Deceleration and rebound of hemagglutinin divergence in influenza B/Victoria across COVID-19 NPI phases (2016–2024)

The COVID-19 pandemic reshaped global viral transmission and created a natural experiment to test how non-pharmaceutical interventions (NPIs) influence the evolution of co-circulating pathogens. We investigated the evolutionary dynamics of the influenza B/Victoria lineage across China, the United States, and Australia-three countries that implemented distinct COVID-19 policy strategies. Using hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) sequences from GISAID (2016-2024), we performed temporal phylogenetic analyses and estimated rate of genetic distance change. Although the duration and strictness of NPIs varied among the three countries, our analysis revealed a transnational common pattern: the evolution of HA showed a marked slowdown during the NPI period. During the post-relaxation period, the population genetic distance of HA in the three countries showed a highly significant increase compared to the pre-pandemic period (comparison between post-relaxation vs. pre-pandemic period, <i>p</i> < 0.001). The magnitude and trajectory of these shifts differed by country, broadly aligning with policy timing and intensity. These findings highlight the sensitivity of influenza evolution to population-level interventions and underscore the value of integrating policy metrics into influenza surveillance and pandemic preparedness.