Overall Health Effects of mRNA COVID-19 Vaccines in Children and Adolescents A Systematic Review and Meta-Analysis

Importance Phase 3 randomized controlled trials (RCTs) of mRNA COVID-19 vaccines in children and adolescents showed efficacy in preventing COVID-19 infections. Vaccines may have non-specific effects. Objective Conduct a systematic review and meta-analysis of the phase 3 trials to assess overall and non-specific health effects of the mRNA COVID-19 vaccines. Data Sources PubMed, Embase, Clinical Trials, Web of Science, and regulatory websites were searched for RCTs of mRNA vaccines. The latest trial data was included. Study Selection All RCTs conducted with mRNA vaccines BNT162b2 and mRNA-1237 in children and adolescents below 18 years, with placebo, adjuvant, or other vaccines as controls. 1199 studies were screened; six were included in the analysis. Data Extraction and Synthesis Data on serious adverse events (“SAEs”) and severe adverse events (“Severe AEs”) as well as organ-specific diseases was extracted following the PRISMA reporting guideline, with a focus on non-specific infectious events. Risk Ratios (RRs) comparing vaccine vs placebo were calculated for each vaccine and combined in Mantel-Haenszel estimates. Main Outcomes and Measures The primary outcomes were SAEs: overall, non-accident SAEs, and infectious SAEs, respectively. Secondary outcomes were Severe AEs and lower respiratory tract infection (LRTI) including RSV. Results The analyses included 25,549 individuals (17,538 received mRNA; 8,011 received placebo). The risk of SAEs was similar for vaccine and placebo recipients. Both mRNA vaccines were associated with increased risk of severe AEs in older children. In a combined analysis, the RR was 3.77 (1.56-9.13[0.4% vs 0.1% in vaccine vs placebo recipients]) in above 5 year-olds, and 0.82 (0.53-1.29)[0.8% vs 0.9%])in younger children, who received a lower dose of vaccine (p=0.003 for same effect in older and younger children). In the younger children, mRNA vaccines were associated with higher risk of LRTI (RR=2.80 (1.32-5.94)[0.6% vs 0.3%]) including a higher risk of RSV infections (RR=2.78 (1.09-7.06)[0.4% vs 0.2%]). Conclusions and Relevance mRNA vaccines did not increase the risk of SAEs but were associated with an increased risk of severe AEs in older children, and an increased risk of LRTI, including RSV, in the young. Further research into the overall and non-specific health effects of mRNA vaccines is warranted.