Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Abstract

The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

“…Despite the importance of determining precisely which entry receptors SARS-CoV-2 uses to infect human cells, there remains considerable uncertainty amid multiple claimed viral receptors with variable qualities of data behind them 9,[32][33][34][35] . We investigated one of the most prominent claims among these, that human BSG acts as an alternate receptor for the virus to interact with, which has been the topic of several studies, news and review articles, and a clinical trial 8,14,15,[36][37][38][39] . Our access to established tools and reagents from previous work studying BSG's role as a host receptor in Plasmodium infection allowed us to rapidly investigate BSG as a SARS-CoV-2 receptor.…”

“…Notably, SARS-CoV-2 has not been found to enter red blood cells 42 . However, the possibility that BSG could act as an accessory binding receptor for the virus has been speculated in several publications to possibly explain in part the link between SARS-CoV-2 infection and hematological symptoms in patients 38,39,43,44 . Our data suggest this hypothesis should be treated cautiously.…”

Reduction of ADAMTS13 Levels Predicts Mortality in SARS-CoV-2 Patients

“…Endothelial dysfunction is a key finding and major determinant of poor prognosis in SARS-CoV-2 patients. 23 Indeed, direct or indirect activation by SARS-CoV-2 on endothelium would cause intensive vWF secretion from Weibel-Palade bodies, as expected upon perturbations on these vascular cells. 13 Our data are consistent with previous findings suggesting that SARS-CoV-2 patients present a low-grade disseminated coagulopathy and localized pulmonary microangiopathy, resulting in organ dysfunction.…”

Serum metabolomic profile of symptomatic and asymptomatic SARS-CoV-2 infected patients 

“…The respiratory symptoms caused in the Covid-19 by the Sars-COV-2 infections are accompanied, in the most severe cases, by other major events such as high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus. The multiorgan involvement indicates that the virus is targeting the endothelium [12] causing a systemic disease. The pathologic mechanisms underlaying the broad spectrum of the clinical courses of the Covid-19, from asymptomatic to multiorgan failure cases, is going to be the object of study and research for the next future.…”