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: 2022-08-17
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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
Myocardial Injury in COVID-19 and Its Implications in Short- and Long-Term Outcomes.
Izquierdo-Marquisá A, Cubero-Gallego H, Aparisi Á, Vaquerizo B, [...], Ribas-Barquet N.
Front Cardiovasc Med. 2022; 9
DOI: 10.3389/fcvm.2022.901245
COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a pandemic with high mortality and morbidity rates. Clinical manifestation is widely variable, including asymptomatic or mild respiratory tract illness to severe pneumonia and death. Myocardial injury is a significant pathogenic feature of COVID-19 and it is associated with worse in-hospital outcomes, mainly due to a higher number of hospital readmissions, with over 50% mortality. These findings suggest that myocardial injury would identify COVID-19 patients with higher risk during active infection and mid-term follow-up. Potential contributors responsible for myocardial damage are myocarditis, vasculitis, acute inflammation, type 1 and type 2 myocardial infarction. However, there are few data about cardiac sequelae and its long-term consequences. Thus, the optimal screening tool for residual cardiac sequelae, clinical follow-up, and the benefits of a specific cardiovascular therapy during the convalescent phase remains unknown. This mini-review explores the different mechanisms of myocardial injury related to COVID-19 and its short and long-term implications.
2022-05-26 2022 other review-article; Review; Journal Article abstract-available 10.3389/fcvm.2022.901245 Myocardial Injury in COVID-19 and Its Implications in Short- and Long-Term Outcomes. Izquierdo-Marquisá A, Cubero-Gallego H, Aparisi Á, Vaquerizo B, Ribas-Barquet N. Front Cardiovasc Med. 2022; 9
Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses.
Sander AL, Moreira-Soto A, Yordanov S, Toplak I, [...], Drexler JF.
Commun Biol. 2022; 5 (1)
DOI: 10.1038/s42003-022-03421-w
The furin cleavage site (FCS) in SARS-CoV-2 is unique within the Severe acute respiratory syndrome-related coronavirus (SrC) species. We re-assessed diverse SrC from European horseshoe bats and analyzed the spike-encoding genomic region harboring the FCS in SARS-CoV-2. We reveal molecular features in SrC such as purine richness and RNA secondary structures that resemble those required for FCS acquisition in avian influenza viruses. We discuss the potential acquisition of FCS through molecular mechanisms such as nucleotide substitution, insertion, or recombination, and show that a single nucleotide exchange in two European bat-associated SrC may suffice to enable furin cleavage. Furthermore, we show that FCS occurrence is variable in bat- and rodent-borne counterparts of human coronaviruses. Our results suggest that furin cleavage sites can be acquired in SrC via conserved molecular mechanisms known in other reservoir-bound RNA viruses and thus support a natural origin of SARS-CoV-2.
2022-05-30 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1038/s42003-022-03421-w Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses. Sander AL, Moreira-Soto A, Yordanov S, Toplak I, Balboni A, Ameneiros RS, Corman V, Drosten C, Drexler JF. Commun Biol. 2022; 5 (1)
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; 74 (4)
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 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; 74 (4)
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
Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail.
Alkhayyat SS, Al-Kuraishy HM, Al-Gareeb AI, El-Bouseary MM, [...], Simal-Gandara J.
Inflamm Res. 2022;
DOI: 10.1007/s00011-022-01615-w

Introduction

Fenofibrate is an agonist of peroxisome proliferator activated receptor alpha (PPAR-α), that possesses anti-inflammatory, antioxidant, and anti-thrombotic properties. Fenofibrate is effective against a variety of viral infections and different inflammatory disorders. Therefore, the aim of critical review was to overview the potential role of fenofibrate in the pathogenesis of SARS-CoV-2 and related complications.

Results

By destabilizing SARS-CoV-2 spike protein and preventing it from binding angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 entry, fenofibrate can reduce SARS-CoV-2 entry in human cells Fenofibrate also suppresses inflammatory signaling pathways, which decreases SARS-CoV-2 infection-related inflammatory alterations. In conclusion, fenofibrate anti-inflammatory, antioxidant, and antithrombotic capabilities may help to minimize the inflammatory and thrombotic consequences associated with SARSCoV-2 infection. Through attenuating the interaction between SARS-CoV-2 and ACE2, fenofibrate can directly reduce the risk of SARS-CoV-2 infection.

Conclusions

As a result, fenofibrate could be a potential treatment approach for COVID-19 control.
2022-08-08 2022 other review-article; Review; Journal Article abstract-available 10.1007/s00011-022-01615-w Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail. Alkhayyat SS, Al-Kuraishy HM, Al-Gareeb AI, El-Bouseary MM, AboKamer AM, Batiha GE, Simal-Gandara J. Inflamm Res. 2022;
Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants.
Monteil V, Eaton B, Postnikova E, Murphy M, [...], Penninger JM.
EMBO Mol Med. 2022; 14 (8)
DOI: 10.15252/emmm.202115230
The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic.
2022-07-04 2022 other research-article; Journal Article abstract-available 10.15252/emmm.202115230 Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants. Monteil V, Eaton B, Postnikova E, Murphy M, Braunsfeld B, Crozier I, Kricek F, Niederhöfer J, Schwarzböck A, Breid H, Devignot S, Klingström J, Thålin C, Kellner MJ, Christ W, Havervall S, Mereiter S, Knapp S, Sanchez Jimenez A, Bugajska-Schretter A, Dohnal A, Ruf C, Gugenberger R, Hagelkruys A, Montserrat N, Kozieradzki I, Hasan Ali O, Stadlmann J, Holbrook MR, Schmaljohn C, Oostenbrink C, Shoemaker RH, Mirazimi A, Wirnsberger G, Penninger JM. EMBO Mol Med. 2022; 14 (8)
Association of blood group A with hospital comorbidity in patients infected by SARS-CoV-2.
Tamayo-Velasco Á, Jiménez García MT, Sanchez Rodríguez A, Hijas Villaizan M, [...], Miramontes-González JP.
Med Clin (Engl Ed). 2022; 159 (1)
DOI: 10.1016/j.medcle.2021.06.028

Background and objectives

In the pandemic caused by SARS-CoV-2, identifying which risk factors are associated with the most serious forms of the disease is important. Blood group A has been presented in various studies as a poor prognostic factor. The objective of this study was to evaluate whether patients with blood group A were associated with more important comorbidities, measured by the Charlson Index, which may explain their worse clinical evolution.

Patients and methods

A prospective and consecutive study examined 100 patients diagnosed with COVID-19 and admitted in March 2020. A multivariate linear regression model was used to evaluate the association of blood group A with the Charlson Index.

Results

Patients in group A had a higher Charlson Index (P = .037), rate of lymphopenia (P = .039) and thrombopenia (P = .014), and hospital mortality (P = .044). Blood group A was an independent factor associated with the Charlson Index (B 0.582, 95% CI 0.02-1.14, P = .041).

Conclusions

Group A was independently associated with greater comorbidity, associated with an increase of 0.582 points in the Charlson Index compared to other blood groups. It was also associated with lower hospital mortality.
2022-06-29 2022 other Case Reports; case-report abstract-available 10.1016/j.medcle.2021.06.028 Association of blood group A with hospital comorbidity in patients infected by SARS-CoV-2. Tamayo-Velasco Á, Jiménez García MT, Sanchez Rodríguez A, Hijas Villaizan M, Carretero Gómez J, Miramontes-González JP. Med Clin (Engl Ed). 2022; 159 (1)
Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths.
Ortega MA, García-Montero C, Fraile-Martinez O, Colet P, [...], Sarría-Santamera A.
J Pers Med. 2022; 12 (6)
DOI: 10.3390/jpm12060995
Over the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to evolve. In this sense, different organizations have identified and classified the different variants that have been emerging, distinguishing between variants of concern (VOC), variants of interest (VOI), or variants under monitoring (VUM). The following review aims to describe the latest updates focusing on VOC and already de-escalated variants, as well as to describe the impact these have had on the global situation. Understanding the intrinsic properties of SARS-CoV-2 and its interaction with the immune system and vaccination is essential to make out the underlying mechanisms that have led to the appearance of these variants, helping to determine the next steps for better public management of this pandemic.
2022-06-18 2022 other review-article; Review; Journal Article abstract-available 10.3390/jpm12060995 Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths. Ortega MA, García-Montero C, Fraile-Martinez O, Colet P, Baizhaxynova A, Mukhtarova K, Alvarez-Mon M, Kanatova K, Asúnsolo A, Sarría-Santamera A. J Pers Med. 2022; 12 (6)
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 Support, Non-U.S. Gov't; 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)
Environmental contributions to the interactions of COVID-19 and asthma: a secondary publication and update.
Urrutia-Pereira M, Chong-Neto HJ, Rosário Filho NA, Annesi Maesano I, [...], D'Amato G.
World Allergy Organ J. 2022;
DOI: 10.1016/j.waojou.2022.100686
Outbreak caused by coronavirus disease 2019 (COVID-19) started in Wuhan, Hubei Province, China and quickly spread around the world. Current evidence is contradictory on the association of asthma with COVID-19 and associated severe outcomes. Type 2 inflammation may reduce the risk for severe COVID-19. Whether asthma diagnosis may be a risk factor for severe COVID-19 especially for those with severe disease or non-allergic phenotypes deserve further attention and clarification. In addition, COVID-19 does not appear to provoke asthma exacerbations and asthma therapeutics should be continued for patients with exposure to COVID-19. Changes in the intensity of pollinization, earlier start and extension of pollinating season, and increase in production and allergenicity of pollen are known direct effects that air pollution has on physical, chemical, and biological properties of the pollen grains. They are influenced and triggered by meteorological variables that could partially explain the effect on COVID-19. SARS-CoV-2 is capable to persist in the environment and can be transported by bioaerosols which can further influence the transmission rate and seasonality of coronavirus. The Covid-19 pandemic has changed the behavior of adults and children globally. A general trend during the pandemic has been human isolation indoors due to school lockdowns, loss of job or implementation of virtual work at home. A consequence of this behavior change would presumably be changes in indoor allergen exposures and reduction of inhaled outdoor allergens. Therefore, lockdowns during the pandemic might have improved some specific allergies, while worsening others, depending on the housing conditions.
2022-08-08 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.waojou.2022.100686 Environmental contributions to the interactions of COVID-19 and asthma: a secondary publication and update. Urrutia-Pereira M, Chong-Neto HJ, Rosário Filho NA, Annesi Maesano I, Ansotegui IJ, Caraballo L, Cecchi L, Galán C, López JF, Aguttes MM, Peden D, Pomés A, Zakzuk J, D'Amato G. World Allergy Organ J. 2022;
Reactive ileal lymphoid hyperplasia related to SARS-CoV-2 infection as a unique clinical feature resembling Crohn's disease.
Qanneta R, Feliu-Masgoret M, García-Pardo G, Marimon-Cortés F.
Rev Gastroenterol Mex (Engl Ed). 2022;
DOI: 10.1016/j.rgmxen.2022.07.010
2022-07-21 2022 other Case Reports; case-report 10.1016/j.rgmxen.2022.07.010 Reactive ileal lymphoid hyperplasia related to SARS-CoV-2 infection as a unique clinical feature resembling Crohn's disease. Qanneta R, Feliu-Masgoret M, García-Pardo G, Marimon-Cortés F. Rev Gastroenterol Mex (Engl Ed). 2022;
Nature of viruses and pandemics: Coronaviruses.
Enjuanes L, Sola I, Zúñiga S, Honrubia JM, [...], Ripoll-Gómez J.
Curr Res Immunol. 2022; 3
DOI: 10.1016/j.crimmu.2022.08.003
Coronaviruses (CoVs) have the largest genome among RNA viruses and store large amounts of information without genome integration as they replicate in the cell cytoplasm. The replication of the virus is a continuous process, whereas the transcription of the subgenomic mRNAs is a discontinuous one, involving a template switch, which resembles a high frequency recombination mechanism that may favor virus genome variability. The origin of the three deadly human CoVs SARS-CoV, MERS-CoV and SARS-CoV-2 are zoonotic events. SARS-CoV-2 has incorporated in its spike protein a furine proteolytic site that facilitates the activation of the virus in any tissue, making this CoV strain highly polytropic and pathogenic. Using MERS-CoV as a model, a propagation-deficient RNA replicon was generated by removing E protein gene (essential for viral morphogenesis and involved in virulence), and accessory genes 3, 4a, 4b and 5 (responsible for antagonism of the innate immune response) to attenuate the virus: MERS-CoV-Δ[3,4a,4b,5,E]. This RNA replicon is strongly attenuated and elicits sterilizing protection after a single immunization in transgenic mice with the receptor for MERS-CoV, making it a promising vaccine candidate for this virus and an interesting platform for vector-based vaccine development. A strategy could be developed for the design of RNA replicon vaccines for other human pathogenic coronaviruses.
2022-08-08 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.crimmu.2022.08.003 Nature of viruses and pandemics: Coronaviruses. Enjuanes L, Sola I, Zúñiga S, Honrubia JM, Bello-Pérez M, Sanz-Bravo A, González-Miranda E, Hurtado-Tamayo J, Requena-Platek R, Wang L, Muñoz-Santos D, Sánchez CM, Esteban A, Ripoll-Gómez J. Curr Res Immunol. 2022; 3
Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells.
Aicher SM, Streicher F, Chazal M, Planas D, [...], Jouvenet N.
J Virol. 2022; 96 (14)
DOI: 10.1128/jvi.00608-22
Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the ability of primary cells from Rhinolophus and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis, and Nyctalus noctula, to support SARS-CoV-2 replication. None of these cells were permissive to infection, not even the ones expressing detectable levels of angiotensin-converting enzyme 2 (ACE2), which serves as the viral receptor in many mammalian species. The resistance to infection was overcome by expression of human ACE2 (hACE2) in three cell lines, suggesting that the restriction to viral replication was due to a low expression of bat ACE2 (bACE2) or the absence of bACE2 binding in these cells. Infectious virions were produced but not released from hACE2-transduced M. myotis brain cells. E. serotinus brain cells and M. myotis nasal epithelial cells expressing hACE2 efficiently controlled viral replication, which correlated with a potent interferon response. Our data highlight the existence of species-specific and cell-specific molecular barriers to viral replication in bat cells. These novel chiropteran cellular models are valuable tools to investigate the evolutionary relationships between bats and coronaviruses. IMPORTANCE Bats are host ancestors of several viruses that cause serious disease in humans, as illustrated by the ongoing SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions has been hampered by a limited number of available bat cellular models. We have generated primary cells and cell lines from several bat species that are relevant for coronavirus research. The various permissivities of the cells to SARS-CoV-2 infection offered the opportunity to uncover some species-specific molecular restrictions to viral replication. All bat cells exhibited a potent entry-dependent restriction. Once this block was overcome by overexpression of human ACE2, which serves at the viral receptor, two bat cell lines controlled well viral replication, which correlated with the inability of the virus to counteract antiviral responses. Other cells potently inhibited viral release. Our novel bat cellular models contribute to a better understanding of the molecular interplays between bat cells and viruses.
2022-07-05 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1128/jvi.00608-22 Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells. Aicher SM, Streicher F, Chazal M, Planas D, Luo D, Buchrieser J, Nemcova M, Seidlova V, Zukal J, Serra-Cobo J, Pontier D, Pain B, Zimmer G, Schwartz O, Roingeard P, Pikula J, Dacheux L, Jouvenet N. J Virol. 2022; 96 (14)
Potential medicinal plants involved in inhibiting 3CLpro activity: A practical alternate approach to combating COVID-19
Yang F, Jiang X, Tariq A, Sadia S, [...], Bussmann R.
J Integr Med. 2022;
DOI:
At present, a variety of vaccines have been approved, and existing antiviral drugs are being tested to find an effective treatment for coronavirus disease 2019 (COVID-19). However, no standardized treatment has yet been approved by the World Health Organization. The virally encoded chymotrypsin-like protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which facilitates the replication of SARS-CoV in the host cells, is one potential pharmacological target for the development of anti-SARS drugs. Online search engines, such as Web of Science, Google Scholar, Scopus and PubMed, were used to retrieve data on the traditional uses of medicinal plants and their inhibitory effects against the SARS-CoV 3CLpro. Various pure compounds, including polyphenols, terpenoids, chalcones, alkaloids, biflavonoids, flavanones, anthraquinones and glycosides, have shown potent inhibition of SARS-CoV-2 3CLpro activity with 50% inhibitory concentration (IC50) values ranging from 2–44 µg/mL. Interestingly, most of these active compounds, including xanthoangelol E (isolated from Angelica keiskei), dieckol 1 (isolated from Ecklonia cava), amentoflavone (isolated from Torreya nucifera), celastrol, pristimerin, tingenone and iguesterin (isolated from Tripterygium regelii), tannic acid (isolated from Camellia sinensis), and theaflavin-3,3'-digallate, 3-isotheaflavin-3 gallate and dihydrotanshinone I (isolated from Salvia miltiorrhiza), had IC50 values of less than 15 µg/mL. Kinetic mechanistic studies of several active compounds revealed that their mode of inhibition was dose-dependent and competitive, with Ki values ranging from 2.4–43.8 μmol/L. Given the significance of plant-based compounds and the many promising results obtained, there is still need to explore the phytochemical and mechanistic potentials of plants and their products. These medicinal plants could serve as an effective inexpensive nutraceutical for the general public to help manage COVID-19.
2022-08-09 2022 other review-article; Review; Journal Article abstract-available Potential medicinal plants involved in inhibiting 3CLpro activity: A practical alternate approach to combating COVID-19 Yang F, Jiang X, Tariq A, Sadia S, Ahmed Z, Sardans J, Aleem M, Ullah R, Bussmann R. J Integr Med. 2022;
Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity.
Batlle D, Monteil V, Garreta E, Hassler L, [...], Penninger JM.
Cell. 2022; 185 (11)
DOI: 10.1016/j.cell.2022.05.004
2022-05-01 2022 other Letter; Comment; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural 10.1016/j.cell.2022.05.004 Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity. Batlle D, Monteil V, Garreta E, Hassler L, Wysocki J, Chandar V, Schwartz RE, Mirazimi A, Montserrat N, Bader M, Penninger JM. Cell. 2022; 185 (11)
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 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)
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
Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later.
Martin-Vicente M, Carrasco I, Muñoz-Gomez MJ, Lobo AH, [...], Martinez I.
Birth. 2022;
DOI: 10.1111/birt.12667

Introduction

Pregnant women are vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Neutralizing antibodies against the SARS-CoV-2 spike (S) protein protect from severe disease. This study analyzes the antibody titers to SARS-CoV-2 S protein in pregnant women and their newborns at delivery, and six months later.

