Endothelial Dysfunction as a Primary Consequence of SARS-CoV-2 Infection

Abstract

A number of different viral species are known to have effects on the endothelium. These include dengue, Ebola, Marburg, Lassa fever, yellow fever and influenza viruses, cytomegalovirus and coronaviruses. There are currently seven human endemic coronaviruses, all of which cause respiratory diseases and bind to receptors found within the endothelium. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) is highly infectious. Like its predecessor, SARS-CoV, it binds to angiotensin-converting enzyme-2 (ACE-2), which is expressed in many cell types, particularly in the lung, including endothelial cells. The initiation of a cytokine storm by the virus along with infection of endothelial cells leads to apoptosis and structural and functional changes that attenuate vascular integrity in many organs including the lungs, heart, liver and kidney. Endothelial damage also enhances the coagulation pathway leading to thrombus formation in major vessels and capillaries. Infection with SARS-CoV-2 has an adverse outcome for individuals with particular comorbid diseases, e.g. hypertension, obesity, type 2 diabetes and cardiovascular disease. It is possible that this is due to the presence of pre-existing endothelial dysfunction and systemic inflammation in subjects with these diseases. Therapies for COVID-19 that target the endothelium, the inflammatory response and the coagulation pathway are currently under trial.

Keywords: COVID-19; Endothelial dysfunction; Inflammation; SARS-CoV-2.