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.