Risk Factors Associated with Adverse Events Following COVID-19 Vaccination in Children Aged 5-11 Years: A Real-World Observational Study.

Background: COVID-19 vaccination has demonstrated a favorable safety profile in children; however, factors associated with the occurrence of adverse events (AEs) following immunization remain insufficiently characterized. This study aimed to identify the demographic and clinical factors associated with AEs following COVID-19 vaccination in children aged 5-11 years. Methods: We conducted an ambispective observational cohort study in Madrid, Spain, including children aged 5-11 years vaccinated with the 10 µg formulation of BNT162b2 (Comirnaty®, Pfizer-BioNTech). Data were obtained from vaccination registries, electronic health records, and structured telephone interviews with parents or legal guardians. Demographic characteristics, anthropometric variables, previous SARS-CoV-2 infection, medical history, and concomitant medication use were evaluated. Univariable analyses and multivariable logistic regression were performed to identify factors independently associated with the occurrence of suspected AEs. Results: A total of 2026 children were included. Suspected AEs were reported in 759 participants (37.5%). In univariable analyses, greater weight, height, pre-existing medical conditions, concomitant medication use, clinically vulnerable status, and previous SARS-CoV-2 infection were significantly associated with AEs. In the multivariable model, previous SARS-CoV-2 infection (OR 4.07, 95% CI 3.13-5.30), number of concomitant medications (OR 7.77, 95% CI 5.22-11.56), number of pre-existing medical conditions (OR 1.86, 95% CI 1.62-2.14), and height (OR 1.03, 95% CI 1.01-1.04) remained independently associated with AEs. Age, sex, body mass index, and clinically vulnerable status were not independently associated with AE occurrence. Conclusions: In this large real-world pediatric cohort, previous SARS-CoV-2 infection, comorbidity burden, and concomitant medication use were independently associated with adverse events following COVID-19 vaccination. These findings suggest that underlying clinical complexity may be a more important determinant of post-vaccination reactogenicity than demographic characteristics and support the value of individualized pre-vaccination assessment in pediatric populations.