On the other hand, a different viewpoint is based on the intriguing observation that several conditions increasing the risk of viral infection and disease severity are all characterized by a certain degree of ACE2 deficiency. As discussed above (section “Structure of ACE2”) ACE2 deficiency has been suggested to play a significant role in the pathophysiology of hypertension, cardiovascular disease and diabetes. The role of ACE2 expression in the panel of comorbidities correlated to SARS-CoV-2 is a matter of intense still unsolved debate, as brilliantly revised by Shyh et al. (2020) in a very recent paper.