Vaccine Effectiveness Against Influenza A(H3N2)–Associated Hospitalized Illness: United States, 2022

Abstract

Abstract Background The COVID-19 pandemic was associated with historically low influenza circulation during the 2020–2021 season, followed by an increase in influenza circulation during the 2021–2022 US season. The 2a.2 subgroup of the influenza A(H3N2) 3C.2a1b subclade that predominated was antigenically different from the vaccine strain. Methods To understand the effectiveness of the 2021–2022 vaccine against hospitalized influenza illness, a multistate sentinel surveillance network enrolled adults aged ≥18 years hospitalized with acute respiratory illness and tested for influenza by a molecular assay. Using the test-negative design, vaccine effectiveness (VE) was measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2–negative controls, adjusting for confounders. A separate analysis was performed to illustrate bias introduced by including SARS-CoV-2–positive controls. Results A total of 2334 patients, including 295 influenza cases (47% vaccinated), 1175 influenza- and SARS-CoV-2–negative controls (53% vaccinated), and 864 influenza-negative and SARS-CoV-2–positive controls (49% vaccinated), were analyzed. Influenza VE was 26% (95% CI: −14% to 52%) among adults aged 18–64 years, −3% (−54% to 31%) among adults aged ≥65 years, and 50% (15–71%) among adults aged 18–64 years without immunocompromising conditions. Estimated VE decreased with inclusion of SARS-CoV-2–positive controls. Conclusions During a season where influenza A(H3N2) was antigenically different from the vaccine virus, vaccination was associated with a reduced risk of influenza hospitalization in younger immunocompetent adults. However, vaccination did not provide protection in adults ≥65 years of age. Improvements in vaccines, antivirals, and prevention strategies are warranted.