Influenza vaccine effectiveness against influenza-associated hospitalization in children: A systematic review and meta-analysis.

Vaccination remains the most effective way to prevent influenza infection, albeit vaccine effectiveness (VE) varies by year. Compared to other age groups, children and elderly adults have the highest risk of developing influenza-related complications and requiring hospitalization. During the last years, "test negative design" (TND) studies have been implemented in order to estimate influenza VE. The aim of this systematic review and meta-analysis was to summarize the findings of TND studies reporting influenza VE against laboratory-confirmed influenza-related hospitalization in children aged 6 months to 17 years. We searched the PubMed and Embase databases and identified 2615 non-duplicate studies that required detailed review. Among them, 28 met our inclusion criteria and we performed a random-effects meta-analysis using adjusted VE estimates. In our primary analysis, influenza vaccine offered significant protection against any type influenza-related hospitalization (57.48%; 95% CI 49.46-65.49). When we examined influenza VE per type and strain, VE was higher against H1N1 (74.07%; 95% CI: 54.85-93.30) and influenza B (50.87%; 95% CI: 41.75-59.98), and moderate against H3N2 (40.77%; 95% CI: 25.65-55.89). Notably, influenza vaccination offered higher protection in children who were fully vaccinated (61.79%; 95% CI: 54.45-69.13), compared to those who were partially vaccinated (33.91%; 95% CI: 21.12 - 46.69). Also, influenza VE was high in children less than 5 years old (61.71%; 95% CI: 49.29-74.12) as well as in children 6-17 years old (54.37%; 95% CI: 35.14-73.60). In conclusion, in the pediatric population, influenza vaccination offered significant protection against influenza-related hospitalization and complete annual vaccination should be encouraged.