Vaccine Effectiveness Against Influenza A–Associated Hospitalization, Organ Failure, and Death: United States, 2022–2023

Background. Influenza circulation during the 2022–2023 season in the United States largely returned to pre–coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. Methods. To understand effectiveness of the 2022–2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2–negative control-patients. Results. A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%–46%) and varied by age (18–64 years: 47% [30%–60%]; ≥65 years: 28% [10%–43%]), and virus (A[H3N2]: 29% [6%–46%], A[H1N1]: 47% [23%–64%]). VE against more severe influenza-associated outcomes included: 41% (29%–50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%–72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%–81%) against influenza with respiratory failure treated with invasive mechanical ventilation. Conclusions. During an early 2022–2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.