(352) Safety of Ancestral Monovalent BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and NVX-CoV2373 (Novavax) COVID-19 Vaccines in US Children Aged 6 months to 17 years

Background: Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes post-licensure.

Objectives: To conduct near-real-time monitoring of health outcomes following receipt of the ancestral monovalent COVID-19 vaccine in the United States (US) pediatric population aged 6 months to 17 years.

Methods: This US population-based study evaluated 21 pre-specified health outcomes after exposure to BNT162b2, mRNA-1273, or NVX-CoV2373 ancestral monovalent COVID-19 vaccines in children 6 months to 17 years old by applying a near-real-time monitoring framework using three US commercial health insurance databases (Optum, Carelon Research, and CVS Health) linked to immunization information systems (IIS) data. Fifteen outcomes were sequentially tested through near-real-time surveillance, and 6 were monitored only descriptively within a cohort of vaccinated children. We tested for an increased rate of each outcome following vaccination compared to historical outcome rates. Children aged 6 months to 17 years were included if they received an ancestral monovalent COVID-19 vaccine dose upto early 2023 and had continuous enrollment in a medical insurance plan from the start of an outcome-specific clean window to the COVID-19 vaccination dose. The primary analysis evaluated the receipt of an ancestral monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-19 vaccine dose 1 and dose 2 combined, and the secondary analyses evaluated each dose separately. Follow-up time was censored at death, disenrollment, end of risk window, end of study period, or a subsequent dose administration.

Results: The study included 4,102,016 enrollees aged 6 months to 17 years. Two of 15 outcomes sequentially tested met the threshold for a statistical signal. In the primary analysis, myocarditis or pericarditis signals were detected following BNT162b2 vaccination in children aged 12-17 years old (n=153 cases) and seizure signals were detected following vaccination with BNT162b2 and mRNA-1273 in children aged 2-4 and 2-5 years (n=72 cases). However, in a post-hoc sensitivity analysis, the seizure signal was sensitive to background rates selection: A statistical signal was observed only following mRNA-1273 in children aged 2-5 when 2019 background rates were selected instead of 2020 rates, and no statistical signal was observed when 2022 rates were selected. Results from secondary analysis were consistent with the primary analysis.

Conclusions: Of the two signaled outcomes, the myocarditis or pericarditis signals are consistent with previously published reports. The new signal detected for seizure among younger children should be further investigated in a robust epidemiological study with better confounding adjustment.