Impact and Effectiveness of COVID-19 mRNA Vaccination Against COVID-19 Hospitalisation in Paediatrics: A Cohort Study Using Two Linked Data Sources in Spain

Purpose: Despite Spain's > 2 million COVID-19 paediatric cases before 2024, few required hospitalisations (8900). We aimed to estimate the effectiveness of two-dose COVID-19 vaccinations against hospitalisation ‘with’ and ‘for’ COVID-19 in paediatrics. Methods: All individuals aged 5–14 years between January 2021 and February 2022 in two databases in Spain (SIDIAP and BIFAP) vaccinated against COVID-19 (two doses) were matched 1:1 to unvaccinated controls with the same age, sex, region and comorbidities on the dates of vaccination. Individuals with previous SARS-CoV-2 infections were excluded. COVID-19 was identified as the main reason (hospitalisation ‘for’ COVID-19; SIDIAP) or as one of the reasons (hospitalisation ‘with’ COVID-19; BIFAP) for hospitalisation with a positive SARS-CoV-2 test ±30 days. Incidence rate differences and vaccine effectiveness (VE; 95% CI; controlled by inverse probability weights) against hospitalisations ‘for’ and ‘with’ COVID-19 were calculated. Results: The cohorts included 75 361 (SIDIAP) and 178 589 (BIFAP) pairs. Among vaccinated individuals (99.99% with mRNA vaccines) and controls, < 5 and 15 hospitalisations ‘for’ COVID-19 were identified (SIDIAP), whereas 21 and 32 hospitalisations ‘with’ COVID-19 (BIFAP), all aged 12–14 years old. Vaccination prevented 2.5 hospitalisations ‘for’ and 0.5 ‘with’ COVID-19 during the Delta period, and 0.8 hospitalisations ‘with’ COVID-19 during Omicron predominance per 10⁶ person-days. The VE was 94% (95% CI: 52%–99%; SIDIAP) and 53% (95% CI: 18%–74%; BIFAP). Conclusions: Given the low incidence of hospitalised COVID-19, two-dose series mRNA vaccination showed moderate-high effectiveness with few averted cases. Including hospitalisation ‘with’ COVID-19 underestimated the effectiveness. If paediatric severe COVID-19 remains rare, larger databases are required to understand precisely the effectiveness and impact of new vaccines. Trial Registration: EU PAS Register number: EUPAS47725.