Methods

We conducted a prospective study on pregnant women with confirmed SARS-CoV-2 infection and newborns. Antibody (IgG, IgM, and IgA) titers were determined using immunoassays in serum and milk samples. An angiotensin-converting enzyme 2 (ACE2) receptor-binding inhibition assay to the S protein was performed on the same serum and milk samples.

Results

At birth, antibodies to SARS-CoV-2 spike protein were detected in 81.9% of mothers' sera, 78.9% of cord blood samples, and 63.2% of milk samples. Symptomatic women had higher antibody titers (IgG, IgM, and IgA) than the asymptomatic ones (P < 0.05). At six months postpartum, IgG levels decreased drastically in children's serum (P < 0.001) but remained high in mothers' serum. Antibody titers correlated positively with its capacity to inhibit the ACE2-spike protein interaction at baseline in maternal sera (R2  = 0.203; P < 0.001), cord sera (R2  = 0.378; P < 0.001), and milk (R2  = 0.564; P < 0.001), and at six months in maternal sera (R2  = 0.600; P < 0.001).

Conclusions

High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.
2022-07-08 2022 other research-article; Journal Article abstract-available 10.1111/birt.12667 Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later. Martin-Vicente M, Carrasco I, Muñoz-Gomez MJ, Lobo AH, Mas V, Vigil-Vázquez S, Vázquez M, Manzanares A, Cano O, Alonso R, Sepúlveda-Crespo D, Tarancón-Díez L, Muñoz-Fernández MÁ, Muñoz-Chapuli M, Resino S, Navarro ML, Martinez I. Birth. 2022;
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)
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)
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)
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)
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
GDF15 and ACE2 stratify COVID-19 patients according to severity while ACE2 mutations increase infection susceptibility.
Torrens-Mas M, Perelló-Reus CM, Trias-Ferrer N, Ibargüen-González L, [...], Gonzalez-Freire M.
Front Cell Infect Microbiol. 2022; 12
DOI: 10.3389/fcimb.2022.942951
Coronavirus disease 19 (COVID-19) is a persistent global pandemic with a very heterogeneous disease presentation ranging from a mild disease to dismal prognosis. Early detection of sensitivity and severity of COVID-19 is essential for the development of new treatments. In the present study, we measured the levels of circulating growth differentiation factor 15 (GDF15) and angiotensin-converting enzyme 2 (ACE2) in plasma of severity-stratified COVID-19 patients and uninfected control patients and characterized the in vitro effects and cohort frequency of ACE2 SNPs. Our results show that while circulating GDF15 and ACE2 stratify COVID-19 patients according to disease severity, ACE2 missense SNPs constitute a risk factor linked to infection susceptibility.
2022-07-22 2022 other research-article; Journal Article abstract-available 10.3389/fcimb.2022.942951 GDF15 and ACE2 stratify COVID-19 patients according to severity while ACE2 mutations increase infection susceptibility. Torrens-Mas M, Perelló-Reus CM, Trias-Ferrer N, Ibargüen-González L, Crespí C, Galmes-Panades AM, Navas-Enamorado C, Sanchez-Polo A, Piérola-Lopetegui J, Masmiquel L, Crespi LS, Barcelo C, Gonzalez-Freire M. Front Cell Infect Microbiol. 2022; 12
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)
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
Overview of coronavirus pandemic
Artiga-Sainz L, Ibáñez-Navarro A, Morante-Ruiz M, Bilbao J, [...], Quintana-Díaz M.
Computational Approaches for Novel Therapeutic and Diagnostic Designing to Mitigate SARS-CoV-2 Infection. 2022;
DOI:
During the last months of 2019, numerous cases of respiratory illness such as pneumonia and acute respiratory distress syndrome were described in Wuhan, the capital city of Hubei province in China. At the same time, several research groups identified and reported the etiological agent, that included within the Coronaviridae family and the order Nidovirales, named SARS-CoV-2. Subsequently, the pathological and clinical status caused by the pathogen is commonly known as Coronavirus disease 2019 (COVID-19). In a short period, the outbreak of emerging spread across the world. Therefore the World Health Organization declared a public health emergency of international concern on January 30, 2020, and as a pandemic on March 11, 2020. Many different public health and epidemiological studies have been published since the COVID-19 outbreak, but fatality rates (those that relate the number of cases to mortality) are difficult to assess with certainty. Mean and median case-fatality rates worldwide are near to 3% and 2%, respectively. The median infection fatality calculated from serologic prevalence varies from 0.00% to 1.63% but is mostly estimated between 0.27% and 0.9%. These indexes are influenced by geographic location, socioeconomic status, sex, age, and health conditions, among others.
2022-01-01 2022 other chapter-article abstract-available Overview of coronavirus pandemic Artiga-Sainz L, Ibáñez-Navarro A, Morante-Ruiz M, Bilbao J, Rodríguez de Lema-Tapetado G, Sarria-Santamera A, Quintana-Díaz M. Computational Approaches for Novel Therapeutic and Diagnostic Designing to Mitigate SARS-CoV-2 Infection. 2022;
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
No Evidence of SARS-CoV-2 Infection in Wild Mink (Mustela lutreola and Neogale vison) from Northern Spain during the First Two Years of Pandemic.
Villanueva-Saz S, Giner J, Palomar AM, Gómez MA, [...], Fernández A.
Animals (Basel). 2022; 12 (15)
DOI: 10.3390/ani12151971
The impact of the SARS-CoV-2 pandemic on wildlife is largely unevaluated, and extended surveillance of animal species is needed to reach a consensus on the role of animals in the emergence and maintenance of SARS-CoV-2. This infection has been detected in farmed and domestic animals and wild animals, mainly in captivity. The interactions or shared resources with wildlife could represent a potential transmission pathway for the SARS-CoV-2 spill over to other wild species and could lead to health consequences or the establishment of new reservoirs in susceptible hosts. This study evaluated the presence of SARS-CoV-2 in European mink (Mustela lutreola) and American mink (Neogale vison) in Spain by enzyme-linked immunosorbent assay (ELISA) using the receptor binding domain (RBD) of Spike antigen in serum samples and/or by RT-qPCR assays in oropharyngeal and rectal swabs. From January 2020 to February 2022, a total of 162 animals (127 European mink and 35 American mink) with no evidence of SARS-CoV-2 infection were included in the study. Antibodies against the SARS-CoV-2 were not found in the serum samples analysed (n = 126), nor was the virus amplified by RT-qPCR (n = 160 swabs). Our results suggest that the potential role of wild mink and the European mink bred in captivity and released to the wild as dispersers of SARS-CoV-2 is so far low. However, wildlife surveillance for early detection of human and animal risks should be continued. In this sense, epidemiological monitoring measures, including serology and molecular analysis, are necessary.
2022-08-03 2022 fondo-covid research-article; Journal Article abstract-available 10.3390/ani12151971 No Evidence of SARS-CoV-2 Infection in Wild Mink (<i>Mustela lutreola</i> and <i>Neogale vison</i>) from Northern Spain during the First Two Years of Pandemic. Villanueva-Saz S, Giner J, Palomar AM, Gómez MA, Põdra M, Aranda MDC, Jiménez MLÁ, Lizarraga P, Hernández R, Portillo A, Oteo JA, Ruíz-Arrondo I, Pérez MD, Tobajas AP, Verde M, Lacasta D, Marteles D, Hurtado-Guerrero R, Santiago L, Ruíz H, Fernández A. Animals (Basel). 2022; 12 (15)
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)
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; 10 (6)
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 research-article; Review; 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; 10 (6)
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)
Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies.
Carmona-Torre F, Mínguez-Olaondo A, López-Bravo A, Tijero B, [...], Gómez-Esteban JC.
Front Neurol. 2022; 13
DOI: 10.3389/fneur.2022.886609

Introduction

On March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting.

Objective

To conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines.

Results

Autonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done.

Conclusion

Symptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.
2022-05-27 2022 other review-article; Review; Journal Article abstract-available 10.3389/fneur.2022.886609 Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies. Carmona-Torre F, Mínguez-Olaondo A, López-Bravo A, Tijero B, Grozeva V, Walcker M, Azkune-Galparsoro H, López de Munain A, Alcaide AB, Quiroga J, Del Pozo JL, Gómez-Esteban JC. Front Neurol. 2022; 13
A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors.
Jo S, Signorile L, Kim S, Kim MS, [...], Shin DH.
Int J Mol Sci. 2022; 23 (12)
DOI: 10.3390/ijms23126468
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech's Artificial Intelligence (AI) technology, SOMAIPRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.
2022-06-09 2022 other research-article; Journal Article abstract-available 10.3390/ijms23126468 A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors. Jo S, Signorile L, Kim S, Kim MS, Huertas O, Insa R, Reig N, Shin DH. Int J Mol Sci. 2022; 23 (12)
Neutralizing Response Against SARS-CoV-2 Variants 8 Months After BNT162b2 Vaccination in Naive and COVID-19-Convalescent Individuals.
Luczkowiak J, Labiod N, Rivas G, Rolo M, [...], Delgado R.
J Infect Dis. 2022; 225 (11)
DOI: 10.1093/infdis/jiab634
We have investigated the evolution of the neutralizing response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants at 8 months after Pfizer-BNT162b2 vaccination in coronavirus disease 2019 (COVID-19)-naive (n = 21) and COVID-19-convalescent (n = 21) individuals. Neutralizing levels declined for all variants (range 2- to 3.7-fold). Eight months after vaccination, a significant proportion (4/21) of naive individuals lacked detectable neutralizing activity against the highly transmissible SARS-CoV-2 delta variant. In the convalescent group, the impressive high initial humoral response resulted in detectable neutralizing antibody levels against all variants throughout this period.
2022-06-01 2022 other brief-report; Research Support, Non-U.S. Gov't; Journal Article abstract-available 10.1093/infdis/jiab634 Neutralizing Response Against SARS-CoV-2 Variants 8 Months After BNT162b2 Vaccination in Naive and COVID-19-Convalescent Individuals. Luczkowiak J, Labiod N, Rivas G, Rolo M, Lasala F, Lora-Tamayo J, Mancheno-Losa M, Rial-Crestelo D, Pérez-Rivilla A, Folgueira MD, Delgado R. J Infect Dis. 2022; 225 (11)
Convolutional Neural Network Applied to SARS-CoV-2 Sequence Classification.
Câmara GBM, Coutinho MGF, Silva LMDD, Gadelha WVDN, [...], Fernandes MAC.
Sensors (Basel). 2022; 22 (15)
DOI: 10.3390/s22155730
COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus belonging to the Coronaviridade family, a single-strand positive-sense RNA genome, has been spreading around the world and has been declared a pandemic by the World Health Organization. On 17 January 2022, there were more than 329 million cases, with more than 5.5 million deaths. Although COVID-19 has a low mortality rate, its high capacities for contamination, spread, and mutation worry the authorities, especially after the emergence of the Omicron variant, which has a high transmission capacity and can more easily contaminate even vaccinated people. Such outbreaks require elucidation of the taxonomic classification and origin of the virus (SARS-CoV-2) from the genomic sequence for strategic planning, containment, and treatment of the disease. Thus, this work proposes a high-accuracy technique to classify viruses and other organisms from a genome sequence using a deep learning convolutional neural network (CNN). Unlike the other literature, the proposed approach does not limit the length of the genome sequence. The results show that the novel proposal accurately distinguishes SARS-CoV-2 from the sequences of other viruses. The results were obtained from 1557 instances of SARS-CoV-2 from the National Center for Biotechnology Information (NCBI) and 14,684 different viruses from the Virus-Host DB. As a CNN has several changeable parameters, the tests were performed with forty-eight different architectures; the best of these had an accuracy of 91.94 ± 2.62% in classifying viruses into their realms correctly, in addition to 100% accuracy in classifying SARS-CoV-2 into its respective realm, Riboviria. For the subsequent classifications (family, genera, and subgenus), this accuracy increased, which shows that the proposed architecture may be viable in the classification of the virus that causes COVID-19.
2022-07-31 2022 other research-article; Journal Article abstract-available 10.3390/s22155730 Convolutional Neural Network Applied to SARS-CoV-2 Sequence Classification. Câmara GBM, Coutinho MGF, Silva LMDD, Gadelha WVDN, Torquato MF, Barbosa RM, Fernandes MAC. Sensors (Basel). 2022; 22 (15)
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)
Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants.
Ballesteros-Sanabria L, Pelaez-Prestel HF, Ras-Carmona A, Reche PA.
Biomedicines. 2022; 10 (5)
DOI: 10.3390/biomedicines10050996
The outbreak of SARS-CoV-2 leading to the declaration of the COVID-19 global pandemic has led to the urgent development and deployment of several COVID-19 vaccines. Many of these new vaccines, including those based on mRNA and adenoviruses, are aimed to generate neutralizing antibodies against the spike glycoprotein, which is known to bind to the receptor angiotensin converting enzyme 2 (ACE2) in host cells via the receptor-binding domain (RBD). Antibodies binding to this domain can block the interaction with the receptor and prevent viral entry into the cells. Additionally, these vaccines can also induce spike-specific T cells which could contribute to providing protection against the virus. However, the emergence of new SARS-CoV-2 variants can impair the immunity generated by COVID-19 vaccines if mutations occur in cognate epitopes, precluding immune recognition. Here, we evaluated the chance of five SARS-CoV-2 variants of concern (VOCs), Alpha, Beta, Gamma, Delta and Omicron, to escape spike-specific immunity induced by vaccines. To that end, we examined the impact of the SARS-CoV-2 variant mutations on residues located on experimentally verified spike-specific epitopes, deposited at the Immune Epitope Database, that are targeted by neutralizing antibodies or recognized by T cells. We found about 300 of such B cell epitopes, which were largely overlapping, and could be grouped into 54 B cell epitope clusters sharing ≥ 7 residues. Most of the B cell epitope clusters map in the RBD domain (39 out of 54) and 20%, 50%, 37%, 44% and 57% of the total are mutated in SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants, respectively. We also found 234 experimentally verified CD8 and CD4 T cell epitopes that were distributed evenly throughout the spike protein. Interestingly, in each SARS-CoV-2 VOC, over 87% and 79% of CD8 and CD4 T cell epitopes, respectively, are not mutated. These observations suggest that SARS-CoV-2 VOCs-particularly the Omicron variant-may be prone to escape spike-specific antibody immunity, but not cellular immunity, elicited by COVID-19 vaccines.
2022-04-26 2022 other research-article; Journal Article abstract-available 10.3390/biomedicines10050996 Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants. Ballesteros-Sanabria L, Pelaez-Prestel HF, Ras-Carmona A, Reche PA. Biomedicines. 2022; 10 (5)
Immunocytochemical Assessment of ACE2 and TMPRSS2 in Nasopharyngeal Swabs from SARS-CoV-2 Patients.
Peña KB, Gumà J, Guilarte C, Delamo L, [...], Parada D.
Front Biosci (Landmark Ed). 2022; 27 (7)
DOI: 10.31083/j.fbl2707217

Background

SARS-CoV-2 is a positive-sense single-stranded RNA virus. It is enveloped by four structural proteins. The entry of the virus into the host cells is mediated by spike protein binding to the angiotensin converting enzyme 2 (ACE2) and proteolytic cleavage by transmembrane protease serine 2 (TMPRSS2). In this study, we analyzed the expression of the ACE2 receptor and TMPRSS2 in cases under investigation for SARS-CoV-2 infection.

Methods

The study was carried out using the viral transport medium of consecutive nasopharyngeal swabs from 300 people under examination for SARS-CoV-2 infection. All samples underwent the SARS-CoV-2 transcriptase-mediated amplification assay (Procleix® SARS-CoV-2) to detect the virus. Immunocytochemistry was used in each sample to detect the presence of the SARS-CoV-2 nucleoprotein, the ACE2 receptor, and TMPRSS2.

Results

An immunocytochemical study with monoclonal antibody against SARS-CoV-2 viral nucleoprotein showed positivity in squamous cells. ACE2 were not detected in the squamous cells obtained from the nasopharyngeal samples.

