Angiotensin Converting Enzyme 2 May Mediate Disease Severity In COVID-19

Gue, Ying Xuan; Kanji, Rahim; Markides, Vias; Gorog, Diana Adrienne

Identification of vulnerability to severe coronavirus disease 2019 (COVID-19) is extremely important and might allow optimised shielding and easing of lockdown. The disease is attributed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which enters host cells through binding to angiotensin converting enzyme 2 (ACE2) on the cell surface. Clinical syndromes such as hypertension that display reduced ACE2 expression tend to correlate with a more severe disease course, whereas treatments which upregulate ACE2 such as the use of angiotensin converting enzyme inhibitors (ACE-i) appear to have a protective effect against COVID-19. Pre-clinical studies have shown that plasma soluble ACE2 could render SARS-CoV-2 inactive in a dose-dependent manner. The association of clinical syndromes or treatments that impact ACE2 expression and clinical severity of COVID-19 infection combined with the reduction in viral load with human recombinant serum ACE2 shown in pre-clinical studies indicate a key role for ACE2 in determining COVID-19 severity. In conclusion, we propose that measurement of ACE2 level may help identify individuals at risk of severe infection where targeted shielding can be used and could provide a novel therapeutic target.