 3" (SOCS1/3), which deactivates the leptin receptor and also other SOCS1/3 sensitive cytokine receptors in immune cells, impairing the type I and III interferon early responses. By also upregulating SOCS1/3, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 adds a significant boost to this. The ensuing consequence is a delayed but over-reactive immune response, characterized by high-grade inflammation (e.g., cytokine storm), endothelial damage, and hypercoagulation, thus leading to severe COVID-19. Superimposing an acute disturbance, such as a SARS-CoV-2 infection, on metaflammation severely tests resilience. In the long run, metaflammation causes the "typical western" conditions associated with metabolic syndrome. Severe COVID-19 and other serious infectious diseases can be added to the list of its short-term consequences. Therefore, preventive measures should include not only vaccination and the well-established actions intended to avoid infection, but also dietary and lifestyle interventions aimed at improving body composition and preventing or reversing metaflammation.
2022-03-26 2022 other IM; review-article; Review; Journal Article abstract-available 10.3390/nu14071388 Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19. Muskiet FAJ, Carrera-Bastos P, Pruimboom L, Lucia A, Furman D. Nutrients. 2022; 14 (7)
High SARS-CoV-2 Viral Load and Low CCL5 Expression Levels in the Upper Respiratory Tract Are Associated With COVID-19 Severity.
Pérez-García F, Martin-Vicente M, Rojas-García RL, Castilla-García L, [...], Martínez I.
J Infect Dis. 2022; 225 (6)
DOI: 10.1093/infdis/jiab604
Mucosal immune response in the upper respiratory tract is crucial for initial control of viral replication, clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and progression of coronavirus disease 2019 (COVID-19). We analyzed SARS-CoV-2 RNA load and expression of selected immune genes in the upper respiratory tract (nasopharynx) of 255 SARS-CoV-2-infected patients and evaluated their association with severe COVID-19. SARS-CoV-2 replication in nasopharyngeal mucosa induces expression of several innate immune genes. High SARS-CoV-2 viral load and low CCL5 expression levels were associated with intensive care unit admission or death, although CCL5 was the best predictor of COVID-19 severity.
2022-03-01 2022 fondo-covid brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1093/infdis/jiab604 High SARS-CoV-2 Viral Load and Low CCL5 Expression Levels in the Upper Respiratory Tract Are Associated With COVID-19 Severity. Pérez-García F, Martin-Vicente M, Rojas-García RL, Castilla-García L, Muñoz-Gomez MJ, Hervás Fernández I, González Ventosa V, Vidal-Alcántara EJ, Cuadros-González J, Bermejo-Martin JF, Resino S, Martínez I. J Infect Dis. 2022; 225 (6)
Differences in saliva ACE2 activity among infected and non-infected adult and pediatric population exposed to SARS-CoV-2.
Jiménez D, Martínez-Sanz J, Sainz T, Calvo C, [...], Serrano-Villar S.
J Infect. 2022;
DOI: 10.1016/j.jinf.2022.04.041

Background

Variations in the ACE2 activity in saliva could explain the striking differences of susceptibility to infection and risk of severe disease.

Methods

We analyze the activity of ACE2 in saliva in different population groups across a wide age range and disease status during April to June 2020, and we establish differences between infected people and participants considered resistant (highly exposed healthcare workers and children who cohabited with parents with COVID-19 without isolation and remain IgG negative).

Results

We included 74 adults, of which 47 (64%) were susceptible and 27 (36%) were resistant, and 79 children, of which 41 (52%) were susceptible and 38 (48%) were resistant. Resistant adults have significantly lower ACE2 activity in saliva than susceptible adults and non-significant higher values than susceptible and resistant children. ACE2 activity is similar in the susceptible and resistant pediatric population (p=0.527). In contrast, we observe an increase in activity as the disease's severity increases among the adult population (mild disease vs. severe disease, 39 vs. 105 FU, p=0.039; severe disease vs. resistant, 105 vs. 31 FU, p<0.001).

Conclusions

using an enzymatic test, we show that ACE2 activity in saliva correlates with the susceptibility to SARS-Cov-2 infection and disease severity. Children and adults with low-susceptibility to SARS-Cov-2 infection showed the lowest ACE2 activity. These findings could inform future strategies to identify at-risk individuals.
2022-04-28 2022 other research-article; Journal Article abstract-available 10.1016/j.jinf.2022.04.041 Differences in saliva ACE2 activity among infected and non-infected adult and pediatric population exposed to SARS-CoV-2. Jiménez D, Martínez-Sanz J, Sainz T, Calvo C, Méndez-Echevarría A, Moreno E, Blázquez-Gamero D, Vizcarra P, Rodríguez M, Jenkins R, Sánchez-Conde M, Ron R, Norman F, Moreno S, Ferrer M, Serrano-Villar S. J Infect. 2022;
Exosomal mediated signal transduction through artificial microRNA (amiRNA): A potential target for inhibition of SARS-CoV-2.
Vadivalagan C, Shitut A, Kamalakannan S, Chen RM, [...], Krishnan A.
Cell Signal. 2022; 95
DOI: 10.1016/j.cellsig.2022.110334
Exosome trans-membrane signals provide cellular communication between the cells through transport and/or receiving the signal by molecule, change the functional metabolism, and stimulate and/or inhibit receptor signal complexes. COVID19 genetic transformations are varied in different geographic positions, and single nucleotide polymorphic lineages were reported in the second waves due to the fast mutational rate and adaptation. Several vaccines were developed and in treatment practice, but effective control has yet to reach in cent presence. It was initially a narrow immune-modulating protein target. Controlling these diverse viral strains may inhibit their transuding mechanisms primarily to target RNA genes responsible for COVID19 transcription. Exosomal miRNAs are the main sources of transmembrane signals, and trans-located miRNAs can directly target COVID19 mRNA transcription. This review discussed targeted viral transcription by delivering the artificial miRNA (amiRNA) mediated exosomes in the infected cells and significant resources of exosome and their efficacy.
2022-04-21 2022 other research-article; Journal Article abstract-available 10.1016/j.cellsig.2022.110334 Exosomal mediated signal transduction through artificial microRNA (amiRNA): A potential target for inhibition of SARS-CoV-2. Vadivalagan C, Shitut A, Kamalakannan S, Chen RM, Serrano-Aroca Á, Mishra V, Aljabali AAA, Singh SK, Chellappan DK, Gupta G, Dua K, El-Tanani M, Tambuwala MM, Krishnan A. Cell Signal. 2022; 95
Inflammation and oxidative stress, the links between obesity and COVID-19: a narrative review.
Moreno-Fernandez J, Ochoa J, Ojeda ML, Nogales F, [...], Díaz-Castro J.
J Physiol Biochem. 2022;
DOI: 10.1007/s13105-022-00887-4
COVID-19, an acute respiratory disease caused by SARS-CoV-2, has rapidly become a pandemic. On the other hand, obesity is also reaching dramatic dimensions and it is a risk factor for morbidity and premature mortality. Obesity has been linked to a high risk of serious-associated complications to COVID-19, due to the increased risk of concomitant chronic diseases, which highlights the health public relevance of the topic. Obese subjects have a pro-inflammatory environment, which can further exacerbate COVID-19-induced inflammation and oxidative stress, explaining the increased risk of serious complications in these patients. Another factor that favors infection in obese patients is the high expression of ACE2 receptors in the adipose tissue. The negative impact of COVID-19 in obesity is also associated with a decrease in respiratory function, the concurrence of multiple comorbidities, a low-degree chronic inflammatory state, immunocompromised situation, and therefore a higher rate of hospitalization, mechanical ventilation, in-hospital complications such as pneumonia, and death. In this review, the link between obesity and COVID-19 was analyzed, exploring the potential common mechanisms in both diseases, with special attention to oxidative stress and inflammation, due to the crucial role of both pathways in the development of the disease.
2022-03-22 2022 other IM; review-article; Review; Journal Article abstract-available 10.1007/s13105-022-00887-4 Inflammation and oxidative stress, the links between obesity and COVID-19: a narrative review. Moreno-Fernandez J, Ochoa J, Ojeda ML, Nogales F, Carreras O, Díaz-Castro J. J Physiol Biochem. 2022;
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)
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; 68 (8)
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; 68 (8)
Renin-angiotensin system blockers during the COVID-19 pandemic: an update for patients with hypertension and chronic kidney disease.
Theodorakopoulou MP, Alexandrou ME, Boutou AK, Ferro CJ, [...], Sarafidis P.
Clin Kidney J. 2022; 15 (3)
DOI: 10.1093/ckj/sfab272
Hypertension and chronic kidney disease (CKD) are among the most common comorbidities associated with coronavirus disease 2019 (COVID-19) severity and mortality risk. Renin-angiotensin system (RAS) blockers are cornerstones in the treatment of both hypertension and proteinuric CKD. In the early months of the COVID-19 pandemic, a hypothesis emerged suggesting that the use of RAS blockers may increase susceptibility for COVID-19 infection and disease severity in these populations. This hypothesis was based on the fact that angiotensin-converting enzyme 2 (ACE2), a counter regulatory component of the RAS, acts as the receptor for severe acute respiratory syndrome coronavirus 2 cell entry. Extrapolations from preliminary animal studies led to speculation that upregulation of ACE2 by RAS blockers may increase the risk of COVID-19-related adverse outcomes. However, these hypotheses were not supported by emerging evidence from observational and randomized clinical trials in humans, suggesting no such association. Herein we describe the physiological role of ACE2 as part of the RAS, discuss its central role in COVID-19 infection and present original and updated evidence from human studies on the association between RAS blockade and COVID-19 infection or related outcomes, with a particular focus on hypertension and CKD.
2021-12-14 2021 other review-article; Review; Journal Article abstract-available 10.1093/ckj/sfab272 Renin-angiotensin system blockers during the COVID-19 pandemic: an update for patients with hypertension and chronic kidney disease. Theodorakopoulou MP, Alexandrou ME, Boutou AK, Ferro CJ, Ortiz A, Sarafidis P. Clin Kidney J. 2022; 15 (3)
Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial.
García-García I, Seco-Meseguer E, Ruiz-Seco P, Navarro-Jimenez G, [...], Borobia AM.
J Clin Med. 2022; 11 (4)
DOI: 10.3390/jcm11041139
We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.
2022-02-21 2022 other research-article; Journal Article abstract-available 10.3390/jcm11041139 Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial. García-García I, Seco-Meseguer E, Ruiz-Seco P, Navarro-Jimenez G, Martínez-Porqueras R, Espinosa-Díaz M, Ortega-Albás JJ, Sagastagoitia I, García-Morales MT, Jiménez-González M, Martínez de Soto L, Bajo-Martínez AI, Del Palacio-Tamarit M, López-García R, Díaz-García L, Queiruga-Parada J, Giesen C, Pérez-Villena A, de Castro-Martínez M, González-García JJ, Rodriguez-Rubio M, de la Oliva P, Arribas JR, Carcas AJ, Borobia AM. J Clin Med. 2022; 11 (4)
SARS-CoV-2 Virus-Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response.
Queirós-Reis L, Gomes da Silva P, Gonçalves J, Brancale A, [...], Mesquita JR.
Int J Mol Sci. 2021; 22 (19)
DOI: 10.3390/ijms221910836
Coronavirus disease 19, or COVID-19, is an infection associated with an unprecedented worldwide pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has led to more than 215 million infected people and more than 4.5 million deaths worldwide. SARS-CoV-2 cell infection is initiated by a densely glycosylated spike (S) protein, a fusion protein, binding human angiotensin converting enzyme 2 (hACE2), that acts as the functional receptor through the receptor binding domain (RBD). In this article, the interaction of hACE2 with the RBD and how fusion is initiated after recognition are explored, as well as how mutations influence infectivity and immune response. Thus, we focused on all structures available in the Protein Data Bank for the interaction between SARS-CoV-2 S protein and hACE2. Specifically, the Delta variant carries particular mutations associated with increased viral fitness through decreased antibody binding, increased RBD affinity and altered protein dynamics. Combining both existing mutations and mutagenesis studies, new potential SARS-CoV-2 variants, harboring advantageous S protein mutations, may be predicted. These include mutations S13I and W152C, decreasing antibody binding, N460K, increasing RDB affinity, or Q498R, positively affecting both properties.
2021-10-07 2021 other IM; review-article; Review; Journal Article abstract-available 10.3390/ijms221910836 SARS-CoV-2 Virus-Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response. Queirós-Reis L, Gomes da Silva P, Gonçalves J, Brancale A, Bassetto M, Mesquita JR. Int J Mol Sci. 2021; 22 (19)
Cross-reactive cellular, but not humoral, immunity is detected between OC43 and SARS-CoV-2 NPs in people not infected with SARS-CoV-2: Possible role of cTFH cells.
García-Jiménez ÁF, Cáceres-Martell Y, Fernández-Soto D, Martínez Fleta P, [...], Reyburn HT.
J Leukoc Biol. 2022;
DOI: 10.1002/jlb.4covcra0721-356rrr
Multiple questions about SARS-CoV-2 humoral and cellular immunity remain unanswered. One key question is whether preexisting memory T or B cells, specific for related coronaviruses in SARS-CoV-2-unexposed individuals, can recognize and suppress COVID-19, but this issue remains unclear. Here, we demonstrate that antibody responses to SARS-CoV-2 antigens are restricted to serum samples from COVID-19 convalescent individuals. In contrast, cross-reactive T cell proliferation and IFN-γ production responses were detected in PBMCs of around 30% of donor samples collected prepandemic, although we found that these prepandemic T cell responses only elicited weak cTFH activation upon stimulation with either HCoV-OC43 or SARS-CoV-2 NP protein. Overall, these observations confirm that T cell cross-reactive with SARS-CoV-2 antigens are present in unexposed people, but suggest that the T cell response to HCoV-OC43 could be deficient in some important aspects, like TFH expansion, that might compromise the generation of cross-reactive TFH cells and antibodies. Understanding these differences in cellular responses may be of critical importance to advance in our knowledge of immunity against SARS-CoV-2.
2022-04-05 2022 other research-article; Journal Article abstract-available 10.1002/jlb.4covcra0721-356rrr Cross-reactive cellular, but not humoral, immunity is detected between OC43 and SARS-CoV-2 NPs in people not infected with SARS-CoV-2: Possible role of cT<sub>FH</sub> cells. García-Jiménez ÁF, Cáceres-Martell Y, Fernández-Soto D, Martínez Fleta P, Casasnovas JM, Sánchez-Madrid F, Frade JMR, Valés-Gómez M, Reyburn HT. J Leukoc Biol. 2022;
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)
COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences.
Martínez-Salazar B, Holwerda M, Stüdle C, Piragyte I, [...], Döring Y.
Front Cell Dev Biol. 2022; 10
DOI: 10.3389/fcell.2022.824851
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease 2019 (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 was not only restricted to infecting the respiratory tract, but the virus was also found in other tissues, including the vasculature. Individuals with underlying pre-existing co-morbidities like diabetes and hypertension have been more prone to develop severe illness and fatal outcomes during COVID-19. In addition, critical clinical observations made in COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, and endothelial dysfunction, which are indicative for an involvement of the vasculature in COVID-19 pathology. Hence, this review summarizes the impact of SARS-CoV-2 infection on the vasculature and details how the virus promotes (chronic) vascular inflammation. We provide a general overview of SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) and the detection of the SARS-CoV-2 in extrapulmonary tissue. Further, we describe the relation between COVID-19 and cardiovascular diseases (CVD) and their impact on the heart and vasculature. Clinical findings on endothelial changes during COVID-19 are reviewed in detail and recent evidence from in vitro studies on the susceptibility of endothelial cells to SARS-CoV-2 infection is discussed. We conclude with current notions on the contribution of cardiovascular events to long term consequences of COVID-19, also known as "Long-COVID-syndrome". Altogether, our review provides a detailed overview of the current perspectives of COVID-19 and its influence on the vasculature.
2022-02-15 2022 other review-article; Review; Journal Article abstract-available 10.3389/fcell.2022.824851 COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences. Martínez-Salazar B, Holwerda M, Stüdle C, Piragyte I, Mercader N, Engelhardt B, Rieben R, Döring Y. Front Cell Dev Biol. 2022; 10
First Detection of SARS-CoV-2 Delta (B.1.617.2) Variant of Concern in a Dog with Clinical Signs in Spain.
Fernández-Bastit L, Rodon J, Pradenas E, Marfil S, [...], Segalés J.
Viruses. 2021; 13 (12)
DOI: 10.3390/v13122526
Several cases of naturally infected dogs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported despite the apparently low susceptibility of this species. Here, we document the first reported case of infection caused by the Delta (B.1.617.2) variant of concern (VOC) in a dog in Spain that lived with several household members suffering from Coronavirus Infectious Disease 2019 (COVID-19). The animal displayed mild digestive and respiratory clinical signs and had a low viral load in the oropharyngeal swab collected at the first sampling. Whole-genome sequencing indicated infection with the Delta variant, coinciding with the predominant variant during the fifth pandemic wave in Spain. The dog seroconverted, as detected 21 days after the first sampling, and developed neutralizing antibodies that cross-neutralized different SARS-CoV-2 variants. This study further emphasizes the importance of studying the susceptibility of animal species to different VOCs and their potential role as reservoirs in the context of COVID-19.
2021-12-16 2021 other IM; Research Support, Non-U.S. Gov't; Case Reports; case-report abstract-available 10.3390/v13122526 First Detection of SARS-CoV-2 Delta (B.1.617.2) Variant of Concern in a Dog with Clinical Signs in Spain. Fernández-Bastit L, Rodon J, Pradenas E, Marfil S, Trinité B, Parera M, Roca N, Pou A, Cantero G, Lorca-Oró C, Carrillo J, Izquierdo-Useros N, Clotet B, Noguera-Julián M, Blanco J, Vergara-Alert J, Segalés J. Viruses. 2021; 13 (12)
Soluble Angiotensin-Converting Enzyme 2 as a Prognostic Biomarker for Disease Progression in Patients Infected with SARS-CoV-2.
Díaz-Troyano N, Gabriel-Medina P, Weber S, Klammer M, [...], Rodríguez-Frías F.
Diagnostics (Basel). 2022; 12 (4)
DOI: 10.3390/diagnostics12040886
Predicting disease severity in patients infected with SARS-CoV-2 is difficult. Soluble angiotensin-converting enzyme 2 (sACE2) arises from the shedding of membrane ACE2 (mACE2), which is a receptor for SARS-CoV-2 spike protein. We evaluated the predictive value of sACE2 compared with known biomarkers of inflammation and tissue damage (CRP, GDF-15, IL-6, and sFlt-1) in 850 patients with and without SARS-CoV-2 with different clinical outcomes. For univariate analyses, median differences between biomarker levels were calculated for the following patient groups (classified by clinical outcome): RT-PCR-confirmed SARS-CoV-2 positive (Groups 1-4); RT-PCR-confirmed SARS-CoV-2 negative following previous SARS-CoV-2 infection (Groups 5 and 6); and 'SARS-CoV-2 unexposed' patients (Group 7). Median levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in hospitalized patients with SARS-CoV-2 compared with discharged patients (all p < 0.001), whereas levels of sACE2 were significantly lower (p < 0.001). ROC curve analysis of sACE2 provided cut-offs for predicting hospital admission (≤0.05 ng/mL (positive predictive value: 89.1%) and ≥0.42 ng/mL (negative predictive value: 84.0%)). These findings support further investigation of sACE2, as a single biomarker or as part of a panel, to predict hospitalization risk and disease severity in patients with SARS-CoV-2 infection.
2022-04-01 2022 other research-article; Journal Article abstract-available 10.3390/diagnostics12040886 Soluble Angiotensin-Converting Enzyme 2 as a Prognostic Biomarker for Disease Progression in Patients Infected with SARS-CoV-2. Díaz-Troyano N, Gabriel-Medina P, Weber S, Klammer M, Barquín-DelPino R, Castillo-Ribelles L, Esteban A, Hernández-González M, Ferrer-Costa R, Pumarola T, Rodríguez-Frías F. Diagnostics (Basel). 2022; 12 (4)
Editorial: COVID-19 in CNS and PNS: Basic and Clinical Focus on the Mechanisms of Infection and New Tools for the Therapeutic Approach.
Matias-Guiu J, Matias-Guiu JA, Garrido C, Pimienta G, [...], Gomez-Pinedo U.
Front Neurol. 2022; 13
DOI: 10.3389/fneur.2022.838227
2022-03-03 2022 other Editorial 10.3389/fneur.2022.838227 Editorial: COVID-19 in CNS and PNS: Basic and Clinical Focus on the Mechanisms of Infection and New Tools for the Therapeutic Approach. Matias-Guiu J, Matias-Guiu JA, Garrido C, Pimienta G, Reyes PF, Baig AM, Gomez-Pinedo U. Front Neurol. 2022; 13
Sensitive SARS-CoV-2 detection in wastewaters using a carbon nanodot-amplified electrochemiluminescence immunosensor
Guerrero-Esteban T, Gutiérrez-Sánchez C, Villa-Manso A, Revenga-Parra M, [...], Lorenzo E.
Talanta. 2022;
DOI:
Given the great utility that having fast, efficient and cost-effective methods for the detection of SARS-CoV-2 in wastewater can have in controlling the pandemic caused by this virus, the development of new dependable and specific SARS-CoV-2 coronavirus sensing devices to be applied to wastewater is essential to promote public health interventions. Therefore, herein we propose a new method to detect SARS-CoV-2 in wastewater based on a carbon nanodots-amplified electrochemiluminescence immunosensor for the determination of the SARS-CoV-2 Spike S1 protein. For the construction of the immunosensor, N-rich carbon nanodots have been synthetized with a double function: to contribute as amplifiers of the electrochemiluminescent signal in presence of [Ru(bpy)3]2+ and as antibody supports by providing functional groups capable of covalently interacting with the SARS-CoV-2 Spike S1 antibody. The proposed ECL immunosensor has demonstrated a high specificity in presence of other virus-related proteins and responded linearly to SARS-CoV-2 Spike S1 concentration over a wide range with a limit of detection of 1.2 pg/mL. The immunosensor has an excellent stability and achieved the detection of SARS-CoV-2 Spike S1 in river and urban wastewater, which supplies a feasible and reliable sensing platform for early virus detection and therefore to protect the population. The detection of SARS-CoV-2 Spike S1 in urban wastewater can be used as a tool to measure the circulation of the virus in the population and to detect a possible resurgence of COVID-19. Graphical abstract Image 1
2022-05-13 2022 other research-article; Journal Article abstract-available Sensitive SARS-CoV-2 detection in wastewaters using a carbon nanodot-amplified electrochemiluminescence immunosensor Guerrero-Esteban T, Gutiérrez-Sánchez C, Villa-Manso A, Revenga-Parra M, Pariente F, Lorenzo E. Talanta. 2022;
Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses.
Aparicio B, Casares N, Egea J, Ruiz M, [...], Sarobe P.
Emerg Microbes Infect. 2021; 10 (1)
DOI: 10.1080/22221751.2021.1978823
Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine. Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins. Immunization with peptide 446-480 from S protein formulated with Freund's adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 104-3 × 105, depending on the adjuvant) and displaying neutralizing capacity (80-95% inhibition capacity; p <0.05) against SARS-CoV-2. Murine CD4 and CD8T-cell epitopes were identified in region 446-480 and vaccination experiments using HLA transgenic mice suggested the presence of multiple human T-cell epitopes. Antibodies induced by peptide 446-480 showed broad recognition of S proteins and S-derived peptides belonging to SARS-CoV-2 variants of concern. Importantly, vaccination with peptide 446-480 or with a cyclic version of peptide 446-488 containing a disulphide bridge between cysteines 480 and 488, protected humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2 (62.5 and 75% of protection; p <0.01 and p <0.001, respectively). This region could be the basis for a peptide vaccine or other vaccine platforms against Covid-19.
2021-12-01 2021 other research-article; Journal Article abstract-available 10.1080/22221751.2021.1978823 Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses. Aparicio B, Casares N, Egea J, Ruiz M, Llopiz D, Maestro S, Olagüe C, González-Aseguinolaza G, Smerdou C, López-Díaz de Cerio A, Inogés S, Prósper F, Yuste JR, Carmona-Torre F, Reina G, Lasarte JJ, Sarobe P. Emerg Microbes Infect. 2021; 10 (1)
Acute necro-hemorrhagic pancreatitis during SARS-CoV-2 infection.
Arche Banzo MJ, Matute Guerrero A, Herrero García S.
Med Clin (Engl Ed). 2022; 158 (7)
DOI: 10.1016/j.medcle.2021.06.015
2022-02-21 2022 other letter; Journal Article 10.1016/j.medcle.2021.06.015 Acute necro-hemorrhagic pancreatitis during SARS-CoV-2 infection. Arche Banzo MJ, Matute Guerrero A, Herrero García S. Med Clin (Engl Ed). 2022; 158 (7)
A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection.
Pérez P, Lázaro-Frías A, Zamora C, Sánchez-Cordón PJ, [...], García-Arriaza J.
Front Immunol. 2021; 12
DOI: 10.3389/fimmu.2021.824728
We generated an optimized COVID-19 vaccine candidate based on the modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, termed MVA-CoV2-S(3P). The S(3P) protein was expressed at higher levels (2-fold) than the non-stabilized S in cells infected with the corresponding recombinant MVA viruses. One single dose of MVA-CoV2-S(3P) induced higher IgG and neutralizing antibody titers against parental SARS-CoV-2 and variants of concern than MVA-CoV2-S in wild-type C57BL/6 and in transgenic K18-hACE2 mice. In immunized C57BL/6 mice, two doses of MVA-CoV2-S or MVA-CoV2-S(3P) induced similar levels of SARS-CoV-2-specific B- and T-cell immune responses. Remarkably, a single administration of MVA-CoV2-S(3P) protected all K18-hACE2 mice from morbidity and mortality caused by SARS-CoV-2 infection, reducing SARS-CoV-2 viral loads, histopathological lesions, and levels of pro-inflammatory cytokines in the lungs. These results demonstrated that expression of a novel full-length prefusion-stabilized SARS-CoV-2 S protein by the MVA poxvirus vector enhanced immunogenicity and efficacy against SARS-CoV-2 in animal models, further supporting MVA-CoV2-S(3P) as an optimized vaccine candidate for clinical trials.
2022-01-27 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2021.824728 A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection. Pérez P, Lázaro-Frías A, Zamora C, Sánchez-Cordón PJ, Astorgano D, Luczkowiak J, Delgado R, Casasnovas JM, Esteban M, García-Arriaza J. Front Immunol. 2021; 12
Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19.
Martín-Vicente M, Berenguer J, Muñoz-Gómez MJ, Díez C, [...], Resino S.
J Infect. 2022; 84 (3)
DOI: 10.1016/j.jinf.2021.11.002
2021-11-06 2021 other Letter; Comment; Research Support, Non-U.S. Gov't 10.1016/j.jinf.2021.11.002 Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19. Martín-Vicente M, Berenguer J, Muñoz-Gómez MJ, Díez C, Micán R, Pérez-Elías MJ, García-Fraile LJ, Peraire J, Suárez-García I, Jiménez-Sousa MÁ, Fernández-Rodríguez A, Vázquez M, Ryan P, González-García J, Jarrín I, Mas V, Martínez I, Resino S. J Infect. 2022; 84 (3)
MVA-CoV2-S Vaccine Candidate Neutralizes Distinct Variants of Concern and Protects Against SARS-CoV-2 Infection in Hamsters.
Boudewijns R, Pérez P, Lázaro-Frías A, Van Looveren D, [...], García-Arriaza J.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.845969
To control the coronavirus disease 2019 (COVID-19) pandemic and the emergence of different variants of concern (VoCs), novel vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed. In this study, we report the potent immunogenicity and efficacy induced in hamsters by a vaccine candidate based on a modified vaccinia virus Ankara (MVA) vector expressing a human codon optimized full-length SARS-CoV-2 spike (S) protein (MVA-S). Immunization with one or two doses of MVA-S elicited high titers of S- and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against parental SARS-CoV-2 and VoC alpha, beta, gamma, delta, and omicron. After SARS-CoV-2 challenge, MVA-S-vaccinated hamsters showed a significantly strong reduction of viral RNA and infectious virus in the lungs compared to the MVA-WT control group. Moreover, a marked reduction in lung histopathology was also observed in MVA-S-vaccinated hamsters. These results favor the use of MVA-S as a potential vaccine candidate for SARS-CoV-2 in clinical trials.
2022-03-16 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.845969 MVA-CoV2-S Vaccine Candidate Neutralizes Distinct Variants of Concern and Protects Against SARS-CoV-2 Infection in Hamsters. Boudewijns R, Pérez P, Lázaro-Frías A, Van Looveren D, Vercruysse T, Thibaut HJ, Weynand B, Coelmont L, Neyts J, Astorgano D, Montenegro D, Puentes E, Rodríguez E, Dallmeier K, Esteban M, García-Arriaza J. Front Immunol. 2022; 13
Molecular Interactions of SARS-CoV-2 in Lung Tissue of Patients with Chronic Obstructive Pulmonary Disease.
Agusti A, Sibila O, Casas-Recasens S, Mendoza N, [...], Faner R.
Ann Am Thorac Soc. 2021; 18 (11)
DOI: 10.1513/annalsats.202006-619rl
2021-11-01 2021 other Letter 10.1513/annalsats.202006-619rl Molecular Interactions of SARS-CoV-2 in Lung Tissue of Patients with Chronic Obstructive Pulmonary Disease. Agusti A, Sibila O, Casas-Recasens S, Mendoza N, Perea L, Lopez-Giraldo A, Faner R. Ann Am Thorac Soc. 2021; 18 (11)
Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms.
Toledano JM, Moreno-Fernandez J, Puche-Juarez M, Ochoa JJ, [...], Diaz-Castro J.
Antioxidants (Basel). 2021; 11 (1)
DOI: 10.3390/antiox11010005
Since the appearance of the coronavirus disease 2019 (COVID-19) and its announcement as a global pandemic, the search for prophylactic and therapeutic options have become a priority for governments and the scientific community. The approval of several vaccines against SARS-CoV-2 is being crucial to overcome this situation, although the victory will not be achieved while the whole population worldwide is not protected against the virus. This is why alternatives should be studied in order to successfully support the immune system before and during a possible infection. An optimal inflammatory and oxidative stress status depends on an adequate diet. Poor levels of several nutrients could be related to an impaired immune response and, therefore, an increased susceptibility to infection and serious outcomes. Vitamins exert a number of anti-microbial, immunomodulatory, anti-inflammatory, and antioxidant activities, which can be of use to fight against this and several other diseases (especially vitamin D and C). Even though they cannot be considered as a definitive therapeutic option, in part owing to the lack of solid conclusions from well-designed clinical trials, currently available evidence from similar respiratory diseases may indicate that it would be rational to deeply explore the use of vitamins during this global pandemic.
2021-12-21 2021 other review-article; Review; Journal Article abstract-available 10.3390/antiox11010005 Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms. Toledano JM, Moreno-Fernandez J, Puche-Juarez M, Ochoa JJ, Diaz-Castro J. Antioxidants (Basel). 2021; 11 (1)
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)
Effects and Causes of Detraining in Athletes Due to COVID-19: A Review
Córdova-Martínez A, Caballero-García A, Roche E, Pérez-Valdecantos D, [...], Noriega D.
Int J Environ Res Public Health. 2022; 19 (9)
DOI:
Several aspects of systemic alterations caused by the SARS-CoV-2 virus and the resultant COVID-19 disease have been currently explored in the general population. However, very little is known about these particular aspects in sportsmen and sportswomen. We believe that the most important element to take into account is the neuromuscular aspect, due to the implications that this system entails in motion execution and coordination. In this context, deficient neuromuscular control when performing dynamic actions can be an important risk factor for injury. Therefore, data in this review refer mainly to problems derived in the short term from athletes who have suffered this pathology, taking into account that COVID-19 is a very new disease and the presented data are still not conclusive. The review addresses two key aspects: performance alteration and the return to regular professional physical activity. COVID-19 causes metabolic-respiratory, muscular, cardiac, and neurological alterations that are accompanied by a situation of stress. All of these have a clear influence on performance but at the same time in the strategy of returning to optimal conditions to train and compete again after infection. From the clinical evidence, the resumption of physical training and sports activity should be carried out progressively, both in terms of time and intensity.
2022-04-28 2022 other review-article; Review; Journal Article abstract-available Effects and Causes of Detraining in Athletes Due to COVID-19: A Review Córdova-Martínez A, Caballero-García A, Roche E, Pérez-Valdecantos D, Noriega D. Int J Environ Res Public Health. 2022; 19 (9)
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;
Neurological consequences of COVID-19 and brain related pathogenic mechanisms: A new challenge for neuroscience.
F S, Haji K E, Vidal-Balle A, J B.
Brain Behav Immun Health. 2021;
DOI: 10.1016/j.bbih.2021.100399
Due to the infection by the SARS-CoV-2 virus (COVID-19) there were also reported neurological symptoms, being the most frequent and best cited those that affect the cerebrovascular, sensorial, cognitive and motor functions, together with the neurological diffuse symptoms as for examples headache or dizziness. Besides, some of them behave high risk of mortality. Consequently, it is crucial to elucidate the mechanisms of action in brain of SARS-CoV-2 virus in order to create new therapeutic targets to fight against this new disease. Since now the mechanisms of arrival to the brain seems to be related with the following processes: blood brain barrier (BBB) disruption together with nervous or axonal transport of the virus by the trigeminal nerve, the vagus nerve, or the brain-gut-axis. Being two the mechanisms of brain affectation most cited: a direct affectation of the virus in the brain through neuroinvasion and an indirect mechanism of action due to the effects of the systemic infection. Both processes include the triggering of inflammation, hypoxia and the increased likelihood of secondary infections. This topic supposes a major novel challenge for neuroscience. Therefore, the aim of this review is to provide summarized information about the neurological symptomatology and the brain pathogenic mechanisms involved and reported in COVID-19.
2021-11-30 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.bbih.2021.100399 Neurological consequences of COVID-19 and brain related pathogenic mechanisms: A new challenge for neuroscience. F S, Haji K E, Vidal-Balle A, J B. Brain Behav Immun Health. 2021;
Efficacy of repurposed antiviral drugs: Lessons from COVID-19.
Martinez MA.
Drug Discov Today. 2022;
DOI: 10.1016/j.drudis.2022.02.012
The clinical, social, and economic impacts of the coronavirus disease 2019 (COVID-19) pandemic, originated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have motivated a massive search and investment to find treatments for this new disease. Repurposing drugs has been an appealing strategy for the rapid translation of in vitro and ex vivo drug discovery to the clinic. Several repurposed drugs have been assessed clinically, but no effective repurposed antiviral has been identified so far. Of note, no effective treatments for COVID-19 or for any other viral disease have been found by repurposing drugs identified through hypothesis-free screens. Here, I discuss whether drug repurposing is the best strategy for developing effective therapies to eradicate COVID-19 and other viral human infections.
2022-02-19 2022 other IM; review-article; Review; Journal Article abstract-available 10.1016/j.drudis.2022.02.012 Efficacy of repurposed antiviral drugs: Lessons from COVID-19. Martinez MA. Drug Discov Today. 2022;
Aptamer Sandwich Assay for the Detection of SARS-CoV-2 Spike Protein Antigen.
Svobodova M, Skouridou V, Jauset-Rubio M, Viéitez I, [...], O'Sullivan CK.
ACS Omega. 2021; 6 (51)
DOI: 10.1021/acsomega.1c05521
The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged at the end of 2019, resulting in the ongoing COVID-19 pandemic. The high transmissibility of the virus and the substantial number of asymptomatic individuals have led to an exponential rise in infections worldwide, urgently requiring global containment strategies. Reverse transcription-polymerase chain reaction is the gold standard for the detection of SARS-CoV-2 infections. Antigen tests, targeting the spike (S) or nucleocapsid (N) viral proteins, are considered as complementary tools. Despite their shortcomings in terms of sensitivity and specificity, antigen tests could be deployed for the detection of potentially contagious individuals with high viral loads. In this work, we sought to develop a sandwich aptamer-based assay for the detection of the S protein of SARS-CoV-2. A detailed study on the binding properties of aptamers to the receptor-binding domain of the S protein in search of aptamer pairs forming a sandwich is presented. Screening of aptamer pairs and optimization of assay conditions led to the development of a laboratory-based sandwich assay able to detect 21 ng/mL (270 pM) of the protein with negligible cross-reactivity with the other known human coronaviruses. The detection of 375 pg of the protein in viral transport medium demonstrates the compatibility of the assay with clinical specimens. Finally, successful detection of the S antigen in nasopharyngeal swab samples collected from suspected patients further establishes the suitability of the assay for screening purposes as a complementary tool to assist in the control of the pandemic.
2021-12-15 2021 fondo-covid research-article; Journal Article abstract-available 10.1021/acsomega.1c05521 Aptamer Sandwich Assay for the Detection of SARS-CoV-2 Spike Protein Antigen. Svobodova M, Skouridou V, Jauset-Rubio M, Viéitez I, Fernández-Villar A, Cabrera Alvargonzalez JJ, Poveda E, Bofill CB, Sans T, Bashammakh A, Alyoubi AO, O'Sullivan CK. ACS Omega. 2021; 6 (51)
Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment.
Labandeira-Garcia JL, Labandeira CM, Valenzuela R, Pedrosa MA, [...], Rodriguez-Perez AI.
Biomedicines. 2022; 10 (2)
DOI: 10.3390/biomedicines10020502
A massive worldwide vaccination campaign constitutes the main tool against the COVID-19 pandemic. However, drug treatments are also necessary. Antivirals are the most frequently considered treatments. However, strategies targeting mechanisms involved in disease aggravation may also be effective. A major role of the tissue renin-angiotensin system (RAS) in the pathophysiology and severity of COVID-19 has been suggested. The main link between RAS and COVID-19 is angiotensin-converting enzyme 2 (ACE2), a central RAS component and the primary binding site for SARS-CoV-2 that facilitates the virus entry into host cells. An initial suggestion that the susceptibility to infection and disease severity may be enhanced by angiotensin type-1 receptor blockers (ARBs) and ACE inhibitors (ACEIs) because they increase ACE2 levels, led to the consideration of discontinuing treatments in thousands of patients. More recent experimental and clinical data indicate that ACEIs and, particularly, ARBs can be beneficial for COVID-19 outcome, both by reducing inflammatory responses and by triggering mechanisms (such as ADAM17 inhibition) counteracting viral entry. Strategies directly activating RAS anti-inflammatory components such as soluble ACE2, Angiotensin 1-7 analogues, and Mas or AT2 receptor agonists may also be beneficial. However, while ACEIs and ARBs are cheap and widely used, the second type of strategies are currently under study.
2022-02-21 2022 other review-article; Review; Journal Article abstract-available 10.3390/biomedicines10020502 Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment. Labandeira-Garcia JL, Labandeira CM, Valenzuela R, Pedrosa MA, Quijano A, Rodriguez-Perez AI. Biomedicines. 2022; 10 (2)
Severe Acute Respiratory Syndrome Coronavirus 2 Spreads to Lymph Nodes and Strongly Expands CD4+ Effector Memory RA Cells in a Patient With Mild Coronavirus Disease 2019.
Roldán-Santiago E, Benito-Berlinches A, Martínez-García L, Quereda C, [...], Pérez-Elías MJ.
Clin Infect Dis. 2021; 73 (11)
DOI: 10.1093/cid/ciaa1422
A woman with mild coronavirus disease 2019 developed cervical adenopathy, being diagnosed of Epstein-Barr virus infectious mononucleosis. We performed fine needle aspiration, and demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in lymph nodes even in mild disease along with a strong expansion of terminally differentiated effector memory CD4+ T cells, a cell population that is practically absent in lymph nodes.
2021-12-01 2021 other brief-report; Journal Article abstract-available 10.1093/cid/ciaa1422 Severe Acute Respiratory Syndrome Coronavirus 2 Spreads to Lymph Nodes and Strongly Expands CD4+ Effector Memory RA Cells in a Patient With Mild Coronavirus Disease 2019. Roldán-Santiago E, Benito-Berlinches A, Martínez-García L, Quereda C, Rodríguez-Martín E, Pérez-Elías P, López-Pintor JM, Walo-Delgado PE, Moreno-Zamora A, Fernández-Velasco JI, García-Abellás P, Ballester-González R, Villar LM, Pérez-Elías MJ. Clin Infect Dis. 2021; 73 (11)
Lipid peroxidation as a hallmark of severity in COVID-19 patients.
Martín-Fernández M, Aller R, Heredia-Rodríguez M, Gómez-Sánchez E, [...], Tamayo-Velasco Á.
Redox Biol. 2021; 48
DOI: 10.1016/j.redox.2021.102181

