Seasonal influenza vaccination was associated with substantial protection against influenza-associated death among US children and adolescents, according to a new analysis published in Pediatrics.1 Investigators found that vaccination reduced the risk of fatal influenza by an estimated 80% overall, reinforcing longstanding recommendations for annual vaccination in children 6 months of age and older.
“Clinicians can frame vaccination as protection against severe outcomes,” said Steven Goldberg, MD, MBA, a practicing physician and Chief Medical Officer of HealthTrack. “An 80% vaccine effectiveness estimate means that fully vaccinated children had about one-fifth the risk of influenza-related death compared with unvaccinated children of the same age, state, and influenza season.”
Researchers led by Jerome S. Leonard, MD, MPH, from the Influenza Division, US Centers for Disease Control and Prevention (CDC), analyzed laboratory-confirmed influenza-associated deaths reported to the CDC’s Influenza-Associated Pediatric Mortality Surveillance System during influenza seasons spanning 2016 to 2017 through 2024 to 2025, excluding the 2020 to 2021 season because influenza activity was minimal. The analysis included 1,234 influenza-associated deaths among children aged 6 months to 17 years, with 1,086 cases containing sufficient vaccination information for vaccine effectiveness analyses.
Reported pediatric deaths peaked during the 2024 to 2025 season, when 289 deaths were recorded, the highest number reported since pediatric influenza mortality surveillance began. Overall, only 18% of children who died from influenza-related illness were fully vaccinated during the season in which infection occurred. Among influenza-associated pediatric deaths, full vaccination was nearly twice as common in children with high-risk medical conditions (23%) than in those without high-risk conditions (12%).
To estimate vaccine effectiveness, investigators compared vaccination rates among children who died with influenza vaccination coverage estimates derived from national survey cohorts matched by age, geography, season, and timing. Average influenza vaccination coverage in the comparison cohorts was approximately 49%. The researchers reported an overall vaccine effectiveness of 80% (95% CI, 75%-84%) against influenza-associated death. Vaccine effectiveness was estimated at 77% (95% CI, 71%-82%) among children with underlying medical conditions and 87% (95% CI, 84%-89%) among children without known high-risk conditions.
One of the study’s most notable findings was that approximately half of pediatric influenza deaths occurred among children without known underlying medical conditions. Vaccination remained highly protective within this population, with effectiveness estimates reaching 89% among children aged 6 months to 4 years and 80% among adolescents aged 13 to 17 years.
The finding highlights the continued vulnerability of otherwise healthy children to severe influenza outcomes.
“Because roughly half of pediatric influenza deaths occur in children with no underlying condition, being healthy is a reason to prioritize vaccination, not skip it,” Goldberg said. “Protection was observed in both healthy children and children with complex medical conditions.”
The analysis also comes amid declining pediatric influenza vaccination rates. According to the data, childhood influenza vaccination coverage has fallen since 2021, while the 2024 to 2025 season produced the highest number of reported pediatric influenza deaths recorded through the surveillance system.
Dr. Goldberg said the large variation in pediatric influenza deaths from season to season reflects multiple contributing factors, including circulating viral strains, vaccine match, population immunity, vaccination coverage, and differences in testing and reporting.
“Season-to-season variation is expected,” he said. “Because clinicians and families cannot predict whether an upcoming season will be mild or severe, annual vaccination remains important.”
The study also highlighted how quickly severe influenza can progress in children.
“Fatal influenza in children can involve complications beyond pneumonia,” Dr. Goldberg said. “The median time from symptom onset to death was only five days, showing how quickly severe influenza can progress.”
Invasive bacterial coinfections, neurologic complications, myocarditis, and severe respiratory disease can all contribute to poor outcomes, he said.
The authors acknowledged several limitations, including potential underreporting because surveillance relies on laboratory-confirmed cases and the possibility of incomplete vaccination records. Nonetheless, they concluded that seasonal influenza vaccination was associated with a substantially reduced risk of influenza-associated death among children and adolescents, regardless of whether they had recognized high-risk medical conditions.
For clinicians, Dr. Goldberg said, vaccination should be paired with prompt recognition and treatment of suspected influenza.
“Vaccination lowers the risk of severe illness; if a child does develop influenza, early recognition and prompt antiviral treatment remain essential, especially for high-risk children,” he said.
References
1. Leonard JS, Reinhart K, Lu PJ, 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
