A systematic review of the literature on the relationship between ACE2 and SARS-CoV infection in animal models

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Rana Kamhawy
April (YiChen) Liu
Kyrillos Faragalla
Dr. Gurmit Singh
Dr. Gilmar Reis
Dr. Lehana Thabane




Similar to the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), research suggests COVID-19 interacts with Angiotensin-Converting-Enzyme-2 (ACE2) to gain entry into cells. The primary objective is to synthesize existing research on the association between ACE2 and coronavirus infections. The secondary objective is to describe the consequences of infection on ACE2 expression.


We performed a systematic literature search of Medline, Embase, and Global Health databases. We included animal studies on the connection between COVID-19 or SARS-CoV infection and variations in ACE2 receptors. Included studies were assessed for quality using the CAMARADES checklist.


We included nine studies all determining the role of ACE2 in SARS-CoV infections. Five low-moderate quality studies showed that increased ACE2 expression was correlated with increased SARS-CoV infection. Post-infection, 5 low-moderate quality studies showed down regulation of ACE2 to be associated with increased clinical symptoms, morbidity, and mortality.


This review shows that pre-infection, greater ACE2 expression correlates with increased infection leading to worse clinical outcomes. Assuming similar mechanisms for COVID-19 as in SARS-CoV, it is plausible that ACE2 has some role and impact in COVID-19 infections. Further high-quality animal model research is needed to determine the role of ACE2, specifically in COVID-19 infections.