Background

Oxidative stress may be a key player in COVID-19 pathogenesis due to its significant role in response to infections. A defective redox balance has been related to viral pathogenesis developing a massive induction of cell death provoked by oxidative stress. The aim of this study is to perform a complete oxidative stress profile evaluation regarding antioxidant enzymes, total antioxidant capacity and oxidative cell damage in order to characterize its role in diagnosis and severity of this disease.

Methods

Blood samples were obtained from 108 COVID-19 patients and 28 controls and metabolites representative of oxidative stress were assessed. The association between lipid peroxidation and 28-day intubation/death risk was evaluated by multivariable regression analysis. Probability of intubation/death to day-28 was analyzed by using Kaplan-Meier curves and tested with the log-rank test.

Results

Antioxidant enzymes (Superoxide dismutase (SOD) and Catalase) and oxidative cell damage (Carbonyl and Lipid peroxidation (LPO)) levels were significantly higher in COVID-19 patients while total antioxidant capacity (ABTS and FRAP) levels were lower in these patients. The comparison of oxidative stress molecules' levels across COVID-19 severity revealed that only LPO was statistically different between mild and intubated/death COVID-19 patients. COX multivariate regression analysis identified LPO levels over the OOP (LPO>1948.17 μM) as an independent risk factor for 28-day intubation/death in COVID-19 patients [OR: 2.57; 95% CI: 1.10-5.99; p = 0.029]. Furthermore, Kaplan-Meier curve analysis revealed that COVID-19 patients showing LPO levels above 1948.17 μM were intubated or died 8.4 days earlier on average (mean survival time 15.4 vs 23.8 days) when assessing 28-day intubation/death risk (p < 0.001).

Conclusion

These findings deepen our knowledge of oxidative stress status in SARS-CoV-2 infection, supporting its important role in COVID-19. In fact, higher lipid peroxidation levels are independently associated to a higher risk of intubation or death at 28 days in COVID-19 patients.
2021-11-06 2021 other research-article; Journal Article abstract-available 10.1016/j.redox.2021.102181 Lipid peroxidation as a hallmark of severity in COVID-19 patients. Martín-Fernández M, Aller R, Heredia-Rodríguez M, Gómez-Sánchez E, Martínez-Paz P, Gonzalo-Benito H, Sánchez-de Prada L, Gorgojo Ó, Carnicero-Frutos I, Tamayo E, Tamayo-Velasco Á. Redox Biol. 2021; 48
SCoV2-MD: a database for the dynamics of the SARS-CoV-2 proteome and variant impact predictions.
Torrens-Fontanals M, Peralta-García A, Talarico C, Guixà-González R, [...], Selent J.
Nucleic Acids Res. 2022; 50 (D1)
DOI: 10.1093/nar/gkab977
SCoV2-MD (www.scov2-md.org) is a new online resource that systematically organizes atomistic simulations of the SARS-CoV-2 proteome. The database includes simulations produced by leading groups using molecular dynamics (MD) methods to investigate the structure-dynamics-function relationships of viral proteins. SCoV2-MD cross-references the molecular data with the pandemic evolution by tracking all available variants sequenced during the pandemic and deposited in the GISAID resource. SCoV2-MD enables the interactive analysis of the deposited trajectories through a web interface, which enables users to search by viral protein, isolate, phylogenetic attributes, or specific point mutation. Each mutation can then be analyzed interactively combining static (e.g. a variety of amino acid substitution penalties) and dynamic (time-dependent data derived from the dynamics of the local geometry) scores. Dynamic scores can be computed on the basis of nine non-covalent interaction types, including steric properties, solvent accessibility, hydrogen bonding, and other types of chemical interactions. Where available, experimental data such as antibody escape and change in binding affinities from deep mutational scanning experiments are also made available. All metrics can be combined to build predefined or custom scores to interrogate the impact of evolving variants on protein structure and function.
2022-01-01 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/nar/gkab977 SCoV2-MD: a database for the dynamics of the SARS-CoV-2 proteome and variant impact predictions. Torrens-Fontanals M, Peralta-García A, Talarico C, Guixà-González R, Giorgino T, Selent J. Nucleic Acids Res. 2022; 50 (D1)
Superior mesenteric vein thrombosis as the only manifestation of SARS-CoV-2 infection.
Navarro-Martínez S, Diez Ares JÁ, Peris Tomás N, Gonzálvez Guardiola P, [...], Pérez-Rubio Á.
Cir Esp (Engl Ed). 2022; 100 (4)
DOI: 10.1016/j.cireng.2022.03.011
2022-04-14 2022 other IM; Case Reports; case-report 10.1016/j.cireng.2022.03.011 Superior mesenteric vein thrombosis as the only manifestation of SARS-CoV-2 infection. Navarro-Martínez S, Diez Ares JÁ, Peris Tomás N, Gonzálvez Guardiola P, Pérez-Rubio Á. Cir Esp (Engl Ed). 2022; 100 (4)
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)
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
Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2.
Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, [...], Mira A.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-03461-y
Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required. ( https://clinicaltrials.gov/ct2/show/NCT04707742 ; Identifier: NCT04707742).
2021-12-22 2021 other research-article; Randomized Controlled Trial; Journal Article abstract-available 10.1038/s41598-021-03461-y Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Ferrer MD, Barrueco ÁS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Márquez V, García-Vázquez E, Puche-Torres M, Giner MJF, González AC, Coello JMS, Rueda IA, Aubá JMV, Español CC, Velasco AL, Abad DS, García-Esteban S, Artacho A, López-Labrador X, Mira A. Sci Rep. 2021; 11 (1)
Sensitivity of SARS-CoV-2 Life Cycle to IFN Effects and ACE2 Binding Unveiled with a Stochastic Model.
Sazonov I, Grebennikov D, Meyerhans A, Bocharov G.
Viruses. 2022; 14 (2)
DOI: 10.3390/v14020403
Mathematical modelling of infection processes in cells is of fundamental interest. It helps to understand the SARS-CoV-2 dynamics in detail and can be useful to define the vulnerability steps targeted by antiviral treatments. We previously developed a deterministic mathematical model of the SARS-CoV-2 life cycle in a single cell. Despite answering many questions, it certainly cannot accurately account for the stochastic nature of an infection process caused by natural fluctuation in reaction kinetics and the small abundance of participating components in a single cell. In the present work, this deterministic model is transformed into a stochastic one based on a Markov Chain Monte Carlo (MCMC) method. This model is employed to compute statistical characteristics of the SARS-CoV-2 life cycle including the probability for a non-degenerate infection process. Varying parameters of the model enables us to unveil the inhibitory effects of IFN and the effects of the ACE2 binding affinity. The simulation results show that the type I IFN response has a very strong effect on inhibition of the total viral progeny whereas the effect of a 10-fold variation of the binding rate to ACE2 turns out to be negligible for the probability of infection and viral production.
2022-02-15 2022 other IM; Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v14020403 Sensitivity of SARS-CoV-2 Life Cycle to IFN Effects and ACE2 Binding Unveiled with a Stochastic Model. Sazonov I, Grebennikov D, Meyerhans A, Bocharov G. Viruses. 2022; 14 (2)
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)
COVID-19 and Pregnancy: Citation Network Analysis and Evidence Synthesis.
Ruiz-Roman R, Martinez-Perez C, Gil Prados I, Cristóbal I, [...], Sánchez-Tena MÁ.
JMIR Pediatr Parent. 2022; 5 (1)
DOI: 10.2196/29189

Background

COVID-19 spread quickly around the world shortly after the first outbreaks of the new coronavirus disease at the end of December 2019, affecting all populations, including pregnant women.

Objective

The aim of this study was to analyze the relationship between different publications on COVID-19 in pregnancy and their authors through citation networks, as well as to identify the research areas and to determine the publication that has been the most highly cited.

Methods

The search for publications was carried out through the Web of Science database using terms such as "pregnancy," "SARS-CoV-2," "pregnant," and "COVID-19" for the period between January and December 2020. Citation Network Explorer software was used for publication analysis and VOSviewer software was used to construct the figures. This approach enabled an in-depth network analysis to visualize the connections between the related elements and explain their network structure.

Results

A total of 1330 publications and 5531 citation networks were identified in the search, with July being the month with the largest number of publications, and the United States, China, and England as the countries with the greatest number of publications. The most cited publication was "Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records" by Chen and colleagues, which was published in March 2020. Six groups identified as being close in the citation network reflect multidisciplinary research, including clinical characteristics and outcomes in pregnancy, vertical transmission, delivery mode, and psychological impacts of the pandemic on pregnant women.

Conclusions

Thousands of articles on COVID-19 have been published in several journals since the disease first emerged. Identifying relevant publications and obtaining a global view of the main papers published on COVID-19 and pregnancy can lead to a better understanding of the topic. With the accumulation of scientific knowledge, we now know that the clinical features of COVID-19 during pregnancy are generally similar to those of infected nonpregnant women. There is a small increase in frequency of preterm birth and cesarean birth, related to severe maternal illness. Vaccination for all pregnant women is recommended. Several agents are being evaluated for the treatment of COVID-19, but with minimal or no information on safety in pregnancy. These results could form the basis for further research. Future bibliometric and scientometric studies on COVID-19 should provide updated information to analyze other relevant indicators in this field.
2022-03-03 2022 other research-article; Journal Article abstract-available 10.2196/29189 COVID-19 and Pregnancy: Citation Network Analysis and Evidence Synthesis. Ruiz-Roman R, Martinez-Perez C, Gil Prados I, Cristóbal I, Sánchez-Tena MÁ. JMIR Pediatr Parent. 2022; 5 (1)
Acute kidney injury, urinary and histopathological disorders in kidney transplant patients with SARS-CoV2 infection
Vigara L, Villanego F, Aguilera A, García T, [...], Mazuecos A.
Transplant Proc. 2022;
DOI:

INTRODUCTION

Acute renal injury (AKI) is a manifestation of SARS-CoV-2 infection. The evidence in kidney transplants (KT) is limited. Specific, there are scarce data about the histological features in graft biopsies of these patients.

MATERIAL AND METHODS

A retrospective cohort study of KTs with SARS-CoV-2 infection from August 28, 2020 to April 23, 2021. We collected the incidence of AKI and the presence of urinary and histopathological disorders. Both groups were compared (AKI vs. no AKI). Immunohistochemical (IQ) and reverse transcription-polymerase chain reaction (RT-PCR) studies were performed on the anatomopathological samples.

RESULTS

Seventy-seven KT had SARS-CoV-2 infection. Twenty-seven patients (35.1%) developed AKI and it was related to increased severity and a worse evolution of the infection, defined by a greater presence of pneumonia (p <.001), hospitalization (p<.001), admission to the intensive care unit (ICU) (p<.001), and the need for ventilation support (p<.001) and continuous renal replacement therapy (CRRT) (p<.001). In the multivariable analysis, pneumonia behaved as an independent predictor for AKI development (p=.046). No differences were observed between proteinuria one month before and after infection (p=.224). Five patients showed microhematuria and two patients presented transient glycosuria without hyperglycemia. One of the five kidney biopsies performed (20%) showed positive SARS-CoV2 RT-PCR.

CONCLUSION

AKI is a frequent and potentially serious complication in KT patients.  Occasionally it could be accompanied by abnormalities in the urinary sediment. One of the five biopsied patients had positive RT-PCR in renal tissue, which suggests the systemic spread of the virus and the tropism for the renal graft.
2022-04-11 2022 other research-article; Journal Article abstract-available Acute kidney injury, urinary and histopathological disorders in kidney transplant patients with SARS-CoV2 infection Vigara L, Villanego F, Aguilera A, García T, Atienza L, Pérez J, García A, Minguez C, Montero M, Mazuecos A. Transplant Proc. 2022;
"Five Keys to Safer Food" and COVID-19.
San Onofre N, Soler C, Merino-Torres JF, Soriano JM.
Nutrients. 2021; 13 (12)
DOI: 10.3390/nu13124491
On 11 March 2020, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) and, up to 18:37 a.m. on 9 December 2021, it has produced 268,440,530 cases and 5,299,511 deaths. This disease, in some patients, included pneumonia and shortness of breath, being transmitted through droplets and aerosols. To date, there is no scientific literature to justify transmission directly from foods. In this review, we applied the precautionary principle for the home and the food industry using the known "Five Keys to Safer Food" manual developed by the World Health Organization (WHO) and extended punctually in its core information from five keys, in the light of new COVID-19 evidence, to guarantee a possible food safety tool.
2021-12-15 2021 other IM; review-article; Review; Journal Article abstract-available 10.3390/nu13124491 "Five Keys to Safer Food" and COVID-19. San Onofre N, Soler C, Merino-Torres JF, Soriano JM. Nutrients. 2021; 13 (12)
First computational design using lambda-superstrings and in vivo validation of SARS-CoV-2 vaccine.
Martínez L, Malaina I, Salcines-Cuevas D, Terán-Navarro H, [...], Alvarez-Dominguez C.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-022-09615-w
Coronavirus disease 2019 (COVID-19) is the greatest threat to global health at the present time, and considerable public and private effort is being devoted to fighting this recently emerged disease. Despite the undoubted advances in the development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, uncertainty remains about their future efficacy and the duration of the immunity induced. It is therefore prudent to continue designing and testing vaccines against this pathogen. In this article we computationally designed two candidate vaccines, one monopeptide and one multipeptide, using a technique involving optimizing lambda-superstrings, which was introduced and developed by our research group. We tested the monopeptide vaccine, thus establishing a proof of concept for the validity of the technique. We synthesized a peptide of 22 amino acids in length, corresponding to one of the candidate vaccines, and prepared a dendritic cell (DC) vaccine vector loaded with the 22 amino acids SARS-CoV-2 peptide (positions 50-71) contained in the NTD domain (DC-CoVPSA) of the Spike protein. Next, we tested the immunogenicity, the type of immune response elicited, and the cytokine profile induced by the vaccine, using a non-related bacterial peptide as negative control. Our results indicated that the CoVPSA peptide of the Spike protein elicits noticeable immunogenicity in vivo using a DC vaccine vector and remarkable cellular and humoral immune responses. This DC vaccine vector loaded with the NTD peptide of the Spike protein elicited a predominant Th1-Th17 cytokine profile, indicative of an effective anti-viral response. Finally, we performed a proof of concept experiment in humans that included the following groups: asymptomatic non-active COVID-19 patients, vaccinated volunteers, and control donors that tested negative for SARS-CoV-2. The positive control was the current receptor binding domain epitope of COVID-19 RNA-vaccines. We successfully developed a vaccine candidate technique involving optimizing lambda-superstrings and provided proof of concept in human subjects. We conclude that it is a valid method to decipher the best epitopes of the Spike protein of SARS-CoV-2 to prepare peptide-based vaccines for different vector platforms, including DC vaccines.
2022-04-19 2022 other research-article; Journal Article abstract-available 10.1038/s41598-022-09615-w First computational design using lambda-superstrings and in vivo validation of SARS-CoV-2 vaccine. Martínez L, Malaina I, Salcines-Cuevas D, Terán-Navarro H, Zeoli A, Alonso S, M De la Fuente I, Gonzalez-Lopez E, Ocejo-Vinyals JG, Gozalo-Margüello M, Calvo-Montes J, Alvarez-Dominguez C. Sci Rep. 2022; 12 (1)
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
Effect of statin therapy on SARS-CoV-2 infection-related mortality in hospitalized patients.
Masana L, Correig E, Rodríguez-Borjabad C, Anoro E, [...], Pedro-Botet J.
Eur Heart J Cardiovasc Pharmacother. 2022; 8 (2)
DOI: 10.1093/ehjcvp/pvaa128

Aim

Assessing the effect of statin therapy (ST) at hospital admission for COVID-19 on in-hospital mortality.

Methods and results

Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk. Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients [1234 men, 923 women; age: 67 y/o (IQR 54-78)] admitted to the hospital were retrieved from the clinical records in anonymized manner. Three hundred and fifty-three deaths occurred. Five hundred and eighty-one patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on ST than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: P = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared with the GM non-statin group (17.4%; P = 0.045). The Cox model applied to the CSH function [HR = 0.58(CI: 0.39-0.89); P = 0.01] and the competing-risks FG model [HR = 0.60 (CI: 0.39-0.92); P = 0.02] suggest that statins are associated with reduced COVID-19-related mortality.

