Editor’s Note: These letters were published on March 2, 2022, at NEJM.org.

Correspondence

More on BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age

To the Editor

Walter et al. (Jan. 6 issue)1 report that the BNT162b2 Covid-19 vaccine was safe and effective in children between 5 and 11 years of age.1 In the midst of successive waves of SARS-CoV-2 variants, the B.1.1.529 (omicron) variant has recently caused a surge in pediatric infections and hospitalizations.2 In France, the shift from the B.1.617.2 (delta) variant to omicron began in mid-December 2021. So far, omicron is considered to be more contagious than the delta variant, but data are needed on its severity in children. The omicron variant is thought to lead to less severe forms of Covid-19 in adults, a reduction that has been at least partly attributed to the widespread receipt of Covid-19 vaccines.3,4

Comparison of Pediatric Hospitalizations for Covid-19 during the Delta and Omicron Waves in One Pulmonary Unit in France.

In our pediatric pulmonology unit, hospitalizations for SARS-CoV-2 infection have more than doubled between the waves of the delta variant (mid-November to mid-December) and the arrival of the omicron variant (from mid-December to mid-January). During the omicron wave, hospitalized children had fewer preexisting conditions than did those during the delta wave, as well as slightly different symptoms at infection onset (Table 1). Only one infection in an asthmatic infant (aged 15 months) resulted in admission to the intensive care unit for acute respiratory distress. None of the hospitalized children who were 12 years of age or older had been fully vaccinated. This report emphasizes the importance of rapidly expanding vaccination against Covid-19 in children who are older than 5 years of age.

Jessica Taytard, M.D., Ph.D.
Sorbonne Université, Paris, France

Blandine Prevost, M.D.
Assistance Publique–Hôpitaux de Paris, Paris, France

Harriet Corvol, M.D., Ph.D.
Sorbonne Université, Paris, France

No potential conflict of interest relevant to this letter was reported.

This letter was published on March 2, 2022, at NEJM.org.

  1. 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. 2. Lima DGS, Figueiredo TMR, Pereira YTG, et al. The effects of the silence on South African children and adolescents against a global alert on the newly identified coronavirus variant: omicron. J Pediatr Nurs 2021 December 17 (Epub ahead of print).

  3. 3. Maslo C, Friedland R, Toubkin M, Laubscher A, Akaloo T, Kama B. Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 omicron wave compared with previous waves. JAMA 2022;327:583-584.

  4. 4. Collie S, Champion J, Moultrie H, Bekker L-G, Gray G. Effectiveness of BNT162b2 vaccine against omicron variant in South Africa. N Engl J Med 2022;386:494-496.

To the Editor

We compared the data presented by Walter et al. with the document that was submitted to the Food and Drug Administration (FDA) and reviewed at the October 26, 2021, meeting of the Vaccines and Related Biological Products Advisory Committee.1 Notably, data regarding nonserious adverse events — adverse events that are not life-threatening and do not lead to death, hospitalization, persistent incapacity, or birth defect — that were submitted to the FDA are not reported in the article, despite the potential of such events to be severe. Moreover, the data cutoff for “any adverse event” in the article was at 1 month after the second dose and not on September 6, 2021, as it was for the rest of the data in Table S7 in the Supplementary Appendix of the article (available at NEJM.org). These discrepancies preclude a well-informed risk–benefit calculation for the present study and hinder future meta-analyses. At the time of the data cutoff, severe events that were classified as nonserious were reported in three children in the vaccine group and in no children in the placebo group. This finding translates to an incidence of 0.2% for nonserious adverse events among the vaccinated children. Since this intervention was performed in healthy young children, such events are of great clinical importance, and their nature should have been clearly described. Such details should have been provided in this pivotal article, and we urge the authors to share these data.

Raya Leibowitz, M.D., Ph.D.
Shamir Medical Center, Zerifin, Israel

Efrat Schurr, M.D.
Meuhedet Health Maintenance Organization, Beit Shemesh, Israel

Omer Hirsch, B.A.
Tel Aviv University, Tel Aviv, Israel

Dr. Leibowitz reports serving in an advisory role for Pfizer. No other potential conflict of interest relevant to this letter was reported.

This letter was published on March 2, 2022, at NEJM.org.

  1. 1. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee meeting document. October 26, 2021 (https://www.fda.gov/media/153409/download).

Response

The authors reply: Leibowitz at al. compare the data regarding nonserious adverse events presented in our article with the safety findings from the associated phase 2–3 clinical trial that were provided to the Vaccines and Related Biological Products Advisory Committee of the FDA to support the emergency use authorization (EUA) of the BNT162b2 vaccine in children between 5 and 11 years of age. In our article, safety data are presented according to protocol-defined end points. For adverse events, the protocol-defined end point was evaluated after the administration of dose 1 until 1 month after the administration of dose 2, and the protocol-defined end point for serious adverse events is being evaluated after the administration of dose 1 to 6 months after the administration of dose 2. Therefore, the data for serious adverse events are presented in Table S7 of our article until the data cutoff of September 6, 2021, since the study is ongoing.

Adverse Events among Children 5 to 11 Years of Age in a Phase 2–3 Study of the BNT162b2 Vaccine (Safety Population).

In contrast to our article, the FDA document presents data regarding adverse events (including nonserious adverse events) according to the protocol-defined end point during the period after the administration of dose 1 to 1 month after the administration of dose 2, as well as for the EUA data cutoff date of September 6, 2021, which represents at least 2 months of follow-up after dose 2. For clarity, Table 1 summarizes the data regarding adverse events that were reported after the administration of dose 1 through September 6, 2021.

Taytard et al. compare pediatric SARS-CoV-2 hospitalizations during waves of infection caused by the delta variant and the omicron variant in their pulmonology unit in France. They found that the number of children who were admitted more than doubled during successive 4-week periods that represent the respective waves of these variants. More younger children were admitted during the omicron wave than during the delta wave, and of the children who were more than 12 years of age, none were fully vaccinated. Their findings underscore the importance of childhood Covid-19 vaccination.

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

Since publication of their article, the authors report no further potential conflict of interest.

This letter was published on March 2, 2022, at NEJM.org.

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