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.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, Therapeutics, Endothelial dysfunction, immunothrombosis, RAAS, bradykinin–kallikrein pathway, ADAM17, pericyte, 【초록키워드】 coronavirus disease, Coronavirus disease 2019, pandemic, severe COVID-19, spike, SARS-COV-2 infection, Respiratory illness, angiotensin-converting enzyme 2, Spike protein, Endothelial dysfunction, Endothelium, Protein, Viral, endothelial cells, human lung, Complication, therapeutic agent, therapeutic agents, respiratory, SARS-CoV-2 replication, COVID-19 patients, binding, Angiotensin-converting enzyme, Endothelial cell, Evidence, angiotensin, Inflammatory, Deleterious, severe disease, manifestation, lead, evidence of, dysfunction, viral spike protein, acute respiratory syndrome, global public health, thrombotic, clinical development, downregulation, renal, Neurological diseases, direct infection, parameter, cellular receptor, infect, recent, event, caused, include, contribute, exacerbate,