Conclusions

A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.
2022-02-01 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article; Observational Study abstract-available 10.1093/ehjcvp/pvaa128 Effect of statin therapy on SARS-CoV-2 infection-related mortality in hospitalized patients. Masana L, Correig E, Rodríguez-Borjabad C, Anoro E, Arroyo JA, Jericó C, Pedragosa A, Miret M, Näf S, Pardo A, Perea V, Pérez-Bernalte R, Plana N, Ramírez-Montesinos R, Royuela M, Soler C, Urquizu-Padilla M, Zamora A, Pedro-Botet J. Eur Heart J Cardiovasc Pharmacother. 2022; 8 (2)
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 IM; 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)
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
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
[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; 157 (9)
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; 157 (9)
SARS-CoV-2 Delta-variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.
Torres I, Bellido-Blasco JB, Gimeno C, Burgos JS, [...], Valencian vaccine research program (ProVaVac) study group.
J Med Virol. 2022;
DOI: 10.1002/jmv.27799
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant breakthrough infections in nursing home residents following vaccination with Comirnaty® COVID-19 vaccine were characterized. In total, 201 participants (median age, 87 years; range, 64-100; 133 female) from two nursing homes in the Valencian community (Spain) were included. SARS-CoV-2-Spike (S) antibody responses were determined by a lateral flow immunocromatography (LFIC) assay and by quantitative electrochemiluminescent assay in LFIC-negative participants. SARS-CoV-2-S-IFNγ T cells were enumerated by flow cytometry in 10 participants. Nasopharyngeal SARS-CoV-2 RNA loads were quantified by real-time polymerase chain reaction assays. Vaccine breakthrough COVID-19 due to the Delta variant occurred in 39 residents (median age, 87 years; range, 69-96; 31 female) at a median of 6.5 months after vaccination (nine requiring hospitalization). Breakthrough infections occurred at a higher rate (p < 0.0001) in residents who had not been previously infected with SARS-CoV-2 (naïve) (33/108; 18%) than in those with prior diagnosis of SARS-CoV-2 infection (experienced) (6/93; 6.4%), and were more likely (p < 0.0001) to develop in residents who tested negative by LFIC (20/49) at 3 months after vaccination as compared to their LFIC-positive counterparts (19/142). Among LFIC-negative residents, a trend towards lower plasma anti-RBD antibody levels was noticed in those developing breakthrough infection (p = 0.16). SARS-CoV-2 RNA loads in nasopharyngeal specimens were lower in SARS-CoV-2-experienced residents (p < 0.001) and in those testing positive by LFIC (p = 0.13). The frequency of SARS-CoV-2-S-reactive T cells at 3 months was similar in LFIC-negative residents with (n = 7) or without (n = 3) breakthrough infection. Prior history of SARS-CoV-2 infection and detection of S-reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta-variant breakthrough infection in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.
2022-04-20 2022 other research-article; Journal Article abstract-available 10.1002/jmv.27799 SARS-CoV-2 Delta-variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID-19 vaccination. Torres I, Bellido-Blasco JB, Gimeno C, Burgos JS, Albert E, Moya-Malo R, Gascó-Laborda JC, Tornero A, Soriano J, Meseguer-Ferrer N, Martínez-Serrano M, Ortíz-Rambla J, Buj H, Hernández N, Peiró S, Salas D, Limón R, Vanaclocha H, Sánchez-Payá J, Díez-Domingo J, Comas I, González-Candelas F, Navarro D, Valencian vaccine research program (ProVaVac) study group. J Med Virol. 2022;
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)
Facts and Challenges about Asthma and COVID-19 among the Paediatric Population: A Systematic Literature Review.
Moreno-Sánchez E, Castillo-Viera E, Vélez-Moreno E, Gago-Valiente FJ.
Medicina (Kaunas). 2021; 57 (12)
DOI: 10.3390/medicina57121306
A systematic review of the literature was conducted to analyse the factors that affect the probability of the paediatric asthma population suffering from COVID-19 or SARS-CoV-2, such as asthma phenotypes, inhaled corticosteroids, and the effects of lockdown. This systematic review was based on PRISMA guidelines. A bibliographic search was conducted using BNE, BVS (LILAC), CSIC (IME, ISOC), IBECS, Scielo, Scopus, Medline, and PubMed, using the following search profile: (COVID-19 or 2019-NCOV or SARS-CoV-2 or COV-19) AND asthma AND (children or adolescents or youths or children or teenagers). The results were limited to those articles published between December 2019 and December 2020, selecting only articles published in Spanish, English and French that included the study population (children aged 0-18 years). Among the 1066 results of the bibliographic search and seven articles selected from a manual search, only 19 articles were found to fit our eligibility criteria. Most of the articles highlight the effects of lockdown on the paediatric asthma population, increased therapeutic compliance, and the role of inhaled corticosteroids and intrinsic factors such as ACE2 receptors as causes of the decreased prevalence of COVID-19 among the paediatric asthma population. This population has unique characteristics that serve as protective factors against COVID-19. The safety measures implemented during the lockdown period along with inhaled corticosteroid treatment also contributed to this protection.
2021-11-29 2021 other IM; Systematic Review; review-article; Review; Journal Article abstract-available 10.3390/medicina57121306 Facts and Challenges about Asthma and COVID-19 among the Paediatric Population: A Systematic Literature Review. Moreno-Sánchez E, Castillo-Viera E, Vélez-Moreno E, Gago-Valiente FJ. Medicina (Kaunas). 2021; 57 (12)
Could Statin Therapy Be Useful in Patients With Coronavirus Disease 2019 (COVID-19)?
Torres-Peña JD, Katsiki N, Perez-Martinez P.
Front Cardiovasc Med. 2021; 8
DOI: 10.3389/fcvm.2021.775749
Acute respiratory distress syndrome (ARDS), resulting from an exaggerated inflammatory response, is the main cause of death from the coronavirus disease 2019 (COVID-19). Apart from respiratory infection, COVID-19 patients can develop cardiovascular disorders such as myocardial injury and myocarditis, pericarditis, cardiac arrest and arrhythmias, cardiomyopathy, heart failure, coagulation abnormalities and thrombosis. Statins can beneficially affect inflammation, oxidative stress, coagulation, thrombosis, angiotensin converting enzyme receptor, lipid rafts, and endothelial function. In this narrative review, we provide a critical overview of the current evidence and future perspectives on the use of statins to modulate the severity, duration and complications of COVID-19 through their pleiotropic properties.
2021-10-27 2021 other review-article; Review; Journal Article abstract-available 10.3389/fcvm.2021.775749 Could Statin Therapy Be Useful in Patients With Coronavirus Disease 2019 (COVID-19)? Torres-Peña JD, Katsiki N, Perez-Martinez P. Front Cardiovasc Med. 2021; 8
Nanobodies Protecting From Lethal SARS-CoV-2 Infection Target Receptor Binding Epitopes Preserved in Virus Variants Other Than Omicron.
Casasnovas JM, Margolles Y, Noriega MA, Guzmán M, [...], Fernández LÁ.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.863831
The emergence of SARS-CoV-2 variants that escape from immune neutralization are challenging vaccines and antibodies developed to stop the COVID-19 pandemic. Thus, it is important to establish therapeutics directed toward multiple or specific SARS-CoV-2 variants. The envelope spike (S) glycoprotein of SARS-CoV-2 is the key target of neutralizing antibodies (Abs). We selected a panel of nine nanobodies (Nbs) from dromedary camels immunized with the receptor-binding domain (RBD) of the S, and engineered Nb fusions as humanized heavy chain Abs (hcAbs). Nbs and derived hcAbs bound with subnanomolar or picomolar affinities to the S and its RBD, and S-binding cross-competition clustered them in two different groups. Most of the hcAbs hindered RBD binding to its human ACE2 (hACE2) receptor, blocked cell entry of viruses pseudotyped with the S protein and neutralized SARS-CoV-2 infection in cell cultures. Four potent neutralizing hcAbs prevented the progression to lethal SARS-CoV-2 infection in hACE2-transgenic mice, demonstrating their therapeutic potential. Cryo-electron microscopy identified Nb binding epitopes in and out the receptor binding motif (RBM), and showed different ways to prevent virus binding to its cell entry receptor. The Nb binding modes were consistent with its recognition of SARS-CoV-2 RBD variants; mono and bispecific hcAbs efficiently bound all variants of concern except omicron, which emphasized the immune escape capacity of this latest variant.
2022-04-25 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.863831 Nanobodies Protecting From Lethal SARS-CoV-2 Infection Target Receptor Binding Epitopes Preserved in Virus Variants Other Than Omicron. Casasnovas JM, Margolles Y, Noriega MA, Guzmán M, Arranz R, Melero R, Casanova M, Corbera JA, Jiménez-de-Oya N, Gastaminza P, Garaigorta U, Saiz JC, Martín-Acebes MÁ, Fernández LÁ. Front Immunol. 2022; 13
SARS-CoV-2 superinfection and reinfection with three different strains.
Pérez-Lago L, Kestler M, Sola-Campoy PJ, Rodriguez-Grande C, [...], Gregorio Marañón Microbiology-ID COVID 19 Study Group.
Transbound Emerg Dis. 2021;
DOI: 10.1111/tbed.14352
We report a corona virus disease (COVID-19) case with unprecedented viral complexity. In the first severe episode, two different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains (superinfection) were identified within a week. Three months after discharge, the patient was readmitted and was infected in a nosocomial outbreak with a different strain, suffering a second milder COVID-19 episode.
2021-10-23 2021 other brief-report; IM; Journal Article abstract-available 10.1111/tbed.14352 SARS-CoV-2 superinfection and reinfection with three different strains. Pérez-Lago L, Kestler M, Sola-Campoy PJ, Rodriguez-Grande C, Flores-García RF, Buenestado-Serrano S, Herranz M, Alcalá L, Martínez-Laperche C, Suárez-González J, Catalán P, Muñoz P, García de Viedma D, Gregorio Marañón Microbiology-ID COVID 19 Study Group. Transbound Emerg Dis. 2021;
Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA).
Cenko E, Badimon L, Bugiardini R, Claeys MJ, [...], Tousoulis D.
Cardiovasc Res. 2021; 117 (14)
DOI: 10.1093/cvr/cvab298
The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.
2021-12-01 2021 other Consensus Development Conference; review-article; Journal Article abstract-available 10.1093/cvr/cvab298 Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA). Cenko E, Badimon L, Bugiardini R, Claeys MJ, De Luca G, de Wit C, Derumeaux G, Dorobantu M, Duncker DJ, Eringa EC, Gorog DA, Hassager C, Heinzel FR, Huber K, Manfrini O, Milicic D, Oikonomou E, Padro T, Trifunovic-Zamaklar D, Vasiljevic-Pokrajcic Z, Vavlukis M, Vilahur G, Tousoulis D. Cardiovasc Res. 2021; 117 (14)
ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNγ-driven immunopathology.
Gawish R, Starkl P, Pimenov L, Hladik A, [...], Knapp S.
Elife. 2022; 11
DOI: 10.7554/elife.74623
Despite tremendous progress in the understanding of COVID-19, mechanistic insight into immunological, disease-driving factors remains limited. We generated maVie16, a mouse-adapted SARS-CoV-2, by serial passaging of a human isolate. In silico modeling revealed how only three Spike mutations of maVie16 enhanced interaction with murine ACE2. maVie16 induced profound pathology in BALB/c and C57BL/6 mice, and the resulting mouse COVID-19 (mCOVID-19) replicated critical aspects of human disease, including early lymphopenia, pulmonary immune cell infiltration, pneumonia, and specific adaptive immunity. Inhibition of the proinflammatory cytokines IFNγ and TNF substantially reduced immunopathology. Importantly, genetic ACE2-deficiency completely prevented mCOVID-19 development. Finally, inhalation therapy with recombinant ACE2 fully protected mice from mCOVID-19, revealing a novel and efficient treatment. Thus, we here present maVie16 as a new tool to model COVID-19 for the discovery of new therapies and show that disease severity is determined by cytokine-driven immunopathology and critically dependent on ACE2 in vivo.
2022-01-13 2022 other IM; Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.7554/elife.74623 ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNγ-driven immunopathology. Gawish R, Starkl P, Pimenov L, Hladik A, Lakovits K, Oberndorfer F, Cronin SJ, Ohradanova-Repic A, Wirnsberger G, Agerer B, Endler L, Capraz T, Perthold JW, Cikes D, Koglgruber R, Hagelkruys A, Montserrat N, Mirazimi A, Boon L, Stockinger H, Bergthaler A, Oostenbrink C, Penninger JM, Knapp S. Elife. 2022; 11
Effective presence of antibodies against common human coronaviruses in immunoglobulin medicinal products.
Díez JM, Romero C, Gajardo R.
Int J Infect Dis. 2022; 116
DOI: 10.1016/j.ijid.2021.12.329

Background

Immunoglobulin products (for intravenous, intramuscular and subcutaneous administration) prepared from geographically diverse plasma pools were tested for activity against common human coronaviruses (HCoVs). Products from plasma obtained from Germany, Czech Republic, Slovak Republic, USA and Spain were tested for antibodies to common HCoVs: 229E, OC43, NL63 and HKU1. As these products are manufactured from pooled plasma from thousands of donors, the antibodies therein are representative of HCoV exposure in the population at large.

Methods

Immunoglobulin products were tested for antibodies to four common HCoVs by enzyme-linked immunosorbent assays (ELISAs). Neutralization assays were conducted using HCoV-229E cultured on to MRC5 cells.

Results

ELISAs showed that when expressed as specific activity (anti-HCoV activity/mg immunoglobulin), similar activity against the four common HCoVs was seen across the immunoglobulin products regardless of concentration or geographic origin. Highest anti-HCoV activity was seen against HCoV-229E, followed by HCoV-OC43, HCoV-NL63 and HCoV-HKU1. The neutralization assays showed similar potency for two immunoglobulin products prepared by different processes.

Conclusions

To the authors' knowledge, this is the first demonstration of antibodies to common HCoVs in immunoglobulin products. These results may explain the cross-reactivity seen with pre-pandemic immunoglobulin products and severe acute respiratory syndrome coronavirus-2, and contribute to differences in severity of illness between patients.
2021-12-17 2021 other research-article; Journal Article abstract-available 10.1016/j.ijid.2021.12.329 Effective presence of antibodies against common human coronaviruses in immunoglobulin medicinal products. Díez JM, Romero C, Gajardo R. Int J Infect Dis. 2022; 116
Povidone-Iodine as a Pre-Procedural Mouthwash to Reduce the Salivary Viral Load of SARS-CoV-2: A Systematic Review of Randomized Controlled Trials.
Garcia-Sanchez A, Peña-Cardelles JF, Ordonez-Fernandez E, Montero-Alonso M, [...], Kozuma W.
Int J Environ Res Public Health. 2022; 19 (5)
DOI: 10.3390/ijerph19052877
The use of pre-procedural rinses has been investigated to reduce the number of viral particles and bacteria in aerosols, potentially decreasing the risk of cross-infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during medical and dental procedures. This review aims to confirm whether there is evidence in the literature describing a reduction in salivary load of SARS-CoV-2 when povidone-iodine (PVP-I) is used as a pre-intervention mouthwash. An search of the MEDLINE, Embase, SCOPUS, and the Cochrane library databases was conducted. The criteria used followed the PRISMA® Statement guidelines. Randomized controlled trials investigating the reduction of salivary load of SARS-CoV-2 using PVP-I were included. Ultimately, four articles were included that met the established criteria. According to the current evidence, PVP-I is effective against SARS-CoV-2 in saliva and could be implemented as a rinse before interventions to decrease the risk of cross-infection in healthcare settings.
2022-03-01 2022 other IM; review-article; Review; Journal Article abstract-available 10.3390/ijerph19052877 Povidone-Iodine as a Pre-Procedural Mouthwash to Reduce the Salivary Viral Load of SARS-CoV-2: A Systematic Review of Randomized Controlled Trials. Garcia-Sanchez A, Peña-Cardelles JF, Ordonez-Fernandez E, Montero-Alonso M, Kewalramani N, Salgado-Peralvo AO, Végh D, Gargano A, Parra G, Guerra-Guajardo LI, Kozuma W. Int J Environ Res Public Health. 2022; 19 (5)
Role of Neutrophil Extracellular Traps in COVID-19 Progression: An Insight for Effective Treatment.
Blanch-Ruiz MA, Ortega-Luna R, Gómez-García G, Martínez-Cuesta MÁ, [...], Álvarez Á.
Biomedicines. 2021; 10 (1)
DOI: 10.3390/biomedicines10010031
The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has resulted in a pandemic with over 270 million confirmed cases and 5.3 million deaths worldwide. In some cases, the infection leads to acute respiratory distress syndrome (ARDS), which is triggered by a cytokine storm and multiple organ failure. Clinical hematological, biochemical, coagulation, and inflammatory markers, such as interleukins, are associated with COVID-19 disease progression. In this regard, neutrophilia, neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-albumin ratio (NAR), have emerged as promising biomarkers of disease severity and progression. In the pathophysiology of ARDS, the inflammatory environment induces neutrophil influx and activation in the lungs, promoting the release of cytokines, proteases, reactive oxygen species (ROS), and, eventually, neutrophil extracellular traps (NETs). NETs components, such as DNA, histones, myeloperoxidase, and elastase, may exert cytotoxic activity and alveolar damage. Thus, NETs have also been described as potential biomarkers of COVID-19 prognosis. Several studies have demonstrated that NETs are induced in COVID-19 patients, and that the highest levels of NETs are found in critical ones, therefore highlighting a correlation between NETs and severity of the disease. Knowledge of NETs signaling pathways, and the targeting of points of NETs release, could help to develop an effective treatment for COVID-19, and specifically for severe cases, which would help to manage the pandemic.
2021-12-23 2021 other review-article; Review; Journal Article abstract-available 10.3390/biomedicines10010031 Role of Neutrophil Extracellular Traps in COVID-19 Progression: An Insight for Effective Treatment. Blanch-Ruiz MA, Ortega-Luna R, Gómez-García G, Martínez-Cuesta MÁ, Álvarez Á. Biomedicines. 2021; 10 (1)
A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells
Garreta E, Prado P, Stanifer M, Monteil V, [...], Montserrat N.
Cell Metab. 2022;
DOI:
It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism. Graphical abstract Garreta et al. developed a human kidney organoid system mirroring early hallmarks of diabetic kidney disease development. This resulted in higher SARS-CoV-2 infections, which were critically dependent on ACE2. Diabetic patient renal cells also showed elevated ACE2 and altered energy metabolism that following chemical targeting resulted in a reduction of SARS-CoV-2 infection.
2022-05-12 2022 other research-article; Journal Article abstract-available A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells Garreta E, Prado P, Stanifer M, Monteil V, Marco A, Ullate-Agote A, Moya-Rull D, Vilas-Zornoza A, Tarantino C, Romero J, Jonsson G, Oria R, Leopoldi A, Hagelkruys A, Gallo M, González F, Domingo-Pedrol P, Gavaldà A, del Pozo C, Hasan Ali O, Ventura-Aguiar P, Campistol J, Prosper F, Mirazimi A, Boulant S, Penninger J, Montserrat N. Cell Metab. 2022;
Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9).
Cesaro S, Ljungman P, Mikulska M, Hirsch HH, [...], Pagano L.
Leukemia. 2022;
DOI: 10.1038/s41375-022-01578-1
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel virus that spread worldwide from 2019 causing the Coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 infection is characterised by an initial viral phase followed in some patients by a severe inflammatory phase. Importantly, immunocompromised patients may have a prolonged viral phase, shedding infectious viral particles for months, and absent or dysfunctional inflammatory phase. Among haematological patients, COVID-19 has been associated with high mortality rate in acute leukaemia, high risk-myelodysplastic syndromes, and after haematopoietic cell transplant and chimeric-antigen-receptor-T therapies. The clinical symptoms and signs were similar to that reported for the overall population, but the severity and outcome were worse. The deferral of immunodepleting cellular therapy treatments is recommended for SARS-CoV-2 positive patient, while in the other at-risk cases, the haematological treatment decisions must be weighed between individual risks and benefits. The gold standard for the diagnosis is the detection of viral RNA by nucleic acid testing on nasopharyngeal-swabbed sample, which provides high sensitivity and specificity; while rapid antigen tests have a lower sensitivity, especially in asymptomatic patients. The prevention of SARS-CoV-2 infection is based on strict infection control measures recommended for aerosol-droplet-and-contact transmission. Vaccinations against SARS-CoV-2 has shown high efficacy in reducing community transmission, hospitalisation and deaths due to severe COVID-19 disease in the general population, but immunosuppressed/haematology patients may have lower sero-responsiveness to vaccinations. Moreover, the recent emergence of new variants may require vaccine modifications and strategies to improve efficacy in these vulnerable patients. Beyond supportive care, the specific treatment is directed at viral replication control (antivirals, anti-spike monoclonal antibodies) and, in patients who need it, to the control of inflammation (dexamethasone, anti-Il-6 agents, and others). However, the benefit of all these various prophylactic and therapeutic treatments in haematology patients deserves further studies.
2022-04-29 2022 other IM; review-article; Review; Journal Article abstract-available 10.1038/s41375-022-01578-1 Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9). Cesaro S, Ljungman P, Mikulska M, Hirsch HH, von Lilienfeld-Toal M, Cordonnier C, Meylan S, Mehra V, Styczynski J, Marchesi F, Besson C, Baldanti F, Masculano RC, Beutel G, Einsele H, Azoulay E, Maertens J, de la Camara R, ECIL 9, Pagano L. Leukemia. 2022;
African derived phytocompounds may interfere with SARS-CoV-2 RNA capping machinery via inhibition of 2'-O-ribose methyltransferase: An in silico perspective.
Gyebi GA, Ogunyemi OM, Adefolalu AA, Rodríguez-Martínez A, [...], Afolabi SO.
J Mol Struct. 2022; 1262
DOI: 10.1016/j.molstruc.2022.133019
Despite the ongoing vaccination against the life-threatening COVID-19, there is need for viable therapeutic interventions. The S-adenosyl-l-Methionine (SAM) dependent 2-O'-ribose methyltransferase (2'-O-MTase) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a therapeutic target against COVID-19 infection. In a bid to profile bioactive principles from natural sources, a custom-made library of 226 phytochemicals from African medicinal plants with especially anti-malarial activity was screened for direct interactions with SARS-CoV-2 2'-O-MTase (S2RMT) using molecular docking and molecular dynamics (MD) simulations as well as binding free energies methods. Based on minimal binding energy lower than sinefungin (a reference methyl-transferase inhibitor) and binding mode analysis at the catalytic site of S2RMT, a list of 26 hit phytocompounds was defined. The interaction of these phytocompounds was compared with the 2'-O-MTase of SARS-CoV and MERS-CoV. Among these compounds, the lead phytocompounds (LPs) viz: mulberrofuran F, 24-methylene cycloartenol, ferulate, 3-benzoylhosloppone and 10-hydroxyusambarensine interacted strongly with the conserved KDKE tetrad within the substrate binding pocket of the 2'-O-MTase of the coronavirus strains which is critical for substrate binding. The thermodynamic parameters analyzed from the MD simulation trajectories of the LPs-S2RMT complexes presented an eminent structural stability and compactness. These LPs demonstrated favorable druggability and in silico ADMET properties over a diverse array of molecular computing descriptors. The LPs show promising prospects in the disruption of S2RMT capping machinery in silico. However, these LPs should be validated via in vitro and in vivo experimental models.
2022-04-12 2022 other research-article; Journal Article abstract-available 10.1016/j.molstruc.2022.133019 African derived phytocompounds may interfere with SARS-CoV-2 RNA capping machinery via inhibition of 2'-O-ribose methyltransferase: An <i>in silico</i> perspective. Gyebi GA, Ogunyemi OM, Adefolalu AA, Rodríguez-Martínez A, López-Pastor JF, Banegas-Luna AJ, Pérez-Sánchez H, Adegunloye AP, Ogunro OB, Afolabi SO. J Mol Struct. 2022; 1262
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 IM; 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)
SARS- CoV-2 infection and oxidative stress in early-onset preeclampsia.
Marín R, Pujol FH, Rojas D, Sobrevia L.
Biochim Biophys Acta Mol Basis Dis. 2022; 1868 (3)
DOI: 10.1016/j.bbadis.2021.166321
SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) also in pregnant women. Infection in pregnancy leads to maternal and placental functional alterations. Pregnant women with vascular defects such as preeclampsia show high susceptibility to SARS-CoV-2 infection by undefined mechanisms. Pregnant women infected with SARS-CoV-2 show higher rates of preterm birth and caesarean delivery, and their placentas show signs of vasculopathy and inflammation. It is still unclear whether the foetus is affected by the maternal infection with this virus and whether maternal infection associates with postnatal affections. The SARS-CoV-2 infection causes oxidative stress and activation of the immune system leading to cytokine storm and next tissue damage as seen in the lung. The angiotensin-converting-enzyme 2 expression is determinant for these alterations in the lung. Since this enzyme is expressed in the human placenta, SARS-CoV-2 could infect the placenta tissue, although reported to be of low frequency compared with maternal lung tissue. Early-onset preeclampsia (eoPE) shows higher expression of ADAM17 (a disintegrin and metalloproteinase 17) causing an imbalanced renin-angiotensin system and endothelial dysfunction. A similar mechanism seems to potentially account for SARS-CoV-2 infection. This review highlights the potentially common characteristics of pregnant women with eoPE with those with COVID-19. A better understanding of the mechanisms of SARS-CoV-2 infection and its impact on the placenta function is determinant since eoPE/COVID-19 association may result in maternal metabolic alterations that might lead to a potential worsening of the foetal programming of diseases in the neonate, young, and adult.
2021-12-14 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1016/j.bbadis.2021.166321 SARS- CoV-2 infection and oxidative stress in early-onset preeclampsia. Marín R, Pujol FH, Rojas D, Sobrevia L. Biochim Biophys Acta Mol Basis Dis. 2022; 1868 (3)
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
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)
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 IM; 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)
Acute pancreatitis in children with covid-19 associated multisistem inflammatory syndrome.
Traba Zubiaurre M, Eizaguirre Arocena FJ, Urrutikoetxea Aiartza M, Izquierdo Iribarren A.
An Pediatr (Engl Ed). 2022; 96 (3)
DOI: 10.1016/j.anpede.2021.01.007
2022-02-07 2022 other Case Reports; case-report 10.1016/j.anpede.2021.01.007 Acute pancreatitis in children with covid-19 associated multisistem inflammatory syndrome. Traba Zubiaurre M, Eizaguirre Arocena FJ, Urrutikoetxea Aiartza M, Izquierdo Iribarren A. An Pediatr (Engl Ed). 2022; 96 (3)
Description of Symptoms Caused by the Infection of the SARS-CoV-2 B.1.621 (Mu) Variant in Patients With Complete CoronaVac Vaccination Scheme: First Case Report From Santiago of Chile.
Barrera-Avalos C, Luraschi R, Acuña-Castillo C, Vidal M, [...], Sandino AM.
Front Public Health. 2022; 10
DOI: 10.3389/fpubh.2022.797569
Vaccine administration is one of the most efficient ways to control the current coronavirus disease 2019 (COVID-19) pandemic. However, the appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can avoid the immunity generated by vaccines. Thus, in patients with a complete vaccine schedule, the infection by SARS-CoV-2 may cause severe, mild, and asymptomatic manifestations of the disease. In this case report, we describe for the first time the clinical symptoms of four patients (three symptomatic; one asymptomatic) from Santiago of Chile, with a complete vaccination schedule with two doses of CoronaVac (Sinovac Life Science) infected with the variant of interest (VOI) B.1.621 (Mu). They were compared with four unvaccinated patients, who had a higher prevalence of symptoms after infection compared to vaccinated patients. In the CoronaVac-vaccinated group, an 80-year-old patient who registered various comorbidities required Invasive mechanical ventilation for 28 days with current home medical recovery discharge. By contrast, in the unvaccinated group, a 71-year-old presented more symptoms with more than 45 days of Invasive mechanical ventilation, which continues to date, presenting greater lung damage than the vaccinated hospitalized patient. This first report evidence differences in the clinical symptomatology of patients vaccinated and non-vaccinated infected with the VOI B.1.621 (Mu) and suggest the protective effects of CoronaVac against this variant.
2022-03-21 2022 other Case Reports; case-report abstract-available 10.3389/fpubh.2022.797569 Description of Symptoms Caused by the Infection of the SARS-CoV-2 B.1.621 (Mu) Variant in Patients With Complete CoronaVac Vaccination Scheme: First Case Report From Santiago of Chile. Barrera-Avalos C, Luraschi R, Acuña-Castillo C, Vidal M, Mella-Torres A, Inostroza-Molina A, Vera R, Vargas S, Hernández I, Perez C, Vallejos-Vidal E, Valdés D, Imarai M, Reyes-López FE, Sandino AM. Front Public Health. 2022; 10
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)
Unravelling the molecular interactions between the SARS-CoV-2 RBD spike protein and various specific monoclonal antibodies.
Martí D, Alsina M, Alemán C, Bertran O, [...], Torras J.
Biochimie. 2022; 193
DOI: 10.1016/j.biochi.2021.10.013
Vaccination against SARS-CoV-2 just started in most of the countries. However, the development of specific vaccines against SARS-CoV-2 is not the only approach to control the virus and monoclonal antibodies (mAbs) start to merit special attention as a therapeutic option to treat COVID-19 disease. Here, the main conformations and interactions between the receptor-binding domain (RBD) of spike glycoprotein of SARS-CoV-2 (S protein) with two mAbs (CR3022 and S309) and the ACE2 cell receptor are studied as the main representatives of three different epitopes on the RBD of S protein. The combined approach of 1 μs accelerated molecular dynamics (aMD) and ab-initio hybrid molecular dynamics is used to identify the most predominant interactions under physiological conditions. Results allow to determine the main receptor-binding mapping, hydrogen bonding network and salt bridges in the most populated antigen-antibody interface conformations. The deep knowledge on the protein-protein interactions involving mAbs and ACE2 receptor with the spike glycoprotein of SARS-CoV-2 increases background knowledge to speed up the development of new vaccines and therapeutic drugs.
2021-10-25 2021 other research-article; Journal Article abstract-available 10.1016/j.biochi.2021.10.013 Unravelling the molecular interactions between the SARS-CoV-2 RBD spike protein and various specific monoclonal antibodies. Martí D, Alsina M, Alemán C, Bertran O, Turon P, Torras J. Biochimie. 2022; 193
Optimization, Production, Purification and Characterization of HIV-1 GAG-Based Virus-like Particles Functionalized with SARS-CoV-2.
Boix-Besora A, Lorenzo E, Lavado-García J, Gòdia F, [...], Cervera L.
Vaccines (Basel). 2022; 10 (2)
DOI: 10.3390/vaccines10020250
Virus-like particles (VLPs) constitute a promising approach to recombinant vaccine development. They are robust, safe, versatile and highly immunogenic supra-molecular structures that closely mimic the native conformation of viruses without carrying their genetic material. HIV-1 Gag VLPs share similar characteristics with wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, making them a suitable platform for the expression of its spike membrane protein to generate a potential vaccine candidate for COVID-19. This work proposes a methodology for the generation of SARS-CoV-2 VLPs by their co-expression with HIV-1 Gag protein. We achieved VLP functionalization with coronavirus spike protein, optimized its expression using a design of experiments (DoE). We also performed the bioprocess at a bioreactor scale followed by a scalable downstream purification process consisting of two clarifications, an ion exchange and size-exclusion chromatography. The whole production process is conceived to enhance its transferability at current good manufacturing practice (cGMP) industrial scale manufacturing. Moreover, the approach proposed could be expanded to produce additional Gag-based VLPs against different diseases or COVID-19 variants.
2022-02-07 2022 other research-article; Journal Article abstract-available 10.3390/vaccines10020250 Optimization, Production, Purification and Characterization of HIV-1 GAG-Based Virus-like Particles Functionalized with SARS-CoV-2. Boix-Besora A, Lorenzo E, Lavado-García J, Gòdia F, Cervera L. Vaccines (Basel). 2022; 10 (2)
First Detection of SARS-CoV-2 B.1.617.2 (Delta) Variant of Concern in a Symptomatic Cat in Spain.
Barroso-Arévalo S, Sánchez-Morales L, Pérez-Sancho M, Domínguez L, [...], Sánchez-Vizcaíno JM.
Front Vet Sci. 2022; 9
DOI: 10.3389/fvets.2022.841430
Natural and experimental SARS-CoV-2 infection in pets has been widely evidenced since the beginning of the COVID-19 pandemic. Among the numerous affected animals, cats are one of the most susceptible species. However, little is known about viral pathogenicity and transmissibility in the case of variants of concern (VOCs) in animal hosts, such as the B.1.617.2 (Delta) variant first detected in India. Here, we have identified the B.1.617.2 (Delta) VOC in a cat living with a COVID-19 positive owner. The animal presented mild symptoms (sneezing) and a high viral load was detected in the oropharyngeal swab, suggesting that an active infection was occurring in the upper respiratory tract of the cat. Transmission from the owner to the cat occurred despite the human being fully vaccinated against SARS-CoV-2. This study documents the first detection of B.1.165.2 VOC in a cat in Spain and emphasizes the importance of performing active surveillance and genomic investigation on infected animals.
2022-04-01 2022 other brief-report; Journal Article abstract-available 10.3389/fvets.2022.841430 First Detection of SARS-CoV-2 B.1.617.2 (Delta) Variant of Concern in a Symptomatic Cat in Spain. Barroso-Arévalo S, Sánchez-Morales L, Pérez-Sancho M, Domínguez L, Sánchez-Vizcaíno JM. Front Vet Sci. 2022; 9
Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity.
Saiz ML, De Diego ML, López-García D, Corte-Iglesias V, [...], Suarez-Alvarez B.
Clin Epigenetics. 2021; 13 (1)
DOI: 10.1186/s13148-021-01168-5

