Unravelling the Mechanistic Role of ACE2 and TMPRSS2 in Hypertension: A Risk Factor for COVID-19

Abstract

Background: This review explores the mechanistic action of angiotensin-converting enzyme-2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the renin-angiotensin-aldosterone system (RAAS) that predisposes hypertensive patients to adverse outcome of severe COVID-19. Methods and Results: Entry of SARS-CoV-2 into the host cell via ACE2 disrupts the RAAS system, creating an imbalance between ACE and ACE2, and this together with an increased inflammatory response leads to hypertension (HTN), pulmonary vasoconstriction and acute respiratory distress. SARS-CoV-2 may also predispose infected individuals with existing HTN to a greater risk of severe COVID-19 complications. In the duality of COVID-19 and HTN, the imbalance of ACE and ACE2 results in an elevation of AngII and a decrease in Ang (1-7), a hyperinflammatory response and endothelial dysfunction. Endothelial dysfunction is the main factor that predisposes hypertensive patients to severe COVID-19 and vice-versa. Conclusion: Conclusion: Despite the increase in ACE2 expression in hypertensive SARS-CoV-2 infected pa-tients, ARBs/ACE inhibitors do not influence their severity and clinical outcomes, implicating continued usage. Future large scale clinical trials are warranted to further elucidate the association between HTN and SARS-CoV-2 infection; as well as the use of ARBs/ACEIs in SARS-CoV-2 hy-pertensive patients.