Comparative Safety of the BNT162b2 Messenger RNA COVID-19 Vaccine vs Other Approved Vaccines in Children Younger Than 5 Years

Abstract

ImportanceSARS-CoV-2 vaccines are authorized for use in most age groups. The safety of SARS-CoV-2 vaccines is unknown in children younger than 5 years.ObjectiveTo retrospectively evaluate the safety of the BNT162b2 vaccine used off-label in children younger than 5 years compared with the safety of non–SARS-CoV-2 vaccines in the same sample.Design, Setting, and ParticipantsThis investigator-initiated retrospective cohort study included parents or caregivers who registered children for SARS-CoV-2 vaccination in outpatient care facilities in Germany. The study was performed as an authenticated online survey. A total of 19 000 email addresses were contacted from vaccination registration databases between April 14 and May 9, 2022. Inclusion criteria were child age younger than 5 years at the first BNT162b2 vaccination and use of a correct authentication code to prove invitation.ExposuresOff-label BNT162b2 vaccination and on-label non–SARS-CoV-2 vaccinations.Main Outcomes and MeasuresReported short-term safety data of 1 to 3 doses of 3 to 10 μg BNT162b2 in children from birth to younger than 60 months are presented. Coprimary outcomes were the frequencies of 11 categories of symptoms after vaccination with bivariate analyses and regression models adjusting for age, sex, weight, and height.ResultsThe study included 7806 children (median age, 3 years [IQR, 2-4 years]; 3824 [49.0%] female) who were followed up of for a mean (SD) of 91.4 (38.8) days since first BNT162b2 vaccination (survey response rate, 41.1%). A 10-μg dosage was more frequently associated with local injection-site symptoms compared with lower dosages. In the active-comparator analysis, the probability of any symptoms (odds ratio [OR], 1.62; 95% CI, 1.43-1.84), local symptoms (OR, 1.68; 95% CI, 1.38-2.05), musculoskeletal symptoms (OR, 2.55; 95% CI, 1.32-4.94), dermatologic symptoms (OR, 2.18; 95% CI, 10.7-4.45), or otolaryngologic symptoms (OR, 6.37; 95% CI, 1.50-27.09) were modestly elevated after BNT162b2 compared with non–SARS-CoV-2 vaccines, whereas the probabilities of general symptoms (OR, 0.77; 95% CI, 0.63-0.95) and fever (OR, 0.42; 95% CI, 0.32-0.55) were lower after BNT162b2. Symptoms requiring hospitalization (n = 10) were reported only at BNT162b2 dosages above 3 μg.Conclusions and RelevanceIn this cohort study, the symptoms reported after BNT162b2 administration were comparable overall to those for on-label non–SARS-CoV-2 vaccines in this cohort of children younger than 5 years. The present data may be used together with prospective licensure studies of BNT162b2 efficacy and safety and could help guide expert recommendations about BNT162b2 vaccinations in this age group.

Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study

“…The original survey was available on a web-based REDCap platform (21) from April 15 th to May 9 th 2022. The survey procedure was pseudonymized and authentication-only as previously described (18). In brief, all eligible potential participants were recruited via the e-mail addresses by which they had previously registered a child aged less than 5 years old for a vaccination with BNT162b2.…”

“…The survey included close-ended questions gathered demographic information, basic medical data, and timing and dosage of vaccinations with BNT162b2, and all non-SARS-CoV-2 vaccinations in the three months preceding the first BNT162b2 administration. Next, questions covered post-vaccination symptoms occurring after BNT162b2 or non-SARS SARS-CoV-2 vaccinations in 9 symptom categories with close-ended and open-ended follow-up questions to narrow down the characteristics of each individual symptom as described in the initial CoVacU5 study (18).…”

“…A population that was the last to become eligible for SARS-CoV-2 vaccines were young children. We have previously reported on the overall safety and effectiveness of BNT162b2 in the retrospective CoVacU5 cohort of children vaccinated off-label in Germany (18,19). Such inclusion and assessment represent a unique opportunity to detect otherwise inaccessible dose-response relationships in post-vaccination symptoms.…”

DNA and mRNA Vaccines for Chronic Viral Infections and Cancer: Rationale, Mechanisms, and Progress

“…Concerns about theoretical integration for DNA vaccines were alleviated by the demonstration that integration did not occur using highly sensitive pre-clinical assays in mice [ 26 , 27 ] and then in the safety of many human clinical trials [ 28 , 29 ]. The mRNA vaccines have been administered in over a billion individuals [ 30 ], with limited adverse events [ 31 , 32 ].…”

Anti‐SARS‐CoV‐2 mRNA vaccines, their efficiency, side effects and controversies

“…14 Even in children younger than 5 years 'the symptoms reported after BNT162b2 administration were comparable overall to those for on-label non-SARS-CoV-2 vaccines in this cohort'. 15 In addition, Townsend et al 16 show that immunity conveyed by mRNA vaccines is likely to last twice longer than immunity from natural infection or by viral vector vaccines. A longer durability of neutralization efficacy would slow the emergence of escape variants.…”