Because it is not possible to conduct experiments on reinfection of SARS-CoV-2 (with low or normal m5C modification) in humans, we used a mouse model to simulate patients with severe and mild COVID-19 and revealed that progeny SARS-CoV-2 virions from Nsun2+/− mice (with low m5C level, simulating patients with severe COVID-19) showed a stronger replication ability and virulence in the new round of infection in a K18-hACE2 mouse model (Fig. 8) than the progeny SARS-CoV-2 virions from Nsun2+/+ mice (with normal m5C level, simulating patients with mild COVID-19 or healthy individuals). This evidence concerns the gene NSUN2 and COVID-19.