Genomic Evidence of HMPV Resurgence in Beijing: Clade B2 Triggers the 2024 Winter Epidemic Peak.

With an unexpected increase of human metapneumovirus (hMPV) cases in northern China since late 2024, concerns arose whether novel hMPV variants triggered this epidemic. Utilizing the Beijing Respiratory Pathogen Surveillance System (RPSS), we conducted a genomic evolutionary analysis spanning 2014-2024 and revealed genetic information for the strains that caused the high rates of hMPV outbreaks during this period. To clarify the epidemic drivers and evolutionary characteristics of the hMPV strains circulating in Beijing, phylogenetic, population dynamic and mutation analyses were performed using high-quality complete sequences from both this study and publicly available data. A total of 348 high-quality hMPV genomes were obtained by next-generation sequencing (NGS), all of which belonged to four known clades: A2b1, A2b2, B1, and B2. Before 2024, A2b2 predominated in Beijing; however, a shift to clade B2 was observed starting in late 2024. In addition, a phylogenetically independent lineage Ⅰ was identified in this study, accounting for 93.1% of B2 genomes collected since late 2024. Furthermore, we identified several unique nonsynonymous mutations in viruses within lineage I that may have phenotypic implications. Our findings indicate that lineage I of clade B2 was the major cause of the unusual increase in hMPV outbreaks in Beijing in late 2024, with no evidence of an emerging novel variant. Although our data were only restricted to samples from Beijing, the findings are likely representative of the hMPV surge across northern China in 2024, given city's high population density and mobility.