Conclusions

SARS-CoV-2 predominantly localizes to squamous cells in cytology samples of patients with positive transcriptase-mediated amplification SARS-CoV-2 assay results. The immunocytochemical negativity for ACE2 evidenced in the present study could be related to the cellular heterogeneity present in the nasopharyngeal smear samples and could be related to variations at the genomic level. Our results suggest that SARS-CoV-2 might be present in the nasopharyngeal region because viral cell junctions are weaker. This facilitates viral concentration, infective capacity and migration to specific organs, where SARS-CoV-2 infects target cells by binding to their receptors and then entering.
2022-07-01 2022 other Journal Article abstract-available 10.31083/j.fbl2707217 Immunocytochemical Assessment of ACE2 and TMPRSS2 in Nasopharyngeal Swabs from SARS-CoV-2 Patients. Peña KB, Gumà J, Guilarte C, Delamo L, Grifol M, Pique B, Hernandez A, Casteñé H, Riu F, Parada D. Front Biosci (Landmark Ed). 2022; 27 (7)
Clinical progress in MSC-based therapies for the management of severe COVID-19.
Rossello-Gelabert M, Gonzalez-Pujana A, Igartua M, Santos-Vizcaino E, [...], Hernandez RM.
Cytokine Growth Factor Rev. 2022;
DOI: 10.1016/j.cytogfr.2022.07.002
Considering the high impact that severe Coronavirus disease 2019 (COVID-19) cases still pose on public health and their complex pharmacological management, the search for new therapeutic alternatives is essential. Mesenchymal stromal cells (MSCs) could be promising candidates as they present important immunomodulatory and anti-inflammatory properties that can combat the acute severe respiratory distress syndrome (ARDS) and the cytokine storm occurring in COVID-19, two processes that are mainly driven by an immunological misbalance. In this review, we provide a comprehensive overview of the intricate inflammatory process derived from the immune dysregulation that occurs in COVID-19, discussing the potential that the cytokines and growth factors that constitute the MSC-derived secretome present to treat the disease. Moreover, we revise the latest clinical progress made in the field, discussing the most important findings of the clinical trials conducted to date, which follow 2 different approaches: MSC-based cell therapy or the administration of the secretome by itself, as a cell-free therapy.
2022-07-06 2022 other review-article; Journal Article abstract-available 10.1016/j.cytogfr.2022.07.002 Clinical progress in MSC-based therapies for the management of severe COVID-19. Rossello-Gelabert M, Gonzalez-Pujana A, Igartua M, Santos-Vizcaino E, Hernandez RM. Cytokine Growth Factor Rev. 2022;
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)
SARS-CoV-2 infection and liver involvement.
Luo M, Ballester MP, Soffientini U, Jalan R, [...], Mehta G.
Hepatol Int. 2022; 16 (4)
DOI: 10.1007/s12072-022-10364-1
The COVID-19 pandemic is the largest public health challenge in living memory. Patients with underlying liver disease have been disproportionately affected, experiencing high morbidity and mortality. In addition, elevated liver enzymes appear to be a risk factor for disease progression, even in the absence of underlying liver disease. Nevertheless, the mechanism of liver injury in SARS-CoV-2 infection remains largely unknown. This review aims to provide an overview of the mechanisms by which SARS-CoV-2 induces liver injury, and the impact of COVID-19 on cirrhosis, alcohol-related liver disease, autoimmune liver disease, non-alcoholic fatty liver disease, hepatitis B and C virus infection, liver-transplant recipients and patients with hepatocellular carcinoma. Finally, emerging data on vaccination in liver diseases is discussed, to help inform public health policy.
2022-06-29 2022 other review-article; Review; Journal Article abstract-available 10.1007/s12072-022-10364-1 SARS-CoV-2 infection and liver involvement. Luo M, Ballester MP, Soffientini U, Jalan R, Mehta G. Hepatol Int. 2022; 16 (4)
Emerging clinically tested detection methods for COVID-19.
Castellanos M, Somoza Á.
FEBS J. 2022;
DOI: 10.1111/febs.16469
At the time of writing, there were 486 761 597 global cases of COVID-19 with 6 142 735 confirmed deaths (World Health Organization, 4 April 2022). According to the scarcity of information about estimation of cases with mild or no symptoms, it is suggested that they could represent 25-80% of all infections. The majority of these cases remain untested, although they are infective. The molecular diagnosis of COVID-19 is based mainly on quantitative reverse transcription PCR. However, this approach faces several challenges related to the shortage of resources and people who are adequately trained to run the tests. Alternative testing methods, targeting effectively several viral compounds at different stages of the infection, have quickly emerged. However, universal systems that are specific, sensitive, affordable, easy, portable and scalable are still warranted. In this review, a comprehensive compilation of the methods available is provided.
2022-05-01 2022 fondo-covid review-article; Review; Journal Article abstract-available 10.1111/febs.16469 Emerging clinically tested detection methods for COVID-19. Castellanos M, Somoza Á. FEBS J. 2022;
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)
An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern.
Du W, Hurdiss DL, Drabek D, Mykytyn AZ, [...], Bosch BJ.
Sci Immunol. 2022; 7 (73)
DOI: 10.1126/sciimmunol.abp9312
The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays notable immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other variants of concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta, and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.
2022-07-29 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1126/sciimmunol.abp9312 An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern. Du W, Hurdiss DL, Drabek D, Mykytyn AZ, Kaiser FK, González-Hernández M, Muñoz-Santos D, Lamers MM, van Haperen R, Li W, Drulyte I, Wang C, Sola I, Armando F, Beythien G, Ciurkiewicz M, Baumgärtner W, Guilfoyle K, Smits T, van der Lee J, van Kuppeveld FJM, van Amerongen G, Haagmans BL, Enjuanes L, Osterhaus ADME, Grosveld F, Bosch BJ. Sci Immunol. 2022; 7 (73)
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)
Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation.
Ceballos FC, Virseda-Berdices A, Resino S, Ryan P, [...], Jiménez-Sousa MÁ.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.925558

Background

metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression.

Material and methods

we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation.

Results

After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis.

Conclusions

This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.
2022-06-30 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2022.925558 Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation. Ceballos FC, Virseda-Berdices A, Resino S, Ryan P, Martínez-González O, Peréz-García F, Martin-Vicente M, Brochado-Kith O, Blancas R, Bartolome-Sánchez S, Vidal-Alcántara EJ, Albóniga-Díez OE, Cuadros-González J, Blanca-López N, Martínez I, Martinez-Acitores IR, Barbas C, Fernández-Rodríguez A, Jiménez-Sousa MÁ. Front Immunol. 2022; 13
Convalescent Plasma Therapy, Therapeutic Formulations of Repurposed Drugs in 20th Century Epidemics against COVID-19: A Systematic Review.
Fernández-Lázaro D, Ortega CD, Sánchez-Serrano N, Beddar Chaib F, [...], Rodríguez-García S.
Pharmaceutics. 2022; 14 (5)
DOI: 10.3390/pharmaceutics14051020
Coronavirus 2019 disease (COVID-19) represents one of the largest pandemics the world has faced, and it is producing a global health crisis. To date, the availability of drugs to treat COVID-19 infections remains limited to supportive care although therapeutic options are being explored. Some of them are old strategies for treating infectious diseases. convalescent plasma (CP) therapy has been used successfully in other viral outbreaks in the 20th century. In this study, we systematically evaluated the effect and safety of CP therapy on hospitalized COVID-19 patients. A structured search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines using Medline (PubMed), SciELO, Cochrane Library Plus, Web of Science, and Scopus. The search included articles published up to January 2022 and was restricted to English- and Spanish-language publications. As such, investigators identified six randomized controlled trials that met the search criteria. The results determined that in hospitalized COVID-19 patients the administration of CP therapy with a volume between 200-500 mL and a single transfusion performed in 1-2 h, compared to the control group, decreased viral load, symptomatology, the period of infection, and mortality, without serious adverse effects. CP did influence clinical outcomes and may be a possible treatment option, although further studies will be necessary.
2022-05-09 2022 other review-article; Review; Journal Article abstract-available 10.3390/pharmaceutics14051020 Convalescent Plasma Therapy, Therapeutic Formulations of Repurposed Drugs in 20th Century Epidemics against COVID-19: A Systematic Review. Fernández-Lázaro D, Ortega CD, Sánchez-Serrano N, Beddar Chaib F, Jerves Donoso D, Jiménez-Callejo E, Rodríguez-García S. Pharmaceutics. 2022; 14 (5)
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)
Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol.
Quesada-Gomez JM, Lopez-Miranda J, Entrenas-Castillo M, Casado-Díaz A, [...], Bouillon R.
Nutrients. 2022; 14 (13)
DOI: 10.3390/nu14132716
The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin-angiotensin-bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents.
2022-06-29 2022 other review-article; Review; Journal Article abstract-available 10.3390/nu14132716 Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol. Quesada-Gomez JM, Lopez-Miranda J, Entrenas-Castillo M, Casado-Díaz A, Nogues Y Solans X, Mansur JL, Bouillon R. Nutrients. 2022; 14 (13)
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)
Alicante-Winter Immunology Symposium in Health (A-Wish) and the Boulle-SEI awards: A collaboration between the Spanish Society for immunology, the University of Alicante and the Jean Boulle Group to honor the Balmis Expedition.
Ochando J, Camara C, Durham L, Sempere JM, [...], Lopez-Hoyos M.
Curr Res Immunol. 2022; 3
DOI: 10.1016/j.crimmu.2022.06.001
Image 1.
2022-06-18 2022 other review-article; Review; Journal Article abstract-available 10.1016/j.crimmu.2022.06.001 Alicante-Winter Immunology Symposium in Health (A-Wish) and the Boulle-SEI awards: A collaboration between the Spanish Society for immunology, the University of Alicante and the Jean Boulle Group to honor the Balmis Expedition. Ochando J, Camara C, Durham L, Sempere JM, Lopez-Hoyos M. Curr Res Immunol. 2022; 3
A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions.
Bauer MS, Gruber S, Hausch A, Gomes PSFC, [...], Lipfert J.
Proc Natl Acad Sci U S A. 2022; 119 (14)
DOI: 10.1073/pnas.2114397119
SignificanceIn the dynamic environment of the airways, where SARS-CoV-2 infections are initiated by binding to human host receptor ACE2, mechanical stability of the viral attachment is a crucial fitness advantage. Using single-molecule force spectroscopy techniques, we mimic the effect of coughing and sneezing, thereby testing the force stability of SARS-CoV-2 RBD:ACE2 interaction under physiological conditions. Our results reveal a higher force stability of SARS-CoV-2 binding to ACE2 compared to SARS-CoV-1, causing a possible fitness advantage. Our assay is sensitive to blocking agents preventing RBD:ACE2 bond formation. It will thus provide a powerful approach to investigate the modes of action of neutralizing antibodies and other agents designed to block RBD binding to ACE2 that are currently developed as potential COVID-19 therapeutics.
2022-03-21 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1073/pnas.2114397119 A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions. Bauer MS, Gruber S, Hausch A, Gomes PSFC, Milles LF, Nicolaus T, Schendel LC, Navajas PL, Procko E, Lietha D, Melo MCR, Bernardi RC, Gaub HE, Lipfert J. Proc Natl Acad Sci U S A. 2022; 119 (14)
Post COVID-19 Condition in Children and Adolescents: An Emerging Problem.
Izquierdo-Pujol J, Moron-Lopez S, Dalmau J, Gonzalez-Aumatell A, [...], Martinez-Picado J.
Front Pediatr. 2022; 10
DOI: 10.3389/fped.2022.894204
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became a pandemic in 2020 and by March 2022 had caused more than 479 million infections and 6 million deaths worldwide. Several acute and long-term symptoms have been reported in infected adults, but it remains unclear whether children/adolescents also experience persistent sequelae. Hence, we conducted a review of symptoms and pathophysiology associated with post-coronavirus disease 2019 (post-COVID-19) condition in children and adolescents. We reviewed the scientific literature for reports on persistent COVID-19 symptoms after SARS-CoV-2 infection in both children/adolescents and adults from 1 January 2020 to 31 March 2022 (based on their originality and relevance to the broad scope of this review, 26 reports were included, 8 focused on adults and 18 on children/adolescents). Persistent sequelae of COVID-19 are less common in children/adolescents than in adults, possibly owing to a lower frequency of SARS-CoV-2 infection and to the lower impact of the infection itself in this age group. However, cumulative evidence has shown prolonged COVID-19 to be a clinical entity, with few pathophysiological associations at present. The most common post-COVID-19 symptoms in children/adolescents are fatigue, lack of concentration, and muscle pain. In addition, we found evidence of pathophysiology associated with fatigue and/or headache, persistent loss of smell and cough, and neurological and/or cardiovascular symptoms. This review highlights the importance of unraveling why SARS-CoV-2 infection may cause post-COVID-19 condition and how persistent symptoms might affect the physical, social, and psychological well-being of young people in the future.
2022-05-11 2022 other review-article; Review; Journal Article abstract-available 10.3389/fped.2022.894204 Post COVID-19 Condition in Children and Adolescents: An Emerging Problem. Izquierdo-Pujol J, Moron-Lopez S, Dalmau J, Gonzalez-Aumatell A, Carreras-Abad C, Mendez M, Rodrigo C, Martinez-Picado J. Front Pediatr. 2022; 10
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)
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)
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)
COVID-19  vaccination in patients receiving allergen immunotherapy (AIT) or biologicals-EAACI recommendations.
Jutel M, Torres MJ, Palomares O, Akdis CA, [...], Agache I.
Allergy. 2022; 77 (8)
DOI: 10.1111/all.15252
Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.
2022-03-18 2022 other research-article; Journal Article abstract-available 10.1111/all.15252 COVID-19  vaccination in patients receiving allergen immunotherapy (AIT) or biologicals-EAACI recommendations. Jutel M, Torres MJ, Palomares O, Akdis CA, Eiwegger T, Untersmayr E, Barber D, Zemelka-Wiacek M, Kosowska A, Palmer E, Vieths S, Mahler V, Canonica WG, Nadeau K, Shamji MH, Agache I. Allergy. 2022; 77 (8)
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; 85 (1)
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, before SARS-CoV-2 vaccine implementation, 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.
2022-04-29 2022 other Research Support, Non-U.S. Gov't; 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; 85 (1)
CoVITEST: A Fast and Reliable Method to Monitor Anti-SARS-CoV-2 Specific T Cells From Whole Blood.
Egri N, Olivé V, Hernández-Rodríguez J, Castro P, [...], Calderón H.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.848586
Cellular and humoral immune responses are essential for COVID-19 recovery and protection against SARS-CoV-2 reinfection. To date, the evaluation of SARS-CoV-2 immune protection has mainly focused on antibody detection, generally disregarding the cellular response, or placing it in a secondary position. This phenomenon may be explained by the complex nature of the assays needed to analyze cellular immunity compared with the technically simple and automated detection of antibodies. Nevertheless, a large body of evidence supports the relevance of the T cell's role in protection against SARS-CoV-2, especially in vulnerable individuals with a weakened immune system (such as the population over 65 and patients with immunodeficiencies). Here we propose to use CoVITEST (Covid19 anti-Viral Immunity based on T cells for Evaluation in a Simple Test), a fast, affordable and accessible in-house assay that, together with a diagnostic matrix, allows us to determine those patients who might be protected with SARS-CoV-2-reactive T cells. The method was established using healthy SARS-CoV-2-naïve donors pre- and post-vaccination (n=30), and further validated with convalescent COVID-19 donors (n=51) in a side-by-side comparison with the gold standard IFN-γ ELISpot. We demonstrated that our CoVITEST presented reliable and comparable results to those obtained with the ELISpot technique in a considerably shorter time (less than 8 hours). In conclusion, we present a simple but reliable assay to determine cellular immunity against SARS-CoV-2 that can be used routinely during this pandemic to monitor the immune status in vulnerable patients and thereby adjust their therapeutic approaches. This method might indeed help to optimize and improve decision-making protocols for re-vaccination against SARS-CoV-2, at least for some population subsets.
2022-07-05 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3389/fimmu.2022.848586 CoVITEST: A Fast and Reliable Method to Monitor Anti-SARS-CoV-2 Specific T Cells From Whole Blood. Egri N, Olivé V, Hernández-Rodríguez J, Castro P, De Guzman C, Heredia L, Segura AC, Fernandez MD, de Moner N, Torradeflot M, Ballús J, Martinez R, Vazquez M, Costa MV, Dobaño C, Mazza M, Mazzotti L, Pascal M, Juan M, González-Navarro EA, Calderón H. Front Immunol. 2022; 13
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)
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; 112 (2)
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; 112 (2)
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)
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)
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 review-article; Review; 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
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)
Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice.
Vidal E, López-Figueroa C, Rodon J, Pérez M, [...], Segalés J.
Vet Pathol. 2022; 59 (4)
DOI: 10.1177/03009858211066841
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.
2021-12-27 2021 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1177/03009858211066841 Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice. Vidal E, López-Figueroa C, Rodon J, Pérez M, Brustolin M, Cantero G, Guallar V, Izquierdo-Useros N, Carrillo J, Blanco J, Clotet B, Vergara-Alert J, Segalés J. Vet Pathol. 2022; 59 (4)
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)
Should we discount the laboratory origin of COVID-19?
Segreto R, Deigin Y, McCairn K, Sousa A, [...], Zhang D.
Environ Chem Lett. 2021; 19 (4)
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; 19 (4)
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)
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)
Thrombosis, cancer, and COVID-19.
Brito-Dellan N, Tsoukalas N, Font C.
Support Care Cancer. 2022;
DOI: 10.1007/s00520-022-07098-z
Cancer and coronavirus disease 2019 (COVID-19) have unusual similarities: they both result in a markedly elevated risk of thrombosis, exceptionally high D-dimer levels, and the failure of anticoagulation therapy in some cases. Cancer patients are more vulnerable to COVID-19 infection and have a higher mortality rate. Science has uncovered much about SARS-CoV-2, and made extraordinary and unprecedented progress on the development of various treatment strategies and COVID-19 vaccines. In this review, we discuss known data on cancer-associated thrombosis (CAT), SARS-CoV-2 infection, and COVID-19 vaccines and discuss considerations for managing CAT in patients with COVID-19. Cancer patients should be given priority for COVID-19 vaccination; however, they may demonstrate a weaker immune response to COVID-19 vaccines than the general population. Currently, the Centers for Disease Control and Prevention recommends an additional dose and booster shot of the COVID-19 vaccine after the primary series in patients undergoing active cancer treatment for solid tumors or hematological cancers, recipients of stem cell transplant within the last 2 years, those taking immunosuppressive medications, and those undergoing active treatment with high-dose corticosteroids or other drugs that suppress the immune response. The mainstay of thrombosis treatment in patients with cancer and COVID-19 is anticoagulation therapy.
2022-05-14 2022 other research-article; Journal Article abstract-available 10.1007/s00520-022-07098-z Thrombosis, cancer, and COVID-19. Brito-Dellan N, Tsoukalas N, Font C. Support Care Cancer. 2022;
Antibody response to the messenger RNA-1273 vaccine (Moderna) in liver transplant recipients.
Cuadrado A, Del Barrio M, Fortea JI, Amigo L, [...], Fábrega E.
Hepatol Commun. 2022; 6 (7)
DOI: 10.1002/hep4.1937
Different reports have shown the clinical and serologic response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in preventing coronavirus disease 2019 (COVID-19) in the general population, but few studies have examined these responses in transplant recipients. We assessed the vaccine immunogenicity of two doses (100 μg) of the mRNA-1273 vaccine (Moderna) administered with a 28-day interval in liver transplant recipients (LTRs) at follow-up at the Marques de Valdecilla University Hospital. LTRs without a history of COVID-19 infection were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies directed against the spike protein (S) a median of 43 days after receiving the second Moderna vaccine dose. Clinical data, including immunosuppressive regimen and routine laboratory data, were obtained from the medical record of each patient up to 3 months before the date of the first vaccination. Factors associated with serologic response were evaluated through logistic regression. In total, 129 LTRs who had anti-S results were included. Most patients were men (n = 99; 76.7%) with a median age of 63 years (interquartile range, 56-68). Alcohol (43.4%) and chronic hepatitis C (18.6%) were the most frequent causes of liver transplantation. A positive anti-S IgG response was observed in 113 LTRs (87.6%; 95% confidence interval [CI], 80.8-92.2). A strong inverse relationship between mycophenolate mofetil use and serologic response was found (odds ratio, 0.07; 95% CI, 0.02-0.26; p = 0.001). Conclusion: Most LTRs develop an immunological response to the Moderna SARS-CoV-2 mRNA-based vaccine. An immunosuppressive regimen that includes mycophenolate predicts a weak serologic response.
2022-03-28 2022 other research-article; Journal Article abstract-available 10.1002/hep4.1937 Antibody response to the messenger RNA-1273 vaccine (Moderna) in liver transplant recipients. Cuadrado A, Del Barrio M, Fortea JI, Amigo L, San Segundo D, Rodriguez-Cundin MP, Rebollo MH, Fernandez-Santiago R, Castillo F, Achalandabaso M, Echeverri J, Anderson EJ, Rodríguez-Sanjuan JC, López-Hoyos M, Crespo J, Fábrega E. Hepatol Commun. 2022; 6 (7)
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
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 Support, Non-U.S. Gov't; 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)
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)
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)
The polyhedric reality of the interaction between COVID-19, asthma and inhaled corticosteroids.
Gonzalez-Barcala FJ, Nieto-Fontarigo JJ, Mendez-Brea P, Salgado FJ.
ERJ Open Res. 2022; 8 (2)
DOI: 10.1183/23120541.00179-2022
The impact of ICS on the prognosis for #COVID19 in #asthma patients requires a thorough evaluation of a range of factors that interact in this process, in order to draw solid conclusions, since at the present time the debate continues https://bit.ly/3xLNBrc.
2022-04-01 2022 other Editorial abstract-available 10.1183/23120541.00179-2022 The polyhedric reality of the interaction between COVID-19, asthma and inhaled corticosteroids. Gonzalez-Barcala FJ, Nieto-Fontarigo JJ, Mendez-Brea P, Salgado FJ. ERJ Open Res. 2022; 8 (2)
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)
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)
Myocardial Injuries in COVID-19: More Questions Than Answers.
Bardaji A.
J Clin Med. 2022; 11 (15)
DOI: 10.3390/jcm11154527
At the end of 2019, the SARS-CoV-2 virus was reported to be responsible for the cases of pneumonia that had begun to appear a few months earlier in the Wuhan province of China [...].
2022-08-03 2022 other Editorial abstract-available 10.3390/jcm11154527 Myocardial Injuries in COVID-19: More Questions Than Answers. Bardaji A. J Clin Med. 2022; 11 (15)
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 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)
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)
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; 78 (3)
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 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; 78 (3)
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)
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)
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
Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells.
Icho S, Rujas E, Muthuraman K, Tam J, [...], Melnyk RA.
Antimicrob Agents Chemother. 2022; 66 (7)
DOI: 10.1128/aac.00439-22
An essential step in the infection life cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the proteolytic activation of the viral spike (S) protein, which enables membrane fusion and entry into the host cell. Two distinct classes of host proteases have been implicated in the S protein activation step: cell-surface serine proteases, such as the cell-surface transmembrane protease, serine 2 (TMPRSS2), and endosomal cathepsins, leading to entry through either the cell-surface route or the endosomal route, respectively. In cells expressing TMPRSS2, inhibiting endosomal proteases using nonspecific cathepsin inhibitors such as E64d or lysosomotropic compounds such as hydroxychloroquine fails to prevent viral entry, suggesting that the endosomal route of entry is unimportant; however, mechanism-based toxicities and poor efficacy of these compounds confound our understanding of the importance of the endosomal route of entry. Here, to identify better pharmacological agents to elucidate the role of the endosomal route of entry, we profiled a panel of molecules identified through a high-throughput screen that inhibit endosomal pH and/or maturation through different mechanisms. Among the three distinct classes of inhibitors, we found that inhibiting vacuolar-ATPase using the macrolide bafilomycin A1 was the only agent able to potently block viral entry without associated cellular toxicity. Using both pseudotyped and authentic virus, we showed that bafilomycin A1 inhibits SARS-CoV-2 infection both in the absence and presence of TMPRSS2. Moreover, synergy was observed upon combining bafilomycin A1 with Camostat, a TMPRSS2 inhibitor, in neutralizing SARS-CoV-2 entry into TMPRSS2-expressing cells. Overall, this study highlights the importance of the endosomal route of entry for SARS-CoV-2 and provides a rationale for the generation of successful intervention strategies against this virus that combine inhibitors of both entry pathways.
2022-06-15 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1128/aac.00439-22 Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells. Icho S, Rujas E, Muthuraman K, Tam J, Liang H, Landreth S, Liao M, Falzarano D, Julien JP, Melnyk RA. Antimicrob Agents Chemother. 2022; 66 (7)
Serum microRNAs targeting ACE2 and RAB14 genes distinguish asymptomatic from critical COVID-19 patients.
Calderon-Dominguez M, Trejo-Gutierrez E, González-Rovira A, Beltrán-Camacho L, [...], Durán-Ruiz MC.
Mol Ther Nucleic Acids. 2022; 29
DOI: 10.1016/j.omtn.2022.06.006
Despite the extraordinary advances achieved to beat COVID-19 disease, many questions remain unsolved, including the mechanisms of action of SARS-CoV-2 and which factors determine why individuals respond so differently to the viral infection. Herein, we performed an in silico analysis to identify host microRNA targeting ACE2, TMPRSS2, and/or RAB14, all genes known to participate in viral entry and replication. Next, the levels of six microRNA candidates previously linked to viral and respiratory-related pathologies were measured in the serum of COVID-19-negative controls (n = 16), IgG-positive COVID-19 asymptomatic individuals (n = 16), and critical COVID-19 patients (n = 17). Four of the peripheral microRNAs analyzed (hsa-miR-32-5p, hsa-miR-98-3p, hsa-miR-423-3p, and hsa-miR-1246) were upregulated in COVID-19 critical patients compared with COVID-19-negative controls. Moreover, hsa-miR-32-5p and hsa-miR-1246 levels were also altered in critical versus asymptomatic individuals. Furthermore, these microRNA target genes were related to viral infection, inflammatory response, and coagulation-related processes. In conclusion, SARS-CoV-2 promotes the alteration of microRNAs targeting the expression of key proteins for viral entry and replication, and these changes are associated with disease severity. The microRNAs identified could be taken as potential biomarkers of COVID-19 progression as well as candidates for future therapeutic approaches against this disease.
2022-06-11 2022 other research-article; Journal Article abstract-available 10.1016/j.omtn.2022.06.006 Serum microRNAs targeting <i>ACE2</i> and <i>RAB14</i> genes distinguish asymptomatic from critical COVID-19 patients. Calderon-Dominguez M, Trejo-Gutierrez E, González-Rovira A, Beltrán-Camacho L, Rojas-Torres M, Eslava-Alcón S, Sanchez-Morillo D, Calderon-Dominguez J, Martinez-Nicolás MP, Gonzalez-Beitia E, Nieto-Martín MD, Trujillo-Soto T, Rodríguez-Iglesias MA, Moreno JA, Moreno-Luna R, Durán-Ruiz MC. Mol Ther Nucleic Acids. 2022; 29
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)
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)
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)
Positive airway pressure longer than 24 h is associated with histopathological volutrauma in severe COVID-19 pneumonia-an ESGFOR based narrative case-control review.
Saegeman V, Cohen MC, Abasolo L, Rello J, [...], Fernandez-Rodriguez A.
Ann Transl Med. 2022; 10 (11)
DOI: 10.21037/atm-22-605