Background

SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors for entry into cells, and the serine protease TMPRSS2 for S protein priming. Inhibition of protease activity or the engagement with ACE2 and NRP1 receptors has been shown to be an effective strategy for blocking infectivity and viral spreading. Valproic acid (VPA; 2-propylpentanoic acid) is an epigenetic drug approved for clinical use. It produces potent antiviral and anti-inflammatory effects through its function as a histone deacetylase (HDAC) inhibitor. Here, we propose VPA as a potential candidate to tackle COVID-19, in which rapid viral spread and replication, and hyperinflammation are crucial elements.

Results

We used diverse cell lines (HK-2, Huh-7, HUVEC, Caco-2, and BEAS-2B) to analyze the effect of VPA and other HDAC inhibitors on the expression of the ACE-2 and NRP-1 receptors and their ability to inhibit infectivity, viral production, and the inflammatory response. Treatment with VPA significantly reduced expression of the ACE2 and NRP1 host proteins in all cell lines through a mechanism mediated by its HDAC inhibitory activity. The effect is maintained after SARS-CoV-2 infection. Consequently, the treatment of cells with VPA before infection impairs production of SARS-CoV-2 infectious viruses, but not that of other ACE2- and NRP1-independent viruses (VSV and HCoV-229E). Moreover, the addition of VPA 1 h post-infection with SARS-CoV-2 reduces the production of infectious viruses in a dose-dependent manner without significantly modifying the genomic and subgenomic messenger RNAs (gRNA and sg mRNAs) or protein levels of N protein. The production of inflammatory cytokines (TNF-α and IL-6) induced by TNF-α and SARS-CoV-2 infection is diminished in the presence of VPA.

