Coronavirus Disease 2019 and Hypertension: The Role of Angiotensin-Converting Enzyme 2 and the Renin-Angiotensin System

Abstract

Hypertension emerged from early reports as a potential risk factor for worse outcomes for persons with coronavirus disease 2019 (COVID-19). Among the putative links between hypertension and COVID-19 is a key counter-regulatory component of the renin-angiotensin system (RAS): angiotensin-converting enzyme 2 (ACE2). ACE2 facilitates entry of severe acute respiratory syndrome coronavirus 2, the virus responsible for COVID-19, into host cells. Because RAS inhibitors have been suggested to increase ACE2 expression, health-care providers and patients have grappled with the decision of whether to discontinue these medications during the COVID-19 pandemic. However, experimental models of analogous viral pneumonias suggest RAS inhibitors may exert protective effects against acute lung injury. We review how RAS and ACE2 biology may affect outcomes in COVID-19 through pulmonary and other systemic effects. In addition, we briefly detail the data for and against continuation of RAS inhibitors in persons with COVID-19 and summarize the current consensus recommendations from select specialty organizations.

Keywords: Angiotensin receptor blocker; Angiotensin-converting enzyme 2; Angiotensin-converting enzyme inhibitor; COVID-19; Coronavirus; Renin-angiotensin system.

Figure 1

Putative helpful and harmful actions of RAS inhibition in COVID-19. The top-left panel depicts the potential for increased ACE2 expression leading to increased SARS-CoV-2 binding sites. The bottom-left panel lists other potential adverse effects from RAS inhibition in persons with COVID-19 outside of increased viral binding sites. The top-right panel depicts the potential for decreased acute lung injury from the shift from ACE/Ang II/AT1R to ACE2/Ang-(1-7)/MasR predominance. The bottom-right panel lists adverse effects of RAS discontinuation in persons with COVID-19. Abbreviations: COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ACE, angiotensin-converting enzyme; Ang, angiotensin; ARB, angiotensin receptor blocker; MasR, Mas receptor; RAS, renin-angiotensin system. (Figure 1 was created with the assistance of BioRender.com.)