Effectiveness of COVID-19 Vaccines Against Hospitalization and Severe Disease in Children with Diabetes Mellitus During Pandemic and Post-Pandemic Eras

Pediatric patients with SARS-CoV-2 infection are at an increased risk of severe disease and adverse outcomes. Nevertheless, comprehensive data on COVID-19 vaccine effectiveness (VE) in children with diabetes during the post-pandemic period remain limited. This study assessed the VE against severe COVID-19 outcomes during both the pandemic and post-pandemic phases in children with and without diabetes mellitus (DM). A cohort study based on population data was carried out, including all patients under 18 years of age with symptomatic SARS-CoV-2 infection as registered in the Brazilian national surveillance systems from February 2020 to June 2025. The main outcomes were hospitalization due to COVID-19 and severe illness, which included admission to the intensive care unit (ICU), need for invasive ventilation, and death. Utilizing a propensity score-matched cohort, we estimated the VE and the number needed to vaccinate (NNV) for a booster dose against these outcomes by comparing vaccinated and unvaccinated individuals, employing conditional logistic regression adjusted for confounding variables. The cohort comprised 3,730,007 pediatric patients with COVID-19, of whom 7675 (0.2%) had DM. At baseline, children with DM exhibited a significantly higher prevalence of hospitalization (11.2% vs. 2.0%), severe COVID-19 (6.4% vs. 0.6%), and mortality (1.9% vs. 0.1%) than those without DM (all p < 0.001). During the pandemic period, the adjusted VE was consistently higher in children with DM. Against severe disease, the VE was 72.8% (95% CI: 12.3–93.2) in the DM cohort compared with 45.7% (28.1–59.0) in the non-DM cohort. This increased effectiveness corresponded to a more favorable NNV; the NNV to prevent one severe case was 24 (95% CI: 12–232) for children with DM versus 243 (168–440) for those without DM. In the post-pandemic period, the VE remained significantly higher in the DM cohort. Against severe disease, the VE was 76.2% (11.5–93.5) for children with DM and 52.9% (32.7–67.1) for those without. The NNV to prevent one severe case was consistently lower in the DM cohort (8 vs. 591). In conclusion, a complete vaccination regimen, including a booster dose, substantially mitigated severe COVID-19 outcomes in children with DM in the pandemic and post-pandemic periods.