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?