Title:Unravelling the Mechanistic Role of ACE2 and TMPRSS2 in Hypertension:
A Risk Factor for COVID-19
Volume: 18
Issue: 2
Author(s): Nalini Govender*, Olive Khaliq, Jagidesa Moodley and Thajasvarie Naicker
Affiliation:
- Department of Basic Medical Sciences, Faculty of Health Sciences, Durban University of Technology, Durban 4001,
South Africa
Keywords:
ACE2, TMPRSS2, COVID-19, hypertension, RAAS, ARBs, ACEI.
Abstract:
Background: This review explores the mechanistic action of angiotensin-converting enzyme-
2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the renin-angiotensinaldosterone
system (RAAS) that predisposes hypertensive patients to the 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, with an increased inflammatory response,
leading to hypertension (HTN), pulmonary vasoconstriction and acute respiratory distress. SARSCoV-
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 predisposing hypertensive patients
to severe COVID-19 and vice-versa.
Conclusion: Despite the increase in ACE2 expression in hypertensive SARS-CoV-2 infected patients,
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 and the use of ARBs/ACEIs in SARS-CoV-2 hypertensive
patients.