Conclusions

Our data showed that VPA blocks three essential processes determining the severity of COVID-19. It downregulates the expression of ACE2 and NRP1, reducing the infectivity of SARS-CoV-2; it decreases viral yields, probably because it affects virus budding or virions stability; and it dampens the triggered inflammatory response. Thus, administering VPA could be considered a safe treatment for COVID-19 patients until vaccines have been rolled out across the world.
2021-10-11 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1186/s13148-021-01168-5 Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity. Saiz ML, De Diego ML, López-García D, Corte-Iglesias V, Baragaño Raneros A, Astola I, Asensi V, López-Larrea C, Suarez-Alvarez B. Clin Epigenetics. 2021; 13 (1)
The importance of accessory protein variants in the pathogenicity of SARS-CoV-2.
Hassan SS, Choudhury PP, Dayhoff GW, Aljabali AAA, [...], Uversky VN.
Arch Biochem Biophys. 2022; 717
DOI: 10.1016/j.abb.2022.109124
The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2) with an estimated fatality rate of less than 1%. The SARS-CoV-2 accessory proteins ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 possess putative functions to manipulate host immune mechanisms. These involve interferons, which appear as a consensus function, immune signaling receptor NLRP3 (NLR family pyrin domain-containing 3) inflammasome, and inflammatory cytokines such as interleukin 1β (IL-1β) and are critical in COVID-19 pathology. Outspread variations of each of the six accessory proteins were observed across six continents of all complete SARS-CoV-2 proteomes based on the data reported before November 2020. A decreasing order of percentage of unique variations in the accessory proteins was determined as ORF3a > ORF8 > ORF7a > ORF6 > ORF10 > ORF7b across all continents. The highest and lowest unique variations of ORF3a were observed in South America and Oceania, respectively. These findings suggest that the wide variations in accessory proteins seem to affect the pathogenicity of SARS-CoV-2.
2022-01-24 2022 other research-article; Journal Article abstract-available 10.1016/j.abb.2022.109124 The importance of accessory protein variants in the pathogenicity of SARS-CoV-2. Hassan SS, Choudhury PP, Dayhoff GW, Aljabali AAA, Uhal BD, Lundstrom K, Rezaei N, Pizzol D, Adadi P, Lal A, Soares A, Mohamed Abd El-Aziz T, Brufsky AM, Azad GK, Sherchan SP, Baetas-da-Cruz W, Takayama K, Serrano-Aroca Ã, Chauhan G, Palu G, Mishra YK, Barh D, Santana Silva RJ, Andrade BS, Azevedo V, Góes-Neto A, Bazan NG, Redwan EM, Tambuwala M, Uversky VN. Arch Biochem Biophys. 2022; 717
The soluble catalytic ectodomain of ACE2 a biomarker of cardiac remodelling: new insights for heart failure and COVID19.
García-Escobar A, Jiménez-Valero S, Galeote G, Jurado-Román A, [...], Moreno R.
Heart Fail Rev. 2021; 26 (4)
DOI: 10.1007/s10741-020-10066-6
The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that was discovered two decades ago. The ACE2 exists as a transmembrane protein and as a soluble catalytic ectodomain of ACE2, also known as the soluble ACE2 that can be found in plasma and other body fluids. ACE2 regulates the local actions of the renin-angiotensin system in cardiovascular tissues, and the ACE2/Angiotensin 1-7 axis exerts protective actions in cardiovascular disease. Increasing soluble ACE2 has been associated with heart failure, cardiovascular disease, and cardiac remodelling. This is a review of the molecular structure and biochemical functions of the ACE2, as well we provided an updated on the evidence, clinical applications, and emerging potential therapies with the ACE2 in heart failure, cardiovascular disease, lung injury, and COVID-19 infection.
2021-01-06 2021 other review-article; Review; Journal Article abstract-available 10.1007/s10741-020-10066-6 The soluble catalytic ectodomain of ACE2 a biomarker of cardiac remodelling: new insights for heart failure and COVID19. García-Escobar A, Jiménez-Valero S, Galeote G, Jurado-Román A, García-Rodríguez J, Moreno R. Heart Fail Rev. 2021; 26 (4)
The 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 IM; 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)
Spatial and temporal distribution of SARS-CoV-2 diversity circulating in wastewater.
Pérez-Cataluña A, Chiner-Oms Á, Cuevas-Ferrando E, Díaz-Reolid A, [...], Sánchez G.
Water Res. 2022; 211
DOI: 10.1016/j.watres.2021.118007
Wastewater-based epidemiology (WBE) has proven to be an effective tool for epidemiological surveillance of SARS-CoV-2 during the current COVID-19 pandemic. Furthermore, combining WBE together with high-throughput sequencing techniques can be useful for the analysis of SARS-CoV-2 viral diversity present in a given sample. The present study focuses on the genomic analysis of SARS-CoV-2 in 76 sewage samples collected during the three epidemiological waves that occurred in Spain from 14 wastewater treatment plants distributed throughout the country. The results obtained demonstrate that the metagenomic analysis of SARS-CoV-2 in wastewater allows the detection of mutations that define the B.1.1.7 lineage and the ability of the technique to anticipate the detection of certain mutations before they are detected in clinical samples. The study proves the usefulness of sewage sequencing to track Variants of Concern that can complement clinical testing to help in decision-making and in the analysis of the evolution of the pandemic.
2021-12-24 2021 other research-article; Journal Article abstract-available 10.1016/j.watres.2021.118007 Spatial and temporal distribution of SARS-CoV-2 diversity circulating in wastewater. Pérez-Cataluña A, Chiner-Oms Á, Cuevas-Ferrando E, Díaz-Reolid A, Falcó I, Randazzo W, Girón-Guzmán I, Allende A, Bracho MA, Comas I, Sánchez G. Water Res. 2022; 211
Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated?
Soldevila B, Puig-Domingo M, Marazuela M.
Rev Endocr Metab Disord. 2022; 23 (2)
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. 2022; 23 (2)
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
Development of a Single-Cycle Infectious SARS-CoV-2 Virus Replicon Particle System for Use in Biosafety Level 2 Laboratories.
Malicoat J, Manivasagam S, Zuñiga S, Sola I, [...], Manicassamy B.
J Virol. 2022; 96 (3)
DOI: 10.1128/jvi.01837-21
Research activities with infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently permitted only under biosafety level 3 (BSL3) containment. Here, we report the development of a single-cycle infectious SARS-CoV-2 virus replicon particle (VRP) system with a luciferase and green fluorescent protein (GFP) dual reporter that can be safely handled in BSL2 laboratories to study SARS-CoV-2 biology. The spike (S) gene of SARS-CoV-2 encodes the envelope glycoprotein, which is essential for mediating infection of new host cells. Through deletion and replacement of this essential S gene with a luciferase and GFP dual reporter, we have generated a conditional SARS-CoV-2 mutant (ΔS-VRP) that produces infectious particles only in cells expressing a viral envelope glycoprotein of choice. Interestingly, we observed more efficient production of infectious particles in cells expressing vesicular stomatitis virus (VSV) glycoprotein G [ΔS-VRP(G)] than in cells expressing other viral glycoproteins, including S. We confirmed that infection from ΔS-VRP(G) is limited to a single round and can be neutralized by anti-VSV serum. In our studies with ΔS-VRP(G), we observed robust expression of both luciferase and GFP reporters in various human and murine cell types, demonstrating that a broad variety of cells can support intracellular replication of SARS-CoV-2. In addition, treatment of ΔS-VRP(G)-infected cells with either of the anti-CoV drugs remdesivir (nucleoside analog) and GC376 (CoV 3CL protease inhibitor) resulted in a robust decrease in both luciferase and GFP expression in a drug dose- and cell-type-dependent manner. Taken together, our findings show that we have developed a single-cycle infectious SARS-CoV-2 VRP system that serves as a versatile platform to study SARS-CoV-2 intracellular biology and to perform high-throughput screening of antiviral drugs under BSL2 containment. IMPORTANCE Due to the highly contagious nature of SARS-CoV-2 and the lack of immunity in the human population, research on SARS-CoV-2 has been restricted to biosafety level 3 laboratories. This has greatly limited participation of the broader scientific community in SARS-CoV-2 research and thus has hindered the development of vaccines and antiviral drugs. By deleting the essential spike gene in the viral genome, we have developed a conditional mutant of SARS-CoV-2 with luciferase and fluorescent reporters, which can be safely used under biosafety level 2 conditions. Our single-cycle infectious SARS-CoV-2 virus replicon system can serve as a versatile platform to study SARS-CoV-2 intracellular biology and to perform high-throughput screening of antiviral drugs under BSL2 containment.
2021-12-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1128/jvi.01837-21 Development of a Single-Cycle Infectious SARS-CoV-2 Virus Replicon Particle System for Use in Biosafety Level 2 Laboratories. Malicoat J, Manivasagam S, Zuñiga S, Sola I, McCabe D, Rong L, Perlman S, Enjuanes L, Manicassamy B. J Virol. 2022; 96 (3)
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)
Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D.
Torres M, Casado G, Vigón L, Rodríguez-Mora S, [...], Contributing members of the Multidisciplinary Group of Study of COVID-19 (in alphabetical order).
Biomed Pharmacother. 2022; 150
DOI: 10.1016/j.biopha.2022.112965
Main cause of severe illness and death in COVID-19 patients appears to be an excessive but ineffectual inflammatory immune response that may cause severe acute respiratory distress syndrome (ARDS). Vitamin D may favour an anti-inflammatory environment and improve cytotoxic response against some infectious diseases. A multicenter, single-blind, prospective, randomized clinical trial was approved in patients with COVID-19 pneumonia and levels of 25-hydroxyvitamin D (25(OH)D) of 14.8 ng/ml (SD: 6.18) to test antiviral efficacy, tolerance and safety of 10,000 IU/day of cholecalciferol (vitamin D3) for 14 days, in comparison with 2000 IU/day. After supplementation, mean serum 25(OH)D levels increased to 19 ng/ml on average in 2000 IU/day versus 29 ng/ml in 10,000 IU/day group (p < 0.0001). Although levels of inflammatory cytokines were not modified by treatment with 10,000 IU/day, there was an increase of anti-inflammatory cytokine IL-10 and higher levels of CD4+ T cells, with predominance of T central memory subpopulation. Cytotoxic response against pseudotyped SARS-CoV-2 infected cells was increased more than 4-fold in patients who received 10,000 IU/day. Moreover, levels of IFNγ were significantly higher in this group. Beneficial effect of supplementation with 10,000 IU/day was also observed in participants who developed ARDS and stayed at the hospital for 8.0 days, whereas those who received 2000 IU/day stayed for 29.2 days (p = 0.0381). Administration of high doses of vitamin D3 as adjuvant of the standard care treatment during hospitalization for COVID-19 may improve the inflammatory environment and cytotoxic response against pseudotyped SARS-CoV-2 infected cells, shortening the hospital stay and, possibly, improving the prognosis.
2022-04-14 2022 other research-article; Journal Article abstract-available 10.1016/j.biopha.2022.112965 Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D. Torres M, Casado G, Vigón L, Rodríguez-Mora S, Mateos E, Ramos-Martín F, López-Wolf D, Sanz-Moreno J, Ryan-Murua P, Taboada-Martínez ML, López-Huertas MR, Cervero M, Coiras M, Multidisciplinary Group of Study of COVID-19 (MGS-COVID), Contributing members of the Multidisciplinary Group of Study of COVID-19 (in alphabetical order). Biomed Pharmacother. 2022; 150
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)
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
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
Coronavirus disease 2019 in liver transplant patients: Clinical and therapeutic aspects.
Loinaz-Segurola C, Marcacuzco-Quinto A, Fernández-Ruiz M.
World J Hepatol. 2021; 13 (10)
DOI: 10.4254/wjh.v13.i10.1299
The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted liver transplant (LT) activity across the world, with notable decreases in the number of donations and procedures in most Western countries, in particular throughout the first wave. The cumulative incidence of COVID-19 in LT recipients (with estimates ranging from 0.34% to 1.56%) appears to be at least comparable to that observed for the general population. Clinical and radiological features at presentation are also similar to non-transplant patients. The risk of death among LT recipients requiring hospital admission is high (from 12% to 19%), although some authors have suggested that overall mortality may be actually lower compared to the general non-transplant population. It is likely that these poor outcomes may be mainly influenced by the older age and higher comorbidity burden of LT recipients, rather than by the transplant status itself. In fact, it has been hypothesized that post-transplant immunosuppression would exert a protective role, with special focus on tacrolimus-containing regimens. There is scarce evidence to guide the optimal management of post-transplant COVID-19 and the use of antiviral or immunomodulatory therapies, although both clinical practice and guidelines support the dose reduction or withdrawal of anti-proliferative agents such as mofetil mycophenolate. Preliminary reports suggest that the antibody response to messenger RNA vaccines is significantly impaired as compared to non-immunocompromised individuals, in line with other transplant populations. Finally, it is foreseeable that the future will be conditioned by the emerging variants of severe acute respiratory syndrome coronavirus 2 with increased transmissibility among LT recipients.
2021-10-01 2021 other review-article; Review; Journal Article abstract-available 10.4254/wjh.v13.i10.1299 Coronavirus disease 2019 in liver transplant patients: Clinical and therapeutic aspects. Loinaz-Segurola C, Marcacuzco-Quinto A, Fernández-Ruiz M. World J Hepatol. 2021; 13 (10)
SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a Proinflammatory Activation Profile on Human Dendritic Cells.
Barreda D, Santiago C, Rodríguez JR, Rodríguez JF, [...], Ávila-Flores A.
Cells. 2021; 10 (12)
DOI: 10.3390/cells10123279
Dendritic cells (DCs) are the most potent antigen-presenting cells, and their function is essential to configure adaptative immunity and avoid excessive inflammation. DCs are predicted to play a crucial role in the clinical evolution of the infection by the severe acute respiratory syndrome (SARS) coronavirus (CoV)-2. DCs interaction with the SARS-CoV-2 Spike protein, which mediates cell receptor binding and subsequent fusion of the viral particle with host cell, is a key step to induce effective immunity against this virus and in the S protein-based vaccination protocols. Here we evaluated human DCs in response to SARS-CoV-2 S protein, or to a fragment encompassing the receptor binding domain (RBD) challenge. Both proteins increased the expression of maturation markers, including MHC molecules and costimulatory receptors. DCs interaction with the SARS-CoV-2 S protein promotes activation of key signaling molecules involved in inflammation, including MAPK, AKT, STAT1, and NFκB, which correlates with the expression and secretion of distinctive proinflammatory cytokines. Differences in the expression of ACE2 along the differentiation of human monocytes to mature DCs and inter-donor were found. Our results show that SARS-CoV-2 S protein promotes inflammatory response and provides molecular links between individual variations and the degree of response against this virus.
2021-11-23 2021 other IM; Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/cells10123279 SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a Proinflammatory Activation Profile on Human Dendritic Cells. Barreda D, Santiago C, Rodríguez JR, Rodríguez JF, Casasnovas JM, Mérida I, Ávila-Flores A. Cells. 2021; 10 (12)
Seroprevalence of SARS-CoV-2 in a Cohort of Patients with Multiple Sclerosis under Disease-Modifying Therapies
Sancho-Saldaña A, Gil Sánchez A, Quirant-Sánchez B, Nogueras L, [...], Brieva L.
J Clin Med. 2022; 11 (9)
DOI:
Background: Disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS) alter the immune system and therefore increase the risk of infection. There is growing concern about the impact of COVID-19 on patients with MS (pwMS), especially those treated with DMTs. Methods: This is a single-center prospective observational study based on data from the Esclerosis Múltiple y COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data and SARS-CoV-2 serology, and symptoms of COVID-19 in pwMS treated with any DTM were extracted. The relationship among demographics, MS status, DMT, and COVID-19 was evaluated. Results: A total of 259 pwMS were included. The administration of interferon was significantly associated with the presence of SARS-CoV-2 antibodies (26.4% vs. 10.7%, p = 0.006). Although patients taking interferon were significantly older (49.1 vs. 43.5, p = 0.003), the association of interferon with the presence of SARS-CoV-2 antibodies was still significant in the multivariate analysis (OR 2.99 (1.38; 6.36), p = 0.006). Conclusions: According to our data, pwMS present a higher risk of COVID-19 infection compared with results obtained from the general population. There is no evidence of a worse COVID-19 outcome in pwMS. DMTs did not significantly change the frequency of COVID-19, except for interferon; however, these findings must be interpreted with caution given the small sample of pwMS taking each DMT.
2022-04-29 2022 other research-article; Journal Article abstract-available Seroprevalence of SARS-CoV-2 in a Cohort of Patients with Multiple Sclerosis under Disease-Modifying Therapies Sancho-Saldaña A, Gil Sánchez A, Quirant-Sánchez B, Nogueras L, Peralta S, Solana M, González-Mingot C, Gallego Y, Quibus L, Ramo-Tello C, Presas-Rodríguez S, Martínez-Cáceres E, Torres P, Hervás J, Valls J, Brieva L. J Clin Med. 2022; 11 (9)
COVID-19 pneumonia: A review of typical radiological characteristics.
Churruca M, Martínez-Besteiro E, Couñago F, Landete P.
World J Radiol. 2021; 13 (10)
DOI: 10.4329/wjr.v13.i10.327
Coronavirus disease 2019 (COVID-19) was first discovered after unusual cases of severe pneumonia emerged by the end of 2019 in Wuhan (China) and was declared a global public health emergency by the World Health Organization in January 2020. The new pathogen responsible for the infection, genetically similar to the beta-coronavirus family, is known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the current gold standard diagnostic tool for its detection in respiratory samples is the reverse transcription-polymerase chain reaction test. Imaging findings on COVID-19 have been widely described in studies published throughout last year, 2020. In general, ground-glass opacities and consolidations, with a bilateral and peripheral distribution, are the most typical patterns found in COVID-19 pneumonia. Even though much of the literature focuses on chest computed tomography (CT) and X-ray imaging and their findings, other imaging modalities have also been useful in the assessment of COVID-19 patients. Lung ultrasonography is an emerging technique with a high sensitivity, and thus useful in the initial evaluation of SARS-CoV-2 infection. In addition, combined positron emission tomography-CT enables the identification of affected areas and follow-up treatment responses. This review intends to clarify the role of the imaging modalities available and identify the most common radiological manifestations of COVID-19.
2021-10-01 2021 other review-article; Review; Journal Article abstract-available 10.4329/wjr.v13.i10.327 COVID-19 pneumonia: A review of typical radiological characteristics. Churruca M, Martínez-Besteiro E, Couñago F, Landete P. World J Radiol. 2021; 13 (10)
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 fondo-covid 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
First Identification of Reinfection by a Genetically Different Variant of SARS-CoV-2 in a Homeless Person from the Metropolitan Area of Santiago, Chile.
Acuña-Castillo C, Vidal M, Inostroza-Molina A, Vallejos-Vidal E, [...], Sandino AM.
J Environ Public Health. 2022; 2022
DOI: 10.1155/2022/3859071
The identification and tracking of SARS-CoV-2 infected patients in the general population are essential components of the global strategy to limit the COVID-19 viral spread, specifically for maintaining traceability and suppressing the resurgence of local outbreaks. Public health programs that include continuous RT-qPCR testing for COVID-19 in the general population, viral sequencing, and genomic surveillance for highly contagious forms of the virus have allowed for the identification of SARS-CoV-2 infections and reinfections. This work identified SARS-CoV-2 reinfection in a homeless person, which occurred 58 days after the first COVID-19 diagnosis. Genomic sequencing identified a different Nextstrain classification clade (20A and 20B) and PANGO lineage, with a divergence of 4 single nucleotide variants (SNVs) in S and ORF1ab genes, suggesting reinfection by different viral variants. This study is the first from the great metropolitan area of Santiago, Chile, one of the top ten countries in the world to live during the COVID-19 pandemic. We support the importance of performing intensive genomic surveillance programs in the whole population and high-risk groups, such as homeless people, nearly 20 thousand people in Chile, and have limited access to health care services and poor viral traceability.
2022-04-27 2022 other research-article; Journal Article abstract-available 10.1155/2022/3859071 First Identification of Reinfection by a Genetically Different Variant of SARS-CoV-2 in a Homeless Person from the Metropolitan Area of Santiago, Chile. Acuña-Castillo C, Vidal M, Inostroza-Molina A, Vallejos-Vidal E, Luraschi R, Figueroa M, Barrera-Avalos C, Vera R, Vargas S, Valdes D, Maisey K, Imarai M, Leiva-Salcedo E, Escobar A, Reyes-Cerpa S, Gaete A, Palma-Vejares R, Travisany D, Rojo LE, Reyes-López FE, Sandino AM. J Environ Public Health. 2022; 2022
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)
Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease.
Sugiyama MG, Cui H, Redka DS, Karimzadeh M, [...], Antonescu CN.
Sci Rep. 2021; 11 (1)
DOI: 10.1038/s41598-021-02432-7
The COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.
2021-12-02 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-021-02432-7 Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease. Sugiyama MG, Cui H, Redka DS, Karimzadeh M, Rujas E, Maan H, Hayat S, Cheung K, Misra R, McPhee JB, Viirre RD, Haller A, Botelho RJ, Karshafian R, Sabatinos SA, Fairn GD, Madani Tonekaboni SA, Windemuth A, Julien JP, Shahani V, MacKinnon SS, Wang B, Antonescu CN. Sci Rep. 2021; 11 (1)
Metabolomics study of COVID-19 patients in four different clinical stages.
Valdés A, Moreno LO, Rello SR, Orduña A, [...], Cifuentes A.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-022-05667-0
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the coronavirus strain causing the respiratory pandemic COVID-19 (coronavirus disease 2019). To understand the pathobiology of SARS-CoV-2 in humans it is necessary to unravel the metabolic changes that are produced in the individuals once the infection has taken place. The goal of this work is to provide new information about the altered biomolecule profile and with that the altered biological pathways of patients in different clinical situations due to SARS-CoV-2 infection. This is done via metabolomics using HPLC-QTOF-MS analysis of plasma samples at COVID-diagnose from a total of 145 adult patients, divided into different clinical stages based on their subsequent clinical outcome (25 negative controls (non-COVID); 28 positive patients with asymptomatic disease not requiring hospitalization; 27 positive patients with mild disease defined by a total time in hospital lower than 10 days; 36 positive patients with severe disease defined by a total time in hospital over 20 days and/or admission at the ICU; and 29 positive patients with fatal outcome or deceased). Moreover, follow up samples between 2 and 3 months after hospital discharge were also obtained from the hospitalized patients with mild prognosis. The final goal of this work is to provide biomarkers that can help to better understand how the COVID-19 illness evolves and to predict how a patient could progress based on the metabolites profile of plasma obtained at an early stage of the infection. In the present work, several metabolites were found as potential biomarkers to distinguish between the end-stage and the early-stage (or non-COVID) disease groups. These metabolites are mainly involved in the metabolism of carnitines, ketone bodies, fatty acids, lysophosphatidylcholines/phosphatidylcholines, tryptophan, bile acids and purines, but also omeprazole. In addition, the levels of several of these metabolites decreased to "normal" values at hospital discharge, suggesting some of them as early prognosis biomarkers in COVID-19 at diagnose.
2022-01-31 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-022-05667-0 Metabolomics study of COVID-19 patients in four different clinical stages. Valdés A, Moreno LO, Rello SR, Orduña A, Bernardo D, Cifuentes A. Sci Rep. 2022; 12 (1)
The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.
Osuchowski MF, Winkler MS, Skirecki T, Cajander S, [...], Rubio I.
Lancet Respir Med. 2021; 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)
Modified SIQR model for the COVID-19 outbreak in several countries.
Pinto CMA, Tenreiro Machado JA, Burgos-Simón C.
Math Methods Appl Sci. 2022;
DOI: 10.1002/mma.8082
In this paper, we propose a modified Susceptible-Infected-Quarantine-Recovered (mSIQR) model, for the COVID-19 pandemic. We start by proving the well-posedness of the model and then compute its reproduction number and the corresponding sensitivity indices. We discuss the values of these indices for epidemiological relevant parameters, namely, the contact rate, the proportion of unknown infectious, and the recovering rate. The mSIQR model is simulated, and the outputs are fit to COVID-19 pandemic data from several countries, including France, US, UK, and Portugal. We discuss the epidemiological relevance of the results and provide insights on future patterns, subjected to health policies.
2022-01-17 2022 other research-article; Journal Article abstract-available 10.1002/mma.8082 Modified SIQR model for the COVID-19 outbreak in several countries. Pinto CMA, Tenreiro Machado JA, Burgos-Simón C. Math Methods Appl Sci. 2022;
Distribution of Interferon Lambda 4 Single Nucleotide Polymorphism rs11322783 Genotypes in Patients with COVID-19.
Sorrentino L, Silvestri V, Oliveto G, Scordio M, [...], Scagnolari C.
Microorganisms. 2022; 10 (2)
DOI: 10.3390/microorganisms10020363
Type III interferons (IFN-III), also known as IFN-Lambda, have a pivotal role during SARS-CoV-2 infection. IFN-Lambda response among individuals is heterogeneous and its association with COVID-19 symptoms severity needs to be further clarified. We analyzed the genotype frequencies of IFNL4 single nucleotide polymorphism (SNP) rs11322783 in patients with COVID-19 (n = 128), in comparison with a validated data set of European healthy controls (n = 14152). The IFNL4 SNP was also analyzed according to the haematological and clinical parameters of patients with COVID-19. The distributions of IFNL4 genotypes among SARS-CoV-2 positive patients [TT/TT 41.4% (n = 53), TT/ΔG 47.7% (n = 61) and ΔG/ΔG 10.9% (n = 14)] and healthy controls were comparable. Different levels of white blood cells (p = 0.036) and neutrophils (p = 0.042) were found in the IFNL4 different genotypes in patients with COVID-19; the ΔG/ΔG genotype was more represented in the groups with low white blood cells and neutrophils. There were no differences in major inflammation parameters (C-reactive protein, D-dimer, Albumin, and Lactate-dehydrogenase (LDH)] and survival rate according to the IFNL4 genotypes. In conclusion, although patients with COVID-19 did not exhibit a different distribution of the IFNL4 SNP, the ΔG/ΔG genotype was associated with a lower count of immune cell populations. These findings need to be confirmed in larger groups of patients with COVID-19 and the role of IFNL4 SNP needs to be also investigated in other respiratory viral infections.
2022-02-04 2022 other research-article; Journal Article abstract-available 10.3390/microorganisms10020363 Distribution of Interferon Lambda 4 Single Nucleotide Polymorphism rs11322783 Genotypes in Patients with COVID-19. Sorrentino L, Silvestri V, Oliveto G, Scordio M, Frasca F, Fracella M, Bitossi C, D'Auria A, Santinelli L, Gabriele L, Pierangeli A, Mastroianni CM, d'Ettorre G, Antonelli G, Caruz A, Ottini L, Scagnolari C. Microorganisms. 2022; 10 (2)
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
A Comparative Study between Spanish and British SARS-CoV-2 Variants.
Jimenez Ruiz JA, Lopez Ramirez C, Lopez-Campos JL.
Curr Issues Mol Biol. 2021; 43 (3)
DOI: 10.3390/cimb43030140
The study of the interaction between the SARS-CoV-2 spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor is key to understanding binding affinity and stability. In the present report, we sought to investigate the differences between two already sequenced genome variants (Spanish and British) of SARS-CoV-2. Methods: In silico model evaluating the homology, identity and similarity in the genome sequence and the structure and alignment of the predictive spike by computational docking methods. Results: The identity results between the Spanish and British variants of the Spike protein were 28.67%. This close correspondence in the results between the Spanish and British SARS-CoV-2 variants shows that they are very similar (99.99%). The alignment obtained results in four deletions. There were 23 nucleotide substitutions also predicted which could affect the functionality of the proteins produced from this sequence. The interaction between the binding receptor domain from the spike protein and the ACE2 receptor produces some of the mutations found and, therefore, the energy of this ligand varies. However, the estimated antigenicity of the British variant is higher than its Spanish counterpart. Conclusions: Our results indicate that minimal mutations could interfere in the infectivity of the virus due to changes in the fitness between host cell recognition and interaction proteins. In particular, the N501Y substitution, situated in the RBD of the spike of the British variant, might be the reason for its extraordinary infective potential.
2021-11-16 2021 other Comparative Study; Journal Article abstract-available 10.3390/cimb43030140 A Comparative Study between Spanish and British SARS-CoV-2 Variants. Jimenez Ruiz JA, Lopez Ramirez C, Lopez-Campos JL. Curr Issues Mol Biol. 2021; 43 (3)
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)
Potential protective effect against SARS-CoV-2 infection by APOE rs7412 polymorphism.
Espinosa-Salinas I, Colmenarejo G, Fernández-Díaz CM, Gómez de Cedrón M, [...], Ramírez de Molina A.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-022-10923-4
The pandemic burden caused by the SARS-CoV-2 coronavirus constitutes a global public health emergency. Increasing understanding about predisposing factors to infection and severity is now a priority. Genetic, metabolic, and environmental factors can play a crucial role in the course and clinical outcome of COVID-19. We aimed to investigate the putative relationship between genetic factors associated to obesity, metabolism and lifestyle, and the presence and severity of SARS-CoV-2 infection. A total of 249 volunteers (178 women and 71 men, with mean and ± SD age of 49 ± 11 years) characterized for dietary, lifestyle habits and anthropometry, were studied for presence and severity of COVID-19 infection, and genotyped for 26 genetic variants related to obesity, lipid profile, inflammation, and biorhythm patterns. A statistically significant association was found concerning a protective effect of APOE rs7412 against SARS-CoV-2 infection (p = 0.039; OR 0.216; CI 0.084, 0.557) after correction for multiple comparisons. This protective effect was also ascribed to the APOɛ2 allele (p = 0.001; OR 0.207; CI 0.0796, 0.538). The genetic variant rs7412 resulting in ApoE2, genetic determinant of lipid and lipoprotein levels, could play a significant role protecting against SARS-CoV-2 infection.
2022-05-04 2022 other research-article; Journal Article abstract-available 10.1038/s41598-022-10923-4 Potential protective effect against SARS-CoV-2 infection by APOE rs7412 polymorphism. Espinosa-Salinas I, Colmenarejo G, Fernández-Díaz CM, Gómez de Cedrón M, Martinez JA, Reglero G, Ramírez de Molina A. Sci Rep. 2022; 12 (1)
Contribution of Host miRNA-223-3p to SARS-CoV-Induced Lung Inflammatory Pathology.
Morales L, Oliveros JC, Enjuanes L, Sola I.
mBio. 2022; 13 (2)
DOI: 10.1128/mbio.03135-21
Severe acute respiratory syndrome coronavirus (SARS-CoV) and the closely related SARS-CoV-2 are emergent highly pathogenic human respiratory viruses causing acute lethal disease associated with lung damage and dysregulated inflammatory responses. SARS-CoV envelope protein (E) is a virulence factor involved in the activation of various inflammatory pathways. Here, we study the contribution of host miRNAs to the virulence mediated by E protein. Small RNAseq analysis of infected mouse lungs identified miRNA-223 as a potential regulator of pulmonary inflammation, since it was significantly increased in SARS-CoV-WT virulent infection compared to the attenuated SARS-CoV-ΔE infection. In vivo inhibition of miRNA-223-3p increased mRNA levels of pro-inflammatory cytokines and NLRP3 inflammasome, suggesting that during lung infection, miRNA-223 might contribute to restrict an excessive inflammatory response. Interestingly, miRNA-223-3p inhibition also increased the levels of the CFTR transporter, which is involved in edema resolution and was significantly downregulated in the lungs of mice infected with the virulent SARS-CoV-WT virus. At the histopathological level, a decrease in the pulmonary edema was observed when miR-223-3p was inhibited, suggesting that miRNA-223-3p was involved in the regulation of the SARS-CoV-induced inflammatory pathology. These results indicate that miRNA-223 participates in the regulation of E protein-mediated inflammatory response during SARS-CoV infection by targeting different host mRNAs involved in the pulmonary inflammation, and identify miRNA-223 as a potential therapeutic target in SARS-CoV infection. IMPORTANCE The SARS-CoV-2 pandemic has emphasized the need to understand the mechanisms of severe lung inflammatory pathology caused by human deadly coronaviruses in order to design new antiviral therapies. Here, we identify miRNA-223-3p as a host miRNA involved in the regulation of lung inflammatory response mediated by envelope (E) protein during SARS-CoV infection. miRNAs downregulate the expression of cellular mRNAs and participate in complex networks of mRNA-miRNA interactions that regulate cellular processes. The inhibition of miRNA-223 in infected mice by intranasal administration of antisense RNAs led to changes in the expression of host factors involved in inflammation (cytokines, chemokines, and NLRP3 inflammasome) and in the resolution of lung edema ion transporter CFTR. These results confirmed the contribution of miRNA-223 to the regulation of SARS-CoV-induced pathogenic processes and support the therapeutic potential of inhibiting miRNAs during coronavirus infection using RNA interference approaches.
2022-03-01 2022 other research-article; Journal Article abstract-available 10.1128/mbio.03135-21 Contribution of Host miRNA-223-3p to SARS-CoV-Induced Lung Inflammatory Pathology. Morales L, Oliveros JC, Enjuanes L, Sola I. mBio. 2022; 13 (2)
The SARS-CoV-2 Spike Glycoprotein Directly Binds Exogeneous Sialic Acids: A NMR View.
Unione L, Moure MJ, Lenza MP, Oyenarte I, [...], Jiménez-Barbero J.
Angew Chem Int Ed Engl. 2022; 61 (18)
DOI: 10.1002/anie.202201432
The interaction of the SARS CoV2 spike glycoprotein with two sialic acid-containing trisaccharides (α2,3 and α2,6 sialyl N-acetyllactosamine) has been demonstrated by NMR. The NMR-based distinction between the signals of those sialic acids in the glycans covalently attached to the spike protein and those belonging to the exogenous α2,3 and α2,6 sialyl N-acetyllactosamine ligands has been achieved by synthesizing uniformly 13 C-labelled trisaccharides at the sialic acid and galactose moieties. STD-1 H,13 C-HSQC NMR experiments elegantly demonstrate the direct interaction of the sialic acid residues of both trisaccharides with additional participation of the galactose moieties, especially for the α2,3-linked analogue. Additional experiments with the spike protein in the presence of a specific antibody for the N-terminal domain and with the isolated receptor binding and N-terminal domains of the spike protein unambiguously show that the sialic acid binding site is located at the N-terminal domain.
2022-03-07 2022 other brief-report; Journal Article abstract-available 10.1002/anie.202201432 The SARS-CoV-2 Spike Glycoprotein Directly Binds Exogeneous Sialic Acids: A NMR View. Unione L, Moure MJ, Lenza MP, Oyenarte I, Ereño-Orbea J, Ardá A, Jiménez-Barbero J. Angew Chem Int Ed Engl. 2022; 61 (18)
Neutralizing antibodies against SARS-CoV-2 variants of concern elicited by the comirnaty COVID-19 vaccine in nursing home residents.
Sánchez-Sendra B, Albert E, Zulaica J, Torres I, [...], Navarro D.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-022-07849-2
Immunosenescence may impact the functionality and breadth of vaccine-elicited humoral immune responses. The ability of sera to neutralize the SARS-CoV-2 spike protein (S) from Beta, Gamma, Delta, and Epsilon variants of concern (VOCs) relative to the ancestral Wuhan-Hu-1 strain was compared in Comirnaty COVID-19-vaccinated elderly nursing home residents, either SARS-CoV-2 naïve (n = 22) or experienced (n = 8), or SARS-CoV-2 naïve younger individuals (n = 18) and non-vaccinated individuals who recovered from severe COVID-19 (n = 19). In all groups, except that including SARS-CoV-2-experienced nursing home residents, some participants lacked NtAb against one or more VOCs, mainly the Beta variant (15-20%). Serum NtAb titers were lowest against the Beta variant followed by Gamma, Delta and Epsilon variants. Overall, fold change reduction in NtAb titers relative to the ancestral strain was greatest for the Beta variant (6.7-19.4) followed by Gamma (4.8-16.0), Epsilon (2.9-13.4), and Delta (3.5-6.5) variants, although subtle differences were observed for Beta, Epsilon and Delta variants across comparison groups. In summary, older age, frailty, and concurrence of co-morbidities had no major impact on the serum NtAb activity profile against SARS-CoV-2 VOCs.
2022-03-08 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s41598-022-07849-2 Neutralizing antibodies against SARS-CoV-2 variants of concern elicited by the comirnaty COVID-19 vaccine in nursing home residents. Sánchez-Sendra B, Albert E, Zulaica J, Torres I, Giménez E, Botija P, Beltrán MJ, Rodado C, Geller R, Navarro D. Sci Rep. 2022; 12 (1)
Efficacy of Pre-Procedural Mouthwashes against SARS-CoV-2: A Systematic Review of Randomized Controlled Trials.
Garcia-Sanchez A, Peña-Cardelles JF, Ruiz S, Robles F, [...], Simon JC.
J Clin Med. 2022; 11 (6)
DOI: 10.3390/jcm11061692
The oral mucosa is one of the first sites to be affected by the SARS-CoV-2. For this reason, healthcare providers performing aerosol-generating procedures (AGPs) in the oral cavity are at high risk of infection with COVID-19. The aim of this systematic review is to verify whether there is evidence in the literature describing a decrease in the salivary viral load of SARS-CoV-2 after using different mouthwashes. An electronic search of the MEDLINE database (via PubMed), Web of Science, SCOPUS, and the Cochrane library database was carried out. The criteria used were those described by the PRISMA® Statement. Randomized controlled trial studies that have used mouthwashes as a form of intervention to reduce the viral load in saliva were included. The risk of bias was analyzed using the Joanna Briggs Institute Critical Appraisal Tool. Ultimately, eight articles were included that met the established criteria. Based on the evidence currently available in the literature, PVP-I, CHX and CPC present significant virucidal activity against SARS-CoV-2 in saliva and could be used as pre-procedural mouthwashes to reduce the risk of cross-infection.
2022-03-18 2022 other review-article; Review; Journal Article abstract-available 10.3390/jcm11061692 Efficacy of Pre-Procedural Mouthwashes against SARS-CoV-2: A Systematic Review of Randomized Controlled Trials. Garcia-Sanchez A, Peña-Cardelles JF, Ruiz S, Robles F, Ordonez-Fernandez E, Salgado-Peralvo AO, Balloch J, Simon JC. J Clin Med. 2022; 11 (6)
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)
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)
Lactoferrin as Immune-Enhancement Strategy for SARS-CoV-2 Infection in Alzheimer's Disease Patients.
Bartolomé F, Rosa L, Valenti P, Lopera F, [...], Carro E.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.878201
Coronavirus 2 (SARS-CoV2) (COVID-19) causes severe acute respiratory syndrome. Severe illness of COVID-19 largely occurs in older people and recent evidence indicates that demented patients have higher risk for COVID-19. Additionally, COVID-19 further enhances the vulnerability of older adults with cognitive damage. A balance between the immune and inflammatory response is necessary to control the infection. Thus, antimicrobial and anti-inflammatory drugs are hopeful therapeutic agents for the treatment of COVID-19. Accumulating evidence suggests that lactoferrin (Lf) is active against SARS-CoV-2, likely due to its potent antiviral and anti-inflammatory actions that ultimately improves immune system responses. Remarkably, salivary Lf levels are significantly reduced in different Alzheimer's disease (AD) stages, which may reflect AD-related immunological disturbances, leading to reduced defense mechanisms against viral pathogens and an increase of the COVID-19 susceptibility. Overall, there is an urgent necessity to protect AD patients against COVID-19, decreasing the risk of viral infections. In this context, we propose bovine Lf (bLf) as a promising preventive therapeutic tool to minimize COVID-19 risk in patients with dementia or AD.
2022-04-25 2022 other review-article; Review; Journal Article abstract-available 10.3389/fimmu.2022.878201 Lactoferrin as Immune-Enhancement Strategy for SARS-CoV-2 Infection in Alzheimer's Disease Patients. Bartolomé F, Rosa L, Valenti P, Lopera F, Hernández-Gallego J, Cantero JL, Orive G, Carro E. Front Immunol. 2022; 13
Short and Long-Term Impact of COVID-19 Infection on Previous Respiratory Diseases.
Chiner-Vives E, Cordovilla-Pérez R, de la Rosa-Carrillo D, García-Clemente M, [...], de Granda-Orive JI.
Arch Bronconeumol. 2022; 58 Suppl 1
DOI: 10.1016/j.arbres.2022.03.011
On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Till now, it affected 452.4 million (Spain, 11.18 million) persons all over the world with a total of 6.04 million of deaths (Spain, 100,992). It is observed that 75% of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. It was shown that people with underlying chronic illnesses are more likely to get it and grow seriously ill. Individuals with COVID-19 who have a past medical history of cardiovascular disorder, cancer, obesity, chronic lung disease, diabetes, or neurological disease had the worst prognosis and are more likely to develop acute respiratory distress syndrome or pneumonia. COVID-19 can affect the respiratory system in a variety of ways and across a spectrum of levels of disease severity, depending on a person's immune system, age and comorbidities. Symptoms can range from mild, such as cough, shortness of breath and fever, to critical disease, including respiratory failure, shock and multi-organ system failure. So, COVID-19 infection can cause overall worsening of these previous respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc. This review aims to provide information on the impact of the COVID-19 disease on pre-existing lung comorbidities.
2022-04-15 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.arbres.2022.03.011 Short and Long-Term Impact of COVID-19 Infection on Previous Respiratory Diseases. Chiner-Vives E, Cordovilla-Pérez R, de la Rosa-Carrillo D, García-Clemente M, Izquierdo-Alonso JL, Otero-Candelera R, Pérez-de Llano L, Sellares-Torres J, de Granda-Orive JI. Arch Bronconeumol. 2022; 58 Suppl 1
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)
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 IM; 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)
Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors.
Zaragoza-Huesca D, Martínez-Cortés C, Banegas-Luna AJ, Pérez-Garrido A, [...], Martínez-Martínez I.
Int J Mol Sci. 2022; 23 (5)
DOI: 10.3390/ijms23052796
The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.
2022-03-03 2022 other IM; research-article; Journal Article abstract-available 10.3390/ijms23052796 Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors. Zaragoza-Huesca D, Martínez-Cortés C, Banegas-Luna AJ, Pérez-Garrido A, Vegara-Meseguer JM, Peñas-Martínez J, Rodenas MC, Espín S, Pérez-Sánchez H, Martínez-Martínez I. Int J Mol Sci. 2022; 23 (5)
Confirmation of SARS-CoV-2 airborne dissemination indoors using "COVID-19 traps".
Orenes-Piñero E, Navas-Carrillo D, Moreno-Docón A, Ortega-García JA, [...], Ramírez P.
J Infect. 2022; 84 (3)
DOI: 10.1016/j.jinf.2021.12.017
2021-12-22 2021 other research-article; Journal Article 10.1016/j.jinf.2021.12.017 Confirmation of SARS-CoV-2 airborne dissemination indoors using "COVID-19 traps". Orenes-Piñero E, Navas-Carrillo D, Moreno-Docón A, Ortega-García JA, Torres-Cantero AM, García-Vázquez E, Ramírez P. J Infect. 2022; 84 (3)
Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice.
Mabrouk MT, Chiem K, Rujas E, Huang WC, [...], Lovell J.
Sci Adv. 2021; 7 (49)
DOI: 10.1126/sciadv.abj1476
The COVID-19 pandemic has spurred interest in potent and thermostable SARS-CoV-2 vaccines. Here, we assess low-dose immunization with lyophilized nanoparticles decorated with recombinant SARS-CoV-2 antigens. The SARS-CoV-2 Spike glycoprotein or its receptor-binding domain (RBD; mouse vaccine dose, 0.1 μg) was displayed on liposomes incorporating a particle-inducing lipid, cobalt porphyrin-phospholipid (dose, 0.4 μg), along with monophosphoryl lipid A (dose, 0.16 μg) and QS-21 (dose, 0.16 μg). Following optimization of lyophilization conditions, Spike or RBD-decorated liposomes were effectively reconstituted and maintained conformational capacity for binding human angiotensin-converting enzyme 2 (hACE2) for at least a week when stored at 60°C in lyophilized but not liquid format. Prime-boost intramuscular vaccination of hACE2-transgenic mice with the reconstituted vaccine formulations induced effective antibody responses that inhibited RBD binding to hACE2 and neutralized pseudotyped and live SARS-CoV-2. Two days following viral challenge, immunized transgenic mice cleared the virus and were fully protected from lethal disease.
2021-12-01 2021 other research-article; Journal Article abstract-available 10.1126/sciadv.abj1476 Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice. Mabrouk MT, Chiem K, Rujas E, Huang WC, Jahagirdar D, Quinn B, Surendran Nair M, Nissly RH, Cavener VS, Boyle NR, Sornberger TA, Kuchipudi SV, Ortega J, Julien JP, Martinez-Sobrido L, Lovell J. Sci Adv. 2021; 7 (49)
Virucidal Activity of Different Mouthwashes Using a Novel Biochemical Assay.
Rodríguez-Casanovas HJ, la Rosa M, Bello-Lemus Y, Rasperini G, [...], Acosta-Hoyos AJ.
Healthcare (Basel). 2021; 10 (1)
DOI: 10.3390/healthcare10010063
Saliva of patients with COVID-19 has a high SARS-CoV-2 viral load. The risk of spreading the virus is not insignificant, and procedures for reducing viral loads in the oral cavity have been proposed. Little research to date has been performed on the effect of mouthwashes on the SARS-CoV-2 virus, and some of their mechanisms of action remain unknown. SARS-CoV-2 positive nasopharyngeal swabs measured by RT-PCR were used for virucidal activity in a 1:1 ratio, with an incubation time of 1 min. The solutions used in this study were: iodopovidone (8 mg); * D-limonene, a terpene extracted from citrus peels (0.3%); † cetylpyridinium chloride (0.1%) (CPC); ‡ chlorhexidine gluconate (10%) (CHX); § a CPC (0.12%) and CHX (0.05%) containing formula; ** a formula containing essential oils; †† a CPC containing formula (0.07%); ‡‡ a D-limonene (0.2%) and CPC (0.05%) containing formula; §§ a solution containing sodium fluoride (0.05%) and CPC (0.075%); *** a solution containing CHX (0.12%) and; ††† a CHX (0.2%) containing formula. ‡‡‡ As a control reaction, saline solution or excipient solution (water, glycerin, citric acid, colorant, sodium citrate) was used. Within the limitations of this study, we can conclude that a mouthwash containing both D-limonene and CPC reduced the virucidal activity in about 6 logs (>99.999% reduction). Hence, establishing a clinical protocol for dentists is suggested, where all patients to be treated rinse pre-operatively with a mouthwash containing both D-limonene and CPC to reduce the likelihood of infection with SARS-CoV-2 for dentists. This is a relatively inexpensive way to reduce viral transmission of SARS-CoV-2 from infected individuals within the community. It is also a simple way to decrease infections from asymptomatic and pre-symptomatic patients.
2021-12-30 2021 other research-article; Journal Article abstract-available 10.3390/healthcare10010063 Virucidal Activity of Different Mouthwashes Using a Novel Biochemical Assay. Rodríguez-Casanovas HJ, la Rosa M, Bello-Lemus Y, Rasperini G, Acosta-Hoyos AJ. Healthcare (Basel). 2021; 10 (1)
Minimally Invasive Tissue Sampling as an Alternative to Complete Diagnostic Autopsies in the Context of Epidemic Outbreaks and Pandemics: The Example of Coronavirus Disease 2019 (COVID-19).
Bassat Q, Varo R, Hurtado JC, Marimon L, [...], Rakislova N.
Clin Infect Dis. 2021; 73 (Suppl_5)
DOI: 10.1093/cid/ciab760

Background

Infectious diseases' outbreak investigation requires, by definition, conducting a thorough epidemiological assessment while simultaneously obtaining biological samples for an adequate screening of potential responsible pathogens. Complete autopsies remain the gold-standard approach for cause-of-death evaluation and characterization of emerging diseases. However, for highly transmissible infections with a significant associated lethality, such as COVID-19, complete autopsies are seldom performed due to biosafety challenges, especially in low-resource settings. Minimally invasive tissue sampling (MITS) is a validated new approach based on obtaining postmortem samples from key organs and body fluids, a procedure that does not require advanced biosafety measures or a special autopsy room.

Methods

We aimed to review the use of MITS or similar procedures for outbreak investigation up to 27 March 2021 and their performance for evaluating COVID-19 deaths.

Results

After a literature review, we analyzed in detail the results of 20 studies conducted at international sites, whereby 216 COVID-19-related deaths were investigated. MITS provided a general and more granular understanding of the pathophysiological changes secondary to the infection and high-quality samples where the extent and degree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related damage could be evaluated.

Conclusions

MITS is a useful addition in the investigation and surveillance of infections occurring in outbreaks or epidemics. Its less invasive nature makes the tool more acceptable and feasible and reduces the risk of procedure-associated contagion, using basic biosafety measures. Standardized approaches protocolizing which samples should be collected-and under which exact biosafety measures-are necessary to facilitate and expand its use globally.
2021-12-01 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1093/cid/ciab760 Minimally Invasive Tissue Sampling as an Alternative to Complete Diagnostic Autopsies in the Context of Epidemic Outbreaks and Pandemics: The Example of Coronavirus Disease 2019 (COVID-19). Bassat Q, Varo R, Hurtado JC, Marimon L, Ferrando M, Ismail MR, Carrilho C, Fernandes F, Castro P, Maixenchs M, Rodrigo-Calvo MT, Guerrero J, Martínez A, Lacerda MVG, Mandomando I, Menéndez C, Martinez MJ, Ordi J, Rakislova N. Clin Infect Dis. 2021; 73 (Suppl_5)
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)
Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease.
Sabater Molina M, Nicolás Rocamora E, Bendicho AI, Vázquez EG, [...], Gimeno Blanes JR.
PLoS One. 2022; 17 (2)
DOI: 10.1371/journal.pone.0263140

Background

Infection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus.

