Annually, thousands of children in the United States are hospitalized and 35–200 die from influenza illness and its complications.^1,2 Influenza vaccines are highly effective against life-threatening influenza in children.³ Even a partially effective influenza vaccine can avert symptomatic illness, hospitalization, and death, and reduce illness severity if a child is infected. The Advisory Committee on Immunization Practices began recommending annual influenza vaccination of all children aged ≥6 months starting in 2010–2011. Vaccination rates among children <18 years of age vary, ranging from 33.4–62.6% during 2010–2019.^4,5 Children who die from influenza often have an underlying condition known to increase the risk of influenza-associated complications and are unvaccinated.⁶ For children with severe influenza, or illness that can result in hospitalization or death, previous vaccination ≥2 weeks before illness reduces disease severity and risk of death.³ We described patient, vaccination, and influenza illness characteristics by underlying condition status among children aged <18 years who died from influenza during 2004–2023 in California.

California law requires reporting pediatric influenza-associated deaths to public health authorities. This activity was reviewed by the Centers for Disease Control and Prevention (CDC), deemed not research, and was conducted consistent with applicable federal law and CDC policy.§ We included all pediatric influenza-associated deaths reported during October 9, 2004–September 30, 2023. Race and ethnicity of fatal pediatric influenza patients were determined by electronic health records and included for descriptive purposes. Duration of illness before death was calculated as the difference between symptom onset date and date of death. Clinical variables of interest included whether a patient was admitted to the intensive care unit, use of antibiotics, use of antivirals, type of medical facility, secondary bacterial infection status, pneumonia status, vaccination status, number of underlying conditions, location of death, and influenza type. Number of underlying conditions was determined by the total number of conditions known to have an association with severe influenza outcomes, including respiratory, metabolic, cardiac, renal, pulmonary, neurologic, and immunocompromising conditions. Clinical variables were determined from chart review and entered into the electronic health record.

During 2004–2023, 0–46 children died from influenza and were reported to public health. There was a significant drop in deaths from 2020–2021 due to the COVID-19 pandemic. Among 245 children who died of influenza, median age was 6.3 years (range: 3 days–17 years) (Table 1). Most (59%; n = 145) were infected with influenza A and 18% (n = 45) with influenza B. Fewer than 1% (n = 1) were coinfected with A and B; 22% (n = 54) had an unknown influenza type. Most children (62%; n = 152) had ≥1 underlying conditions (median 1; range = 1–6). Of children with known vaccination status, 27% (37/135) had documented vaccination ≥2 weeks before illness onset; 29% (27/92) of children with underlying conditions were vaccinated vs 23% (10/43) of previously healthy children. Many children died in the intensive care unit (58%, n = 142/245). Most children with underlying conditions had pneumonia (55%) and frequently received antiviral treatment (53%) (Table 1). Median duration of illness before death was 7.5 days for children with preexisting conditions and 4.0 days for healthy children. Previously healthy children accounted for 38% of the influenza deaths in California.

Our findings demonstrate that some children with influenza can have rapid evolution to severe disease; though counterintuitive, this phenomenon is most striking in previously healthy children. Over 50% of children without underlying conditions died at home or in an emergency department; only 25% received antiviral treatment. Vaccination coverage of children dying of influenza in California was low compared to national estimates for children 6 months–17 years, which range between 43.7–63.7% depending on influenza season.^6,7 This analysis is limited by unknown vaccination status for some children, because reporting of vaccine doses to an immunization registry was not mandatory in California until 2023; data prior to 2023 were gathered from multiple sources to improve data quality.

This analysis highlights potential missed opportunities for prevention of fatal influenza illness among children with and without underlying conditions. Future investigation should assess effects of vaccination on influenza illness severity, while accounting for other factors such as prior season vaccination, severity of preexisting conditions, and propensity to seek healthcare. Vaccination is recommended for all children ≥6 months of age, and messaging directed at both clinicians and parents to support increased influenza vaccination is vital to reducing influenza burden.

§ See e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. §241(d); 5 U.S.C. §552a; 44 U.S.C. §3501 et seq.