Background and objective

A thorough understanding of the pathogenic mechanisms elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still requires further research. Until recently, only a restricted number of autopsies have been performed, therefore limiting the accurate knowledge of the lung injury associated with SARS-CoV-2. A multidisciplinary European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group of Forensic and Post-mortem Microbiology-ESGFOR team conducted a non-systematic narrative literature review among coronavirus 2019 disease (COVID-19) pneumonia cases assessing the histopathological (HP) effects of positive airways pressure. HP lung features were recorded and compared between mechanically ventilated (>24 hours) and control (ventilation <24 hours) patients. A logistic regression analysis was performed to identify associations between mechanical ventilation (MV) and HP findings.

Methods

A PubMed and MEDLINE search was conducted in order to identify studies published between March 1st 2020 and June 30th 2021.

Key content and findings

Seventy patients (median age: 69 years) from 24 studies were analysed, among whom 38 (54.2%) underwent MV longer than 24 hours. Overall, main HP features were: diffuse alveolar damage (DAD) in 53 (75.7%), fibrosis (interstitial/intra-alveolar) in 43 (61.4%), vascular damage-including thrombosis/emboli- in 41 (58.5%), and endotheliitis in only 8 (11.4%) patients. Association of DAD, fibrosis and vascular damage was detected in 30 (42.8%) patients. Multivariate analysis, adjusted by age and gender, identified MV >24 hours as an independent variable associated with DAD (OR =5.40, 95% CI: 1.48-19.62), fibrosis (OR =3.88, 95% CI: 1.25-12.08), vascular damage (OR =5.49, 95% CI: 1.78-16.95) and association of DAD plus fibrosis plus vascular damage (OR =6.99, 95% CI: 2.04-23.97).

Conclusions

We identified that patients mechanically ventilated >24 hours had a significantly higher rate of pulmonary injury on histopathology independently of age and gender. Our findings emphasize the importance of maintaining a protective ventilator strategy when subjects with COVID-19 pneumonia undergo intubation.
2022-06-01 2022 other review-article; Review; Journal Article abstract-available 10.21037/atm-22-605 Positive airway pressure longer than 24 h is associated with histopathological volutrauma in severe COVID-19 pneumonia-an ESGFOR based narrative case-control review. Saegeman V, Cohen MC, Abasolo L, Rello J, Fernandez-Gutierrez B, Fernandez-Rodriguez A. Ann Transl Med. 2022; 10 (11)
Antidepressant Drugs and COVID-19: A Review of Basic and Clinical Evidence.
Mas M, García-Vicente JA, Estrada-Gelonch A, Pérez-Mañá C, [...], Farré M.
J Clin Med. 2022; 11 (14)
DOI: 10.3390/jcm11144038
The COVID-19 pandemic has encouraged the repurposing of existing drugs as a shorter development strategy in order to support clinicians with this difficult therapeutic dilemma. There is evidence to support the theory that some antidepressants can reduce concentrations of different cytokines in humans and animals and, recently, the antiviral activity of some antidepressants against SARS-CoV-2 has been reported. The aims of this narrative review are to evaluate the possible role of antidepressants in the treatment of COVID-19 infection and the possible benefits and risks of patients taking antidepressants for mental disorders and COVID-19 infection. A review was performed to analyse the current literature to identify the role of antidepressant medication in the treatment of COVID-19 patients. The electronic search was completed in MEDLINE and MedRxiv/BioRxiv for published literature and in ClinicalTrials.gov for ongoing clinical trials. The results show some evidence from preclinical data and observational studies about the possible efficacy of some specific antidepressants for treating COVID-19 infection. In addition, two published phase II studies testing fluvoxamine showed positive results for clinical deterioration and hospitalization rate versus a placebo. Seven ongoing clinical trials testing fluvoxamine, fluoxetine, and tramadol (as per its anti-inflammatory and antidepressant effect) are still in the early phases. Although the available evidence is limited, the sum of the antiviral and anti-inflammatory preclinical studies and the results from several observational studies and two phase II clinical trials provide the basis for ongoing clinical trials evaluating the possible use of antidepressants for COVID-19 infection in humans. Further investigations will be needed to support the possible use of antidepressants for this application.
2022-07-12 2022 other review-article; Review; Journal Article abstract-available 10.3390/jcm11144038 Antidepressant Drugs and COVID-19: A Review of Basic and Clinical Evidence. Mas M, García-Vicente JA, Estrada-Gelonch A, Pérez-Mañá C, Papaseit E, Torrens M, Farré M. J Clin Med. 2022; 11 (14)
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
The Robustness of Cellular Immunity Determines the Fate of SARS-CoV-2 Infection.
Moga E, Lynton-Pons E, Domingo P.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.904686
Two years after the appearance of the SARS-CoV-2 virus, the causal agent of the current global pandemic, it is time to analyze the evolution of the immune protection that infection and vaccination provide. Cellular immunity plays an important role in limiting disease severity and the resolution of infection. The early appearance, breadth and magnitude of SARS-CoV-2 specific T cell response has been correlated with disease severity and it has been thought that T cell responses may be sufficient to clear infection with minimal disease in COVID-19 patients with X-linked or autosomal recessive agammaglobulinemia. However, our knowledge of the phenotypic and functional diversity of CD8+ cytotoxic lymphocytes, CD4+ T helper cells, mucosal-associated invariant T (MAIT) cells and CD4+ T follicular helper (Tfh), which play a critical role in infection control as well as long-term protection, is still evolving. It has been described how CD8+ cytotoxic lymphocytes interrupt viral replication by secreting antiviral cytokines (IFN-γ and TNF-α) and directly killing infected cells, negatively correlating with stages of disease progression. In addition, CD4+ T helper cells have been reported to be key pieces, leading, coordinating and ultimately regulating antiviral immunity. For instance, in some more severe COVID-19 cases a dysregulated CD4+ T cell signature may contribute to the greater production of pro-inflammatory cytokines responsible for pathogenic inflammation. Here we discuss how cellular immunity is the axis around which the rest of the immune system components revolve, since it orchestrates and leads antiviral response by regulating the inflammatory cascade and, as a consequence, the innate immune system, as well as promoting a correct humoral response through CD4+ Tfh cells. This review also analyses the critical role of cellular immunity in modulating the development of high-affinity neutralizing antibodies and germinal center B cell differentiation in memory and long-lived antibody secreting cells. Finally, since there is currently a high percentage of vaccinated population and, in some cases, vaccine booster doses are even being administered in certain countries, we have also summarized newer approaches to long-lasting protective immunity and the cross-protection of cellular immune response against SARS-CoV-2.
2022-06-27 2022 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fimmu.2022.904686 The Robustness of Cellular Immunity Determines the Fate of SARS-CoV-2 Infection. Moga E, Lynton-Pons E, Domingo P. Front Immunol. 2022; 13
Characteristics of 24 SARS-CoV-2-Sequenced Reinfection Cases in a Tertiary Hospital in Spain.
Borras-Bermejo B, Piñana M, Andrés C, Zules R, [...], Antón A.
Front Microbiol. 2022; 13
DOI: 10.3389/fmicb.2022.876409

Background

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the main concern is whether reinfections are possible, and which are the associated risk factors. This study aims to describe the clinical and molecular characteristics of 24 sequence-confirmed reinfection SARS-CoV-2 cases over 1 year in Barcelona (Catalonia, Spain).

Methods

Patients with > 45 days between two positive PCR tests regardless of symptoms and negative tests between episodes were initially considered as suspected reinfection cases from November 2020 to May 2021. Whole-genome sequencing (WGS) was performed to confirm genetic differences between consensus sequences and for phylogenetic studies based on PANGOLIN nomenclature. Reinfections were confirmed by the number of mutations, change in lineage, or epidemiological criteria.

Results

From 39 reported suspected reinfection cases, complete viral genomes could be sequenced from both episodes of 24 patients, all were confirmed as true reinfections. With a median age of 44 years (interquartile range [IQR] 32-65), 66% were women and 58% were healthcare workers (HCWs). The median days between episodes were 122 (IQR 72-199), occurring one-third within 3 months. Reinfection episodes were frequently asymptomatic and less severe than primary infections. The absence of seroconversion was associated with symptomatic reinfections. Only one case was reinfected with a variant of concern (VOC).

Conclusion

Severe acute respiratory syndrome coronavirus 2 reinfections can occur in a shorter time than previously reported and are mainly found in immunocompetent patients. Surveillance through WGS is useful to identify viral mutations associated with immune evasion.
2022-05-26 2022 other research-article; Journal Article abstract-available 10.3389/fmicb.2022.876409 Characteristics of 24 SARS-CoV-2-Sequenced Reinfection Cases in a Tertiary Hospital in Spain. Borras-Bermejo B, Piñana M, Andrés C, Zules R, González-Sánchez A, Esperalba J, Parés-Badell O, García-Cehic D, Rando A, Campos C, Codina MG, Martín MC, Castillo C, García-Comuñas K, Vásquez-Mercado R, Martins-Martins R, Colomer-Castell S, Pumarola T, Campins M, Quer J, Antón A. Front Microbiol. 2022; 13
Iron oxide and iron oxyhydroxide nanoparticles impair SARS-CoV-2 infection of cultured cells.
DeDiego ML, Portilla Y, Daviu N, López-García D, [...], Barber DF.
J Nanobiotechnology. 2022; 20 (1)
DOI: 10.1186/s12951-022-01542-2

Background

Coronaviruses usually cause mild respiratory disease in humans but as seen recently, some human coronaviruses can cause more severe diseases, such as the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the global spread of which has resulted in the ongoing coronavirus pandemic.

Results

In this study we analyzed the potential of using iron oxide nanoparticles (IONPs) coated with biocompatible molecules like dimercaptosuccinic acid (DMSA), 3-aminopropyl triethoxysilane (APS) or carboxydextran (FeraSpin™ R), as well as iron oxyhydroxide nanoparticles (IOHNPs) coated with sucrose (Venofer®), or iron salts (ferric ammonium citrate -FAC), to treat and/or prevent SARS-CoV-2 infection. At non-cytotoxic doses, IONPs and IOHNPs impaired virus replication and transcription, and the production of infectious viruses in vitro, either when the cells were treated prior to or after infection, although with different efficiencies. Moreover, our data suggest that SARS-CoV-2 infection affects the expression of genes involved in cellular iron metabolism. Furthermore, the treatment of cells with IONPs and IOHNPs affects oxidative stress and iron metabolism to different extents, likely influencing virus replication and production. Interestingly, some of the nanoparticles used in this work have already been approved for their use in humans as anti-anemic treatments, such as the IOHNP Venofer®, and as contrast agents for magnetic resonance imaging in small animals like mice, such as the FeraSpin™ R IONP.

