TMPRSS2 and pneumonia: In fact, immune evasion and accumulation of near-neutral mutations both compromise the functionality of viral genes, leading to codon deoptimization and reduced replication capacity. Meanwhile, loss of sensitivity to the TMPRSS2 protease and increased affinity to the ACE2 receptor probably contributed to the change in tissue tropism, resulting in more symptoms of the upper respiratory tract, fewer cases of pneumonia, less involvement of other systems, shorter incubation periods, and enhanced transmissibility.