COVID-19 and Microvascular Disease: Pathophysiology of SARS-CoV-2 Infection With Focus on the Renin-Angiotensin System

Abstract

The recently described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people, with thousands of fatalities. It has prompted global efforts in research, with focus on the pathophysiology of coronavirus disease-19 (COVID-19), and a rapid surge of publications. COVID-19 has been associated with a myriad of clinical manifestations, including the lungs, heart, kidneys, central nervous system, gastrointestinal system, skin, and blood coagulation abnormalities. The endothelium plays a key role in organ dysfunction associated with severe infection, and current data suggest that it is also involved in SARS-CoV-2-induced sepsis. This critical review aimed to address a possible unifying mechanism underlying the diverse complications of COVID-19: microvascular dysfunction, with emphasis on the renin-angiotensin system. In addition, research perspectives are suggested in order to expand understanding of the pathophysiology of the infection.

Keywords: COVID-19; Microcirculation; Renin-angiotensin system.

Figure 1

A schematic representation of mechanisms proposed for COVID-19 pathophysiology regarding the renin-angiotensin system. Abbreviations: ACE, angiotensin-converting enzyme; ACE2, angiotensin-converting enzyme type 2; Ang-(1-7), angiotensin-(1-7); Ang II, angiotensin II; ARDS, acute respiratory distress syndrome; IL-6, Interleukin-6; RAS, renin-angiotensin system; ROS, reactive oxygen species; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; S protein, spike protein; TNF-α, tumor necrosis factor-α.