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

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.
Competing Interests: Potential conflicts of interest. M. G. reports grants from the Centers for Disease Control and Prevention (CDC), CDC-Abt Associates, CDC-Westat, and Janssen, and a leadership position as co-chair of the Infection Diseases and Immunizations Committee. J. S. S. reports a grant from the National Institutes of Health (NIH). A. D. reports grants from the NIH-PETAL Network, ACTIV-3b, ACTIV-4d, and GRAIL and consulting fees from Alung Technologies. M. E. P. reports a grant from the US Department of Defense and support for speaking at the 2022 North American Congress of Clinical Toxicology. I. D. P. reports grants from NIH, Janssen, Regeneron, and Asahi Kasei Pharma. D. N. H. reports grants from NIH (ACTIV-4d and Host Tissue-Nectar Trial). M. N. G. reports a grant from the National Heart, Lung, and Blood Institute (NHLBI); consulting fees for scientific advisory from Endpoint; support for attending an ATS Board of Executives Meeting; and participation in a Regeneron Data Safety and Monitoring Board (DSMB) for a monoclonal antibody trial. M. C. E. reports grants from NIH, Regeneron Pharmaceuticals, and payment from Abbott Labs for attending/lecture at the ASPEN Annual Meeting and on an Abbott webinar on nutrition in patients with COVID019. A. A. G. reports grants from NIH, Department of Defense, AbbVie, and Faron Pharmaceuticals. N. M. M. reports grants from the US CDC. E. T. M. reports grants from NIH and Merck and payment for lectures from the Michigan Infectious Diseases Society. K. W. G. reports grants from the Department of Defense and NIH support for ACTIV-4HT and Department of Defence support for Military Health System Research Symposium 2022 travel. J. H. K. is supported by grant 1K23AI137321-01A1 from the National Institute of Allergy and Infectious Diseases. N. H. reports grants from Sanofi and Quidel. A. S. L. reports grants from the US CDC, National Institute of Allergy and Infectious Diseases, and Burroughs Wellcome Fund; consulting fees from Sanofi and Roche; and membership on the American Society of Virology governing council (unpaid). C. J. L. reports grants from NIH, Department of Defense, CDC, bioMerieux, Entegrion Inc, Endpoint Health, Astra Zeneca, and AbbVie; patents for risk stratification in sepsis and septic shock issued to the Cincinnati Children's Hospital Medical Center; participation on DSMBs for clinical trials for Study Principal Investigators unrelated to the current work; and stock options in Bioscape Digital unrelated to the current work. C. G. G. reports grants from NIH, CDC, the Food and Drug Administration, the Agency for Healthcare Research and Quality, Sanofi, and Syneos Health and consulting fees from Pfizer, Merck, and Sanofi. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)