Conclusions

Therefore, our results suggest that IONPs and IOHNPs may be repurposed to be used as prophylactic or therapeutic treatments in order to combat SARS-CoV-2 infection.
2022-07-30 2022 other research-article; Journal Article abstract-available 10.1186/s12951-022-01542-2 Iron oxide and iron oxyhydroxide nanoparticles impair SARS-CoV-2 infection of cultured cells. DeDiego ML, Portilla Y, Daviu N, López-García D, Villamayor L, Mulens-Arias V, Ovejero JG, Gallo-Cordova Á, Veintemillas-Verdaguer S, Morales MP, Barber DF. J Nanobiotechnology. 2022; 20 (1)
Anti-ACTH antibodies in critically ill Covid-19 patients: A potential immune evasion mechanism of SARS-CoV-2.
Pérez-Torres D, Díaz-Rodríguez C, Armentia-Medina A.
Med Intensiva (Engl Ed). 2022; 46 (8)
DOI: 10.1016/j.medine.2021.09.001
2022-08-01 2022 other Case Reports; case-report 10.1016/j.medine.2021.09.001 Anti-ACTH antibodies in critically ill Covid-19 patients: A potential immune evasion mechanism of SARS-CoV-2. Pérez-Torres D, Díaz-Rodríguez C, Armentia-Medina A. Med Intensiva (Engl Ed). 2022; 46 (8)
Inanimate Surfaces as a Source of Hospital Infections Caused by Fungi, Bacteria and Viruses with Particular Emphasis on SARS-CoV-2.
Jabłońska-Trypuć A, Makuła M, Włodarczyk-Makuła M, Wołejko E, [...], Wiater J.
Int J Environ Res Public Health. 2022; 19 (13)
DOI: 10.3390/ijerph19138121
The carriers of nosocomial infections are the hands of medical personnel and inanimate surfaces. Both hands and surfaces may be contaminated as a result of contact with the patient, their body fluids, and touching contaminated surfaces in the patient's surroundings. Visually clean inanimate surfaces are an important source of pathogens. Microorganisms have properties thanks to which they can survive in unfavorable conditions, from a few days to several months. Bacteria, viruses and fungi are able to transmit from inanimate surfaces to the skin of the patient and the medical staff. These pathogens include SARS-CoV-2, which can survive on various types of inanimate surfaces, being a potential source of infection. By following the recommendations related to washing and disinfecting hands and surfaces, and using appropriate washing and disinfecting agents with a broad biocidal spectrum, high material compatibility and the shortest duration of action, we contribute to breaking the chain of nosocomial infections.
2022-07-01 2022 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3390/ijerph19138121 Inanimate Surfaces as a Source of Hospital Infections Caused by Fungi, Bacteria and Viruses with Particular Emphasis on SARS-CoV-2. Jabłońska-Trypuć A, Makuła M, Włodarczyk-Makuła M, Wołejko E, Wydro U, Serra-Majem L, Wiater J. Int J Environ Res Public Health. 2022; 19 (13)
Sensitive SARS-CoV-2 detection in wastewaters using a carbon nanodot-amplified electrochemiluminescence immunosensor.
Guerrero-Esteban T, Gutiérrez-Sánchez C, Villa-Manso AM, Revenga-Parra M, [...], Lorenzo E.
Talanta. 2022; 247
DOI: 10.1016/j.talanta.2022.123543
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.
2022-05-13 2022 other research-article; Journal Article abstract-available 10.1016/j.talanta.2022.123543 Sensitive SARS-CoV-2 detection in wastewaters using a carbon nanodot-amplified electrochemiluminescence immunosensor. Guerrero-Esteban T, Gutiérrez-Sánchez C, Villa-Manso AM, Revenga-Parra M, Pariente F, Lorenzo E. Talanta. 2022; 247
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
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)
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
Evolution of SARS-CoV-2 in Spain during the First Two Years of the Pandemic: Circulating Variants, Amino Acid Conservation, and Genetic Variability in Structural, Non-Structural, and Accessory Proteins.
Troyano-Hernáez P, Reinosa R, Holguín Á.
Int J Mol Sci. 2022; 23 (12)
DOI: 10.3390/ijms23126394
Monitoring SARS-CoV-2's genetic diversity and emerging mutations in this ongoing pandemic is crucial to understanding its evolution and ensuring the performance of COVID-19 diagnostic tests, vaccines, and therapies. Spain has been one of the main epicenters of COVID-19, reaching the highest number of cases and deaths per 100,000 population in Europe at the beginning of the pandemic. This study aims to investigate the epidemiology of SARS-CoV-2 in Spain and its 18 Autonomous Communities across the six epidemic waves established from February 2020 to January 2022. We report on the circulating SARS-CoV-2 variants in each epidemic wave and Spanish region and analyze the mutation frequency, amino acid (aa) conservation, and most frequent aa changes across each structural/non-structural/accessory viral protein among the Spanish sequences deposited in the GISAID database during the study period. The overall SARS-CoV-2 mutation frequency was 1.24 × 10-5. The aa conservation was >99% in the three types of protein, being non-structural the most conserved. Accessory proteins had more variable positions, while structural proteins presented more aa changes per sequence. Six main lineages spread successfully in Spain from 2020 to 2022. The presented data provide an insight into the SARS-CoV-2 circulation and genetic variability in Spain during the first two years of the pandemic.
2022-06-07 2022 other research-article; Journal Article abstract-available 10.3390/ijms23126394 Evolution of SARS-CoV-2 in Spain during the First Two Years of the Pandemic: Circulating Variants, Amino Acid Conservation, and Genetic Variability in Structural, Non-Structural, and Accessory Proteins. Troyano-Hernáez P, Reinosa R, Holguín Á. Int J Mol Sci. 2022; 23 (12)
Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice.
Tarrés-Freixas F, Trinité B, Pons-Grífols A, Romero-Durana M, [...], Blanco J.
Front Microbiol. 2022; 13
DOI: 10.3389/fmicb.2022.840757
The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2.
2022-05-04 2022 other research-article; Journal Article abstract-available 10.3389/fmicb.2022.840757 Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice. Tarrés-Freixas F, Trinité B, Pons-Grífols A, Romero-Durana M, Riveira-Muñoz E, Ávila-Nieto C, Pérez M, Garcia-Vidal E, Perez-Zsolt D, Muñoz-Basagoiti J, Raïch-Regué D, Izquierdo-Useros N, Andrés C, Antón A, Pumarola T, Blanco I, Noguera-Julián M, Guallar V, Lepore R, Valencia A, Urrea V, Vergara-Alert J, Clotet B, Ballana E, Carrillo J, Segalés J, Blanco J. Front Microbiol. 2022; 13
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 Support, Non-U.S. Gov't; 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
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)
SARS-CoV-2 infection at the Huanan seafood market.
Courtier-Orgogozo V, de Ribera FA.
Environ Res. 2022; 214 (Pt 1)
DOI: 10.1016/j.envres.2022.113702
The Huanan market harbored many of the early COVID-19 cases in 2019 and is a key element to understanding the origin of the pandemic. Whether the initial animal-to-human transmission did occur at this market is still debated. Here we do not examine how SARS-CoV-2 virus was introduced at the market, but focus on how early cases may have been infected at the market. Based on available evidence, we suggest that several early infections at the Huanan market may have occurred via human-to-human transmission in closed spaces such as canteens, Mahjong rooms or toilets. We advocate for further studies to investigate this hypothesis.
2022-06-22 2022 other research-article; Journal Article abstract-available 10.1016/j.envres.2022.113702 SARS-CoV-2 infection at the Huanan seafood market. Courtier-Orgogozo V, de Ribera FA. Environ Res. 2022; 214 (Pt 1)
Analysis of pancreatic function in pediatric patients with COVID-19 Análisis de la función pancreática en pacientes pediátricos con COVID-19
Molina Gutiérrez M, Alcázar Villar M, Ruíz Domínguez J, Sagastizábal Cardelús B, [...], .
An Pediatr (Engl Ed). 2022;
DOI:
2022-07-28 2022 other Case Reports; case-report Analysis of pancreatic function in pediatric patients with COVID-19 Análisis de la función pancreática en pacientes pediátricos con COVID-19 Molina Gutiérrez M, Alcázar Villar M, Ruíz Domínguez J, Sagastizábal Cardelús B, García Cuartero B, . An Pediatr (Engl Ed). 2022;
Comparative effectiveness of N95, surgical or medical, and non-medical facemasks in protection against respiratory virus infection: A systematic review and network meta-analysis.
Kim MS, Seong D, Li H, Chung SK, [...], Smith L.
Rev Med Virol. 2022;
DOI: 10.1002/rmv.2336
The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask-wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23-0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20-0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID-19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings.
2022-02-26 2022 other review-article; Review; Journal Article abstract-available 10.1002/rmv.2336 Comparative effectiveness of N95, surgical or medical, and non-medical facemasks in protection against respiratory virus infection: A systematic review and network meta-analysis. Kim MS, Seong D, Li H, Chung SK, Park Y, Lee M, Lee SW, Yon DK, Kim JH, Lee KH, Solmi M, Dragioti E, Koyanagi A, Jacob L, Kronbichler A, Tizaoui K, Cargnin S, Terrazzino S, Hong SH, Abou Ghayda R, Radua J, Oh H, Kostev K, Ogino S, Lee IM, Giovannucci E, Barnett Y, Butler L, McDermott D, Ilie PC, Shin JI, Smith L. Rev Med Virol. 2022;
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)
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;
Pharmacology of COVID-19.
Sureda A, Habtemariam S, Nabavi SM.
Chem Biol Interact. 2022; 362
DOI: 10.1016/j.cbi.2022.110005
2022-05-31 2022 other Editorial 10.1016/j.cbi.2022.110005 Pharmacology of COVID-19. Sureda A, Habtemariam S, Nabavi SM. Chem Biol Interact. 2022; 362
SARS-CoV-2 Spike Protein Vaccine-Induced Immune Imprinting Reduces Nucleocapsid Protein Antibody Response in SARS-CoV-2 Infection.
Delgado JF, Vidal-Pla M, Moya MC, Espasa M, [...], Peña P.
J Immunol Res. 2022; 2022
DOI: 10.1155/2022/8287087
Immune imprinting or original antigenic sin (OAS) is the process by which the humoral memory response to an antigen can inhibit the response to new epitopes of that antigen originating from a second encounter with the pathogen. Given the situation of the COVID-19 pandemic, multiple vaccines have been developed against SARS-CoV-2 infection. These vaccines are directed to the spike protein (S protein) of the original variant of Wuhan D614G. Vaccine memory immune response against S protein in noninfected subjects could inhibit, through the OAS mechanism, the response to new epitopes of SARS-CoV-2 after infection. The present study analyzes whether the memory antibody B cell response generated by mRNA vaccines against S protein can inhibit the primary antibody immune response to other SARS-CoV-2 antigens, such as nucleocapsid protein (N protein). SARS-CoV-2 primary infection in vaccinated healthcare workers (HCWs) produced significantly lower titers of anti-N antibodies than that in nonvaccinated HCWs: 5.7 (IQR 2.3-15.2) versus 12.2 (IQR 4.2-32.0), respectively (p = 0.005). Therefore, spike protein vaccine-induced immune imprinting (original antigenic sin) reduces N protein antibody response.
2022-07-29 2022 other research-article; Journal Article abstract-available 10.1155/2022/8287087 SARS-CoV-2 Spike Protein Vaccine-Induced Immune Imprinting Reduces Nucleocapsid Protein Antibody Response in SARS-CoV-2 Infection. Delgado JF, Vidal-Pla M, Moya MC, Espasa M, Casabella A, Seda M, Calvet J, Gratacós J, Serrano RM, Peña P. J Immunol Res. 2022; 2022
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 DC.
Int J Environ Res Public Health. 2022; 19 (9)
DOI: 10.3390/ijerph19095400
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 Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3390/ijerph19095400 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 DC. Int J Environ Res Public Health. 2022; 19 (9)
Efficacy of repurposed antiviral drugs: Lessons from COVID-19.
Martinez MA.
Drug Discov Today. 2022; 27 (7)
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 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; 27 (7)
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)
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
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 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)
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
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)
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)
Varicella-Zoster virus reactivation following severe acute respiratory syndrome coronavirus 2 vaccination or infection: New insights.
Martinez-Reviejo R, Tejada S, Adebanjo GAR, Chello C, [...], Rello J.
Eur J Intern Med. 2022;
DOI: 10.1016/j.ejim.2022.07.022

Introduction

Varicella zoster virus (VZV) reactivation has been reported following vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the real extent remains unknown.

Methods

We conducted a systematic review to summarize evidence of VZV reactivation or infection following SARS-CoV-2 vaccination. Episodes after coronavirus disease-2019 (COVID-19) were also identified. Related articles were identified in PubMed and EMBASE databases till December 31, 2021 using the terms "varicella zoster" and "COVID-19″. PROSPERO Register Number: CRD42021289399.

Results

The search revealed 314 articles, of which 55 met the inclusion criteria. VZV manifestations were documented in 179 (82.1%) subjects following SARS-CoV-2 vaccination and in 39 (17.9%) patients with COVID-19. Among the vaccinated, median (IQR) age was 56.5 (42-70) years, and 56.8% were female. Twenty-one (16.8%) were immunosuppressed. The median (IQR) latency time after vaccination was 6 (3-10) days, and 84.4% received mRNA vaccines. VZV reactivation occurred following a first dose (68.2%), a second dose (12.8%) or a booster (0.6%). The most important VZV manifestation was dermatome herpes zoster rash, which accounted for 86.4% of events in vaccinated subjects. Twenty patients (11.3%) presented serious VZV events after vaccination, with Herpes Zoster ophthalmicus (5.6%) and post-herpetic neuralgia (3.4%) predominating. No VZV pneumonia or deaths were recorded. Antiviral prescriptions were made in 96.2% of vaccinated subjects. No significant differences between vaccinated and infected subjects were found.

Conclusion

This study indicates that the occurrence of VZV reactivation is clinically relevant. However, our findings suggest that COVID-19 vaccination is safe, and remains strongly recommended.
2022-08-01 2022 other research-article; Journal Article abstract-available 10.1016/j.ejim.2022.07.022 Varicella-Zoster virus reactivation following severe acute respiratory syndrome coronavirus 2 vaccination or infection: New insights. Martinez-Reviejo R, Tejada S, Adebanjo GAR, Chello C, Machado MC, Parisella FR, Campins M, Tammaro A, Rello J. Eur J Intern Med. 2022;
[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)
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
SARS-CoV-2 Transmission by Arthropod Vectors: A Scoping Review
Nekoei S, Khamesipour F, Benchimol M, Bueno-Marí R, [...], Ommi D.
Biomed Res Int. 2022; 2022
DOI:
COVID-19 is a respiratory disease of worldwide importance as it has brought enormous health problems to the world's population. The best-known way of transmission of the virus is through aerosolization. However, research is needed to explore other transmission routes. Researchers hypothesized that arthropods could transmit SARs-CoV-2. This study is aimed at reviewing research on arthropods as possible reservoirs and/or vectors of SARS-CoV-2, the causative agent of COVID-19. Following PRISMA guidelines, we conducted a systematic review using several electronic databases/academic searches with the search terms “arthropods,” “coronavirus,” and “transmission.” A total of 64 unique articles were identified, of which 58 were included in the review. The SARS-CoV-2 virus is tiny and invisible to the naked eye, and its presence in stools, droplets, and surfaces was detected. One doubt is whether insects can transmit the virus from one place to another. Thus, a healthy carrier of the COVID-19 virus can be at the root of the contamination of their community or their family through the transport of the virus by insects from the interior (flies, cockroaches, etc.) from their feces and food surfaces. Hygiene care within communities and families becomes a prime factor. Coronavirus infection is a significant public health problem around the world. The prevention and control of outbreaks remain very important, even with the production of new vaccines. The main option to achieve this is the proper management of the transmission of the virus. The registry of infected people is currently the basis for the transmission of COVID-19. However, questions about the possibility of infection from other sources and its prevention are not receiving adequate attention. Numerous studies have shown the possibility that SARS-COV-2 fragments could have a longer life than shed respiratory droplets. Also, this virus is larger than those of other coronavirus families.
2022-01-01 2022 other review-article; Review; Journal Article abstract-available SARS-CoV-2 Transmission by Arthropod Vectors: A Scoping Review Nekoei S, Khamesipour F, Benchimol M, Bueno-Marí R, Ommi D. Biomed Res Int. 2022; 2022
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)
SARS-CoV2 Infection During Pregnancy Causes Persistent Immune Abnormalities in Women Without Affecting the Newborns.
Vazquez-Alejo E, Tarancon-Diez L, Carrasco I, Vigil-Vázquez S, [...], Muñoz-Fernández MÁ.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.947549
SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.
2022-07-14 2022 other research-article; Journal Article abstract-available 10.3389/fimmu.2022.947549 SARS-CoV2 Infection During Pregnancy Causes Persistent Immune Abnormalities in Women Without Affecting the Newborns. Vazquez-Alejo E, Tarancon-Diez L, Carrasco I, Vigil-Vázquez S, Muñoz-Chapuli M, Rincón-López E, Saavedra-Lozano J, Santos-Sebastián M, Aguilera-Alonso D, Hernanz-Lobo A, Santiago-García B, de León-Luis JA, Muñoz P, Sánchez-Luna M, Navarro ML, Muñoz-Fernández MÁ. Front Immunol. 2022; 13
Ozone treatment effectively eliminates SARS-CoV-2 from infected face masks.
Córdoba-Lanús E, García-Pérez O, Rodríguez-Esparragón F, Bethencourt-Estrella CJ, [...], Lorenzo-Morales J.
PLoS One. 2022; 17 (7)
DOI: 10.1371/journal.pone.0271826
The current COVID-19 pandemic is causing profound health, economic, and social problems worldwide. The global shortage of medical and personal protective equipment (PPE) in specialized centers during the outbreak demonstrated the need for efficient methods to disinfect and recycle them in times of emergency. We have previously described that high ozone concentrations destroyed viral RNA in an inactivated SARS-CoV-2 strain within a few minutes. However, the efficient ozone dosages for active SARS-CoV-2 are still unknown. The present study aimed to evaluate the systematic effects of ozone exposure on face masks from hospitalized patients infected with SARS-CoV-2. Face masks from COVID-19 patients were collected and treated with a clinical ozone generator at high ozone concentrations in small volumes for short periods. The study focused on SARS-CoV-2 gene detection (assessed by real-time quantitative polymerase chain reaction (RT-qPCR)) and on the virus inactivation by in vitro studies. We assessed the effects of different high ozone concentrations and exposure times on decontamination efficiency. We showed that high ozone concentrations (10,000, 2,000, and 4,000 ppm) and short exposure times (10, 10, and 2 minutes, respectively), inactivated both the original strain and the B.1.1.7 strain of SARS-CoV-2 from 24 contaminated face masks from COVID-19 patients. The validation results showed that the best condition for SARS-CoV-2 inactivation was a treatment of 4,000 ppm of ozone for 2 minutes. Further studies are in progress to advance the potential applications of these findings.
2022-07-22 2022 fondo-covid Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1371/journal.pone.0271826 Ozone treatment effectively eliminates SARS-CoV-2 from infected face masks. Córdoba-Lanús E, García-Pérez O, Rodríguez-Esparragón F, Bethencourt-Estrella CJ, Torres-Mata LB, Blanco A, Villar J, Sanz O, Díaz JJ, Martín-Barrasa JL, Serrano-Aguilar P, Piñero JE, Clavo B, Lorenzo-Morales J. PLoS One. 2022; 17 (7)
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; 94 (8)
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.
2022-04-27 2022 other Research Support, Non-U.S. Gov't; 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; 94 (8)
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)
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)
COVID-19 mRNA vaccines have no effect on endometrial receptivity after euploid embryo transfer.
Brandão P, Pellicer A, Meseguer M, Remohí J, [...], García-Velasco JA.
Reprod Biomed Online. 2022;
DOI: 10.1016/j.rbmo.2022.05.017

Research question

Does the COVID-19 vaccination affect endometrial receptivity after single euploid embryo transfer, measured by sustained implantation rate?

