Thus, in the present study, we aimed to (i) reveal the landscape of the polymorphic patterns within the exons of the ACE2 gene, (ii) evaluate the association of flanking intronic variants with COVID-19 disease severity, (iii) study the relationship between plasma ACE2 levels and COVID-19 severity, and (iv) explore the roles of the ACE2 variants on plasma ACE2 levels. Here, ACE2 is linked to COVID-19.