Distinct variabilities of infection rates, epidemiological transmission, and clinical outcomes during COVID-19 pandemic raises an intriguing question, whether the emergence of SARS-CoV-2 variants of concern (VOCs) with function-specific mutations in ACE2, furin, and TMPRSS2 expression has played any role in disease manifestations and case fatality rates (CFR)55,75. The gene discussed is ACE2; the disease is infection.