Omicron’s reduced ability to replicate effectively in TMPRSS2 expressing cells such as alveolar tissue (which is the main anatomical site of COVID-19 pathogenesis) and its effective entry into cells of the upper respiratory tract [875,876] (mainly through the cathepsin-L pathway) might explain this reduction in disease severity in immunologically naïve individuals. Here, TMPRSS2 is linked to COVID-19.