Identifying the viral and epidemiological factors behind the apparent global extinction of influenza B/Yamagata

Until 2020, two lineages of the influenza B virus had co-circulated globally. Measures to control the COVID-19 pandemic led to a near-absence of influenza infections. While B/Victoria reemerged in late 2021, there have been no reports of B/Yamagata since the pandemic. To investigate which epidemiological and immunological factors were primarily responsible for the extinction of B/Yamagata, we developed a global model for the two influenza B lineages. To mimic the transmission impacts of the pandemic, we implemented a transient reduction in contacts and identified parameter values that recapitulated viral coexistence dynamic before the pandemic and the qualitative post-pandemic outcomes of B/Victoria (reemergence in late 2021) and B/Yamagata (extinction). Our results suggest that, rather than immunological or evolutionary mechanisms, the extinction of B/Yamagata was mainly driven by its lower basic reproduction number making the virus particularly vulnerable during the early phase of the pandemic. Stochastic simulations of our best-fitting model suggest that B/Victoria was also close to extinction during this period. We investigate the model to assess the feasibility of B/Victoria eradication through vaccination and the potential for a sustained re-emergence of B/Yamagata in the 2026-27 flu season, thus highlighting important considerations for biosafety.