Intra-host variation and transmission dynamics of SARS-CoV-2 Omicron outbreaks in Shandong, China

Understanding the mechanisms behind viral evolution and transmission is crucial, as novel SARS-CoV-2 variants continue to emerge and spread worldwide. Viral evolution is driven not only by variants that circulate globally but also by mutations arising within individual hosts, resulting in the emergence of iSNVs. The role of iSNVs in shaping SARS-CoV-2 evolution and transmission remains poorly characterized. Our results showed a significant enrichment of shared iSNVs in high-density genomic regions, potentially contributing to the formation of co-mutation patterns. However, the presence of shared iSNVs in samples lacking epidemiological links indicates that they alone are insufficient for accurately reconstructing transmission routes. Instead, iSNVs may act as a reservoir for the emergence of single nucleotide polymorphisms. Our study offers new insights into the evolution of SARS-CoV-2 and the interpretation of transmission from sequencing data.