Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination

Abstract

Introduction: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination.

Methods: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-μg doses were randomized to receive BNT162b2 30 μg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 μg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 μg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed.

Results: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported.

Conclusions: Among 5- to < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified.

Keywords: BNT162b2; COVID-19; Clinical trials; Myocarditis; Pericarditis; Safety; Troponin I; Vaccines.

Fig. 1

Disposition of participants in a C4591031 Substudy B (12–30 years of age), b in Study C4591007 (5– < 12 years of age), and c in Study C4591007 (12–15 years of age). ^aTwo participants (0.1%) were randomized to Sequence 2 (placebo → BNT162b2) in error and were withdrawn from the study before receiving the study vaccine. ^bOne participant randomized to Sequence 1 (BNT162b2 → placebo) received BNT162b2 instead of placebo for their second vaccination. ^cOne participant received BNT162b2 10 µg as dose 1 because of a dosing error, and BNT162b2 30 µg was received for dose 2 and dose 3. In C4591031 Substudy B, participants received BNT162b2 at the 30-µg dose level. In Study C4591007, the decrease in the number of participants who received placebo as dose 2 and with no participants receiving placebo as dose 3 is a result of the emergency use authorization. In Study C4591007, 149 participants were unblinded after the first vaccination, 110 were unblinded after the second vaccination, and one participant was not unblinded but lost to follow-up after the first vaccination

Fig. 2

Participants a 12–30 years of age in C4591031 Substudy B and b 5–15 years of age in Study C4591007 with elevated troponin I levels. Elevated troponin I levels were defined as > 35 ng/l in male participants and > 17 ng/l in female participants

Fig. 3

Participants in C4591031 Substudy B (12–30 years of age) with elevated troponin I levels by a age group and b sex. The exact two-sided 95% confidence interval (CI) was based on the Clopper–Pearson method. Data by troponin I level are summarized in Fig. S2