TMPRSS2 and infection: Thus, the Omicron S protein, unlike the S proteins of WT virus and all previous VOCs, fails to use the serine protease TMPRSS2 for efficient S protein activation.5 Although the Omicron variant employs the cysteine protease cathepsin L for infection of nasal epithelium, an unknown, possibly TMPRSS2-related serine protease promotes infection of airway epithelium but might be absent from alveolar type 2 cells, which could account for the inability of the Omicron variant to infect these cells and to efficiently spread in lung tissue.5