Design

A retrospective cohort study analysing two groups of single euploid embryo transfers using own oocytes: one historical cohort of 3272 transfers 1 year before the pandemic; and one comprising 890 transfers in women previously vaccinated with mRNA vaccines against severe acute respiratory syndrome coronavirus 2. The main outcomes were clinical pregnancy rate (CPR) and sustained implantation rate (SIR) per embryo transfer. These outcomes were compared between non-vaccinated and vaccinated women, and women who had received one and two doses. Lastly, vaccinated women were divided into quartiles according to the time from last dose to embryo transfer.

Results

Similar CPR and SIR were found between non-vaccinated and vaccinated women, and the odds ratio for both outcomes was not statistically significant after being controlled for potential confounders (OR 0.937, 95% CI 0.695 to 1.265 and OR 0.910, 95% CI 0.648 to 1.227 respectively). Within the vaccinated group, women who had received one or two doses also had similar outcomes. In addition, no differences were found according to the time interval from vaccination to embryo transfer.

Conclusion

The administration of mRNA vaccines against COVID-19 had no effect on endometrial receptivity and embryo implantation, regardless of the number of doses and time interval from vaccination to embryo transfer. The potential negative effect of the vaccine on endometrial receptivity and reproductive outcomes is reassuring for patients in the process of undergoing assisted reproductive treatment.
2022-05-29 2022 other research-article; Journal Article abstract-available 10.1016/j.rbmo.2022.05.017 COVID-19 mRNA vaccines have no effect on endometrial receptivity after euploid embryo transfer. Brandão P, Pellicer A, Meseguer M, Remohí J, Garrido N, García-Velasco JA. Reprod Biomed Online. 2022;
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)
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
Associated-Onset Symptoms and Post-COVID-19 Symptoms in Hospitalized COVID-19 Survivors Infected with Wuhan, Alpha or Delta SARS-CoV-2 Variant.
Fernández-de-Las-Peñas C, Cancela-Cilleruelo I, Rodríguez-Jiménez J, Gómez-Mayordomo V, [...], Torres-Macho J.
Pathogens. 2022; 11 (7)
DOI: 10.3390/pathogens11070725
This study compared associated-symptoms at the acute phase of infection and post-COVID-19 symptoms between individuals hospitalized with the Wuhan, Alpha or Delta SARS-CoV-2 variant. Non-vaccinated individuals hospitalized because of SARS-CoV-2 infection in one hospital during three different waves of the pandemic (Wuhan, Alpha or Delta) were scheduled for a telephone interview. The presence of post-COVID-19 symptoms was systematically assessed. Hospitalization and clinical data were collected from medical records. A total of 201 patients infected with the Wuhan variant, 211 with the Alpha variant and 202 with Delta variant were assessed six months after hospitalization. Patients infected with the Wuhan variant had a greater number of symptoms at hospital admission (higher prevalence of fever, dyspnea or gastrointestinal problems) than those infected with Alpha or Delta variant (p < 0.01). A greater proportion of patients infected with the Delta variant reported headache, anosmia or ageusia as onset symptoms (p < 0.01). The mean number of post-COVID-19 symptoms was higher (p < 0.001) in individuals infected with the Wuhan variant (mean: 2.7 ± 1.3) than in those infected with the Alpha (mean: 1.8 ± 1.1) or Delta (mean: 2.1 ± 1.5) variant. Post-COVID-19 dyspnea was more prevalent (p < 0.001) in people infected with the Wuhan variant, whereas hair loss was higher in those infected with the Delta variant (p = 0.002). No differences in post-COVID-19 fatigue by SARS-CoV-2 variant were found (p = 0.594). Differences in COVID-19 associated onset symptoms and post-COVID-19 dyspnea were observed depending on the SARS-CoV-2 variant. The presence of fatigue was a common post-COVID-19 symptom to all SARS-CoV-2 variants.
2022-06-25 2022 other research-article; Journal Article abstract-available 10.3390/pathogens11070725 Associated-Onset Symptoms and Post-COVID-19 Symptoms in Hospitalized COVID-19 Survivors Infected with Wuhan, Alpha or Delta SARS-CoV-2 Variant. Fernández-de-Las-Peñas C, Cancela-Cilleruelo I, Rodríguez-Jiménez J, Gómez-Mayordomo V, Pellicer-Valero OJ, Martín-Guerrero JD, Hernández-Barrera V, Arendt-Nielsen L, Torres-Macho J. Pathogens. 2022; 11 (7)
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)
Factors affecting climacteric women with SARS-CoV-2 infection: A multinational Latin America study (REDLINC XI).
Vallejo MS, Blümel JE, Bencosme A, Calle A, [...], Pérez-López FR.
Maturitas. 2022; 165
DOI: 10.1016/j.maturitas.2022.07.006

Objective

To evaluate the association between factors, especially those linked to the climacteric, and a history of COVID-19 infection.

Methods

This was an observational, cross-sectional, and analytical study in which women from ten Latin American countries, aged 40-64, who attended a routine health check-up were invited to participate. A positive history for COVID-19 was based on reverse transcription-polymerase chain reaction reports. We evaluated sociodemographic, clinical, lifestyle, anthropometric variables, and menopausal symptoms using the Menopause Rating Scale (MRS).

Results

A total of 1238 women were included for analysis, of whom 304 (24.6 %) had a positive history for COVID-19. The median [interquartile range: IQR] age of participants was 53 [IQR 12] years, duration of formal education was 16 [6] years, body mass index 25.6 [5.1] kg/m2, and total MRS score 10 [13]. In a logistic regression model, factors positively associated with COVID-19 included postmenopausal status and having a family history of dementia (OR: 1.53; 95 % CI: 1.13-2.07, and 2.40; 1.65-3.48, respectively), whereas negatively associated were use of menopausal hormone therapy (current or past), being a housewife, and being nulliparous (OR: 0.47; 95 % CI: 0.30-0.73; 0.72; 0.53-0.97 and 0.56; 0.34-0.92, respectively). Smoking, being sexually active, and use of hypnotics were also factors positively associated with COVID-19.

Conclusion

Postmenopausal status and a family history of dementia were more frequent among women who had had COVID-19, and the infection was less frequent among current or past menopause hormone therapy users and in those with less physical contact.
2022-07-22 2022 other research-article; Journal Article abstract-available 10.1016/j.maturitas.2022.07.006 Factors affecting climacteric women with SARS-CoV-2 infection: A multinational Latin America study (REDLINC XI). Vallejo MS, Blümel JE, Bencosme A, Calle A, Dextre M, Díaz K, López M, Miranda C, Ñañez M, Ojeda E, Rey C, Rodrigues MA, Salinas C, Tserotas K, Pérez-López FR. Maturitas. 2022; 165
Major Histocompatibility Complex Class I Chain-Related α (MICA) STR Polymorphisms in COVID-19 Patients.
Gutiérrez-Bautista JF, Martinez-Chamorro A, Rodriguez-Nicolas A, Rosales-Castillo A, [...], Ruiz-Cabello F.
Int J Mol Sci. 2022; 23 (13)
DOI: 10.3390/ijms23136979
The SARS-CoV-2 disease presents different phenotypes of severity. Comorbidities, age, and being overweight are well established risk factors for severe disease. However, innate immunity plays a key role in the early control of viral infections and may condition the gravity of COVID-19. Natural Killer (NK) cells are part of innate immunity and are important in the control of virus infection by killing infected cells and participating in the development of adaptive immunity. Therefore, we studied the short tandem repeat (STR) transmembrane polymorphisms of the major histocompatibility complex class I chain-related A (MICA), an NKG2D ligand that induces activation of NK cells, among other cells. We compared the alleles and genotypes of MICA in COVID-19 patients versus healthy controls and analyzed their relation to disease severity. Our results indicate that the MICA*A9 allele is related to infection as well as to symptomatic disease but not to severe disease. The MICA*A9 allele may be a risk factor for SARS-CoV-2 infection and symptomatic disease.
2022-06-23 2022 other research-article; Journal Article abstract-available 10.3390/ijms23136979 Major Histocompatibility Complex Class I Chain-Related α (MICA) STR Polymorphisms in COVID-19 Patients. Gutiérrez-Bautista JF, Martinez-Chamorro A, Rodriguez-Nicolas A, Rosales-Castillo A, Jiménez P, Anderson P, López-Ruz MÁ, López-Nevot MÁ, Ruiz-Cabello F. Int J Mol Sci. 2022; 23 (13)
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
"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)
Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection.
Yang CX, Tomchaney M, Landecho MF, Zamacona BR, [...], Polverino F.
Cells. 2022; 11 (12)
DOI: 10.3390/cells11121864
People with pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19). Still, an interrogation of the immune response to COVID-19 infection, spatially throughout the lung structure, is lacking in patients with COPD. For this study, we characterized the immune microenvironment of the lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, all of whom died of COVID-19, using spatial transcriptomic and proteomic profiling. The parenchyma, airways, and vessels of COPD patients, compared to control lungs had (1) significant enrichment for lung-resident CD45RO+ memory CD4+ T cells; (2) downregulation of genes associated with T cell antigen priming and memory T cell differentiation; and (3) higher expression of proteins associated with SARS-CoV-2 entry and primary receptor ubiquitously across the ROIs and in particular the lung parenchyma, despite similar SARS-CoV-2 structural gene expression levels. In conclusion, the lung parenchyma, airways, and vessels of COPD patients have increased T-lymphocytes with a blunted memory CD4 T cell response and a more invasive SARS-CoV-2 infection pattern and may underlie the higher death toll observed with COVID-19.
2022-06-07 2022 other research-article; Journal Article; Research Support, N.I.H., Extramural abstract-available 10.3390/cells11121864 Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection. Yang CX, Tomchaney M, Landecho MF, Zamacona BR, Marin Oto M, Zulueta J, Malo J, Knoper S, Contoli M, Papi A, Vasilescu DM, Sauler M, Straub C, Tan C, Martinez FD, Bhattacharya D, Rosas IO, Kheradmand F, Hackett TL, Polverino F. Cells. 2022; 11 (12)
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)
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)
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)
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
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; 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;
The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: The case of the spike A222V mutation.
Ginex T, Marco-Marín C, Wieczór M, Mata CP, [...], Carazo JM.
PLoS Pathog. 2022; 18 (7)
DOI: 10.1371/journal.ppat.1010631
The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has since reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness.
2022-07-11 2022 fondo-covid research-article; Journal Article abstract-available 10.1371/journal.ppat.1010631 The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: The case of the spike A222V mutation. Ginex T, Marco-Marín C, Wieczór M, Mata CP, Krieger J, Ruiz-Rodriguez P, López-Redondo ML, Francés-Gómez C, Melero R, Sánchez-Sorzano CÓ, Martínez M, Gougeard N, Forcada-Nadal A, Zamora-Caballero S, Gozalbo-Rovira R, Sanz-Frasquet C, Arranz R, Bravo J, Rubio V, Marina A, IBV-Covid19-Pipeline, Geller R, Comas I, Gil C, Coscolla M, Orozco M, Llácer JL, Carazo JM. PLoS Pathog. 2022; 18 (7)
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; research-article; 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)
Oral antivirals for the prevention and treatment of SARS-CoV-2 infection.
Soriano V, de-Mendoza C, Edagwa B, Treviño A, [...], Gendelman HE.
AIDS Rev. 2022; 24 (1)
DOI: 10.24875/aidsrev.22000001
Vaccines and antivirals are the classical weapons deployed to contain, prevent, and treat life-threatening viral illnesses. Specifically, for SARS-CoV-2 infection, vaccines protect against severe COVID-19 disease manifestations and complications. However, waning immunity and emergence of vaccine escape mutants remains a growing threat. This is highlighted by the current surge of the omicron COVID-19 variant. Thus, there is a race to find treatment alternatives. We contend that oral small molecule antivirals that halt SARSCoV- 2 infection are essential. Compared to currently available monoclonal antibodies and remdesivir, where parenteral administration is required, oral antivirals offer treatments in an outpatient setting with dissemination available on a larger scale. In response to this need at 2021's end, regulatory agencies provided emergency use authorization for both molnupiravir and nirmatrelvir. These medicines act on the viral polymerase and protease, respectively. Each is given for 5 days and can reduce disease progression by 30% and 89%, respectively. The advent of additional oral antivirals, the assessment of combination therapies, the formulation of extended-release medications, and their benefit for both early treatment and prophylaxis will likely transform the landscape of the COVID-19 pandemic.
2022-03-01 2022 other research-article; Journal Article abstract-available 10.24875/aidsrev.22000001 Oral antivirals for the prevention and treatment of SARS-CoV-2 infection. Soriano V, de-Mendoza C, Edagwa B, Treviño A, Barreiro P, Fernandez-Montero JV, Gendelman HE. AIDS Rev. 2022; 24 (1)
The Other Side of SARS-CoV-2 Infection: Neurological Sequelae in Patients.
Alonso-Bellido IM, Bachiller S, Vázquez G, Cruz-Hernández L, [...], Ruiz R.
Front Aging Neurosci. 2021; 13
DOI: 10.3389/fnagi.2021.632673
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the globe causing coronavirus disease 2019 (COVID-19). Because it affects the respiratory system, common symptoms are cough and breathing difficulties with fever and fatigue. Also, some cases progress to acute respiratory distress syndrome (ARDS). The acute phase of COVID-19 has been also related to nervous system symptoms, including loss of taste and smell as well as encephalitis and cerebrovascular disorders. However, it remains unclear if neurological complications are due to the direct viral infection of the nervous system, or they appear as a consequence of the immune reaction against the virus in patients who presented pre-existing deficits or had a certain detrimental immune response. Importantly, the medium and long-term consequences of the infection by SARS-CoV-2 in the nervous system remain at present unknown. This review article aims to give an overview of the current neurological symptoms associated with COVID-19, as well as attempting to provide an insight beyond the acute affectation.
2021-04-06 2021 other research-article; Journal Article abstract-available 10.3389/fnagi.2021.632673 The Other Side of SARS-CoV-2 Infection: Neurological Sequelae in Patients. Alonso-Bellido IM, Bachiller S, Vázquez G, Cruz-Hernández L, Martínez E, Ruiz-Mateos E, Deierborg T, Venero JL, Real LM, Ruiz R. Front Aging Neurosci. 2021; 13
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 fondo-covid Research Support, Non-U.S. Gov't; 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
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 Support, Non-U.S. Gov't; 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
Mapping the Serum Proteome of COVID-19 Patients; Guidance for Severity Assessment.
Nuñez E, Orera I, Carmona-Rodríguez L, Paño JR, [...], Corrales FJ.
Biomedicines. 2022; 10 (7)
DOI: 10.3390/biomedicines10071690
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), whose outbreak in 2019 led to an ongoing pandemic with devastating consequences for the global economy and human health. According to the World Health Organization, COVID-19 has affected more than 481 million people worldwide, with 6 million confirmed deaths. The joint efforts of the scientific community have undoubtedly increased the pace of production of COVID-19 vaccines, but there is still so much uncharted ground to cover regarding the mechanisms of SARS-CoV-2 infection, replication and host response. These issues can be approached by proteomics with unprecedented capacity paving the way for the development of more efficient strategies for patient care. In this study, we present a deep proteome analysis that has been performed on a cohort of 72 COVID-19 patients aiming to identify serum proteins assessing the dynamics of the disease at different age ranges. A panel of 53 proteins that participate in several functions such as acute-phase response and inflammation, blood coagulation, cell adhesion, complement cascade, endocytosis, immune response, oxidative stress and tissue injury, have been correlated with patient severity, suggesting a molecular basis for their clinical stratification. Eighteen protein candidates were further validated by targeted proteomics in an independent cohort of 84 patients including a group of individuals that had satisfactorily resolved SARS-CoV-2 infection. Remarkably, all protein alterations were normalized 100 days after leaving the hospital, which further supports the reliability of the selected proteins as hallmarks of COVID-19 progression and grading. The optimized protein panel may prove its value for optimal severity assessment as well as in the follow up of COVID-19 patients.
2022-07-13 2022 other research-article; Journal Article abstract-available 10.3390/biomedicines10071690 Mapping the Serum Proteome of COVID-19 Patients; Guidance for Severity Assessment. Nuñez E, Orera I, Carmona-Rodríguez L, Paño JR, Vázquez J, Corrales FJ. Biomedicines. 2022; 10 (7)
Neuroimmune disorders in COVID-19.
Ariño H, Heartshorne R, Michael BD, Nicholson TR, [...], Vogrig A.
J Neurol. 2022; 269 (6)
DOI: 10.1007/s00415-022-11050-w
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the aetiologic agent of the coronavirus disease 2019 (COVID-19), is now rapidly disseminating throughout the world with 147,443,848 cases reported so far. Around 30-80% of cases (depending on COVID-19 severity) are reported to have neurological manifestations including anosmia, stroke, and encephalopathy. In addition, some patients have recognised autoimmune neurological disorders, including both central (limbic and brainstem encephalitis, acute disseminated encephalomyelitis [ADEM], and myelitis) and peripheral diseases (Guillain-Barré and Miller Fisher syndrome). We systematically describe data from 133 reported series on the Neurology and Neuropsychiatry of COVID-19 blog ( https://blogs.bmj.com/jnnp/2020/05/01/the-neurology-and-neuropsychiatry-of-covid-19/ ) providing a comprehensive overview concerning the diagnosis, and treatment of patients with neurological immune-mediated complications of SARS-CoV-2. In most cases the latency to neurological disorder was highly variable and the immunological or other mechanisms involved were unclear. Despite specific neuronal or ganglioside antibodies only being identified in 10, many had apparent responses to immunotherapies. Although the proportion of patients experiencing immune-mediated neurological disorders is small, the total number is likely to be underestimated. The early recognition and improvement seen with use of immunomodulatory treatment, even in those without identified autoantibodies, makes delayed or missed diagnoses risk the potential for long-term disability, including the emerging challenge of post-acute COVID-19 sequelae (PACS). Finally, potential issues regarding the use of immunotherapies in patients with pre-existent neuro-immunological disorders are also discussed.
2022-03-30 2022 other review-article; Review; Journal Article abstract-available 10.1007/s00415-022-11050-w Neuroimmune disorders in COVID-19. Ariño H, Heartshorne R, Michael BD, Nicholson TR, Vincent A, Pollak TA, Vogrig A. J Neurol. 2022; 269 (6)
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)
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 Support, Non-U.S. Gov't; 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)
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)
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)
The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection.
de La Flor JC, Gomez-Berrocal A, Marschall A, Valga F, [...], Rodeles M.
Med Clin (Engl Ed). 2022; 159 (1)
DOI: 10.1016/j.medcle.2021.07.021

Background

SARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium <135 mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20-37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyse the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19.

