Is ACE2 a friend or foe in the fight against the COVID19 pandemic?

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for an unprecedented global pandemic that has prompted attempts to mitigate its rapid transmission. A major barrier has been a limited understanding of the mechanisms that underlie its pathogenesis. Angiotensin converting enzyme (ACE) 2 may be an important receptor that the virus targets to establish infection, and this is upregulated with ACE inhibitor and angiotensin-receptor blocker (ARB) therapy. It has been suggested that avoidance of ACE inhibitor/ARB therapy may be advisable due to the theoretical risk of SARS-CoV-2 infection in these patients. A review of the literature to further investigate this possibility corroborated the significance of ACE2 for viral entry of SARS-CoV-2. However, the development of potentially fatal respiratory complications (i.e. acute respiratory distress syndrome; ARDS) appears to be influenced by a downregulation of ACE2 activity, rather than an increase. The literature suggests ACE2 has a protective role against lung injury by cleaving angiotensin II (Ang II). The effects of this are twofold: accumulated Ang II is associated with more pronounced lung deterioration, and the loss of its degradation products that have anti-inflammatory properties enables unopposed lung damage to take place. There is emerging evidence that this is also true for SARS-CoV-2 infection; increased viral load is associated with higher Ang II and extent of lung damage. Overall, the evidence indicates that viral attachment decreases, rather than increases, ACE2 activity which may contribute to the respiratory complications seen in severe cases. As such, discontinuation of ACE inhibitor/ARB therapy is currently not warranted.