ABSTRACT

China experienced a resurgence of seasonal influenza activity throughout 2021 despite intermittent control measures and prolonged international border closure. We show genomic evidence for multiple A(H3N2), A(H1N1), and B/Victoria transmission lineages circulating over three years, with the 2021 resurgence mainly driven by two B/Victoria clades. Phylodynamic analysis revealed unsampled ancestry prior to widespread outbreaks in December 2020, showing influenza lineages can circulate cryptically under non-pharmaceutical interventions (NPIs) enacted against COVID-19. Novel hemagglutinin (HA) gene mutations and altered age profiles of infected individuals were observed, and Jiangxi province was identified as a major source for nationwide outbreaks. Following major holiday periods, fluctuations in the effective reproduction number were observed, underscoring the importance of influenza vaccination prior to holiday periods or travel. Extensive heterogeneity in seasonal influenza circulation patterns in China determined by historical strain circulation indicate a better understanding of demographic patterns is needed for improving effective controls.