Introduction
SARS-CoV-2 is a novel coronavirus similar to the SARS-CoV virus that caused the SARS epidemic in 2003, but with two critical differences. The infamous spike protein is vastly more adept at cell entry through ACE2, (1) destroying ACE2 in the process (2) and the replicating virus is able to subvert the innate immune response, silencing the incubation period until after viral shedding has occurred. (3) Both features hamper efforts to reduce spread by immediate isolation of symptomatic patients, as was done during the SARS epidemic. If SARS-CoV-2 does indeed inhibit the immune reactivity, what triggers the delayed immune response in some patients?
The variable impact of ACE2 depletion may explain the broad range of host responses to infection in which 20% of infected people become ill, 10% become severely ill and 1-5% die. Those most at risk for severe COVID-19 illness are the elderly, obese, males and certain race groups such as African Americans and those with predisposing conditions such as hypertension, diabetes, cardiovascular disease, cancer and chronic lung and kidney diseases. (4) The renin-angiotensin-aldosterone system (RAAS) appears to be the link between the at-risk population and the acute ACE2-deficiency state induced by COVID-19. (2) Could the severe inflammation seen in Covid-19 be simply viral-induced or does ACE2 depletion cause an aldosterone crisis in patients already affected by RAAS stress? Could reducing RAAS stress effectively prevent the cytokine storm that predicts severe illness or death with COVID-19?