Comparative Safety of Tozinameran in Children versus Adolescents: An Analysis of First Pharmacovigilance Data

Background: Based on a good efficacy and immune response in clinical trials, emergency use of Tozinameran, a mRNA-based COVID-19 vaccine was approved by the U.S Food and Drug Administration and by the European Medicines Agency in children of 5-11 years of age. Although there is no serious safety signal in first clinical evaluations, the number of children exposed to Tozinameran was too limited to detect rare adverse events. There is a need to investigate the Tozinameran safety profile in real life in children.

Objectives: In this observational study, we compared the risk of reporting adverse effects with Tozinameran between children of 5-11 years and adolescent of 12-17 years.

Methods: Using Vigibase, the World Health Organization's Global Individual Case Safety Reports database, we conducted a pharmacovigilance study. Reports with Tozinameran in children (5-11 years) and adolescents (12-17 years) recorded until February 3th 2022 were included. Disproportionality analyses were performed to assess a potential increased risk of reporting an adverse effect with Tozinameran in children compared to adolescents. Multivariate logistic regression model were performed to calculate the Reporting Odds Ratios (ROR) with their 95% confidence interval (CI).

Results: We found 4,153 reports in children and 41,716 in adolescents registered in VigiBase. In children and adolescents, the reports originated mainly from the U.S (70% and 38%, respectively) following by European countries (16% and 26%) and Australia (8% and 6%). In children, the most frequent adverse effects reported were malaise/dizziness (31%), and nausea or vomiting (19%). Only 363 reports in children (9%) were considered as serious (as defined by WHO). Compared with adolescents, most of adverse effects in children were less reported or there was no significant difference. We have only found that compared to vaccination in adolescents, vaccination in children was associated with increased reporting odd ratio for digestive adverse drug reaction as diarrhea (1.81; 95%CI 1.49, 2.18) and cutaneous reactions as pruritus (1.94; 95%CI 1.65, 2.27) or urticaria (2.48; 2.20, 2.74). For myocarditis, our analysis could not find any evidence of an increased risk of reporting this effect in children compared to adolescent (0.12; 95%CI 0.08-0.18).

Conclusions: Based on the first four thousand reports of adverse effects in children vaccinated with Tozinameran, no increased risk of reporting, except minor reactions, have been found in children compared to adolescents. This first pharmacovigilance study yield reassuring results about tozinameran safety profile in children and suggests a favorable benefit-risk balance. Further, larger studies are needed to corroborate our results.