Emergence of SARS-CoV-2 serotype(s): Is it a matter of time?

Since its identification in late 2019, SARS-CoV-2 has undergone numerous mutations, resulting in the emergence of several viral variants, which may differ in transmissibility, virulence and/or evasion from host immunity. Particularly, immunity-related changes have been well documented in the Omicron variant, including reports of escaping neutralizing antibodies induced by infection/vaccination with heterologous SARS-CoV-2 or used in serological therapy. These findings may encourage some discussions about the possibility that Omicron is a distinct SARS-CoV-2 serotype. To contribute to this issue, we combined concepts from immunology, virology and evolution and performed an interesting brainstorm on the hypothesis that Omicron is a distinct SARS-CoV-2 serotype. Furthermore, we also discussed the likelihood of emergence of SARS-CoV-2 serotypes over time, which may not necessarily be related to Omicron. Finally, insights into this topic may have direct implications for vaccine formulations, immunodiagnostic platforms and serological therapies, contributing to better management of future outbreaks or waves. •Currently, Omicron is the main target of investigation into the possible emergence of distinct SARS-CoV-2 serotypes.•In addition to the S gene, mutations in non-structural proteins may indirectly influence the emergence of SARS-CoV-2 serotypes.•Recombination events involving the S gene could contribute to the emergence of SARS-CoV-2 serotypes.•SARS-CoV-2 variants must be constantly monitored for the possible emergence of a distinct viral serotype.•The emergence of SARS-CoV-2 serotypes would have direct implications for vaccines, immunodiagnosis and serological therapies.