Methods

Observational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March-May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge.

Results

91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72-96 h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio 0.165; 95% confidence interval: 0.018-0.686; p = 0.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, p = 0.041).

Conclusion

We conclude that persistence of hyponatremia at 72-96 h of hospital admission was associated with higher mortality in patients with SARS-Cov-2.
2022-06-29 2022 other research-article; Journal Article abstract-available 10.1016/j.medcle.2021.07.021 The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection. de La Flor JC, Gomez-Berrocal A, Marschall A, Valga F, Linares T, Albarracin C, Ruiz E, Gallegos G, Gómez A, de Los Santos A, Rodeles M. Med Clin (Engl Ed). 2022; 159 (1)
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)
Pilot Investigation of SARS-CoV-2 Variants in the Island of Sicily Prior to and in the Second Wave of the COVID-19 Pandemic.
Padilla-Blanco M, Gucciardi F, Guercio A, Rubio V, [...], Rubio-Guerri C.
Front Microbiol. 2022; 13
DOI: 10.3389/fmicb.2022.869559
After 2 years of the COVID-19 pandemic, we continue to face vital challenges stemming from SARS-CoV-2 variation, causing changes in disease transmission and severity, viral adaptation to animal hosts, and antibody/vaccine evasion. Since the monitoring, characterization, and cataloging of viral variants are important and the existing information on this was scant for Sicily, this pilot study explored viral variants circulation on this island before and in the growth phase of the second wave of COVID-19 (September and October 2020), and in the downslope of that wave (early December 2020) through sequence analysis of 54 SARS-CoV-2-positive samples. The samples were nasopharyngeal swabs collected from Sicilian residents by a state-run one-health surveillance laboratory in Palermo. Variant characterization was based on RT-PCR amplification and sequencing of four regions of the viral genome. The B.1.177 variant was the most prevalent one, strongly predominating before the second wave and also as the wave downsized, although its relative prevalence decreased as other viral variants, particularly B.1.160, contributed to virus circulation. The occurrence of the B.1.160 variant may have been driven by the spread of that variant in continental Europe and by the relaxation of travel restrictions in the summer of 2020. No novel variants were identified. As sequencing of the entire viral genome in Sicily for the period covered here was restricted to seven deposited viral genome sequences, our results shed some light on SARS-CoV-2 variant circulation during that wave in this insular region of Italy which combines its partial insular isolation with being a major entry point for the African immigration.
2022-04-26 2022 other research-article; Journal Article abstract-available 10.3389/fmicb.2022.869559 Pilot Investigation of SARS-CoV-2 Variants in the Island of Sicily Prior to and in the Second Wave of the COVID-19 Pandemic. Padilla-Blanco M, Gucciardi F, Guercio A, Rubio V, Princiotta A, Veses V, Terrana M, Sheth CC, Pascual-Ortiz M, Maiques E, Purpari G, Rubio-Guerri C. Front Microbiol. 2022; 13
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)
Current RT-qPCR to detect SARS-CoV-2 may give positive results for related coronaviruses.
Martínez-Murcia A, García-Sirera A, Navarro A, Pérez L.
Arch Microbiol. 2022; 204 (7)
DOI: 10.1007/s00203-022-03029-y
Some weeks after the first CoVID-19 outbreak, the World Health Organization published some real-time PCR (qPCR) protocols developed by different health reference centers. These qPCR designs are being used worldwide to detect SARS-CoV-2 in the population, to monitor the prevalence of the virus during the pandemic. Moreover, some of these protocols to detect SARS-CoV-2 have widely been applied to environmental samples for epidemiological surveillance purposes. In the present work, the specificity of these currently used RT-qPCR designs was validated in vitro using SARS-CoV-2 and highly related coronaviral genomic sequences and compared to performance of the commercially available GPS™ CoVID-19 dtec-RT-qPCR Test. Assays performed with SARS-CoV-2-related genomes showed positive amplification when using some of these qPCR methods, indicating they may give SARS-CoV-2 false positives. This finding may be particularly relevant for SARS-CoV-2 monitoring of environmental samples, where an unknown pool of phylogenetically close-related viruses may exist.
2022-06-23 2022 other research-article; Journal Article abstract-available 10.1007/s00203-022-03029-y Current RT-qPCR to detect SARS-CoV-2 may give positive results for related coronaviruses. Martínez-Murcia A, García-Sirera A, Navarro A, Pérez L. Arch Microbiol. 2022; 204 (7)
Associations and Disease-Disease Interactions of COVID-19 with Congenital and Genetic Disorders: A Comprehensive Review.
Hromić-Jahjefendić A, Barh D, Ramalho Pinto CH, Gabriel Rodrigues Gomes L, [...], Lundstrom K.
Viruses. 2022; 14 (5)
DOI: 10.3390/v14050910
Since December 2019, the COVID-19 pandemic, which originated in Wuhan, China, has resulted in over six million deaths worldwide. Millions of people who survived this SARS-CoV-2 infection show a number of post-COVID complications. Although, the comorbid conditions and post-COVID complexities are to some extent well reviewed and known, the impact of COVID-19 on pre-existing congenital anomalies and genetic diseases are only documented in isolated case reports and case series, so far. In the present review, we analyzed the PubMed indexed literature published between December 2019 and January 2022 to understand this relationship from various points of view, such as susceptibility, severity and heritability. Based on our knowledge, this is the first comprehensive review on COVID-19 and its associations with various congenital anomalies and genetic diseases. According to reported studies, some congenital disorders present high-risk for developing severe COVID-19 since these disorders already include some comorbidities related to the structure and function of the respiratory and cardiovascular systems, leading to severe pneumonia. Other congenital disorders rather cause psychological burdens to patients and are not considered high-risk for the development of severe COVID-19 infection.
2022-04-27 2022 other review-article; Review; Journal Article abstract-available 10.3390/v14050910 Associations and Disease-Disease Interactions of COVID-19 with Congenital and Genetic Disorders: A Comprehensive Review. Hromić-Jahjefendić A, Barh D, Ramalho Pinto CH, Gabriel Rodrigues Gomes L, Picanço Machado JL, Afolabi OO, Tiwari S, Aljabali AAA, Tambuwala MM, Serrano-Aroca Á, Redwan EM, Uversky VN, Lundstrom K. Viruses. 2022; 14 (5)
Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework.
Clerbaux LA, Albertini MC, Amigó N, Beronius A, [...], Landesmann B.
J Clin Med. 2022; 11 (15)
DOI: 10.3390/jcm11154464
Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors (age, sex, genetic factors, lipid disorders, heart failure, gut dysbiosis, diet, vitamin D deficiency, air pollution and exposure to chemicals) influence COVID-19 by applying the Adverse Outcome Pathway (AOP), which is well-established in regulatory toxicology. This framework aims to model the sequence of events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how those eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.
2022-07-31 2022 other review-article; Review; Journal Article abstract-available 10.3390/jcm11154464 Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework. Clerbaux LA, Albertini MC, Amigó N, Beronius A, Bezemer GFG, Coecke S, Daskalopoulos EP, Del Giudice G, Greco D, Grenga L, Mantovani A, Muñoz A, Omeragic E, Parissis N, Petrillo M, Saarimäki LA, Soares H, Sullivan K, Landesmann B. J Clin Med. 2022; 11 (15)
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)
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)
Effects of vaccination against COVID-19 on the evolution of critically ill patients.
Morales Varas G, Sánchez Casado M, Padilla Peinado R, Morán Gallego F, [...], Rodríguez Villamizar A.
Med Intensiva (Engl Ed). 2022;
DOI: 10.1016/j.medine.2022.06.017
2022-07-04 2022 other Case Reports; case-report 10.1016/j.medine.2022.06.017 Effects of vaccination against COVID-19 on the evolution of critically ill patients. Morales Varas G, Sánchez Casado M, Padilla Peinado R, Morán Gallego F, Buj Vicente M, Rodríguez Villamizar A. Med Intensiva (Engl Ed). 2022;
Hydrodynamics of spike proteins dictate a transport-affinity competition for SARS-CoV-2 and other enveloped viruses.
Moreno N, Moreno-Chaparro D, Usabiaga FB, Ellero M.
Sci Rep. 2022; 12 (1)
DOI: 10.1038/s41598-022-14884-6
Many viruses, such as SARS-CoV-2 or Influenza, possess envelopes decorated with surface proteins (a.k.a. spikes). Depending on the virus type, a large variability is present in the surface-proteins number, morphology and reactivity, which remains generally unexplained. Since viruses' transmissibility depends on features beyond their genetic sequence, new tools are required to discern the effects of spikes functionality, interaction, and morphology. Here, we postulate the relevance of hydrodynamic interactions in the viral infectivity of enveloped viruses and propose micro-rheological characterization as a platform for virus differentiation. To understand how the spikes affect virion mobility and infectivity, we investigate the diffusivity of spike-decorated structures using mesoscopic-hydrodynamic simulations. Furthermore, we explored the interplay between affinity and passive viral transport. Our results revealed that the diffusional mechanism of SARS-CoV-2 is strongly influenced by the size and distribution of its spikes. We propose and validate a universal mechanism to explain the link between optimal virion structure and maximal infectivity for many virus families.
2022-06-30 2022 other research-article; Journal Article abstract-available 10.1038/s41598-022-14884-6 Hydrodynamics of spike proteins dictate a transport-affinity competition for SARS-CoV-2 and other enveloped viruses. Moreno N, Moreno-Chaparro D, Usabiaga FB, Ellero M. Sci Rep. 2022; 12 (1)
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
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 ML, Monteil V, [...], Montserrat N.
Cell Metab. 2022; 34 (6)
DOI: 10.1016/j.cmet.2022.04.009
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.
2022-05-12 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.1016/j.cmet.2022.04.009 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 ML, Monteil V, Marco A, Ullate-Agote A, Moya-Rull D, Vilas-Zornoza A, Tarantino C, Romero JP, Jonsson G, Oria R, Leopoldi A, Hagelkruys A, Gallo M, González F, Domingo-Pedrol P, Gavaldà A, Del Pozo CH, Hasan Ali O, Ventura-Aguiar P, Campistol JM, Prosper F, Mirazimi A, Boulant S, Penninger JM, Montserrat N. Cell Metab. 2022; 34 (6)
SARS-CoV-2 infection in multiple sclerosis patients: interaction with treatments, adjuvant therapies, and vaccines against COVID-19.
Muñoz-Jurado A, Escribano BM, Agüera E, Caballero-Villarraso J, [...], Túnez I.
J Neurol. 2022; 269 (9)
DOI: 10.1007/s00415-022-11237-1
The SARS-CoV-2 pandemic has raised particular concern for people with Multiple Sclerosis, as these people are believed to be at increased risk of infection, especially those being treated with disease-modifying therapies. Therefore, the objective of this review was to describe how COVID-19 affects people who suffer from Multiple Sclerosis, evaluating the risk they have of suffering an infection by this virus, according to the therapy to which they are subjected as well as the immune response of these patients both to infection and vaccines and the neurological consequences that the virus can have in the long term. The results regarding the increased risk of infection due to treatment are contradictory. B-cell depletion therapies may cause patients to have a lower probability of generating a detectable neutralizing antibody titer. However, more studies are needed to help understand how this virus works, paying special attention to long COVID and the neurological symptoms that it causes.
2022-07-05 2022 other review-article; Review; Journal Article abstract-available 10.1007/s00415-022-11237-1 SARS-CoV-2 infection in multiple sclerosis patients: interaction with treatments, adjuvant therapies, and vaccines against COVID-19. Muñoz-Jurado A, Escribano BM, Agüera E, Caballero-Villarraso J, Galván A, Túnez I. J Neurol. 2022; 269 (9)
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
Prediction of Conserved HLA Class I and Class II Epitopes from SARS-CoV-2 Licensed Vaccines Supports T-Cell Cross-Protection against SARS-CoV-1.
López D.
Biomedicines. 2022; 10 (7)
DOI: 10.3390/biomedicines10071622
Heterologous immunity-inducing vaccines against different pathogens are necessary to deal with new pandemics. In this study, the possible impact of COVID-19 licensed formulations in the cytotoxic and the helper cellular immune responses against SARS-CoV-1 is analyzed for the 567 and 41 most abundant HLA class I and II alleles, respectively. Computational prediction showed that most of these 608 alleles, which cover >90% of the human population, contain enough conserved T-cell epitopes among SARS-CoV-1 and SARS-CoV-2 spike proteins. In addition, the vast majority of these predicted peptides were defined as epitopes recognized by CD4+ or CD8+ T lymphocytes, showing a very high correlation between the bioinformatics prediction and the experimental assays. These data suggest that both cytotoxic and helper cellular immune protection elicited by the currently licensed COVID-19 vaccines should be effective against SARS-CoV-1 infection. Lastly, this study has potential implications for public health against current and future pandemics, given that the SARS-CoV-1 vaccines in pipeline since the early 20th century could generate similarly cross-protection against COVID-19.
2022-07-07 2022 other research-article; Journal Article abstract-available 10.3390/biomedicines10071622 Prediction of Conserved HLA Class I and Class II Epitopes from SARS-CoV-2 Licensed Vaccines Supports T-Cell Cross-Protection against SARS-CoV-1. López D. Biomedicines. 2022; 10 (7)
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)
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)
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)
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)
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
Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19.
Battaglini D, Lopes-Pacheco M, Castro-Faria-Neto HC, Pelosi P, [...], Rocco PRM.
Front Immunol. 2022; 13
DOI: 10.3389/fimmu.2022.857573
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes a wide spectrum of clinical manifestations, with progression to multiorgan failure in the most severe cases. Several biomarkers can be altered in coronavirus disease 2019 (COVID-19), and they can be associated with diagnosis, prognosis, and outcomes. The most used biomarkers in COVID-19 include several proinflammatory cytokines, neuron-specific enolase (NSE), lactate dehydrogenase (LDH), aspartate transaminase (AST), neutrophil count, neutrophils-to-lymphocytes ratio, troponins, creatine kinase (MB), myoglobin, D-dimer, brain natriuretic peptide (BNP), and its N-terminal pro-hormone (NT-proBNP). Some of these biomarkers can be readily used to predict disease severity, hospitalization, intensive care unit (ICU) admission, and mortality, while others, such as metabolomic and proteomic analysis, have not yet translated to clinical practice. This narrative review aims to identify laboratory biomarkers that have shown significant diagnostic and prognostic value for risk stratification in COVID-19 and discuss the possible clinical application of novel analytic strategies, like metabolomics and proteomics. Future research should focus on identifying a limited but essential number of laboratory biomarkers to easily predict prognosis and outcome in severe COVID-19.
2022-04-27 2022 other Research Support, Non-U.S. Gov't; review-article; Review; Journal Article abstract-available 10.3389/fimmu.2022.857573 Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19. Battaglini D, Lopes-Pacheco M, Castro-Faria-Neto HC, Pelosi P, Rocco PRM. Front Immunol. 2022; 13
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)
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)
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)
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)
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)
Protection against severe clinical outcomes with adenovirus or mRNA SARS-CoV-2 vaccines in patients hospitalized with Covid-19.
Llibre JM, Revollo B, Aguilar S, Calomarde-Gomez C, [...], Martin-Iguacel R.
J Infect Dis. 2022;
DOI: 10.1093/infdis/jiac256
2022-06-28 2022 other letter; Journal Article 10.1093/infdis/jiac256 Protection against severe clinical outcomes with adenovirus or mRNA SARS-CoV-2 vaccines in patients hospitalized with Covid-19. Llibre JM, Revollo B, Aguilar S, Calomarde-Gomez C, Bruguera A, Martin-Iguacel R. J Infect Dis. 2022;
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
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 Research Support, Non-U.S. Gov't; 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
The Comparative Analysis of Two RT-qPCR Kits for Detecting SARS-CoV-2 Reveals a Higher Risk of False-Negative Diagnosis in Samples with High Quantification Cycles for Viral and Internal Genes.
Luraschi R, Barrera-Avalos C, Vallejos-Vidal E, Alarcón J, [...], Sandino AM.
Can J Infect Dis Med Microbiol. 2022; 2022
DOI: 10.1155/2022/2594564
The early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the real-time quantitative polymerase chain reaction (RT-qPCR) as a gold-standard molecular tool has allowed to test and trace the viral spread and the isolation of COVID-19-infected patients. The detection capacity of viral and internal genes is an essential parameter to consider and analyze during the assay. In this study, we analyze the performance of the two commercial RT-qPCR kits used in Chile, TaqMan™ 2019-nCoV Control Kit v1 (Thermo Fisher) and MaxCov19 (TAAG Genetics), for the COVID-19 diagnosis from nasopharyngeal swab samples (NPSs). Our results show a lower sensitivity of the TAAG kit compared to the Thermo Fisher kit, even in the detection of SARS-CoV-2 mutations associated with its variants. This study reinforces the relevance of evaluating the performance of RT-qPCR kits before being used massively since those with lower sensitivity can generate false negatives and produce outbreaks of local infections.
2022-07-05 2022 other research-article; Journal Article abstract-available 10.1155/2022/2594564 The Comparative Analysis of Two RT-qPCR Kits for Detecting SARS-CoV-2 Reveals a Higher Risk of False-Negative Diagnosis in Samples with High Quantification Cycles for Viral and Internal Genes. Luraschi R, Barrera-Avalos C, Vallejos-Vidal E, Alarcón J, Mella-Torres A, Hernández F, Inostroza-Molina A, Valdés D, Imarai M, Acuña-Castillo C, Reyes-López FE, Sandino AM. Can J Infect Dis Med Microbiol. 2022; 2022
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)
Systemic Inflammation and Astrocyte Reactivity in the Neuropsychiatric Sequelae of COVID-19: Focus on Autism Spectrum Disorders.
Valenza M, Steardo L, Steardo L, Verkhratsky A, [...], Scuderi C.
Front Cell Neurosci. 2021; 15
DOI: 10.3389/fncel.2021.748136
2021-11-29 2021 other discussion; Journal Article 10.3389/fncel.2021.748136 Systemic Inflammation and Astrocyte Reactivity in the Neuropsychiatric Sequelae of COVID-19: Focus on Autism Spectrum Disorders. Valenza M, Steardo L, Steardo L, Verkhratsky A, Scuderi C. Front Cell Neurosci. 2021; 15
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
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
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; 36 (6)
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 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; 36 (6)
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
Impact of COVID-19 Lockdown on the Nasopharyngeal Microbiota of Children and Adults Self-Confined at Home.
Rocafort M, Henares D, Brotons P, Launes C, [...], Muñoz-Almagro C.
Viruses. 2022; 14 (7)
DOI: 10.3390/v14071521
The increased incidence of COVID-19 cases and deaths in Spain in March 2020 led to the declaration by the Spanish government of a state of emergency imposing strict confinement measures on the population. The objective of this study was to characterize the nasopharyngeal microbiota of children and adults and its relation to SARS-CoV-2 infection and COVID-19 severity during the pandemic lockdown in Spain. This cross-sectional study included family households located in metropolitan Barcelona, Spain, with one adult with a previous confirmed COVID-19 episode and one or more exposed co-habiting child contacts. Nasopharyngeal swabs were used to determine SARS-CoV-2 infection status, characterize the nasopharyngeal microbiota and determine common respiratory DNA/RNA viral co-infections. A total of 173 adult cases and 470 exposed children were included. Overall, a predominance of Corynebacterium and Dolosigranulum and a limited abundance of common pathobionts including Haemophilus and Streptococcus were found both among adults and children. Children with current SARS-CoV-2 infection presented higher bacterial richness and increased Fusobacterium, Streptococcus and Prevotella abundance than non-infected children. Among adults, persistent SARS-CoV-2 RNA was associated with an increased abundance of an unclassified member of the Actinomycetales order. COVID-19 severity was associated with increased Staphylococcus and reduced Dolosigranulum abundance. The stringent COVID-19 lockdown in Spain had a significant impact on the nasopharyngeal microbiota of children, reflected in the limited abundance of common respiratory pathobionts and the predominance of Corynebacterium, regardless of SARS-CoV-2 detection. COVID-19 severity in adults was associated with decreased nasopharynx levels of healthy commensal bacteria.
2022-07-12 2022 other Research Support, Non-U.S. Gov't; research-article; Journal Article abstract-available 10.3390/v14071521 Impact of COVID-19 Lockdown on the Nasopharyngeal Microbiota of Children and Adults Self-Confined at Home. Rocafort M, Henares D, Brotons P, Launes C, Fernandez de Sevilla M, Fumado V, Barrabeig I, Arias S, Redin A, Ponomarenko J, Mele M, Millat-Martinez P, Claverol J, Balanza N, Mira A, Garcia-Garcia JJ, Bassat Q, Jordan I, Muñoz-Almagro C. Viruses. 2022; 14 (7)
Seizures and COVID-19: Results from the Spanish Society of Neurology's COVID-19 registry.
Fernández SF, Pérez Sánchez JR, Pérez GH, Pérez MR, [...], Ezpeleta D.
J Clin Neurosci. 2022; 101
DOI: 10.1016/j.jocn.2022.05.013
We describea series of patients with COVID-19 who presented with seizures, reported in the Spanish Society of Neurology's COVID-19 Registry. This observational, descriptive,multicentre, registry-based study includes patients with confirmed COVID-19 who experienced seizures during active infection.Wedescribe theclinicalpresentation of COVID-19,seizures,and resultsof complementary tests.Wealsodescribe the suspectedaetiologyof the seizures. Of 232 reported cases, 26 (11.2%) presented with seizures;7 of these patients (26.9%) had prior history of epilepsy, whereas the remaining 19 (73.1%) had no history of seizures.In most cases, seizures presented on days 0 and 7 after onset of COVID-19. By seizure type, 8 patients (30.7%) presentedgeneralised tonic-clonic seizures, 7 (26.9%) status epilepticus, 8 (30.7%) focal impaired-awareness seizures, and 4 (11.7%) secondary generalised seizures.Six patients (23.1%) also presented other neurological symptoms, includingaltered mental status and decreased level of consciousness. Predisposing factors for seizures (eg, dementia, tumour, cerebrovascular disease) were observed in 10 of the 19 patients with no prior history of epilepsy (52.6%). Patients with COVID-19 may present with seizures over the course of the disease,either alone or in the context of encephalopathy.Seizures may present in patients with no prior history of epilepsy; however, most of these patients present predisposing factors.
2022-05-16 2022 other research-article; Journal Article; Observational Study abstract-available 10.1016/j.jocn.2022.05.013 Seizures and COVID-19: Results from the Spanish Society of Neurology's COVID-19 registry. Fernández SF, Pérez Sánchez JR, Pérez GH, Pérez MR, Castro CG, García-Azorín D, Ezpeleta D. J Clin Neurosci. 2022; 101
Pathological Findings Associated With SARS-CoV-2 on Postmortem Core Biopsies: Correlation With Clinical Presentation and Disease Course.
Ramos-Rincon JM, Herrera-García C, Silva-Ortega S, Portilla-Tamarit J, [...], Aranda I.
Front Med (Lausanne). 2022; 9
DOI: 10.3389/fmed.2022.874307