Methods

318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed.

Results

Four SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12-0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14-0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12-115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26-125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (p<0.05), which might be due to the association with the disease. No association between COVID-19 disease and the different AGTR1 SNPs was evidenced on multivariable, nevertheless the A/A genotype for rs5183 showed an higher hospitalization risk in patients with comorbidities.

Conclusions

Different genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.
2022-02-04 2022 fondo-covid Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1371/journal.pone.0263140 Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease. Sabater Molina M, Nicolás Rocamora E, Bendicho AI, Vázquez EG, Zorio E, Rodriguez FD, Gil Ortuño C, Rodríguez AI, Sánchez-López AJ, Jara Rubio R, Moreno-Docón A, Marcos PJ, García Pavía P, Villa RB, Gimeno Blanes JR. PLoS One. 2022; 17 (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)
Bibliometric Analysis of International Scientific Production on Pharmacologic Treatments for SARS-CoV-2/COVID-19 During 2020.
Ruiz-Fresneda MA, Jiménez-Contreras E, Ruiz-Fresneda C, Ruiz-Pérez R.
Front Public Health. 2021; 9
DOI: 10.3389/fpubh.2021.778203

Background

COVID-19 is causing a grave global health and economic crisis and the fight against the pandemic has led to unprecedented scientific activity. Bibliometrics could be a useful tool for guiding future researches lines and promoting international collaboration for an effective treatment. For this purpose, we have conducted a bibliometric analysis of scientific publications on drugs and therapies used to treat COVID-19 during 2020.

Methods

Data source: Web of Science. We gathered data on scientific production relating to drugs used to treat COVID-19. We calculated impact factors and analyzed production by institution, country, and journal, visualizing our results in bibliometric networks.

Results

In 1 year, production relating to COVID-19 exceeded 100 000 publications, with over 6,500 on Drugs and COVID-19. Research into hydroxychloroquine and chloroquine, remdesivir, lopinavir and ritonavir, tocilizumab and convalescent plasma is particularly noteworthy. Mean citations/study range from 11.9 to 15.4. Producer institutions fall into three groups: one in the US and centered on Harvard Medical School; another in Europe led by INSERS; and another in China led by Huazhong University of Science and Technology. Production by journal is widespread but the Journal of Medical Virology, International Journal of Antimicrobial Agents, and American Journal of Transplantation are noteworthy.

Conclusions

The volume of research that is currently under way is comparable to the magnitude of the pandemic itself. Such a high volume of studies is infrequent and the impact they have achieved has no known precedent. The producing countries are those with highest incidence of the pandemic and greatest scientific potential; moreover, inter-agency and international collaboration has reached extraordinarily high levels.
2021-01-01 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fpubh.2021.778203 Bibliometric Analysis of International Scientific Production on Pharmacologic Treatments for SARS-CoV-2/COVID-19 During 2020. Ruiz-Fresneda MA, Jiménez-Contreras E, Ruiz-Fresneda C, Ruiz-Pérez R. Front Public Health. 2021; 9
Monoclonal antibody therapies in the management of SARS-CoV-2 infection.
Miguez-Rey E, Choi D, Kim S, Yoon S, [...], Săndulescu O.
Expert Opin Investig Drugs. 2022; 31 (1)
DOI: 10.1080/13543784.2022.2030310

Introduction

Neutralizing antibodies (NAbs) that target key domains of the spike protein in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have therapeutic value because of their specificity. Depending on the targeted epitope, single agents may be effective, but combined treatment involving multiple NAbs may be necessary to prevent the emergence of resistant variants.

Areas covered

This article highlights the accelerated regulatory processes established to facilitate the review and approval of potential therapies. An overview of treatment approaches for SARS-CoV-2 infection, with detailed examination of the preclinical and clinical evidence supporting the use of NAbs, is provided. Finally, insights are offered into the potential benefits and challenges associated with the use of these agents.

Expert opinion

NAbs offer an effective, evidence-based therapeutic intervention during the early stages of SARS-CoV-2 infection when viral replication is the primary factor driving disease progression. As the pandemic progresses, appropriate use of NAbs will be important to minimize the risk of escape variants. Ultimately, the availability of effective treatments for COVID-19 will allow the establishment of treatment algorithms for minimizing the substantial rates of hospitalization, morbidity (including long COVID) and mortality currently associated with the disease.
2022-01-01 2022 other review-article; Journal Article abstract-available 10.1080/13543784.2022.2030310 Monoclonal antibody therapies in the management of SARS-CoV-2 infection. Miguez-Rey E, Choi D, Kim S, Yoon S, Săndulescu O. Expert Opin Investig Drugs. 2022; 31 (1)
Acute and Chronic Effects of COVID-19 on the Cardiovascular System.
Arévalos V, Ortega-Paz L, Rodríguez-Arias JJ, Calvo López M, [...], Brugaletta S.
J Cardiovasc Dev Dis. 2021; 8 (10)
DOI: 10.3390/jcdd8100128
COVID-19 has shown significant morbidity with the involvement of multiple systems, including the cardiovascular system. Cardiovascular manifestations in the acute phase can include myocardial injury itself, myocardial infarction, venous thromboembolic events, myocarditis, Takotsubo syndrome, and different arrhythmic events. Myocardial injury defined by the rise of cardiac biomarkers in blood has been found in multiple studies with a prevalence of about 20%. Its presence is related to worse clinical outcomes and in-hospital mortality. The mechanisms of myocardial injury have been the subject of intense research but still need to be clarified. The characterization of the cardiac affectation with echocardiography and cardiac magnetic resonance has found mixed results in different studies, with a striking incidence of imaging criteria for myocarditis. Regarding post-acute and chronic follow-up results, the persistence of symptoms and imaging changes in recovered COVID-19 patients has raised concerns about the duration and the possible significance of these findings. Even though the knowledge about this disease has increased incredibly in the last year, many aspects are still unclear and warrant further research.
2021-10-05 2021 other review-article; Review; Journal Article abstract-available 10.3390/jcdd8100128 Acute and Chronic Effects of COVID-19 on the Cardiovascular System. Arévalos V, Ortega-Paz L, Rodríguez-Arias JJ, Calvo López M, Castrillo-Golvano L, Salazar-Rodríguez A, Sabaté-Tormos M, Spione F, Sabaté M, Brugaletta S. J Cardiovasc Dev Dis. 2021; 8 (10)
Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro.
Silva RC, Freitas HF, Campos JM, Kimani NM, [...], Santos CBR.
Int J Mol Sci. 2021; 22 (21)
DOI: 10.3390/ijms222111739
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received global attention due to the serious threat it poses to public health. Since the outbreak in December 2019, millions of people have been affected and its rapid global spread has led to an upsurge in the search for treatment. To discover hit compounds that can be used alone or in combination with repositioned drugs, we first analyzed the pharmacokinetic and toxicological properties of natural products from Brazil's semiarid region. After, we analyzed the site prediction and druggability of the SARS-CoV-2 main protease (Mpro), followed by docking and molecular dynamics simulation. The best SARS-CoV-2 Mpro complexes revealed that other sites were accessed, confirming that our approach could be employed as a suitable starting protocol for ligand prioritization, reinforcing the importance of catalytic cysteine-histidine residues and providing new structural data that could increase the antiviral development mainly against SARS-CoV-2. Here, we selected 10 molecules that could be in vitro assayed in response to COVID-19. Two compounds (b01 and b02) suggest a better potential for interaction with SARS-CoV-2 Mpro and could be further studied.
2021-10-29 2021 other IM; research-article; Journal Article abstract-available 10.3390/ijms222111739 Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro. Silva RC, Freitas HF, Campos JM, Kimani NM, Silva CHTP, Borges RS, Pita SSR, Santos CBR. Int J Mol Sci. 2021; 22 (21)
Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses.
Fernández-Bellon H, Rodon J, Fernández-Bastit L, Almagro V, [...], Vergara-Alert J.
Viruses. 2021; 13 (9)
DOI: 10.3390/v13091683
To date, no evidence supports the fact that animals play a role in the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus infectious disease 2019 (COVID-19). However, several animal species are naturally susceptible to SARS-CoV-2 infection. Besides pets (cats, dogs, Syrian hamsters, and ferrets) and farm animals (minks), different zoo animal species have tested positive for SARS-CoV-2 (large felids and non-human primates). After the summer of 2020, a second wave of SARS-CoV-2 infection occurred in Barcelona (Spain), reaching a peak of positive cases in November. During that period, four lions (Panthera leo) at the Barcelona Zoo and three caretakers developed respiratory signs and tested positive for the SARS-CoV-2 antigen. Lion infection was monitored for several weeks and nasal, fecal, saliva, and blood samples were taken at different time-points. SARS-CoV-2 RNA was detected in nasal samples from all studied lions and the viral RNA was detected up to two weeks after the initial viral positive test in three out of four animals. The SARS-CoV-2 genome was also detected in the feces of animals at different times. Virus isolation was successful only from respiratory samples of two lions at an early time-point. The four animals developed neutralizing antibodies after the infection that were detectable four months after the initial diagnosis. The partial SARS-CoV-2 genome sequence from one animal caretaker was identical to the sequences obtained from lions. Chronology of the events, the viral dynamics, and the genomic data support human-to-lion transmission as the origin of infection.
2021-08-25 2021 other IM; Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v13091683 Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses. Fernández-Bellon H, Rodon J, Fernández-Bastit L, Almagro V, Padilla-Solé P, Lorca-Oró C, Valle R, Roca N, Grazioli S, Trogu T, Bensaid A, Carrillo J, Izquierdo-Useros N, Blanco J, Parera M, Noguera-Julián M, Clotet B, Moreno A, Segalés J, Vergara-Alert J. Viruses. 2021; 13 (9)
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;
CA 15-3 prognostic biomarker in SARS-CoV-2 pneumonia.
Ros-Lucas JA, Pascual-Figal DA, Noguera-Velasco JA, Hernández-Vicente Á, [...], Ruiz-López FJ.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-022-10726-7
The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p < 0.001), who required intensive medical support (n = 78, 14.4%; 31.17 ± 27.83 vs. 18.68 ± 11.83; p < 0.001), and who were discharged with supplemental oxygen (n = 64, 13.3%; 22.65 ± 14.41 vs. 18.2 ± 11.7; p = 0.011). Elevated CA 15-3 levels (above 34.5 U/mL) were a strong predictor of a complicated in-hospital course, in terms of a higher risk of death (adjusted odds ratio [OR] 3.74, 95% confidence interval [CI]: 1.22-11.9, p = 0.022) and need for intensive care (adjusted OR 4.56, 95% CI: 1.37-15.8) after adjusting for all other risk factors. The degree of lung damage and fibrosis evaluated in terms of CA 15-3 concentrations may allow early identification of the increased risk of complications in patients with SARS-CoV-2 pneumonia.
2022-04-25 2022 other research-article; Journal Article; Observational Study abstract-available 10.1038/s41598-022-10726-7 CA 15-3 prognostic biomarker in SARS-CoV-2 pneumonia. Ros-Lucas JA, Pascual-Figal DA, Noguera-Velasco JA, Hernández-Vicente Á, Cebreiros-López I, Arnaldos-Carrillo M, Martínez-Ardil IM, García-Vázquez E, Aparicio-Vicente M, Solana-Martínez E, Ruiz-Martínez SY, Fernández-Mula L, Andujar-Espinosa R, Fernández-Suarez B, Sánchez-Caro MD, Peñalver-Mellado C, Ruiz-López FJ. Sci Rep. 2022; 12 (1)
The Development of SARS-CoV-2 Variants: The Gene Makes the Disease.
Perez-Gomez R.
J Dev Biol. 2021; 9 (4)
DOI: 10.3390/jdb9040058
A novel coronavirus (SARS-CoV-2) emerged towards the end of 2019 that caused a severe respiratory disease in humans called COVID-19. It led to a pandemic with a high rate of morbidity and mortality that is ongoing and threatening humankind. Most of the mutations occurring in SARS-CoV-2 are synonymous or deleterious, but a few of them produce improved viral functions. The first known mutation associated with higher transmissibility, D614G, was detected in early 2020. Since then, the virus has evolved; new mutations have occurred, and many variants have been described. Depending on the genes affected and the location of the mutations, they could provide altered infectivity, transmissibility, or immune escape. To date, mutations that cause variations in the SARS-CoV-2 spike protein have been among the most studied because of the protein's role in the initial virus-cell contact and because it is the most variable region in the virus genome. Some concerning mutations associated with an impact on viral fitness have been described in the Spike protein, such as D614G, N501Y, E484K, K417N/T, L452R, and P681R, among others. To understand the impact of the infectivity and antigenicity of the virus, the mutation landscape of SARS-CoV-2 has been under constant global scrutiny. The virus variants are defined according to their origin, their genetic profile (some characteristic mutations prevalent in the lineage), and the severity of the disease they produce, which determines the level of concern. If they increase fitness, new variants can outcompete others in the population. The Alpha variant was more transmissible than previous versions and quickly spread globally. The Beta and Gamma variants accumulated mutations that partially escape the immune defenses and affect the effectiveness of vaccines. Nowadays, the Delta variant, identified around March 2021, has spread and displaced the other variants, becoming the most concerning of all lineages that have emerged. The Delta variant has a particular genetic profile, bearing unique mutations, such as T478K in the spike protein and M203R in the nucleocapsid. This review summarizes the current knowledge of the different mutations that have appeared in SARS-CoV-2, mainly on the spike protein. It analyzes their impact on the protein function and, subsequently, on the level of concern of different variants and their importance in the ongoing pandemic.
2021-12-15 2021 other review-article; Review; Journal Article abstract-available 10.3390/jdb9040058 The Development of SARS-CoV-2 Variants: The Gene Makes the Disease. Perez-Gomez R. J Dev Biol. 2021; 9 (4)
The Antiviral Activity of Bacterial, Fungal, and Algal Polysaccharides as Bioactive Ingredients: Potential Uses for Enhancing Immune Systems and Preventing Viruses.
Chaisuwan W, Phimolsiripol Y, Chaiyaso T, Techapun C, [...], Seesuriyachan P.
Front Nutr. 2021; 8
DOI: 10.3389/fnut.2021.772033
Viral infections may cause serious human diseases. For instance, the recent appearance of the novel virus, SARS-CoV-2, causing COVID-19, has spread globally and is a serious public health concern. The consumption of healthy, proper, functional, and nutrient-rich foods has an important role in enhancing an individual's immune system and preventing viral infections. Several polysaccharides from natural sources such as algae, bacteria, and fungi have been considered as generally recognized as safe (GRAS) by the US Food and Drug Administration. They are safe, low-toxicity, biodegradable, and have biological activities. In this review, the bioactive polysaccharides derived from various microorganisms, including bacteria, fungi, and algae were evaluated. Antiviral mechanisms of these polysaccharides were discussed. Finally, the potential use of microbial and algal polysaccharides as an antiviral and immune boosting strategy was addressed. The microbial polysaccharides exhibited several bioactivities, including antioxidant, anti-inflammatory, antimicrobial, antitumor, and immunomodulatory activities. Some microbes are able to produce sulfated polysaccharides, which are well-known to exert a board spectrum of biological activities, especially antiviral properties. Microbial polysaccharide can inhibit various viruses using different mechanisms. Furthermore, these microbial polysaccharides are also able to modulate immune responses to prevent and/or inhibit virus infections. There are many molecular factors influencing their bioactivities, e.g., functional groups, conformations, compositions, and molecular weight. At this stage of development, microbial polysaccharides will be used as adjuvants, nutrient supplements, and for drug delivery to prevent several virus infections, especially SARS-CoV-2 infection.
2021-11-05 2021 other review-article; Review; Journal Article abstract-available 10.3389/fnut.2021.772033 The Antiviral Activity of Bacterial, Fungal, and Algal Polysaccharides as Bioactive Ingredients: Potential Uses for Enhancing Immune Systems and Preventing Viruses. Chaisuwan W, Phimolsiripol Y, Chaiyaso T, Techapun C, Leksawasdi N, Jantanasakulwong K, Rachtanapun P, Wangtueai S, Sommano SR, You S, Regenstein JM, Barba FJ, Seesuriyachan P. Front Nutr. 2021; 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)
Brief Research Report: Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients.
Tajuelo A, Carretero O, García-Ríos E, López-Siles M, [...], Pérez-Romero P.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.878812

Introduction

There is robust evidence indicating that the SARS-CoV-2-specific humoral response is associated with protection against severe disease. However, relatively little data exist regarding how the humoral immune response at the time of hospital admission correlates with disease severity in unimmunized patients. Our goal was toidentify variables of the humoral response that could potentially serve as prognostic markers for COVID-19 progressionin unvaccinated SARS-CoV-2 patients.

Methods

A prospective cross-sectional study was carried out in a cohort of 160 unimmunized, adult COVID-19 patients from the Hospital Universitario 12Octubre. Participants were classified into four clinical groups based on disease severity: non-survivors with respiratory failure (RF), RF survivors, patients requiring oxygen therapy and those not receiving oxygen therapy. Serum samples were taken on admission and IgM, IgG, IgG subclass antibody titers were determined by ELISA, and neutralizing antibody titersusing a surrogate neutralization assay. The differences in the antibody titers between groups and the association between the clinical and analytical characteristics of the patients and the antibody titers were analyzed.

Results

Patients that developed RF and survived had IgM titers that were 2-fold higher than non-survivors (p = 0.001), higher levels of total IgG than those who developed RF and succumbed to infection (p< 0.001), and than patients who required oxygen therapy (p< 0.05), and had 5-fold higher IgG1 titers than RF non-survivors (p< 0.001) and those who needed oxygen therapy (p< 0.001), and 2-fold higher than patients that did not require oxygen therapy during admission (p< 0.05). In contrast, RF non-survivorshad the lowest neutralizing antibodylevels, which were significantly lower compared those with RF that survived (p = 0.03). A positive correlation was found between IgM, total IgG, IgG1 and IgG3 titers and neutralizing antibody titers in the total cohort (p ≤ 0.0036).

Conclusions

We demonstrate that patients with RF that survived infection had significantly higher IgM, IgG, IgG1 and neutralizing titers compared to patients with RF that succumb to infection, suggesting that using humoral response variables could be used as a prognostic marker for guiding the clinical management of unimmunized patients admitted to the hospital for SARS-CoV-2 infection.
2022-04-25 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.878812 Brief Research Report: Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients. Tajuelo A, Carretero O, García-Ríos E, López-Siles M, Cano O, Vázquez M, Más V, Rodríguez-Goncer I, Lalueza A, López-Medrano F, Juan RS, Fernández-Ruiz M, Aguado JM, McConnell MJ, Pérez-Romero P. Front Immunol. 2022; 13
SARS-CoV-2 research using human pluripotent stem cells and organoids.
Deguchi S, Serrano-Aroca Á, Tambuwala MM, Uhal BD, [...], Takayama K.
Stem Cells Transl Med. 2021; 10 (11)
DOI: 10.1002/sctm.21-0183
Experimental cell models are indispensable for clarifying the pathophysiology of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and for developing therapeutic agents. To recapitulate the symptoms and drug response of COVID-19 patients in vitro, SARS-CoV-2 studies using physiologically relevant human embryonic stem (ES)/induced pluripotent stem (iPS) cell-derived somatic cells and organoids are ongoing. These cells and organoids have been used to show that SARS-CoV-2 can infect and damage various organs including the lung, heart, brain, intestinal tract, kidney, and pancreas. They are also being used to develop COVID-19 therapeutic agents, including evaluation of their antiviral efficacy and safety. The relationship between COVID-19 aggravation and human genetic backgrounds has been investigated using genetically modified ES/iPS cells and patient-derived iPS cells. This review summarizes the latest results and issues of SARS-CoV-2 research using human ES/iPS cell-derived somatic cells and organoids.
2021-07-24 2021 other research-article; Review; Journal Article abstract-available 10.1002/sctm.21-0183 SARS-CoV-2 research using human pluripotent stem cells and organoids. Deguchi S, Serrano-Aroca Á, Tambuwala MM, Uhal BD, Brufsky AM, Takayama K. Stem Cells Transl Med. 2021; 10 (11)
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)
COVID-19 pandemic: lessons learned from more than a century of pandemics and current vaccine development for pandemic control.
Buchy P, Buisson Y, Cintra O, Dwyer DE, [...], Petersen E.
Int J Infect Dis. 2021; 112
DOI: 10.1016/j.ijid.2021.09.045
Pandemic dynamics and health care responses are markedly different during the COVID-19 pandemic than in earlier outbreaks. Compared with established infectious disease such as influenza, we currently know relatively little about the origin, reservoir, cross-species transmission and evolution of SARS-CoV-2. Health care services, drug availability, laboratory testing, research capacity and global governance are more advanced than during 20th century pandemics, although COVID-19 has highlighted significant gaps. The risk of zoonotic transmission and an associated new pandemic is rising substantially. COVID-19 vaccine development has been done at unprecedented speed, with the usual sequential steps done in parallel. The pandemic has illustrated the feasibility of this approach and the benefits of a globally coordinated response and infrastructure. Some of the COVID-19 vaccines recently developed or currently in development might offer flexibility or sufficiently broad protection to swiftly respond to antigenic drift or emergence of new coronaviruses. Yet many challenges remain, including the large-scale production of sufficient quantity of vaccines, delivery of vaccines to all countries and ensuring vaccination of relevant age groups. This wide vaccine technology approach will be best employed in tandem with active surveillance for emerging variants or new pathogens using antigen mapping, metagenomics and next generation sequencing.
2021-09-23 2021 other review-article; Review; Journal Article abstract-available 10.1016/j.ijid.2021.09.045 COVID-19 pandemic: lessons learned from more than a century of pandemics and current vaccine development for pandemic control. Buchy P, Buisson Y, Cintra O, Dwyer DE, Nissen M, Ortiz de Lejarazu R, Petersen E. Int J Infect Dis. 2021; 112
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 IM; 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 Mycobacterium tuberculosis. González-Domenech CM, Pérez-Hernández I, Gómez-Ayerbe C, Viciana Ramos I, Palacios-Muñoz R, Santos J. Viruses. 2021; 13 (5)
Associations Between Recently Diagnosed Conditions and Hospitalization due to COVID-19 in Patients Aged 50 Years and Older-A SHARE-Based Analysis.
López-Bueno R, Torres-Castro R, Koyanagi A, Smith L, [...], Calatayud J.
J Gerontol A Biol Sci Med Sci. 2022; 77 (4)
DOI: 10.1093/gerona/glab199

Background

Only a few studies have been carried out with a large sample size on the relationship between chronic conditions and hospitalization for coronavirus disease 2019 (COVID-19), and there is no research examining recently diagnosed conditions. Our purpose was to evaluate this association in a large sample including the older population from Europe and Israel.

Method

Data from the Survey of Health, Ageing and Retirement in Europe COVID-19 Survey, a representative survey of individuals aged 50 or older residing in 27 European countries and Israel, were retrieved. Associations between recently diagnosed chronic conditions (ie, conditions detected over the last 3 years) (exposure) and hospitalization due to COVID-19 (outcome) were assessed using multivariable logistic regression.

Results

A total of 51 514 participants on average 71.0 (SD = 9.2) years old were included. Participants with multimorbidity (ie, 2 or more recently diagnosed conditions) had significantly higher odds for COVID-19 hospitalization (adjusted odds ratio [AOR] = 3.91 [95% CI = 2.14-7.12]). Independent conditions such as lung disease (AOR = 16.94 [95% CI = 9.27-30.95]), heart disease (AOR = 3.29 [95% CI = 1.50-7.21]), or cancer (AOR = 3.45 [95% CI = 1.26-9.48]) showed particularly high odds for hospitalization due to COVID-19.

Conclusions

People with recently diagnosed diseases, and in particular those having lung disease, heart disease, or cancer, were significantly more likely to be hospitalized for COVID-19.
2022-04-01 2022 other brief-report; Research Support, Non-U.S. Gov't; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.1093/gerona/glab199 Associations Between Recently Diagnosed Conditions and Hospitalization due to COVID-19 in Patients Aged 50 Years and Older-A SHARE-Based Analysis. López-Bueno R, Torres-Castro R, Koyanagi A, Smith L, Soysal P, Calatayud J. J Gerontol A Biol Sci Med Sci. 2022; 77 (4)
Phospholipids dock SARS-CoV-2 spike protein via hydrophobic interactions: a minimal in-silico study of lecithin nasal spray therapy.
Qaisrani MN, Belousov R, Rehman JU, Goliaei EM, [...], Roldán É.
Eur Phys J E Soft Matter. 2021; 44 (11)
DOI: 10.1140/epje/s10189-021-00137-3
Understanding the physical and chemical properties of viral infections at molecular scales is a major challenge for the scientific community more so with the outbreak of global pandemics. There is currently a lot of effort being placed in identifying molecules that could act as putative drugs or blockers of viral molecules. In this work, we computationally explore the importance in antiviral activity of a less studied class of molecules, namely surfactants. We employ all-atoms molecular dynamics simulations to study the interaction between the receptor-binding domain of the SARS-CoV-2 spike protein and the phospholipid lecithin (POPC), in water. Our microsecond simulations show a preferential binding of lecithin to the receptor-binding motif of SARS-CoV-2 with binding free energies significantly larger than [Formula: see text]. Furthermore, hydrophobic interactions involving lecithin non-polar tails dominate these binding events, which are also accompanied by dewetting of the receptor binding motif. Through an analysis of fluctuations in the radius of gyration of the receptor-binding domain, its contact maps with lecithin molecules, and distributions of water molecules near the binding region, we elucidate molecular interactions that may play an important role in interactions involving surfactant-type molecules and viruses. We discuss our minimal computational model in the context of lecithin-based liposomal nasal sprays as putative mitigating therapies for COVID-19.
2021-10-30 2021 other research-article; Journal Article abstract-available 10.1140/epje/s10189-021-00137-3 Phospholipids dock SARS-CoV-2 spike protein via hydrophobic interactions: a minimal in-silico study of lecithin nasal spray therapy. Qaisrani MN, Belousov R, Rehman JU, Goliaei EM, Girotto I, Franklin-Mergarejo R, Güell O, Hassanali A, Roldán É. Eur Phys J E Soft Matter. 2021; 44 (11)
Cardiac involvement in Adult Multisystemic Inflammatory Syndrome related to COVID-19. Two case reports.
Carrasco-Molina S, Ramos-Ruperto L, Ibáñez-Mendoza P, Martín-Gutiérrez JC, [...], Robles-Marhuenda Á.
J Cardiol Cases. 2022;
DOI: 10.1016/j.jccase.2022.01.017
In this article we describe two cases that presented with persistent fever and a hyperinflammatory state in association with severe acute respiratory syndrome-coronavirus-2 infection with various negative reverse transcription-polymerase chain reaction results. These cases subsequently developed myocarditis with cardiogenic shock that required vasoactive drugs and had a good response to corticosteroid treatment. All cases met criteria for a definitive case of multisystemic inflammatory syndrome in adults, a recently described entity associated with coronavirus disease 2019, which has a good response to immunomodulators and a good prognosis in most cases.
2022-02-14 2022 other Case Reports; case-report abstract-available 10.1016/j.jccase.2022.01.017 Cardiac involvement in Adult Multisystemic Inflammatory Syndrome related to COVID-19. Two case reports. Carrasco-Molina S, Ramos-Ruperto L, Ibáñez-Mendoza P, Martín-Gutiérrez JC, Ruíz-Bravo E, Iniesta-Manjavacas ÁM, Prieto-Moriche E, Robles-Marhuenda Á. J Cardiol Cases. 2022;
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. 2022; 77 (1)
DOI: 10.1093/gerona/glab206
Understanding how older people respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical if we are to confront the coronavirus disease 2019 (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 analyzed 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 interferon-γ (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 enzyme-linked immunosorbent assay (ELISA). Memory T lymphocytes were found in peripheral blood of most of the studied donors, more than 7 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.
2022-01-01 2022 fondo-covid Research Support, Non-U.S. Gov't; 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-Fernández 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. 2022; 77 (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)
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)
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)
Scientific evidence in the COVID-19 treatment: A comprehensive review.
Iturricastillo G, Ávalos Pérez-Urría E, Couñago F, Landete P.
World J Virol. 2021; 10 (5)
DOI: 10.5501/wjv.v10.i5.217
In December 2019, cases of unknown origin pneumonia appeared in Wuhan, China; the causal agent of this pneumonia was a new virus of the coronaviridae family called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). According to the clinical severity, symptoms and response to the different treatments, the evolution of the disease is divided in three phases. We analysed the most used treatments for coronavirus disease 2019 and the phase in which they are supposed to be effective. In the viral phase, remdesivir has demonstrated reduction in recovery time but no mortality reduction. Other drugs proposed for viral phase such as convalescent plasma and lopinavir/ritonavir did not demonstrate to be effective. In the inflammatory phase, corticosteroids demonstrated reduction of 28-d mortality in patients who needed oxygen, establishing that a corticosteroid regimen should be part of the standard treatment of critically ill patients. There are other immunosuppressive and immunomodulatory treatments such as anakinra, sarilumab, tocilizumab, colchicine or baricitinib that are being studied. Other treatments that were proposed at the beginning, like hydroxichloroquine or azithromycin, demonstrated no efficacy and increased mortality when combined.
2021-09-01 2021 other review-article; Review; Journal Article abstract-available 10.5501/wjv.v10.i5.217 Scientific evidence in the COVID-19 treatment: A comprehensive review. Iturricastillo G, Ávalos Pérez-Urría E, Couñago F, Landete P. World J Virol. 2021; 10 (5)
Surveillance of SARS-CoV-2 virus circulation using Acute Respiratory Infections sentinel system of Catalonia (PIDIRAC) during the 2019-2020 season: A retrospective observational study.
Jané M, Martínez A, Ciruela P, Mosquera M, [...], Marcos MA.
PLoS One. 2022; 17 (3)
DOI: 10.1371/journal.pone.0264949

Background

In the context of COVID-19 pandemic in Catalonia (Spain), the present study analyses respiratory samples collected by the primary care network using Acute Respiratory Infections Sentinel Surveillance System (PIDIRAC) during the 2019-2020 season to complement the pandemic surveillance system in place to detect SARS-CoV-2. The aim of the study is to describe whether SARS-CoV-2 was circulating before the first confirmed case was detected in Catalonia, on February 25th, 2020.

