Journal
VIRUSES-BASEL
Volume 13, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/v13010029
Keywords
COVID-19; SARS-CoV-2; ACE2; RAAS; bradykinin-kallikrein pathway; ADAM17; endothelial dysfunction; pericyte; immunothrombosis; therapeutics
Categories
Funding
- Canadian Institutes of Health Research [PJT-148699, OV3-172302, PJT-162417]
- Li Ka Shing Institute of Virology
- Alberta Innovates Summer Research Studentship
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The ongoing COVID-19 pandemic poses a persistent threat to global public health, with extrapulmonary manifestations including gastrointestinal, cardiovascular, renal, and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate deleterious events through inflammatory and microvascular thrombotic processes, potentially due to SARS-CoV-2 infecting endothelial cells via ACE2 receptor binding.
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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