Pediatric Vaccine Effectiveness Against Influenza Hospitalization and Outpatient Visits: 2021–2024

OBJECTIVES: Understanding the protection from influenza vaccines could help inform vaccine counseling, which might improve pediatric influenza vaccination uptake. We estimated vaccine effectiveness (VE) against influenza-associated hospitalization and outpatient visits during 3 influenza seasons (2021-2024). METHODS: We used data from 7 US pediatric medical centers within the New Vaccine Surveillance Network. We included children aged 6 months to 17 years who were hospitalized or received outpatient care for acute respiratory illness (ARI). We estimated VE against influenza-associated hospitalizations and outpatient visits with subgroup analyses for each season, stratifying by health care setting, age, and influenza virus type/subtype/genetic clade. RESULTS: Among 19 917 children with ARI, 2831 (14%) were positive and 17 086 (86%) were negative for influenza; 8523 (43%) were vaccinated, and 11 394 (57%) were unvaccinated. Vaccination uptake among children testing negative for influenza ranged from 44% to 51% by season. VE overall ranged from 34% to 60% across seasons, with the lowest VE estimates during 2021 to 2022. Effectiveness was 53% against influenza A/H1N1, 43% against A/H3N2, and 69% against B, with further variation by clade. CONCLUSIONS: From 2021 to 2024, pediatric influenza VE ranged from 34% to 60%, and overall was effective at preventing influenza-associated hospitalizations and outpatient visits. Effectiveness was higher against influenza B and lower during the 2021 to 2022 season. Vaccine uptake was low among children, with only half or fewer receiving the influenza vaccine each season. Influenza vaccination is the best way to reduce the risk of influenza for children. Improved pediatric influenza vaccination uptake would prevent additional influenza-associated hospitalizations and outpatient visits.