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

  1. Nicole Toepfner
  2. Wolfgang C. G. von Meißner
  3. Christoph Strumann
  4. Denisa Drinka
  5. David Stuppe
  6. Maximilian Jorczyk
  7. Jeanne Moor
  8. Johannes Püschel
  9. Melanie Liss
  10. Emilie von Poblotzki
  11. Reinhard Berner
  12. Matthias B. Moor
  13. Cho-Ming Chao

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Abstract

SARS-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.

Objective

To 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 Participants

This 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.

Exposures

Off-label BNT162b2 vaccination and on-label non–SARS-CoV-2 vaccinations.

Main Outcomes and Measures

Reported 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.

Results

The 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 Relevance

In 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.

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  1. Version published to 10.1001/jamanetworkopen.2022.37140
  2. ScreenIT

    SciScore for 10.1101/2022.05.17.22275005: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Inclusion criteria were having registered in a database for at least one dose of BNT162b2 that was administered before reaching the age of 5 years, and informed consent of a parent/legal representative to participate in the survey of the current study.
    IRB: The present study protocol was approved by the Ethics Committee of the University of Rostock, Germany (ID: A 2022-0065).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using MATLAB R2020a and STATA version 15. Chi-Square or Fisher’s exact tests were used to compare categorical variables over pre-defined strata of age groups and BNT162b2 dosage.
    MATLAB
    suggested: (MATLAB, RRID:SCR_001622)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The present study contains some limitations. First, the study relies on retrospective self-reported data by proxy, which i) may not directly reflect what a child had experienced and ii) underlies a risk of recall bias i.e. not recalling some not life-threatening symptoms several months later. However, the extensive public debate about SARS-CoV-2 vaccinations including their potential side effects, the off-label use investigated, and the study results showing dosage-dependent associations between vaccination and local reactions in ≥24 to <60 months old children suggest that symptoms were adequately reported. The retrospective design did not allow for a structured real-time documentation of symptoms nor an estimation of causality and severity to infer the frequency of vaccine-related serious adverse reactions, but such data should be expected from the ongoing prospective manufacturer-sponsored BNT162b2 studies (5). As vaccinations themselves were not directly part of the study, the study relied on vaccination information as reported by the respondents. However, a potential risk of manipulation by individual respondents was minimized by dispensing study participation codes only via vaccinating centers/initiatives, and the availability of BNT162b2 lot numbers. Moreover, potential duplicate entries were identified by overlap in demographic data and were removed. The reported post-vaccination symptoms could potentially be unrelated to the vaccine. To mitigate this problem, a non-BN...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.05.17.22275005v1 on medRxiv