Abstract

ACE2 has emerged as a double agent in the COVID-19 ordeal being physiologically protective yet conducive of viral infection. The identification of ACE2 in as many as 72 tissues suggests that extra-pulmonary invasion and damage is likely, which indeed has already been demonstrated by cardiovascular and gastro-intestinal symptoms. On the other hand, identifying ACE2 dysregulation in patients with co-morbidities may offer insight as to why COVID-19 symptoms are often more severe in these individuals. This may be attributed to a pre-existing pro-inflammatory state that is further propelled with the cytokine storm induced by SARS-CoV-2 infection or the loss of functional ACE2 expression as a result of viral internalization. Here, we aim to characterize the distribution and role of ACE2 in various organs in order to highlight the scope of damage that may arise upon SARS-CoV-2 invasion. Furthermore, by examining the disruption of ACE2 in several co-morbid diseases, we offer insight into potential causes of increased severity of COVID-19 symptoms in certain individuals.

Significance Statement Cell surface expression of ACE2 determines the tissue susceptibility for COVID-19 infection. Co-morbid disease conditions altering ACE2 expression could increase the patient’s vulnerability for the disease and its complications directly through modulation of viral infection, or indirectly through alteration of inflammatory status.