Recent studies, including ours, have suggested that L452R4–9, N460K2,6,10,11, and R346T2 increase the binding affinity of the SARS-CoV-2 S protein to human angiotensin-converting enzyme 2 (ACE2), the receptor for viral infection, while R346T12,13, K444T13 and F486V2,4,5,13–15 contribute to evasion of antiviral humoral immunity induced by vaccination and natural SARS-CoV-2 infection. This evidence concerns the gene ACE2 and viral infectious disease.