ACE2 and COVID-19 and the resulting ARDS

Abstract

This article reviews the correlation between ACE2 and COVID-19 and the resulting acute respiratory distress syndrome (ARDS). ACE2 is a crucial component of the renin-angiotensin system (RAS). The classical ACE-angiotensin Ⅱ (Ang II)-angiotensin type 1 receptor (AT1R) axis and the ACE2-Ang(1-7)-Mas counter-regulatory axis play an essential role in RAS system. ACE2 antagonises the activation of the classical RAS ACE-Ang II-AT1R axis and protects against lung injury. Similar to severe acute respiratory syndrome-related coronavirus, 2019 novel coronavirus (2019-nCoV) also uses ACE2 for cell entry. ARDS is a clinical high-mortality disease which is probably due to the excessive activation of RAS caused by 2019-nCoV infection, and ACE2 has a protective effect on ARDS caused by COVID-19. Because of these protective effects of ACE2 on ARDS, the development of drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the near future. In the meantime, however, the use of RAS blockers such as ACE inhibitors and angiotensin II receptor blockers that inhibit the damaging (ACE-Ang II) arm of the RAS cascade in the lung may also be promising. Trial registration number: NCT04287686.

Figure 1

Schematic diagram of the renin-angiotensin system (RAS) in the lung showing the role of ACE2 as a key element in the counter-regulatory axis of the RAS. ACE2 opposes the harmful effects on lung injury of the ACE-angiotensin Ⅱ (Ang II)-angiotensin type 1 receptor (AT1R) axis by activating Mas and AT2R signalling. Pharmacological treatment with angiotensin Ⅱ receptor blockers (ARB) or ACE inhibitors (ACEI) will modulate several components of the RAS system. Treatment with ARB protects against lung injury by AT1R receptor blockade. rhACE2, recombinant human ACE2.