BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age
To the Editor
Walter et al. (Jan. 6 issue)1 report the results of a randomized, controlled trial showing that two doses of the messenger RNA (mRNA) vaccine BNT162b2 against Covid-19 were safe, immunogenic, and efficacious in children 5 to 11 years of age. However, this trial was not powered to detect potential serious side effects of mRNA vaccines.
Adverse Events after Injection of an mRNA Vaccine or Placebo, as Reported in Three Clinical Trials. Data are from Ali et al.,2 Frenck et al.,3 and Walter et al. The Mantel–Haenszel test was used to estimate the pooled risk ratio in a fixed-effects model. The size of the data points is proportional to the number of participants and events, and the arrows indicate that the boundary of the 95% confidence interval (CI) is outside the graphed area. The horizontal lines indicate the 95% confidence interval of the estimates. The diamonds represent the summary risk ratio estimates, with the width indicating the 95% confidence interval. The extent of statistical consistency was measured by means of the 𝙸2 statistic, which was defined as 100%×(Q−df)÷Q, in which Q denotes Cochran’s heterogeneity statistic and df the degrees of freedom. Data on confirmed Covid-19 in participants who had not had previous SARS-CoV-2 infection (Panel F) were not reported by Ali et al.2 The abbreviation mRNA denotes messenger RNA, and NE could not be estimated.
Here, we present the pooled results of the trial conducted by Walter et al. and two other randomized, controlled trials2,3 (through November 15, 2021). Our analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.4 The risks of injection-related and total adverse events after the first or second injection (Figure 1A and 1B) were significantly higher after vaccination with an mRNA vaccine than after injection of placebo. However, the risks of serious adverse events (risk ratio, 1.63; 95% confidence interval [CI], 0.45 to 5.88) (Figure 1C) and the risks of any adverse event leading to nonreceipt of the second injection (risk ratio, 2.99; 95% CI, 0.36 to 24.93) (Figure 1D) did not differ significantly between the vaccine and placebo groups.
Two doses of mRNA vaccine effectively prevented the occurrence of Covid-19 in participants with previous severe SARS-CoV-2 infection and in those without previous infection (Figure 1E and 1F). No cases of severe Covid-19, multisystem inflammatory syndrome in children, or death were reported. Our findings provide support for the use of mRNA vaccines against Covid-19 in children and adolescents.
Shuang-fang Fang, M.D.
Nan Liu, M.D.
Hou-wei Du, M.D.
Fujian Medical University Union Hospital, Fuzhou, China
[email protected]
No potential conflict of interest relevant to this letter was reported.
This letter was published on January 19, 2022, at NEJM.org.
1. Walter EB, Talaat KR, Sabharwal C, et al. Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age. N Engl J Med 2022;386:35-46.
2. Ali K, Berman G, Zhou H, et al. Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents. N Engl J Med 2021;385:2241-2251.
3. Frenck RW Jr, Klein NP, Kitchin N, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med 2021;385:239-250.
4. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009;62(10):e1-e34.
To the Editor
In the Methods section of their article, Walter et al. state, “Effectiveness was inferred by an ‘immunobridging’ approach, in which neutralizing titers elicited by BNT162b2 in 5-to-11-year-olds were compared with titers elicited by BNT162b2 in 16-to-25-year-olds (in whom efficacy had been demonstrated).” The authors then cite a trial1 in which neutralizing titers after the second dose of the BNT162b2 vaccine in participants who were 12 to 15 years of age were compared with those in participants who were 16 to 25 years of age. However, in that cited article, including its Supplementary Appendix, no efficacy data are reported for the 16-to-25-year age group. Lacking these data, the reader cannot infer efficacy. Could the authors report the efficacy data for 16-to-25-year-old participants in previous trials?
Yishai Mintzker, M.D.
Bar-Ilan University, Safed, Israel
[email protected]
No potential conflict of interest relevant to this letter was reported.
This letter was published on January 19, 2022, at NEJM.org.
1. Frenck RW Jr, Klein NP, Kitchin N, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med 2021;385:239-250.
Response
The analysis by Fang et al. combines data from our trial of the BNT162b2 vaccine, which was administered in two injections (each injection containing either a 10-μg dose for younger children or a 30-μg dose for adolescents), with data from a trial of the mRNA-1273 vaccine, which was administered to adolescents in two injections, each containing a dose of 100 μg. The limitations of pooling these data include variation in the age of participants in the trial populations and the differences in vaccines and vaccine dosages. Despite these limitations, the analysis by Fang et al. lends support to the use of mRNA Covid-19 vaccines for the prevention of Covid-19.
In our article, we state that vaccine efficacy has been established for persons 16 to 25 years of age. In the pivotal trial, consistent vaccine efficacy was observed in stratified age groups, including participants who were 16 to 55 years of age, from 7 days through 2 months after the second dose of the BNT162b2 vaccine (vaccine efficacy, 96%)3 and through 6 months after the second dose of the BNT162b2 vaccine (vaccine efficacy, 91%).2 Nevertheless, in response to Mintzker’s request, we can present, in an analysis also funded by Pfizer, subgroup data specifically regarding participants who were 16 to 25 years of age; these data were not published with the original 6-month analysis of efficacy.4
Among participants who were 16 to 25 years of age and did not have evidence of previous SARS-CoV-2 infection, 8 cases of Covid-19 (with an onset from 7 days through 6 months after the second dose) were noted among BNT162b2 vaccine recipients, and 80 cases were observed among placebo recipients. The corresponding observed vaccine efficacy was 90.3% (95% CI, 80.0 to 90.6). It should be noted that the trial was not powered to analyze this age group independently; thus, this is a descriptive analysis.
Emmanuel B. Walter, M.D.
Duke Human Vaccine Institute, Durham, NC
Kawsar R. Talaat, M.D.
Johns Hopkins University, Baltimore, MD
Alejandra Gurtman, M.D.
Pfizer Vaccine Research and Development, Pearl River, NY
[email protected]
Since publication of their article, the authors report no further potential conflict of interest.
This letter was published on January 19, 2022, at NEJM.org.
1. Ali K, Berman G, Zhou H, et al. Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents. N Engl J Med 2021;385:2241-2251.
2. Frenck RW Jr, Klein NP, Kitchin N, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med 2021;385:239-250.
3. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-2615.
4. Thomas SJ, Moreira ED Jr, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine through 6 months. N Engl J Med 2021;385:1761-1773.
