Is the use of RAS inhibitors safe in the current era of COVID-19 pandemic?

Abstract

Antihypertensive drugs are one of the most widely used pharmacologic agent in the world and it is predominantly used in the elderly subjects. Pneumonia is the most common cause of death in the extremely old subject. During infection and its complication such as sepsis, hypotension could be exacerbated by antihypertensive drugs because homeostasis mechanisms such as sodium balance, renin angiotensin aldosterone system and/or sympathetic nervous system can be mitigated by antihypertensive drug therapy. Severe Acute Respiratory Syndrome-Coronavirus-1 and 2 viral surface protein is known to attach angiotensin converting enzyme 2 (ACE2) on the cell membrane to facilitate viral entry into the cytoplasm. Despite the theoretical concerns of increased ACE2 expression by Renin-Angiotensin-Aldosterone system (RAS) blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection and have in fact been shown to be beneficial in animal studies. Therefore, it is recommended to maintain RAS blockade during the current corona virus pandemic.

Keywords: 2019 novel coronavirus; ACE inhibitor; ACE2; Angiotensin receptor blocker; Antihypertensive drugs; COVID-19; Hypertension; Infection; Pandemic; SARS; SARS-CoV-2; Sepsis.

Fig. 1

Angiotensin Converting Enzyme 2 in Classical Renin Angiotensin System and SARS-CoV-1. Panel a. In classical renin angiotensin system, ACE2 convert angiotensin I and II to Angiotensin 1–9 and 1–7, respectively. Panel b. Complex interaction among SARS-CoV-1, ACE2, TMPRSS2, and ADAM17 in lung epithelial cells. In SARS-CoV-1 infection and presumably in SARS-CoV-2 infection, binding of spike protein to ACE2 together with lysosome degradation resulting in ACE2 down regulation, ADAM17 mediated ACE2 shedding from cell membrane resulting in promotion of viral entry, facilitation of ACE2 mediated viral entry by TMPRSS2 make a complex expression or interplay between ACE2 and the virus. ACE, angiotensin converting enzyme; ADAM17, a disintegrin and metallopeptidase domain 17; ARB; angiotensin receptor blocker; S, spike protein; SARS-CoV, severe acute respiratory syndrome corona virus; TMPRSS2, The type II transmembrane serine proteases