Safety of mRNA-Platform based Covid-19 Vaccines in Pediatric Population: An Analysis of the European Pharmacovigilance Database Eudravigilance: An International Journal of Medical Toxicology and Drug Experience

ABSTRACT

Introduction: Recently mRNA-based COVID-19 vaccines have been approved also for use in pediatric population. Vaccines safety require particular attention in this population. Analysis of pharmacovigilance database allows to extrapolate important information to identify possible safety signals. Objective: Our pharmacovigilance study aims to describe and evaluate the onset of adverse events following immunization (AEFIs) with COVID-19 mRNA vaccines in the pediatric population. Methods: We retrieved all pediatric Individual Case Safety Reports (ICSRs) collected in the European pharmacovigilance database, Eudravigilance from the 01/01/2021 to 4/03/2022 related to Spikevax and Comirnaty. We carried out a disproportionality analysis (Reporting Odds Ratio-95% CI) to compare the reporting probability of some AEFIs of interest (seizure, pericarditis, myocarditis, multisystem inflammatory syndrome (MIS), menstrual disorders, failure and anaphylactic shock) between Comirnaty and Spikevax. Results: We retrieved in Eudravigilance 25.019 ICSR related to Comirnaty describing a total of 75.040 AEFIs and 1.862 ICSRs referred to Spikevax reporting overall 5.361 AEFIs occurred in pediatric population. Majority of ICSRs reported well-known general disorders (headache, pyrexia, fatigue and nausea) for both mRNA vaccines. ICSRs were more frequently referred the adolescent patients (Comirnaty, 86.2%;Spikevax, 86.4%). We found a slight prevalence of female gender for both mRNA vaccine (Spikevax, 52.6 %;Comirnaty 53.9%). Reproductive system disorders were more frequently referred to females. In particular, these events included menstrual disorders (N = 609, Comirnaty;N = 23, Spikevax), amenorrhoea (N = 408, Comirnaty;N = 16, Spikevax) or intermenstrual bleeding (N = 169, Comirnaty;N = 10, Spikevax), polymenorrhoea (N = 172, Comirnaty;N = 10, Spikevax). Few cases described reproductive system disorders in males, mainly related to Comirnaty. These AEFIs included testicular pain (N = 14, Comirnaty;N = 1, Spikevax), erectile dysfunction (N = 5, Comirnaty), testicular torsion (N = 4, Comirnaty) or swelling (N = 4, Comirnaty), scrotal pain (N = 3, Comirnaty) or oedema (N = 1, Comirnaty). Outcome of AEFIs was unknown in 14.8% and 21.1% cases for Spikevax and Comirnaty, respectively. AEFIs had a favorable outcome in more than 50% of cases for both mRNA vaccines, including a complete resolution (30%) or an ongoing resolution (20%). From disproportionality analysis emerged a statistically significant ROR for menstrual disorders (ROR 1.72, 95% CI 1.43-2.10;p < 0.05), failure (ROR 8.11, 95% CI 5.05-13.97;p < 0.05) and seizure (ROR 1.54, 95% CI 1.03-2.41;p = 0.037) when compared Comirnaty versus Spikevax. Conclusion: Majority of pediatric AEFIs are mild and with a positive outcome, supporting the role of ongoing COVID-19 vaccination campaign in this population as a critical public health tool for disease prevention and control of pandemic. Further investigations are needed in this population.