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

[tetano]

Viruses


. 2020 Dec 26;13(1):E29.
doi: 10.3390/v13010029.
Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19


Isabelle Bernard ¹ , Daniel Limonta ^{2 3} , Lara K Mahal ⁴ , Tom C Hobman ^{1 2 3 5}



Affiliations

• PMID: 33375371
• DOI: 10.3390/v13010029

Abstract

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.

Keywords: ACE2; ADAM17; COVID-19; RAAS; SARS-CoV-2; bradykinin–kallikrein pathway; endothelial dysfunction; immunothrombosis; pericyte; therapeutics.