Methods

The study sample was made up of all samples collected by the PIDIRAC primary care network as part of the Influenza and Acute Respiratory Infections (ARI) surveillance system activities. The study on respiratory virus included coronavirus using multiple RT-PCR assays. All positive samples for human coronavirus were subsequently typed for HKU1, OC43, NL63, 229E. Every respiratory sample was frozen at-80°C and retrospectively studied for SARS-CoV-2 detection. A descriptive study was performed, analysing significant differences among variables related to SARS-CoV- 2 cases comparing with rest of coronaviruses cases through a bivariate study with Chi-squared test and statistical significance at 95%.

Results

Between October 2019 and April 2020, 878 respiratory samples from patients with acute respiratory infection or influenza syndrome obtained by PIDIRAC were analysed. 51.9% tested positive for influenza virus, 48.1% for other respiratory viruses. SARS-CoV-2 was present in 6 samples. The first positive SARS-CoV-2 case had symptom onset on 2 March 2020. These 6 cases were 3 men and 3 women, aged between 25 and 50 years old. 67% had risk factors, none had previous travel history nor presented viral coinfection. All of them recovered favourably.

Conclusion

Sentinel Surveillance PIDIRAC enhances global epidemiological surveillance by allowing confirmation of viral circulation and describes the epidemiology of generalized community respiratory viruses' transmission in Catalonia. The system can provide an alert signal when identification of a virus is not achieved in order to take adequate preparedness measures.
2022-03-14 2022 other research-article; Journal Article; Observational Study abstract-available 10.1371/journal.pone.0264949 Surveillance of SARS-CoV-2 virus circulation using Acute Respiratory Infections sentinel system of Catalonia (PIDIRAC) during the 2019-2020 season: A retrospective observational study. Jané M, Martínez A, Ciruela P, Mosquera M, Martínez MJ, Basile L, Vidal MJ, Nogueras MM, de Molina P, Vila J, Marcos MA. PLoS One. 2022; 17 (3)
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
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)
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)
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 Historical Article; Research Support, Non-U.S. Gov't; 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)
SARS-CoV-2 Infection Triggers Auto-Immune Response in ARDS.
Juanes-Velasco P, Landeira-Viñuela A, García-Vaquero ML, Lecrevisse Q, [...], Fuentes M.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.732197
Acute respiratory distress syndrome (ARDS) is a severe pulmonary disease, which is one of the major complications in COVID-19 patients. Dysregulation of the immune system and imbalances in cytokine release and immune cell activation are involved in SARS-CoV-2 infection. Here, the inflammatory, antigen, and auto-immune profile of patients presenting COVID-19-associated severe ARDS has been analyzed using functional proteomics approaches. Both, innate and humoral responses have been characterized through acute-phase protein network and auto-antibody signature. Severity and sepsis by SARS-CoV-2 emerged to be correlated with auto-immune profiles of patients and define their clinical progression, which could provide novel perspectives in therapeutics development and biomarkers of COVID-19 patients. Humoral response in COVID-19 patients' profile separates with significant differences patients with or without ARDS. Furthermore, we found that this profile can be correlated with COVID-19 severity and results more common in elderly patients.
2022-01-28 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2022.732197 SARS-CoV-2 Infection Triggers Auto-Immune Response in ARDS. Juanes-Velasco P, Landeira-Viñuela A, García-Vaquero ML, Lecrevisse Q, Herrero R, Ferruelo A, Góngora R, Corrales F, Rivas JL, Lorente JA, Hernández ÁP, Fuentes M. Front Immunol. 2022; 13
Molecular and Cellular Mechanisms of M. tuberculosis and SARS-CoV-2 Infections-Unexpected Similarities of Pathogenesis and What to Expect from Co-Infection.
Starshinova AA, Kudryavtsev I, Malkova A, Zinchenko U, [...], Yablonskiy P.
Int J Mol Sci. 2022; 23 (4)
DOI: 10.3390/ijms23042235
Tuberculosis is still an important medical and social problem. In recent years, great strides have been made in the fight against M. tuberculosis, especially in the Russian Federation. However, the emergence of a new coronavirus infection (COVID-19) has led to the long-term isolation of the population on the one hand and to the relevance of using personal protective equipment on the other. Our knowledge regarding SARS-CoV-2-induced inflammation and tissue destruction is rapidly expanding, while our understanding of the pathology of human pulmonary tuberculosis gained through more the 100 years of research is still limited. This paper reviews the main molecular and cellular differences and similarities caused by M. tuberculosis and SARS-CoV-2 infections, as well as their critical immunological and pathomorphological features. Immune suppression caused by the SARS-CoV-2 virus may result in certain difficulties in the diagnosis and treatment of tuberculosis. Furthermore, long-term lymphopenia, hyperinflammation, lung tissue injury and imbalance in CD4+ T cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression.
2022-02-17 2022 other IM; review-article; Review; Journal Article abstract-available 10.3390/ijms23042235 Molecular and Cellular Mechanisms of M. tuberculosis and SARS-CoV-2 Infections-Unexpected Similarities of Pathogenesis and What to Expect from Co-Infection. Starshinova AA, Kudryavtsev I, Malkova A, Zinchenko U, Karev V, Kudlay D, Glushkova A, Starshinova AY, Dominguez J, Villar-Hernández R, Dovgalyk I, Yablonskiy P. Int J Mol Sci. 2022; 23 (4)
Detection of SARS-CoV-2 antibodies in febrile patients from an endemic region of dengue and chikungunya in Peru.
Tarazona-Castro Y, Troyes-Rivera L, Martins-Luna J, Cabellos-Altamirano F, [...], Del Valle-Mendoza J.
PLoS One. 2022; 17 (4)
DOI: 10.1371/journal.pone.0265820

Introduction

The rapid expansion of the novel SARS-CoV-2 virus has raised serious public health concerns due to the possibility of misdiagnosis in regions where arboviral diseases are endemic. We performed the first study in northern Peru to describe the detection of SARS-CoV-2 IgM antibodies in febrile patients with a suspected diagnosis of dengue and chikungunya fever.

Materials and methods

A consecutive cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through March 2021. Patients enrolled underwent serum sample collection for the molecular and serological detection of DENV and CHIKV. Also, serological detection of IgM antibodies against SARS-CoV-2 was performed.

Results

464 patients were included during the study period, of which (40.51%) were positive for one pathogen, meanwhile (6.90%) presented co-infections between 2 or more pathogens. The majority of patients with monoinfections were positive for SARS-CoV-2 IgM with (73.40%), followed by DENV 18.09% and CHIKV (8.51%). The most frequent co-infection was DENV + SARS-CoV-2 with (65.63%), followed by DENV + CHIKV and DENV + CHIKV + SARS-CoV-2, both with (12.50%). The presence of polyarthralgias in hands (43.75%, p<0.01) and feet (31.25%, p = 0.05) were more frequently reported in patients with CHIKV monoinfection. Also, conjunctivitis was more common in patients positive for SARS-CoV-2 IgM (11.45%, p<0.01). The rest of the symptoms were similar among all the study groups.

Conclusion

SARS-CoV-2 IgM antibodies were frequently detected in acute sera from febrile patients with a clinical suspicion of arboviral disease. The presence of polyarthralgias in hands and feet may be suggestive of CHIKV infection. These results reaffirm the need to consider SARS-CoV-2 infection as a main differential diagnosis of acute febrile illness in arboviruses endemic areas, as well as to consider co-infections between these pathogens.
2022-04-08 2022 other research-article; Journal Article abstract-available 10.1371/journal.pone.0265820 Detection of SARS-CoV-2 antibodies in febrile patients from an endemic region of dengue and chikungunya in Peru. Tarazona-Castro Y, Troyes-Rivera L, Martins-Luna J, Cabellos-Altamirano F, Aguilar-Luis MA, Carrillo-Ng H, Del Valle LJ, Kym S, Miranda-Maravi S, Silva-Caso W, Levy-Blitchtein S, Del Valle-Mendoza J. PLoS One. 2022; 17 (4)
Lung Cancer and Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Identifying Important Knowledge Gaps for Investigation.
Rolfo C, Meshulami N, Russo A, Krammer F, [...], Hirsch FR.
J Thorac Oncol. 2022; 17 (2)
DOI: 10.1016/j.jtho.2021.11.001
Patients with lung cancer are especially vulnerable to coronavirus disease 2019 (COVID-19) with a greater than sevenfold higher rate of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19, a greater than threefold higher hospitalization rate with high complication rates, and an estimated case fatality rate of more than 30%. The reasons for the increased vulnerability are not known. In addition, beyond the direct impact of the pandemic on morbidity and mortality among patients with lung cancer, COVID-19, with its disruption of patient care, has also resulted in substantial impact on lung cancer screening and treatment/management.COVID-19 vaccines are safe and effective in people with lung cancer. On the basis of the available data, patients with lung cancer should continue their course of cancer treatment and get vaccinated against the SARS-CoV-2 virus. For unknown reasons, some patients with lung cancer mount poor antibody responses to vaccination. Thus, boosting vaccination seems urgently indicated in this subgroup of vulnerable patients with lung cancer. Nevertheless, many unanswered questions regarding vaccination in this population remain, including the magnitude, quality, and duration of antibody response and the role of innate and acquired cellular immunities for clinical protection. Additional important knowledge gaps also remain, including the following: how can we best protect patients with lung cancer from developing COVID-19, including managing care in patient with lung cancer and the home environment of patients with lung cancer; are there clinical/treatment demographics and tumor molecular demographics that affect severity of COVID-19 disease in patients with lung cancer; does anticancer treatment affect antibody production and protection; does SARS-CoV-2 infection affect the development/progression of lung cancer; and are special measures and vaccine strategies needed for patients with lung cancer as viral variants of concern emerge.
2021-11-10 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.1016/j.jtho.2021.11.001 Lung Cancer and Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Identifying Important Knowledge Gaps for Investigation. Rolfo C, Meshulami N, Russo A, Krammer F, García-Sastre A, Mack PC, Gomez JE, Bhardwaj N, Benyounes A, Sirera R, Moore A, Rohs N, Henschke CI, Yankelevitz D, King J, Shyr Y, Bunn PA, Minna JD, Hirsch FR. J Thorac Oncol. 2022; 17 (2)
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; Systematic Review; 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)
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
Diagnostic performance of two serological assays for the detection of SARS-CoV-2 specific antibodies: surveillance after vaccination.
Fresco-Taboada A, García-Durán M, Aira C, López L, [...], Vela C.
Diagn Microbiol Infect Dis. 2022; 102 (4)
DOI: 10.1016/j.diagmicrobio.2022.115650
Massive vaccination programs are being carried out to limit the SARS-CoV-2 pandemic that started in December 2019. Serological tests are of major importance as an indicator of circulation of the virus and to assess how vaccine-induced immunity progresses. An Enzyme-Linked Immunosorbent Assay (ELISA) and a Lateral Flow Assay (LFA) have been developed based on the SARS-CoV-2 recombinant Receptor Binding Domain (RBD) and the combination of Spike and Nucleoprotein, respectively. The validation with 1272 serum samples by comparison with INgezim COVID 19 DR showed good diagnostic performance (sensitivity: 93.2%-97.2%; specificity: 98.3%-99.3%) for detection of previous contact with SARS-CoV-2. Moreover, according to our results, these assays can help in the serosurveillance during and after vaccination, by detecting the humoral immune response as soon as 15 days postvaccination and identifying low-respondents. Hence, these tests could play a key role in the progression to a COVID-19 free world, helping to adjust future vaccination protocols.
2022-01-26 2022 other research-article; Journal Article abstract-available 10.1016/j.diagmicrobio.2022.115650 Diagnostic performance of two serological assays for the detection of SARS-CoV-2 specific antibodies: surveillance after vaccination. Fresco-Taboada A, García-Durán M, Aira C, López L, Sastre P, van der Hoek L, van Gils MJ, Brouwer PJM, Sanders RW, Holzer B, Zimpernikc I, López-Collazo E, Muñoz P, Rueda P, Vela C. Diagn Microbiol Infect Dis. 2022; 102 (4)
Persistence of SARS-CoV-2 Infection in Severely Immunocompromised Patients With Complete Remission B-Cell Lymphoma and Anti-CD20 Monoclonal Antibody Therapy: A Case Report of Two Cases.
Martínez-Chinchilla C, Vazquez-Montero L, Palazón-Carrión N, Fernández-Román IM, [...], Palacios-Baena ZR.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.860891
Immunosuppressant conditions such as hematological malignancies increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It has been described in the literature that patients on anti-CD20 maintenance therapies for lymphoid malignancies are susceptible to having recurrent flares together with viral replication or reinfections, although these cases are scarce. These patients are not well represented in randomized controlled trials, and as a consequence, the evidence for the use of certain treatments in this scenario is lacking. We present two cases of patients with B-cell lymphoma on remission and treated with rituximab on maintenance. They developed at least 1 flare of coronavirus disease 2019 (COVID-19) after acute infection and always after receiving rituximab. RT-PCR was positive in the nasopharyngeal swab and also in plasma. Patients were treated during flares with remdesivir, hyperimmune plasma, and corticosteroids. These two cases showed the unresolved problem of COVID-19 in immunosuppressant patients and showed that despite the vast amount of information available on SARS-CoV-2, information in this subgroup of patients is lacking.
2022-04-14 2022 other Research Support, Non-U.S. Gov't; Randomized Controlled Trial; Case Reports; case-report abstract-available 10.3389/fimmu.2022.860891 Persistence of SARS-CoV-2 Infection in Severely Immunocompromised Patients With Complete Remission B-Cell Lymphoma and Anti-CD20 Monoclonal Antibody Therapy: A Case Report of Two Cases. Martínez-Chinchilla C, Vazquez-Montero L, Palazón-Carrión N, Fernández-Román IM, López-Barba J, de la Cruz-Merino L, Rodríguez-Baño J, Palacios-Baena ZR. Front Immunol. 2022; 13
Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2.
Mooij P, García-Arriaza J, Pérez P, Lázaro-Frías A, [...], Esteban M.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.845887
Novel safe, immunogenic, and effective vaccines are needed to control the COVID-19 pandemic, caused by SARS-CoV-2. Here, we describe the safety, robust immunogenicity, and potent efficacy elicited in rhesus macaques by a modified vaccinia virus Ankara (MVA) vector expressing a full-length SARS-CoV-2 spike (S) protein (MVA-S). MVA-S vaccination was well tolerated and induced S and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against SARS-CoV-2 and several variants of concern. S-specific IFNγ, but not IL-4, -producing cells were also elicited. After SARS-CoV-2 challenge, vaccinated animals showed a significant strong reduction of virus loads in bronchoalveolar lavages (BAL) and decreased levels in throat and nasal mucosa. Remarkably, MVA-S also protected macaques from fever and infection-induced cytokine storm. Computed tomography and histological examination of the lungs showed reduced lung pathology in MVA-S-vaccinated animals. These findings favor the use of MVA-S as a potential vaccine for SARS-CoV-2 in clinical trials.
2022-03-16 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.845887 Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2. Mooij P, García-Arriaza J, Pérez P, Lázaro-Frías A, Verstrepen BE, Böszörményi KP, Mortier D, Fagrouch Z, Kiemenyi-Kayere G, Niphuis H, Acar RF, Meijer L, Stammes MA, Kondova I, Verschoor EJ, GeurtsvanKessel CH, de Bruin E, Sikkema RS, Luczkowiak J, Delgado R, Montenegro D, Puentes E, Rodríguez E, Bogers WMJM, Koopman G, Esteban M. Front Immunol. 2022; 13
Angiotensin System Autoantibodies Correlate With Routine Prognostic Indicators for COVID-19 Severity.
Labandeira CM, Pedrosa MA, Suarez-Quintanilla JA, Cortes-Ayaso M, [...], Rodríguez-Pérez AI.
Front Med (Lausanne). 2022; 9
DOI: 10.3389/fmed.2022.840662

Objective

We previously showed that angiotensin type-1 receptor and ACE2 autoantibodies (AT1-AA, ACE2-AA) are associated with COVID-19 severity. Our aim is to find correlations of these autoantibodies with routine biochemical parameters that allow an initial classification of patients.

Methods

In an initial cohort of 119 COVID-19 patients, serum AT1-AA and ACE2-AA concentrations were obtained within 24 h after diagnosis. In 50 patients with a complete set of routine biochemical parameters, clinical data and disease outcome information, a Random Forest algorithm was used to select prognostic indicators, and the Spearman coefficient was used to analyze correlations with AT1-AA, ACE2-AA.

Results

Hemoglobin, lactate dehydrogenase and procalcitonin were selected. A decrease in one unit of hemoglobin, an increase in 0.25 units of procalcitonin, or an increase in 100 units of lactate dehydrogenase increased the severity of the disease by 35.27, 69.25, and 3.2%, respectively. Our binary logistic regression model had a predictive capability to differentiate between mild and moderate/severe disease of 84%, and between mild/moderate and severe disease of 76%. Furthermore, the selected parameters showed strong correlations with AT1-AA or ACE2-AA, particularly in men.

Conclusion

Hemoglobin, lactate dehydrogenase and procalcitonin can be used for initial classification of COVID-19 patients in the admission day. Subsequent determination of more complex or late arrival biomarkers may provide further data on severity, mechanisms, and therapeutic options.
2022-03-09 2022 other research-article; Journal Article abstract-available 10.3389/fmed.2022.840662 Angiotensin System Autoantibodies Correlate With Routine Prognostic Indicators for COVID-19 Severity. Labandeira CM, Pedrosa MA, Suarez-Quintanilla JA, Cortes-Ayaso M, Labandeira-García JL, Rodríguez-Pérez AI. Front Med (Lausanne). 2022; 9
Evaluation of the clinical evolution and transmission of SARS-CoV-2 infection in cats by simulating natural routes of infection.
Barroso-Arévalo S, Sánchez-Morales L, Barasona JA, Rivera B, [...], Sánchez-Vizcaíno JM.
Vet Res Commun. 2022;
DOI: 10.1007/s11259-022-09908-5
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic disease denominated as Coronavirus Disease 2019 (COVID-19). Several studies suggest that the original source of this virus was a spillover from an animal reservoir and its subsequent adaptation to humans. Of all the different animals affected, cats are one of the most susceptible species. Moreover, several cases of natural infection in domestic and stray cats have been reported in the last few months. Although experimental infection assays have demonstrated that cats are successfully infected and can transmit the virus to other cats by aerosol, the conditions used for these experiments have not been specified in terms of ventilation. We have, therefore, evaluated the susceptibility of cats using routes of infection similar to those expected under natural conditions (exposure to a sneeze, cough, or contaminated environment) by aerosol and oral infection. We have also evaluated the transmission capacity among infected and naïve cats using different air exchange levels. Despite being infected using natural routes and shed virus for a long period, the cats did not transmit the virus to contact cats when air renovation features were employed. The infected animals also developed gross and histological lesions in several organs. These outcomes confirm that cats are at risk of infection when exposed to infected people, but do not transmit the virus to other cats with high rates of air renovation.
2022-03-03 2022 other IM; research-article; Journal Article abstract-available 10.1007/s11259-022-09908-5 Evaluation of the clinical evolution and transmission of SARS-CoV-2 infection in cats by simulating natural routes of infection. Barroso-Arévalo S, Sánchez-Morales L, Barasona JA, Rivera B, Sánchez R, Risalde MA, Agulló-Ros I, Sánchez-Vizcaíno JM. Vet Res Commun. 2022;
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;
Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain.
Dobaño C, Alonso S, Fernández de Sevilla M, Vidal M, [...], Jordan I.
BMC Med. 2021; 19 (1)
DOI: 10.1186/s12916-021-02184-1

Background

Surveillance tools to estimate viral transmission dynamics in young populations are essential to guide recommendations for school opening and management during viral epidemics. Ideally, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We aimed to estimate SARS-CoV-2 infection rates in children and adult populations in a school-like environment during the initial COVID-19 pandemic waves using an antibody-based field-deployable and non-invasive approach.

Methods

Saliva antibody conversion defined as ≥ 4-fold increase in IgM, IgA, and/or IgG levels to five SARS-CoV-2 antigens including spike and nucleocapsid constructs was evaluated in 1509 children and 396 adults by high-throughput Luminex assays in samples collected weekly in 22 summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st, 2020.

Results

Saliva antibody conversion between two visits over a 5-week period was 3.22% (49/1518) or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) assessed by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19.

