Safety of Ancestral Monovalent BNT162b2, mRNA-1273, and NVX-CoV2373 COVID-19 Vaccines in US Children Aged 6 Months to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes after COVID-19 vaccination in the US pediatric population. Design, Setting, and Participants: This cohort study evaluated 21 prespecified health outcomes after exposure before early 2023 to BNT162b2, mRNA-1273, or NVX-CoV2373 ancestral monovalent COVID-19 vaccines in children aged 6 months to 17 years by applying a near-real-time monitoring framework using health care data from 3 commercial claims databases in the US (Optum [through April 2023], Carelon Research [through March 2023], and CVS Health [through February 2023]). Increased rates of each outcome after vaccination were compared with annual historical rates from January 1 to December 31, 2019, and January 1 to December 31, 2020, as well as between April 1 and December 31, 2020. Exposure: Receipt of an ancestral monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-19 vaccine dose identified through administrative claims data linked with Immunization Information Systems data. Main Outcomes and Measures: Twenty-one prespecified health outcomes, of which 15 underwent sequential testing and 6 were only monitored descriptively due to lack of historical rates. Results: Among 4 102 016 vaccinated enrollees aged 6 months to 17 years, 2 058 142 (50.2%) were male and 3 901 370 (95.1%) lived in an urban area. Thirteen of 15 sequentially tested outcomes did not meet the threshold for a statistical signal. Statistical signals were detected for myocarditis or pericarditis after BNT162b2 vaccination in children aged 12 to 17 years and seizure after vaccination with BNT162b2 and mRNA-1273 in children aged 2 to 4 or 5 years. However, in post hoc sensitivity analyses, a statistical signal for seizure was observed only after mRNA-1273 when 2019 background rates were selected; no statistical signal was observed when 2022 rates were selected. Conclusions and Relevance: In this cohort study of pediatric enrollees across 3 commercial health insurance databases, statistical signals detected for myocarditis or pericarditis after BNT162b2 (ages 12-17 years) were consistent with previous reports, and seizures after BNT162b2 (ages 2-4 years) and mRNA-1273 vaccinations (ages 2-5 years) should be further investigated in a robust epidemiologic study with confounding adjustment. The US Food and Drug Administration concludes that the known and potential benefits of COVID-19 vaccination outweigh the known and potential risks of COVID-19 infection.

Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination offers early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the US pediatric population aged 5 to 17 years. Design, Setting, and Participants: This population-based study was conducted under a public health surveillance mandate from the US Food and Drug Administration. Participants aged 5 to 17 years were included if they received BNT162b2 COVID-19 vaccination through mid 2022 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window until the COVID-19 vaccination. Surveillance of 20 prespecified health outcomes was conducted in near real time within a cohort of vaccinated individuals from the earliest Emergency Use Authorization date for the BNT162b2 vaccination (December 11, 2020) and was expanded as more pediatric age groups received authorization through May and June 2022. All 20 health outcomes were monitored descriptively, 13 of which additionally underwent sequential testing. For these 13 health outcomes, the increased risk of each outcome after vaccination was compared with a historical baseline with adjustments for repeated looks at the data as well as a claims processing delay. A sequential testing approach was used, which declared a safety signal when the log likelihood ratio comparing the observed rate ratio against the null hypothesis exceeded a critical value. Exposure: Exposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (dose 1 + dose 2), and dose-specific secondary analyses were conducted. Follow-up time was censored for death, disenrollment, end of the outcome-specific risk window, end of the study period, or a receipt of a subsequent vaccine dose. Main Outcomes: Twenty prespecified health outcomes: 13 were assessed using sequential testing and 7 were monitored descriptively because of a lack of historical comparator data. Results: This study included 3 017 352 enrollees aged 5 to 17 years. Of the enrollees across all 3 databases, 1 510 817 (50.1%) were males, 1 506 499 (49.9%) were females, and 2 867 436 (95.0%) lived in an urban area. In the primary sequential analyses, a safety signal was observed only for myocarditis or pericarditis after primary series vaccination with BNT162b2 in the age group 12 to 17 years across all 3 databases. No safety signals were observed for the 12 other outcomes assessed using sequential testing. Conclusions and Relevance: Among 20 health outcomes that were monitored in near real time, a safety signal was identified for only myocarditis or pericarditis. Consistent with other published reports, these results provide additional evidence that COVID-19 vaccines are safe in children.