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Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascu...

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Autores principales: Bernard, Isabelle, Limonta, Daniel, Mahal, Lara K., Hobman, Tom C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823949/
https://www.ncbi.nlm.nih.gov/pubmed/33375371
http://dx.doi.org/10.3390/v13010029
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author Bernard, Isabelle
Limonta, Daniel
Mahal, Lara K.
Hobman, Tom C.
author_facet Bernard, Isabelle
Limonta, Daniel
Mahal, Lara K.
Hobman, Tom C.
author_sort Bernard, Isabelle
collection PubMed
description The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.
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spelling pubmed-78239492021-01-24 Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19 Bernard, Isabelle Limonta, Daniel Mahal, Lara K. Hobman, Tom C. Viruses Review The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process. MDPI 2020-12-26 /pmc/articles/PMC7823949/ /pubmed/33375371 http://dx.doi.org/10.3390/v13010029 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bernard, Isabelle
Limonta, Daniel
Mahal, Lara K.
Hobman, Tom C.
Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19
title Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19
title_full Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19
title_fullStr Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19
title_full_unstemmed Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19
title_short Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19
title_sort endothelium infection and dysregulation by sars-cov-2: evidence and caveats in covid-19
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823949/
https://www.ncbi.nlm.nih.gov/pubmed/33375371
http://dx.doi.org/10.3390/v13010029
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