The Central Role of the Aldosterone in COVID-19 Provides a Treatment
Target.
Abstract
Striking features of the COVID-19 pandemic are the rapid spread of the
SARS-CoV-2 virus and the relatively narrow profile of patients adversely
affected. SARS-CoV-2 enters human cells by means of ACE2, destroying the
protein in the process. ACE2 maintains renin-angiotensin-aldosterone
system (RAAS) homeostasis and is upregulated in the setting of chronic
RAAS disequilibrium seen in COVID-19-susceptible patients. The
ACE2-depletion effect on angiotensin II (AngII) levels likely
contributes to the spectrum of cytokine responses found in COVID-19
patients. However, as most of the inflammatory effects of AngII are
amplified through aldosterone-activated mineralocorticoid receptors
(MRs), blocking MRs may provide much-needed benefit. The MR-blockers,
spironolactone and eplerenone, are relatively selective in exerting
downstream dampening effects on RAAS stress and target the
pathophysiological processes in COVID-19-susceptible patients where
acute viral-induced ACE2 depletion could be responsible for a
catastrophic aldosterone surge in severely ill patients.