COVID-19 and the renin-angiotensin system (RAS): A spark that sets the forest alight?

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has increased exponentially in numbers with more than 20 million people infected around the globe. It is clear that COVID-19 is not a simple viral pneumonia, but presents with unusual pathophysiological effects. Of special interest is that SARS-CoV-2 utilises the angiotensin-converting enzyme-2 (ACE2) for cell entry and therefore has a direct effect on the renin angiotensin system (RAS). The RAS is primarily responsible for blood pressure control via the classic pathway. Recently numerous other pathological processes have been described due to stimulation of this classic pathway. There is also a protective RAS pathway medicated by ACE2 which may be suppressed in COVID-19. This leads to overstimulation of the classic pathway with adverse cardiovascular and respiratory effects, hypercoagulation, endothelial dysfunction, inflammation and insulin resistance. We hypothesize that overreaction of the renin-angiotensin-aldosterone may account for the myriad of unusual biochemical and clinical abnormalities noted in patients infected with SARS-CoV-2.

Fig. 1

The RAS pathway showing the classical and protective arms as well as the various receptors and their downstream effects. RAS: Renin Angiotensin System. ACEi: Angiotensin Converting Enzyme inhibitor. ARB: Angiotensin Receptor Blocker. AT1: Angiotensin 1 receptor. AT2: Angiotensin 2 receptor.