In summary, the effects of the RNA modifications Ψ, m 5 C, m A, m 1 A and m 3 C on the catalytic activity of SC2RC were investigated. The modifications Ψ, m 5 C and m 6 A, which do not disrupt canonical hydrogen bonding, only slightly slowed the RNA extension reaction. Both m 1 A and m 3 C disrupt canonical hydrogen bonding, but their effects were opposite. The former severely hindered the RNA extension reaction, and truncated product predominated. The latter was able to be read through by SC2RC with a similar rate as Ψ, m 5 C and m 6 A. Without considering the effects of the modifications on the severity of COVID-19 via mechanisms such as induced immunity, genome stabilization and transcription promotion, individuals with elevated m 1 A modification potential would be expected to be less vulnerable to SARS-CoV-2. However, individuals with cancer, obesity and diabetes, who typically have upregulated m 1 A, are more vulnerable to SARS-CoV-2. A potential explanation is that the dynamics of the modification is more important. The m 1 A modification, although inhibits genome replication, may be beneficial or required for viral survival via mechanisms such as viral genome stabilization and immune evasion. Individuals with cancer, obesity and diabetes, while having high potential to install the m 1 A modification, also have upregulated demethylases such as FTO. As a result, it is possible that the virus in these individuals can benefit from the m 1 A modification while the modification can be readily erased to allow efficient replication of genome by SC2RC. The discovery that m 1 A severely inhibits SC2RC while m 3 C does not is interesting, and may provide new insights useful for the prevention, diagnosis and treatment of infectious diseases including COVID-19.