Seasonal influenza vaccination remained strongly protective against influenza-associated pediatric death in children with and without underlying medical conditions, reinforcing current recommendations to improve pediatric influenza vaccination coverage.
Influenza vaccination is associated with a markedly lower risk of influenza-associated death among children in the United States, regardless of whether they had underlying medical conditions, according to study findings published in Pediatrics
Pediatric influenza deaths continue to occur each influenza season despite longstanding recommendations for annual vaccination in children aged 6 months and older. Following a decline in pediatric influenza vaccine uptake after the COVID-19 pandemic, the US recorded its highest number of influenza-associated pediatric deaths during the 2024-2025 season since national reporting began
Researchers conducted a nationwide case-cohort analysis to evaluate vaccine effectiveness (VE) against influenza-associated death across 8 influenza seasons to better quantify the protection afforded by vaccination. They used data from the US Influenza-Associated Pediatric Mortality Surveillance System collected during the 2016-2017 through 2024-2025 influenza seasons. The 2020-2021 season was excluded due to minimal influenza activity. Vaccination status among children who died from laboratory-confirmed influenza was compared with age-, state-, and season-specific influenza vaccination coverage estimates obtained from national immunization surveys. Logistic regression was employed for statistical analysis.
[F]indings of this analysis highlight the importance of seasonal influenza vaccination to prevent severe illness and complications of influenza in children and adolescents
The analysis included 1234 laboratory-confirmed influenza-associated deaths among children aged 6 months to 17 years reported from 51 US jurisdictions. Nearly half (48%) of deaths occurred among children with at least 1 underlying medical condition associated with severe influenza, while 52% occurred among children without a documented high-risk condition. Children aged 5 to 12 years represented the largest age group (45%), followed by those aged 6 months to 4 years (37%) and adolescents aged 13 to 17 years (18%). Overall, 56% of children died after hospital admission, 25% died in the emergency department, and 17% died outside the hospital.
Vaccination status was available for 1117 children. Overall, only 17% of patients were fully vaccinated against influenza during the season in which their fatal illness occurred. Among children with underlying medical conditions, 23% had been fully vaccinated compared with just 12% of those without known high-risk conditions. Across all seasons, approximately 18% of influenza A-associated deaths and 17% of influenza B-associated deaths occurred among fully vaccinated children
After excluding partially vaccinated children, the researchers found that influenza vaccination was associated with an 80% (95% CI, 75-84) reduction in the risk of influenza-associated death overall. Protection remained substantial among children with underlying medical conditions (VE, 77%; 95% CI, 71-82) and was even greater among children without known high-risk conditions (VE, 87%; 95% CI, 84-89)
Age-specific analyses showed that VE among children with underlying medical conditions was highest for those aged 6 months to 4 years (83%; 95% CI, 78-88) and lowest among adolescents aged 13 to 17 years (66%; 95% CI, 57-73). Among children without underlying medical conditions, VE ranged from 80% to 89% across age groups. The researchers reported similar levels of protection against influenza A- and influenza B-associated deaths, and findings remained statistically significant across multiple sensitivity analyses designed to account for missing vaccination information and possible overestimation of vaccination coverage in national surveys.
The researchers also observed declining influenza vaccine uptake over the study period. Average vaccination coverage among comparison cohorts without known high-risk conditions fell from approximately 51% to 59% before the COVID-19 pandemic to 39% to 48% during the 2021-2025 seasons. Among children with underlying medical conditions, estimated coverage declined from approximately 50% to 58% before the pandemic to 42% to 50% afterward
Study limitations include the reliance on laboratory-confirmed cases reported through national surveillance, which may not capture every influenza-associated pediatric death. In addition, incomplete vaccination records or medical histories for some children could have resulted in misclassification, and assumptions used to estimate vaccination coverage among children with high-risk conditions may have influenced VE estimates
“[F]indings of this analysis highlight the importance of seasonal influenza vaccination to prevent severe illness and complications of influenza in children and adolescents,” the researchers concluded
Leonard JS, Reinhart K, Lu P-J, et al.Influenza vaccine effectiveness against pediatric death in the United States: 2016-2025.Pediatrics. 2026;158(2):e2026076453. doi:10.1542/peds.2026-076453
