A prospective, comparative cohort analysis of influenza antibody waning in Michigan and Hong Kong during periods of low influenza circulation

BackgroundReduced influenza transmission during the COVID-19 pandemic prompted concern about waning of population immunity that could lead to subsequent surges in circulation. We evaluated this by comparing longitudinal influenza antibody titers in Michigan and Hong Kong, two regions with reduced influenza transmission during the COVID-19 pandemic. MethodsIn two prospective cohort studies (HIVE, Michigan; EPI-HK, Hong Kong), we analyzed longitudinal serum samples collected from 2020 through 2023 from participants without documented influenza virus infection or vaccination. Sera were tested using hemagglutination inhibition assays (HAI) against relevant vaccine strains. Geometric mean titers (GMTs) and fold changes were estimated by region and time. Linear mixed-effects models were used to assess temporal trends. ResultsWe analyzed 173 sera from 57 HIVE participants and 259 sera from 60 EPI-HK participants. Initial GMTs in 2020-21 ranged from 12.3-123.4 in HIVE and 6.3-40.9 in EPI-HK (B/Yamagata-H1N1). Fold changes in GMTs ranged from 1.2-2.6 in HIVE and 0.7-1.0 in EPI-HK. In HIVE models, no significant change in HAI titers over time was detected. In EPI-HK, small but statistically significant monthly declines were observed for select H1N1 (A/Michigan) and H3N2 (A/Hong Kong) strains (e.g., A/Hong Kong: -0.98%, 95% CI: -1.82% to -0.11%). ConclusionMinimal HAI titer waning was observed in both regions. In some cases, antibody levels increased in Michigan, possibly indicating cryptic circulation of strains prior to the 2022/23 influenza season. These findings do not support an "immunity debt" during pandemic restrictions and could help explain the lack of a substantial surge in influenza impact after the COVID-19 pandemic.