Conclusion

Saliva antibody profiling including three isotypes and multiplexing antigens is a useful and user-friendlier tool for screening pediatric populations to detect low viral load exposures among children, particularly while they are not vaccinated and vulnerable to highly contagious variants, and to recommend public health policies during pandemics.
2021-11-23 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1186/s12916-021-02184-1 Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain. Dobaño C, Alonso S, Fernández de Sevilla M, Vidal M, Jiménez A, Pons Tomas G, Jairoce C, Melé Casas M, Rubio R, Hernández García M, Ruiz-Olalla G, Girona-Alarcón M, Barrios D, Santano R, Mitchell RA, Puyol L, Mayer L, Chi J, Rodrigo Melero N, Carolis C, Garcia-Miquel A, Bonet-Carne E, Claverol J, Cubells M, Fortuny C, Fumadó V, Jou C, Muñoz-Almagro C, Izquierdo L, Bassat Q, Gratacós E, Aguilar R, García-García JJ, Moncunill G, Jordan I. BMC Med. 2021; 19 (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)
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)
Pregnancy and Birth Outcomes during the Early Months of the COVID-19 Pandemic: The MOACC-19 Cohort.
Rodríguez-Díaz M, Alonso-Molero J, Cabero-Perez MJ, Llorca J, [...], The Moacc-Group.
Int J Environ Res Public Health. 2021; 18 (20)
DOI: 10.3390/ijerph182010931
The new coronavirus, SARS-CoV-2, is devastating for specific groups of patients, but currently there is not enough information concerning its effects on pregnant women. The purpose of this study is to identify the impact of SARS-CoV-2 infection on pregnancy and the consequences that it could cause. We studied a cohort of pregnant ladies who were tested for SARS-CoV-2 infection by RT-PCR and classified as infected or not infected. The recruitment was carried out in the HUMV hospital, a third-level hospital located in Santander, northern Spain. It started on 23 March 2020 and ended on 14 October 2020. Data from our cohort were compared to another cohort recruited in 2018 at the same hospital. We found that gestational hypertension, placental abruptio, and home exposure to an infected person, among other variables, could be associated with SARS-CoV-2 infection. In conclusion, we consider pregnant women a high-risk group of patients towards a possible SARS-CoV-2 infection, especially those who present with conditions such as gestational hypertension or obesity; moreover, we think that SARS-CoV-2 infection could increase the possibilities of having an abruptio placentae, although this result was found in only a few women, so it requires further confirmation.
2021-10-18 2021 other IM; Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/ijerph182010931 Pregnancy and Birth Outcomes during the Early Months of the COVID-19 Pandemic: The MOACC-19 Cohort. Rodríguez-Díaz M, Alonso-Molero J, Cabero-Perez MJ, Llorca J, Dierssen-Sotos T, Gómez-Acebo I, The Moacc-Group. Int J Environ Res Public Health. 2021; 18 (20)
Next-Generation Sequencing for Confronting Virus Pandemics.
Quer J, Colomer-Castell S, Campos C, Andrés C, [...], Tabernero D.
Viruses. 2022; 14 (3)
DOI: 10.3390/v14030600
Virus pandemics have happened, are happening and will happen again. In recent decades, the rate of zoonotic viral spillover into humans has accelerated, mirroring the expansion of our global footprint and travel network, including the expansion of viral vectors and the destruction of natural spaces, bringing humans closer to wild animals. Once viral cross-species transmission to humans occurs, transmission cannot be stopped by cement walls but by developing barriers based on knowledge that can prevent or reduce the effects of any pandemic. Controlling a local transmission affecting few individuals is more efficient that confronting a community outbreak in which infections cannot be traced. Genetic detection, identification, and characterization of infectious agents using next-generation sequencing (NGS) has been proven to be a powerful tool allowing for the development of fast PCR-based molecular assays, the rapid development of vaccines based on mRNA and DNA, the identification of outbreaks, transmission dynamics and spill-over events, the detection of new variants and treatment of vaccine resistance mutations, the development of direct-acting antiviral drugs, the discovery of relevant minority variants to improve knowledge of the viral life cycle, strengths and weaknesses, the potential for becoming dominant to take appropriate preventive measures, and the discovery of new routes of viral transmission.
2022-03-14 2022 other IM; Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3390/v14030600 Next-Generation Sequencing for Confronting Virus Pandemics. Quer J, Colomer-Castell S, Campos C, Andrés C, Piñana M, Cortese MF, González-Sánchez A, Garcia-Cehic D, Ibáñez M, Pumarola T, Rodríguez-Frías F, Antón A, Tabernero D. Viruses. 2022; 14 (3)
Accelerated biological aging in COVID-19 patients.
Cao X, Li W, Wang T, Ran D, [...], Yu H.
Nat Commun. 2022; 13 (1)
DOI: 10.1038/s41467-022-29801-8
Chronological age is a risk factor for SARS-CoV-2 infection and severe COVID-19. Previous findings indicate that epigenetic age could be altered in viral infection. However, the epigenetic aging in COVID-19 has not been well studied. In this study, DNA methylation of the blood samples from 232 healthy individuals and 413 COVID-19 patients is profiled using EPIC methylation array. Epigenetic ages of each individual are determined by applying epigenetic clocks and telomere length estimator to the methylation profile of the individual. Epigenetic age acceleration is calculated and compared between groups. We observe strong correlations between the epigenetic clocks and individual's chronological age (r > 0.8, p < 0.0001). We also find the increasing acceleration of epigenetic aging and telomere attrition in the sequential blood samples from healthy individuals and infected patients developing non-severe and severe COVID-19. In addition, the longitudinal DNA methylation profiling analysis find that the accumulation of epigenetic aging from COVID-19 syndrome could be partly reversed at late clinic phases in some patients. In conclusion, accelerated epigenetic aging is associated with the risk of SARS-CoV-2 infection and developing severe COVID-19. In addition, the accumulation of epigenetic aging from COVID-19 may contribute to the post-COVID-19 syndrome among survivors.
2022-04-19 2022 other research-article; Journal Article abstract-available 10.1038/s41467-022-29801-8 Accelerated biological aging in COVID-19 patients. Cao X, Li W, Wang T, Ran D, Davalos V, Planas-Serra L, Pujol A, Esteller M, Wang X, Yu H. Nat Commun. 2022; 13 (1)
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)
Vitamin D Endocrine System and COVID-19.
Bouillon R, Quesada-Gomez JM.
JBMR Plus. 2021; 5 (12)
DOI: 10.1002/jbm4.10576
Preclinical data strongly suggest that the vitamin D endocrine system (VDES) may have extraskeletal effects. Cells of the immune and cardiovascular systems and lungs can express the vitamin D receptor, and overall these cells respond in a coherent fashion when exposed to 1,25-dihydroxyvitamin D, the main metabolite of the VDES. Supplementation of vitamin D-deficient subjects may decrease the risk of upper respiratory infections. The VDES also has broad anti-inflammatory and anti-thrombotic effects, and other mechanisms argue for a potential beneficial effect of a good vitamin D status on acute respiratory distress syndrome, a major complication of this SARS-2/COVID-19 infection. Activation of the VDES may thus have beneficial effects on the severity of COVID-19. Meta-analysis of observational data show that a better vitamin D status decreased the requirement of intensive care treatment or decreased mortality. A pilot study in Cordoba indicated that admission to intensive care was drastically reduced by administration of a high dose of calcifediol early after hospital admission for COVID-19. A large observational study in Barcelona confirmed that such therapy significantly decreased the odds ratio (OR) of mortality (OR = 0.52). This was also the conclusion of a retrospective study in five hospitals of Southern Spain. A retrospective study on all Andalusian patients hospitalized because of COVID-19, based on real-world data from the health care system, concluded that prescription of calcifediol (hazard ratio [HR] = 0.67) or vitamin D (HR = 0.75), 15 days before hospital admission decreased mortality within the first month. In conclusion, a good vitamin D status may have beneficial effects on the course of COVID-19. This needs to be confirmed by large, randomized trials, but in the meantime, we recommend (rapid) correction of 25 hydroxyvitamin D (25OHD) deficiency in subjects exposed to this coronavirus. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
2021-11-17 2021 other research-article; Journal Article abstract-available 10.1002/jbm4.10576 Vitamin D Endocrine System and COVID-19. Bouillon R, Quesada-Gomez JM. JBMR Plus. 2021; 5 (12)
A Collection of Designed Peptides to Target SARS-CoV-2 Spike RBD-ACE2 Interaction.
Fernandez-Fuentes N, Molina R, Oliva B.
Int J Mol Sci. 2021; 22 (21)
DOI: 10.3390/ijms222111627
The angiotensin-converting enzyme 2 (ACE2) is the receptor used by SARS-CoV and SARS-CoV-2 coronaviruses to attach to cells via the receptor-binding domain (RBD) of their viral spike protein. Since the start of the COVID-19 pandemic, several structures of protein complexes involving ACE2 and RBD as well as monoclonal antibodies and nanobodies have become available. We have leveraged the structural data to design peptides to target the interaction between the RBD of SARS-CoV-2 and ACE2 and SARS-CoV and ACE2, as contrasting exemplar, as well as the dimerization surface of ACE2 monomers. The peptides were modelled using our original method: PiPreD that uses native elements of the interaction between the targeted protein and cognate partner(s) that are subsequently included in the designed peptides. These peptides recapitulate stretches of residues present in the native interface plus novel and highly diverse conformations surrogating key interactions at the interface. To facilitate the access to this information we have created a freely available and dedicated web-based repository, PepI-Covid19 database, providing convenient access to this wealth of information to the scientific community with the view of maximizing its potential impact in the development of novel therapeutic and diagnostic agents.
2021-10-27 2021 other IM; research-article; Journal Article abstract-available 10.3390/ijms222111627 A Collection of Designed Peptides to Target SARS-CoV-2 Spike RBD-ACE2 Interaction. Fernandez-Fuentes N, Molina R, Oliva B. Int J Mol Sci. 2021; 22 (21)
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)
[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)
Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2.
Calina D, Hernández AF, Hartung T, Egorov AM, [...], Docea AO.
Life (Basel). 2021; 11 (9)
DOI: 10.3390/life11090907
In the context of the current COVID-19 pandemic, traditional, complex and lengthy methods of vaccine development and production would not have been able to ensure proper management of this global public health crisis. Hence, a number of technologies have been developed for obtaining a vaccine quickly and ensuring a large scale production, such as mRNA-based vaccine platforms. The use of mRNA is not a new concept in vaccine development but has leveraged on previous knowledge and technology. The great number of human resources and capital investements for mRNA vaccine development, along with the experience gained from previous studies on infectious diseases, allowed COVID-19 mRNA vaccines to be developed, conditionally approved and commercialy available in less than one year, thanks to decades of basic research. This review critically presents and discusses the COVID-19 mRNA vaccine-induced immunity, and it summarizes the most common anaphylactic and autoimmune adverse effects that have been identified until now after massive vaccination campaigns.
2021-08-31 2021 other review-article; Review; Journal Article abstract-available 10.3390/life11090907 Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2. Calina D, Hernández AF, Hartung T, Egorov AM, Izotov BN, Nikolouzakis TK, Tsatsakis A, Vlachoyiannopoulos PG, Docea AO. Life (Basel). 2021; 11 (9)
Transmission of SARS-CoV-2 infections and exposure in surfaces, points and wastewaters: A global one health perspective
Chu D, Singh V, Vu Ngoc S, Nguyen T, [...], Barceló D.
Case Studies in Chemical and Environmental Engineering. 2022; 5
DOI:
The persistence of SARS-CoV-2 or its RNA on surfaces, points, or wastewaters may increase the risk of transmission of this virus. Therefore, we conducted this review to discuss the places and surfaces with the highest potential for infection and spread of the SARS-CoV-2 virus. Several common and public areas, hospitals, elevators, public transport, local markets, and surfaces such as public toilets, door handles, untreated and treated wastewaters, wastewater plants, and public washrooms are also considered major points for spreading of SARS-CoV-2. Highly contaminated surfaces or places often have materials or contain items made of materials on which the SARS-CoV-2 virus can persist (e.g., metal, wood, and plastic). For example, SARS-CoV-2 can exist up to 4 days on doorknobs made by those materials. For public places such as public transports, elevators, and local markets, crowding and enclosed spaces are major source for transmission. Several measures such as using copper alloy surfaces instead of metal surfaces, disinfectants, and suitable personal protective equipment have been suggested. Our research could be the basis to help develop studies on the existence and transmissibility of SARS-CoV-2 as well as its RNA to take measures to prevent and limit the harmful effects of COVID-19 pandemic.
2022-01-24 2022 other Case Reports; case-report abstract-available Transmission of SARS-CoV-2 infections and exposure in surfaces, points and wastewaters: A global one health perspective Chu D, Singh V, Vu Ngoc S, Nguyen T, Barceló D. Case Studies in Chemical and Environmental Engineering. 2022; 5
Efficacy and Safety of Lithium Treatment in SARS-CoV-2 Infected Patients.
Spuch C, López-García M, Rivera-Baltanás T, Cabrera-Alvargonzález JJ, [...], Olivares JM.
Front Pharmacol. 2022; 13
DOI: 10.3389/fphar.2022.850583
At the beginning of the pandemic, we observed that lithium carbonate had a positive effect on the recovery of severely ill patients with COVID-19. Lithium is able to inhibit the replication of several types of viruses, some of which are similar to the SARS-CoV-2 virus, increase the immune response and reduce inflammation by preventing or reducing the cytokine storm. Previously, we published an article with data from six patients with severe COVID-19 infection, where we proposed that lithium carbonate could be used as a potential treatment for COVID-19. Now, we set out to conduct a randomized clinical trial number EudraCT 2020-002008-37 to evaluate the efficacy and safety of lithium treatment in patients infected with severe SARS-CoV-2. We showed that lithium was able to reduce the number of days of hospital and intensive care unit admission as well as the risk of death, reduces inflammatory cytokine levels by preventing cytokine storms, and also reduced the long COVID syndromes. We propose that lithium carbonate can be used to reduce the severity of COVID-19.
2022-04-14 2022 other research-article; Journal Article abstract-available 10.3389/fphar.2022.850583 Efficacy and Safety of Lithium Treatment in SARS-CoV-2 Infected Patients. Spuch C, López-García M, Rivera-Baltanás T, Cabrera-Alvargonzález JJ, Gadh S, Rodrigues-Amorim D, Álvarez-Estévez T, Mora A, Iglesias-Martínez-Almeida M, Freiría-Martínez L, Pérez-Rodríguez M, Pérez-González A, López-Domínguez A, Longueira-Suarez MR, Sousa-Domínguez A, Araújo-Ameijeiras A, Mosquera-Rodríguez D, Crespo M, Vila-Fernández D, Regueiro B, Olivares JM. Front Pharmacol. 2022; 13
SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression.
Álvarez H, Ruiz-Mateos E, Juiz-González PM, Vitallé J, [...], Llibre JM.
Microorganisms. 2022; 10 (1)
DOI: 10.3390/microorganisms10010143
Intra-host evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in cases with persistent coronavirus disease 2019 (COVID-19). In this study, we describe a severely immunosuppressed individual with HIV-1/SARS-CoV-2 coinfection with a long-term course of SARS-CoV-2 infection. A 28-year-old man was diagnosed with HIV-1 infection (CD4+ count: 3 cells/µL nd 563000 HIV-1 RNA copies/mL) and simultaneous Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection and SARS-CoV-2 infection. SARS-CoV-2 real-time reverse transcription polymerase chain reaction positivity from nasopharyngeal samples was prolonged for 15 weeks. SARS-CoV-2 was identified as variant Alpha (PANGO lineage B.1.1.7) with mutation S:E484K. Spike-specific T-cell response was similar to HIV-negative controls although enriched in IL-2, and showed disproportionately increased immunological exhaustion marker levels. Despite persistent SARS-CoV-2 infection, adaptive intra-host SARS-CoV-2 evolution, was not identified. Spike-specific T-cell response protected against a severe COVID-19 outcome and the increased immunological exhaustion marker levels might have favoured SARS-CoV-2 persistence.
2022-01-11 2022 other Case Reports; case-report abstract-available 10.3390/microorganisms10010143 SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression. Álvarez H, Ruiz-Mateos E, Juiz-González PM, Vitallé J, Viéitez I, Vázquez-Friol MDC, Torres-Beceiro I, Pérez-Gómez A, Gallego-García P, Estévez-Gómez N, De Chiara L, Poveda E, Posada D, Llibre JM. Microorganisms. 2022; 10 (1)
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; IM; 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)
Respiratory co-and superinfections in COVID-19.
Del Pozo JL.
Rev Esp Quimioter. 2021; 34 Suppl 1
DOI: 10.37201/req/s01.20.2021
There are few publications on the impact of coinfection and superinfection in patients with COVID-19. Patients with higher severity are much more prone to secondary bacterial, fungal or viral infections. The overuse of antimicrobials in many viral infections (including SARS-CoV-2 infections) undoubtedly contributes to the current antimicrobial resistance crisis. In the context of COVID-19, we are witnessing an increase in multidrug-resistant bacterial infections in our hospitals. The heterogeneity of published studies makes it critical to perform more large-scale studies to better understand the pathogenesis of coinfections or superinfections in the COVID-19 patient.
2021-09-30 2021 other research-article; Review; Journal Article abstract-available 10.37201/req/s01.20.2021 Respiratory co-and superinfections in COVID-19. Del Pozo JL. Rev Esp Quimioter. 2021; 34 Suppl 1
Comparison of cytokines levels among COVID-19 patients living at sea level and high altitude.
Del Valle-Mendoza J, Tarazona-Castro Y, Merino-Luna A, Carrillo-Ng H, [...], Silva-Caso W.
BMC Infect Dis. 2022; 22 (1)
DOI: 10.1186/s12879-022-07079-x

Background

At the end of 2019, a novel coronavirus denominated SARS-CoV-2 rapidly spread through the world causing the pandemic coronavirus disease known as COVID-19. The difference in the inflammatory response against SARS-CoV-2 infection among people living at different altitudes is a variable not yet studied.

Methods

A descriptive cross-sectional study was performed in two Peruvian cities at different altitudes for comparison: Lima and Huaraz. Five important proinflammatory cytokines were measured including: IL-6, IL-2, IL-10, IFN-γ and TNF-α using ELISA assays.

Results

A total of 35 COVID-19 patients and 10 healthy subjects were recruited from each study site. The mean levels of IL-6 (p < 0.03) and TNF-α (p < 0.01) were significantly different among the study groups. In the case of IL-6, patients from Lima had a mean level of 16.2 pg/ml (healthy) and 48.3 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 67.3 pg/ml (healthy) and 97.9 pg/ml (COVID-19). Regarding TNF-α, patients from Lima had a mean level of 25.9 pg/ml (healthy) and 61.6 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 89.0 pg/ml (healthy) and 120.6 pg/ml (COVID-19). The levels of IL-2, IL-10 and IFN-γ were not significantly different in the study groups.

Conclusion

Patients with COVID-19 residing at high-altitude tend to have higher levels of inflammatory cytokines compared to patients living at sea level, particularly IL-6 and TNF-α. A better understanding of the inflammatory response in different populations can contribute to the implementation of therapeutic and preventive approaches. Further studies evaluating more patients, a greater variety of cytokines and their clinical impact are required.
2022-01-28 2022 other Comparative Study; research-article; Journal Article abstract-available 10.1186/s12879-022-07079-x Comparison of cytokines levels among COVID-19 patients living at sea level and high altitude. Del Valle-Mendoza J, Tarazona-Castro Y, Merino-Luna A, Carrillo-Ng H, Kym S, Aguilar-Luis MA, Del Valle LJ, Aquino-Ortega R, Martins-Luna J, Peña-Tuesta I, Silva-Caso W. BMC Infect Dis. 2022; 22 (1)
Persistent SARS-CoV-2 infection with repeated clinical recurrence in a patient with common variable immunodeficiency.
Cabañero-Navalon MD, Garcia-Bustos V, Ruiz-Rodriguez P, Comas I, [...], Moral Moral P.
Clin Microbiol Infect. 2022; 28 (2)
DOI: 10.1016/j.cmi.2021.10.021
2021-11-10 2021 other Letter 10.1016/j.cmi.2021.10.021 Persistent SARS-CoV-2 infection with repeated clinical recurrence in a patient with common variable immunodeficiency. Cabañero-Navalon MD, Garcia-Bustos V, Ruiz-Rodriguez P, Comas I, Coscollá M, Martinez-Priego L, Todolí J, Moral Moral P. Clin Microbiol Infect. 2022; 28 (2)
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)
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)
[Valproic Acid Could Help in the Fight Against COVID-19: a case-control study].
Moreno-Pérez O, Merino E, Ramos JM, Rodríguez JC, [...], Portilla J.
Neurologia. 2022;
DOI: 10.1016/j.nrl.2022.01.007
There is early evidence about Valproic acid (VPA) antiviral effect. Our aim was to investigate the incidence and severity of SARS-CoV-2 infection in VPA users as compared with the general population. A case-control study nested within a cohort, carried out between March 1 and December 17, 2020. Retrospectively, we identified confirmed SARS-CoV-2 infection patients exposed to VPA in our health department (defined as case). We ascertained VPA regimen (all the time (AT)(292 days) or at least 20% of the study period (notAT)(≥58 days) and if VPA levels were in therapeutic range (ATR) (50-100 mcg/mL) in the last 24 months. We calculated the cumulative incidence of SARS-CoV-2 infection and hospital admission in the cases, comparing it with the general unexposed VPA population (controls). During the study period, 6183 PCR+ were detected among 281035 inhabitants, of these, 746 were hospitalized. 691 patients were on VPA notAT and 628 (90.1%) AT. The indication for VPA use was epilepsy in 54.9%. The incidence of PCR+ was 1.736 % (OR 0.785 (95%CI 0.443-1.390) and 1.910 % (OR 0.865 (95%CI 0.488-1.533), on VPA notAT and VPA AT patients, respectively vs. 2.201% in people without VPA regimen. Those patients with VPA ATR had a lower risk of PCR + (OR 0.233 (95%CI 0.057-0.951) notAT; OR 0.218 (95%CI 0.053-0.890) AT). Hospital admission incidence was lower in patient on VPA (OR was 0.543 (95% CI 0.076 to 3.871). Patients with VPA within the therapeutic range had a reduction of SARS-Cov-2 infection incidence greater than 75%. There is a downward trend in the risk of COVID-19 admission by SARS-CoV-2 in patients on VPA therapy. These findings warrant further investigation.
2022-02-14 2022 other research-article; Journal Article; English Abstract abstract-available 10.1016/j.nrl.2022.01.007 [Valproic Acid Could Help in the Fight Against COVID-19: a case-control study]. Moreno-Pérez O, Merino E, Ramos JM, Rodríguez JC, Diaz C, Mas P, Reus S, Sánchez-Martínez R, Boix V, Chico-Sánchez P, Sánchez-Payá J, Portilla J. Neurologia. 2022;
High incidence of pulmonary thromboembolism in hospitalized SARS-CoV-2 infected patients despite thrombo-prophylaxis.
El-Qutob D, Alvarez-Arroyo L, Barreda I, Nieto M, [...], Carrera-Hueso FJ.
Heart Lung. 2022; 53
DOI: 10.1016/j.hrtlng.2022.02.003

Background

SARS-CoV-2 infected patients present thrombotic complications caused by direct endothelial cells injury of the microvessels. Pulmonary thromboembolism (PE) has been reported by Computed Tomography pulmonary angiogram (CTPA) in patients with COVID-19 pneumonia with high D-dimer levels.

Objectives

We present the characteristics of SARS-CoV-2 infected patients diagnosed of PE by CTPA in our hospital. We also present the comparison of these findings with non-infected patients with PE data.

Methods

Retrospective observational cohort study that included patients over 18 years of age hospitalised consecutively between 26th February and 20th May 2020 in an European Hospital with SARS-CoV2 virus infection, and with suspected infection at beginning of admission but with negative PCR, who were studied with CTPA for suspicion of VTE, during their hospitalization.

Results

During the study period, 52 CTPA were performed in our hospital, sixteen in SARS-CoV-2 infected patients, with 4 cases (33%) of PE in the infected group, and 11 (44%) in the non-infected group. No significant differences in age (p = 0.43) and sex (p = 0.31) were found between the two groups, infected and non-infected patients. In the infected group, the patients who had PE had a much lower median age (47.8 years) than those without PE (73.3 years). No differences between infected and non-infected patients were detected in the diagnosis of PE with CTPA, 28.6% versus 27.8% (p = 1.00). Overall patient mortality was 1.9%; one patient died (6.3%) in the infected group, and none in the non-infected group (p = 0.31).

Conclusion

A considerable incidence of PE diagnosed by CTPA in SARS-CoV-2 infected patients has been observed, despite thrombo-prophylaxis.
2022-02-08 2022 other research-article; Journal Article; Observational Study abstract-available 10.1016/j.hrtlng.2022.02.003 High incidence of pulmonary thromboembolism in hospitalized SARS-CoV-2 infected patients despite thrombo-prophylaxis. El-Qutob D, Alvarez-Arroyo L, Barreda I, Nieto M, Pin M, Poveda-Andrés JL, Carrera-Hueso FJ. Heart Lung. 2022; 53
Pulmonary Inflammatory Response in Lethal COVID-19 Reveals Potential Therapeutic Targets and Drugs in Phases III/IV Clinical Trials.
López-Cortés A, Guerrero S, Ortiz-Prado E, Yumiceba V, [...], Kyriakidis NC.
Front Pharmacol. 2022; 13
DOI: 10.3389/fphar.2022.833174
Background: It is imperative to identify drugs that allow treating symptoms of severe COVID-19. Respiratory failure is the main cause of death in severe COVID-19 patients, and the host inflammatory response at the lungs remains poorly understood. Methods: Therefore, we retrieved data from post-mortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, and shortest pathways to physiological phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials. Results: Herein, we analyzed transcriptomics data of 719 inflammatory response genes across 19 cell types (116,313 nuclei) from lung autopsies. The functional enrichment analysis of the 233 significantly expressed genes showed that the most relevant biological annotations were inflammatory response, innate immune response, cytokine production, interferon production, macrophage activation, blood coagulation, NLRP3 inflammasome complex, and the TLR, JAK-STAT, NF-κB, TNF, oncostatin M signaling pathways. Subsequently, we identified 34 essential inflammatory proteins with both high-confidence protein interactions and shortest pathways to inflammation, cell death, glycolysis, and angiogenesis. Conclusion: We propose three small molecules (baricitinib, eritoran, and montelukast) that can be considered for treating severe COVID-19 symptoms after being thoroughly evaluated in COVID-19 clinical trials.
2022-03-29 2022 other research-article; Journal Article abstract-available 10.3389/fphar.2022.833174 Pulmonary Inflammatory Response in Lethal COVID-19 Reveals Potential Therapeutic Targets and Drugs in Phases III/IV Clinical Trials. López-Cortés A, Guerrero S, Ortiz-Prado E, Yumiceba V, Vera-Guapi A, León Cáceres Á, Simbaña-Rivera K, Gómez-Jaramillo AM, Echeverría-Garcés G, García-Cárdenas JM, Guevara-Ramírez P, Cabrera-Andrade A, Puig San Andrés L, Cevallos-Robalino D, Bautista J, Armendáriz-Castillo I, Pérez-Villa A, Abad-Sojos A, Ramos-Medina MJ, León-Sosa A, Abarca E, Pérez-Meza ÁA, Nieto-Jaramillo K, Jácome AV, Morillo A, Arias-Erazo F, Fuenmayor-González L, Quiñones LA, Kyriakidis NC. Front Pharmacol. 2022; 13
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)
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
Vitamin D and COVID-19: where are we now?
Contreras-Bolívar V, García-Fontana B, García-Fontana C, Muñoz-Torres M.
Postgrad Med. 2021;
DOI: 10.1080/00325481.2021.2017647
The pandemic caused by the SARS-CoV-2 virus has triggered great interest in the search for the pathophysiological mechanisms of COVID-19 and its associated hyperinflammatory state. The presence of prognostic factors such as diabetes, cardiovascular disease, hypertension, obesity, and age influence the expression of the disease's clinical severity. Other elements, such as 25-hydroxyvitamin D (25(OH)D3) concentrations, are currently being studied. Various studies, mostly observational, have sought to demonstrate whether there is truly a relationship between 25(OH)D3 levels and the acquisition and/or severity of the disease. The objective of this study was to carry out a review of the current data that associate vitamin D status with the acquisition, evolution, and/or severity of infection by the SARS-CoV-2 virus and to assess whether prevention through vitamin D supplementation can prevent infection and/or improve the evolution once acquired. Vitamin D system has an immunomodulatory function and plays a significant role in various bacterial and viral infections. The immune function of vitamin D is explained in part by the presence of its receptor (VDR) and its activating enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1) in immune cells. The vitamin D, VDR, and Retinoid X Receptor complex allows the transcription of genes with antimicrobial activities, such as cathelicidins and defensins. COVID-19 characteristically presents a marked hyperimmune state, with the release of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β. Thus, there are biological factors linking vitamin D to the cytokine storm, which can herald some of the most severe consequences of COVID-19, such as acute respiratory distress syndrome. Hypovitaminosis D is widespread worldwide, so the prevention of COVID-19 through vitamin D supplementation is being considered as a possible therapeutic strategy easy to implement. However, more-quality studies and well-designed randomized clinical trials are needed to address this relevant question.
2021-12-27 2021 other review-article; Journal Article abstract-available 10.1080/00325481.2021.2017647 Vitamin D and COVID-19: where are we now? Contreras-Bolívar V, García-Fontana B, García-Fontana C, Muñoz-Torres M. Postgrad Med. 2021;
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 fondo-covid 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)
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
SARS-CoV-2 Vaccines and the Skin.
Galván-Casas C, Català A, Muñoz-Santos C.
Actas Dermosifiliogr. 2021; 112 (9)
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; 112 (9)
Host Defence RNases as Antiviral Agents against Enveloped Single Stranded RNA Viruses.
Li J, Boix E.
Virulence. 2021; 12 (1)
DOI: 10.1080/21505594.2021.1871823
Owing to the recent outbreak of Coronavirus Disease of 2019 (COVID-19), it is urgent to develop effective and safe drugs to treat the present pandemic and prevent other viral infections that might come in the future. Proteins from our own innate immune system can serve as ideal sources of novel drug candidates thanks to their safety and immune regulation versatility. Some host defense RNases equipped with antiviral activity have been reported over time. Here, we try to summarize the currently available information on human RNases that can target viral pathogens, with special focus on enveloped single-stranded RNA (ssRNA) viruses. Overall, host RNases can fight viruses by a combined multifaceted strategy, including the enzymatic target of the viral genome, recognition of virus unique patterns, immune modulation, control of stress granule formation, and induction of autophagy/apoptosis pathways. The review also includes a detailed description of representative enveloped ssRNA viruses and their strategies to interact with the host and evade immune recognition. For comparative purposes, we also provide an exhaustive revision of the currently approved or experimental antiviral drugs. Finally, we sum up the current perspectives of drug development to achieve successful eradication of viral infections.
2021-12-01 2021 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.1080/21505594.2021.1871823 Host Defence RNases as Antiviral Agents against Enveloped Single Stranded RNA Viruses. Li J, Boix E. Virulence. 2021; 12 (1)
Fulminant myocarditis in a patient with a lung adenocarcinoma after the third dose of modern COVID-19 vaccine. A case report and literature review.
Terán Brage E, Roldán Ruíz J, González Martín J, Oviedo Rodríguez JD, [...], Fonseca Sánchez E.
Curr Probl Cancer Case Rep. 2022; 6
DOI: 10.1016/j.cpccr.2022.100153
Introduction COVID-19 disease has caused a global health and economic crisis. The introduction of the different COVID-19 vaccines has resulted in a significant decrease in the morbidity and mortality associated with this disease. Adverse effects have been reported, including cardiological ones such as myocarditis or pericarditis after administration. Likewise, tyrosine kinase inhibitor drugs such as osimertinib used in lung cancer patients with epidermal growth factor receptor (EGFR) mutation are associated with heart failure or prolongation of the QT interval. Case report 62-year-old woman diagnosed in September 2019 of lung adenocarcinoma stage IV with bilateral lung and lymph node involvement, carrier of an EGFR mutation (Ex19Del) on treatment with osimertinib. She attended emergency department for fever and hypotension 24 h after administration of the third dose of Moderna® COVID-19 vaccine in the context of acute myocarditis with evidence of severe left ventricular (LV) dysfunction in cardiogenic shock. She required vasoactive support, non-invasive mechanical ventilation, corticotherapy, immunoglobulins and subsequent ventricular support with Impella, with improvement of the clinical picture after 3 days. Cardiac magnetic resonance imaging (MRI) showed evidence of global myocardial oedema compatible with acute myocarditis. Coronary CT showed a lesion in the anterior descending coronary artery requiring revascularization. A few days later, she presented febrile symptoms with isolation of Staphylococcus aureus in the central line catheter and antibiotherapy with cloxacillin was started, with subsequent resolution of the infectious symptoms. Conclusion This is an exceptional and controversial case of fulminant myocarditis probably related to the Modern COVID-19 vaccine in a patient diagnosed with metastatic lung adenocarcinoma on treatment with osimertinib. An increasing number of cases of myocarditis and pericarditis have been reported following vaccination with COVID-19 mRNA vaccines. In addition, retrospective data have shown an increased risk of QT prolongation and heart failure in patients treated with tyrosine kinase inhibitors. Hence, the need for close monitoring of cardiac function during treatment of these patients. Future studies will be necessary to evaluate unknown adverse reactions of these vaccines and their possible interaction with other antineoplastic drugs.
2022-03-31 2022 other Case Reports; case-report abstract-available 10.1016/j.cpccr.2022.100153 Fulminant myocarditis in a patient with a lung adenocarcinoma after the third dose of modern COVID-19 vaccine. A case report and literature review. Terán Brage E, Roldán Ruíz J, González Martín J, Oviedo Rodríguez JD, Vidal Tocino R, Rodríguez Diego S, Sánchez Hernández PL, Bellido Hernández L, Fonseca Sánchez E. Curr Probl Cancer Case Rep. 2022; 6
Sex Hormones and Hormone Therapy during COVID-19 Pandemic: Implications for Patients with Cancer.
Cattrini C, Bersanelli M, Latocca MM, Conte B,