Background

Autopsies can shed light on the pathogenesis of new and emerging diseases.

Aim

To describe needle core necropsy findings of the lung, heart, and liver in decedents with COVID-19.

Material

Cross-sectional study of needle core necropsies in patients who died with virologically confirmed COVID-19. Histopathological analyses were performed, and clinical data and patient course evaluated.

Results

Chest core necropsies were performed in 71 decedents with a median age of 81 years (range 52-97); 47 (65.3%) were men. The median interval from symptoms onset to death was 17.5 days (range 1-84). Samples of lung (n = 62, 87.3%), heart (n = 48, 67.6%) and liver (n = 39, 54.9%) were obtained. Fifty-one lung samples (82.3%) were abnormal: 19 (30.6%) showed proliferative diffuse alveolar damage (DAD), 12 (19.4%) presented exudative DAD, and 10 (16.1%) exhibited proliferative plus exudative DAD. Of the 46 lung samples tested for SARS-CoV-19 by RT-PCR, 39 (84.8%) were positive. DAD was associated with premortem values of lactate dehydrogenase of 400 U/L or higher [adjusted odds ratio (AOR) 21.73; 95% confidence interval (CI) 3.22-146] and treatment with tocilizumab (AOR 6.91; 95% CI 1.14-41.7). Proliferative DAD was associated with an onset-to-death interval of over 15 days (AOR 7.85, 95% CI 1.29-47.80). Twenty-three of the 48 (47.9%) heart samples were abnormal: all showed fiber hypertrophy, while 9 (18.8%) presented fibrosis. Of the liver samples, 29/39 (74.4%) were abnormal, due to steatosis (n = 12, 30.8%), cholestasis (n = 6, 15.4%) and lobular central necrosis (n = 5, 12.8%).

Conclusion

Proliferative DAD was the main finding on lung core needle necropsy in people who died from COVID-19; this finding was related to a longer disease course. Changes in the liver and heart were common.
2022-07-07 2022 other research-article; Journal Article abstract-available 10.3389/fmed.2022.874307 Pathological Findings Associated With SARS-CoV-2 on Postmortem Core Biopsies: Correlation With Clinical Presentation and Disease Course. Ramos-Rincon JM, Herrera-García C, Silva-Ortega S, Portilla-Tamarit J, Alenda C, Jaime-Sanchez FA, Arenas-Jiménez J, Fornés-Riera FE, Scholz A, Escribano I, Pedrero-Castillo V, Muñoz-Miguelsanz C, Orts-Llinares P, Martí-Pastor A, Amo-Lozano A, García-Sevila R, Ribes-Mengual I, Moreno-Perez O, Concepcion-Aramendía L, Merino E, Sánchez-Martínez R, Aranda I. Front Med (Lausanne). 2022; 9
The Emergence of SARS-CoV-2 Variants With a Lower Antibody Response: A Genomic and Clinical Perspective.
Biswas S, Mahmud S, Mita MA, Afrose S, [...], Kim B.
Front Med (Lausanne). 2022; 9
DOI: 10.3389/fmed.2022.825245
The emergence of several novel SARS-CoV-2 variants regarded as variants of concern (VOCs) has exacerbated pathogenic and immunologic prominences, as well as reduced diagnostic sensitivity due to phenotype modification-capable mutations. Furthermore, latent and more virulent strains that have arisen as a result of unique mutations with increased evolutionary potential represent a threat to vaccine effectiveness in terms of incoming and existing variants. As a result, resisting natural immunity, which leads to higher reinfection rates, and avoiding vaccination-induced immunization, which leads to a lack of vaccine effectiveness, has become a crucial problem for public health around the world. This study attempts to review the genomic variation and pandemic impact of emerging variations of concern based on clinical characteristics management and immunization effectiveness. The goal of this study is to gain a better understanding of the link between genome level polymorphism, clinical symptom manifestation, and current vaccination in the instance of VOCs.
2022-05-06 2022 other review-article; Review; Journal Article abstract-available 10.3389/fmed.2022.825245 The Emergence of SARS-CoV-2 Variants With a Lower Antibody Response: A Genomic and Clinical Perspective. Biswas S, Mahmud S, Mita MA, Afrose S, Hasan MR, Paul GK, Shimu MSS, Uddin MS, Zaman S, Park MN, Siyadatpanah A, Obaidullah AJ, Saleh MA, Simal-Gandara J, Kim B. Front Med (Lausanne). 2022; 9
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
Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19-Results From a Pilot Open-Label, Randomized Controlled Trial.
Khan A, Iqtadar S, Mumtaz SU, Heinrich M, [...], Abaidullah S.
Front Pharmacol. 2022; 13
DOI: 10.3389/fphar.2022.898062
Background: Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities. Objective: The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan. Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) (n = 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC (n = 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven. Results: Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm, p = 0.009. COVID-19- associated acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the control arm, p = 0.154. Patients in the CQC arm experienced a greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, 16.0) mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, 25.0) mg/dl, p = 0.006. The adjuvant therapy of co-supplementation of CQC was safe and well-tolerated by all 25 patients and no treatment-emergent effects, complications, side effects, or serious adverse events were reported. Conclusion: The co-supplementation of CQC may possibly have a therapeutic role in the early stage of COVID-19 infection including speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and modulation of the hyperinflammatory response. In combination with routine care, the adjuvant co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to moderate symptoms of COVID-19. Further research is warranted. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT05130671.
2022-06-07 2022 other research-article; Journal Article abstract-available 10.3389/fphar.2022.898062 Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19-Results From a Pilot Open-Label, Randomized Controlled Trial. Khan A, Iqtadar S, Mumtaz SU, Heinrich M, Pascual-Figal DA, Livingstone S, Abaidullah S. Front Pharmacol. 2022; 13
Reply to Ayuso García et al. Health Perception among Female COVID-19 Patients. Comment on "Fernández-de-las-Peñas et al. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J. Clin. Med. 2022, 11, 413".
Fernández-de-Las-Peñas C, Martín-Guerrero JD, Pellicer-Valero ÓJ, Navarro-Pardo E, [...], Arendt-Nielsen L.
J Clin Med. 2022; 11 (13)
DOI: 10.3390/jcm11133616
We have read with great interest the comment by Ayuso García et al [...].
2022-06-23 2022 other reply; Journal Article abstract-available 10.3390/jcm11133616 Reply to Ayuso García et al. Health Perception among Female COVID-19 Patients. Comment on "Fernández-de-las-Peñas et al. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. <i>J. Clin. Med.</i> 2022, <i>11</i>, 413". Fernández-de-Las-Peñas C, Martín-Guerrero JD, Pellicer-Valero ÓJ, Navarro-Pardo E, Gómez-Mayordomo V, Cuadrado ML, Arias-Navalón JA, Cigarán-Méndez M, Hernández-Barrera V, Arendt-Nielsen L. J Clin Med. 2022; 11 (13)
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)
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
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
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C): A multicenter, retrospective study.
Davalos V, García-Prieto CA, Ferrer G, Aguilera-Albesa S, [...], Esteller M.
EClinicalMedicine. 2022; 50
DOI: 10.1016/j.eclinm.2022.101515

Background

Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic or develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. However, a small proportion of pediatric patients develop a severe clinical condition, multisystem inflammatory syndrome in children (MIS-C). The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C.

Methods

Peripheral blood samples were recruited from 43 confirmed MIS-C patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants.

Findings

The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts. The EPIMISC signature was also overrepresented in Kawasaki disease patients, a childhood pathology with a possible viral trigger, that shares many of the clinical features of MIS-C.

Interpretation

We have characterized DNA methylation loci that are associated with MIS-C diagnosis. The identified genes are likely contributors to the characteristic exaggerated host inflammatory response observed in these patients. The described epigenetic signature could also provide new targets for more specific therapies for the disorder.

Funding

Unstoppable campaign of Josep Carreras Leukaemia Foundation, Fundació La Marató de TV3, Cellex Foundation and CERCA Programme/Generalitat de Catalunya.
2022-06-25 2022 other research-article; Journal Article abstract-available 10.1016/j.eclinm.2022.101515 Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C): A multicenter, retrospective study. Davalos V, García-Prieto CA, Ferrer G, Aguilera-Albesa S, Valencia-Ramos J, Rodríguez-Palmero A, Ruiz M, Planas-Serra L, Jordan I, Alegría I, Flores-Pérez P, Cantarín V, Fumadó V, Viadero MT, Rodrigo C, Méndez-Hernández M, López-Granados E, Colobran R, Rivière JG, Soler-Palacín P, Pujol A, Esteller M. EClinicalMedicine. 2022; 50
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
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 Research Support, Non-U.S. Gov't; 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
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)
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)
Comparison of pneumonia features in children caused by SARS-CoV-2 and other viral respiratory pathogens.
Del Valle R, Ballesteros Á, Calvo C, Sainz T, [...], Tagarro A.
Pediatr Pulmonol. 2022;
DOI: 10.1002/ppul.26042

Background

Pneumonia is a frequent manifestation of coronavirus disease 2019 (COVID-19) in hospitalized children.

Methods

The study involved 80 hospitals in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spanish Pediatric National Cohort. Participants were children <18 years, hospitalized with SARS-CoV-2 community-acquired pneumonia (CAP). We compared the clinical and radiological characteristics of SARS-CoV-2-associated CAP with CAP due to other viral etiologies from ValsDance (retrospective) cohort.

Results

In total, 151 children with SARS-CoV-2-associated CAP and 138 with other viral CAP were included. Main clinical features of SARS-CoV-2-associated CAP were cough, fever, or dyspnea. Lymphopenia was found in 43% patients and 15% required admission to the pediatric intensive care unit (PICU). Chest X-ray revealed condensation (42%) and other infiltrates (58%). Compared with CAP from other viral pathogens, COVID-19 patients were older, with lower C-reactive protein (CRP) levels, less wheezing, and greater need of mechanical ventilation (MV). There were no differences in the use of continuous positive airway pressure (CPAP) or HVF, or PICU admission between groups.

Conclusion

SARS-CoV-2-associated CAP in children presents differently to other virus-associated CAP: children are older and rarely have wheezing or high CRP levels; they need less oxygen but more CPAP or MV. However, several features overlap and differentiating the etiology may be difficult. The overall prognosis is good.
2022-06-26 2022 other research-article; Journal Article abstract-available 10.1002/ppul.26042 Comparison of pneumonia features in children caused by SARS-CoV-2 and other viral respiratory pathogens. Del Valle R, Ballesteros Á, Calvo C, Sainz T, Mendez A, Grasa C, Molina PR, Mellado MJ, Sanz-Santaeufemia FJ, Herrero B, Calleja L, Soriano-Arandes A, Melendo S, Rincón-López E, Hernánz A, Epalza C, García-Baeza C, Rupérez-García E, Berzosa A, Ocaña A, Villarroya-Villalba A, Barrios A, Otheo E, Galán JC, Rodríguez MJ, Mesa JM, Domínguez-Rodríguez S, Moraleda C, Tagarro A. Pediatr Pulmonol. 2022;
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)
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)
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)
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)
Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target.
Veljkovic V, Vergara-Alert J, Segalés J, Paessler S.
F1000Res. 2020; 9
DOI: 10.12688/f1000research.22149.4
A novel coronavirus recently identified in Wuhan, China (SARS-CoV-2) has expanded the number of highly pathogenic coronaviruses affecting humans. The SARS-CoV-2 represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging SARS-CoV-2 is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Actin protein was also suggested as a host factor that participates in cell entry and pathogenesis of SARS-CoV-2; therefore, drugs modulating biological activity of this protein (e.g. ibuprofen) were suggested as potential candidates for treatment of this viral infection. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the SARS-CoV-2, and that domain 288-330 of S1 protein from the SARS-CoV-2 represents promising therapeutic and/or vaccine target.
2020-01-27 2020 other brief-report; Journal Article abstract-available 10.12688/f1000research.22149.4 Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. Veljkovic V, Vergara-Alert J, Segalés J, Paessler S. F1000Res. 2020; 9
The 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)
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)
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)
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)
Antimalarial phytochemicals as potential inhibitors of SARS-CoV-2 guanine N7-methyltransferase (nsp 14): an integrated computational approach.
Gyebi GA, Ogunyemi OM, Adefolalu AA, López-Pastor JF, [...], Batiha GE.
J Biomol Struct Dyn. 2022;
DOI: 10.1080/07391102.2022.2078408
The inhibition of capping enzymes such as guanine-N7-methyltransferase (GMT) is an attractive target for regulating viral replication, transcription, virulence, and pathogenesis. Thus, compounds that target the Severe Acute Respiratory Syndrome Corona Virus 2 GMT (S2GMT) will enhance drug development against COVID-19. In this study, an in-house library of 249 phytochemicals from African medicinal plants was screened using computational approaches including homology modeling, molecular docking, molecular dynamic simulations, binding free energy calculations based on molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) and Absorption-Distribu