Influenza vaccination effectiveness in children with underlying medical conditions: a case-control study

Children with underlying medical conditions are at increased risk of severe influenza outcomes. The aim of this study was to evaluate the effectiveness of influenza vaccination for children and adolescents with underlying medical conditions. We conducted a multicentre case-control study over three influenza seasons (2021/22, 2022/23; 2023/24) in Spain. Hospitalized children and adolescents aged 6 months to 17 years with underlying medical conditions were included. Cases were patients hospitalized with acute respiratory infection (ARI) and laboratory-confirmed influenza. Two different hospitalized control groups were included: test-negative controls and non-ARI controls. Adjusted vaccination effectiveness (VE) was estimated using multivariate logistic regression. A total of 274 children were included (66 influenza cases and 208 controls), 21.5% of whom were vaccinated. VE against influenza-associated hospitalization was not statistically significant in the overall study population. In immunocompetent children, adjusted VE was 80.6% (95% CI: 36.7-95.9) considering all controls and 81.7% (95% CI: 39.3-95.9) considering with test-negative controls. No statistically significant VE was observed among immunocompromised children. Results were consistent after excluding SARS-CoV-2-positive participants. No significant effectiveness were found by age group, influenza type or subtype, or time since vaccination.

Influenza vaccination provided protection against influenza-related hospitalization among immunocompetent children with underlying medical conditions. The low proportion of vaccinated children among hospitalized cases highlights the need to improve influenza vaccination uptake among children with underlying medical conditions and to further evaluate preventive strategies for immunocompromised children.

• Children with underlying medical conditions are at increased risk of influenza-related hospitalization. • Despite influenza vaccination recommendations, vaccination coverage among children with underlying medical conditions remains suboptimal.

• Seasonal influenza vaccination was associated with protection against influenza-related hospitalization among immunocompetent children with underlying medical conditions. • The low proportion of vaccinated children among hospitalized cases highlighting missed prevention opportunities and the need to improve vaccination uptake and explore alternative preventive strategies for immunocompromised children.