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Cited by 593SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesVaccine Coverage and Hesitancy

Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age

Open access
Walter, Emmanuel B., Talaat, Kawsar R., Sabharwal, Charu, Gurtman, Alejandra, Lockhart, Stephen, Paulsen, Grant C., Barnett, Elizabeth D., Muñoz, Flor M. +26 more·2022·New England Journal of Medicine
DOI 10.1056/nejmoa2116298PMC PMC8609605
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Abstract

BACKGROUND: Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age. METHODS: A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-μg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed. RESULTS: During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3). CONCLUSIONS: A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

AI snapshot

Written from the paper’s full text.

TL;DR

Two 10-μg doses of BNT162b2 given 21 days apart were safe, immunogenic, and efficacious in children 5 to 11 years of age. Vaccine efficacy against Covid-19 at ≥7 days after the second dose was 90.7%, with neutralizing titers noninferior to those in 16-to-25-year-olds.

Key findings

  • In the phase 2–3 trial, 2268 children received injections: 1517 BNT162b2 and 751 placebo; median follow-up was 2.3 months.
  • Immunobridging met prespecified criteria: the geometric mean ratio of SARS-CoV-2 neutralizing titers in 5-to-11-year-olds versus 16-to-25-year-olds was 1.04 (95% CI, 0.93 to 1.18); seroresponse was 99.2% in both age groups, with a difference of 0.0 percentage points (95% CI, −2.0 to 2.2).
  • Vaccine efficacy against Covid-19 with onset ≥7 days after the second dose was 90.7% (95% CI, 67.7 to 98.3) among participants without evidence of previous SARS-CoV-2 infection, based on 3 cases in BNT162b2 recipients and 16 in placebo recipients; among all participants with data, efficacy was 90.7% (95% CI, 67.4 to 98.3).
  • No vaccine-related serious adverse events were noted; no myocarditis, pericarditis, hypersensitivity, or anaphylaxis in BNT162b2 recipients was reported. Injection-site pain occurred in 71 to 74% of BNT162b2 recipients, fever in 8.3%, and lymphadenopathy in 0.9% versus 0.1% of placebo recipients.

Methods

  • Phase 1 open-label dose-finding study in 48 children 5 to 11 years of age who received 10 μg, 20 μg, or 30 μg BNT162b2 (16 per dose level); 10 μg was selected for further study based on reactogenicity and immunogenicity.
  • Ongoing phase 2–3 randomized trial: children 5 to 11 years of age were assigned 2:1 to two doses, 21 days apart, of BNT162b2 10 μg or saline placebo; immunogenicity was bridged to 16-to-25-year-olds from an earlier pivotal trial of two 30-μg doses.
  • Efficacy was assessed against confirmed Covid-19 with onset at least 7 days after the second dose; vaccine efficacy was defined as 100×(1−IRR), with 95% CI derived by the Clopper–Pearson method adjusted for surveillance time.

Limitations

  • The paper states lack of longer-term follow-up to assess duration of immune responses, efficacy, and safety; follow-up will continue for 2 years.
  • The paper states the study was not powered to detect potential rare side effects of BNT162b2 in 5-to-11-year-olds.
  • The paper states concomitant administration with other vaccines was not assessed and cell-mediated responses were not yet available; evident from the text, median follow-up was only 2.3 months and efficacy was based on few events (3 vs. 16 cases), limiting precision and durability conclusions.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1056/nejmoa2116298

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 51 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In the phase 1 study, 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine, with 16 children at each dose level.

    “During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile.

    “In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile.”
    Quote in the paperSubstantial claim
  • Findingown data

    In the phase 2-3 trial, 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children).

    “In the phase 2–3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children).”
    Quote in the paperSubstantial claim
  • Findingown data

    No vaccine-related serious adverse events were noted in the trial.

    “No vaccine-related serious adverse events were noted.”
    Quote in the paperSubstantial claim
  • Findingown data

    On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study in 5-to-11-year-olds.

    “On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study.”
    • Also stated in: § Phase 1 Safety and Immunogenicity · plain
      “On the basis of these safety and immunogenicity findings, the 10-μg dose level was selected for further assessment in 5-to-11-year-olds in phase 2–3.”
    Quote in the paperSubstantial claim
  • May combine two claims. 36
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Findingown data

    Covid-19 with onset 7 days or more after the second dose was reported in three BNT162b2 recipients and 16 placebo recipients, with observed vaccine efficacy of 90.7% (95% CI, 67.7 to 98.3).

    “Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3).”
    • Also stated in: § Phase 2–3 Efficacy · plain
      “Among participants without evidence of previous SARS-CoV-2 infection, there were three cases of Covid-19 (with onset 7 days or more after the second dose) among BNT162b2 recipients and 16 among placebo recipients; the observed vaccine efficacy was 90.7% (95% CI, 67.7 to 98.3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    One month after the second dose, the geometric mean ratio of SARS-CoV-2 neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% CI, 0.93 to 1.18), meeting the prespecified immunogenicity success criterion.

    “One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Neutralizing antibody titers are a valid surrogate for protection against Covid-19, such that immunobridging from 16-to-25-year-olds can infer vaccine efficacy in 5-to-11-year-olds.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    At data cutoff, the median follow-up was 2.3 months.

    “At data cutoff, the median follow-up was 2.3 months.”
    • Also stated in: § Participants · plain
      “At the data cutoff date, the median follow-up time was 2.3 months (range, 0 to 2.5); 95% of participants had at least 2 months of available follow-up safety data after the second dose.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Three serious adverse events in two participants were reported by the cutoff date; all three were considered unrelated to the vaccine or placebo.

    “Three serious adverse events in two participants were reported by the cutoff date; all three (postinjury abdominal pain and pancreatitis in a placebo recipient and arm fracture in a BNT162b2 recipient) were considered to be unrelated to the vaccine or placebo.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Frequencies of fatigue, headache, and chills were similar among BNT162b2 and placebo recipients after the first dose and were more frequent among BNT162b2 recipients after the second dose.

    “Frequencies of fatigue, headache, and chills were similar among BNT162b2 and placebo recipients after the first dose and were more frequent among BNT162b2 recipients than among placebo recipients after the second dose.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    No cases of severe Covid-19 or MIS-C were reported.

    “No cases of severe Covid-19 or MIS-C were reported.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In phase 2-3, 2316 children 5 to 11 years of age were screened, 2285 underwent randomization across 81 sites, and 2268 received injections, with 1517 assigned to BNT162b2 and 751 to placebo.

    “From June 7 through June 19, 2021, a total of 2316 children 5 to 11 years of age were screened for inclusion and 2285 underwent randomization across 81 sites in the United States, Spain, Finland, and Poland; 2268 participants received injections, with 1517 randomly assigned to receive BNT162b2 and 751 assigned to receive placebo (Figure 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingreasoning

    One participant randomly assigned to placebo was administered BNT162b2 in error for both doses; therefore, 1518 participants received dose 1 of BNT162b2 and 750 received dose 1 of placebo.

    “One participant who was randomly assigned to receive placebo was administered BNT162b2 in error for both doses; therefore, 1518 participants received dose 1 of BNT162b2 and 750 participants received dose 1 of placebo.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The reactions and events reported were generally mild to moderate, lasting 1 to 2 days.

    “The reactions and events reported were generally mild to moderate, lasting 1 to 2 days (Table S4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No deaths or adverse events leading to withdrawal were reported.

    “No deaths or adverse events leading to withdrawal were reported.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Adverse events from the first dose through 1 month after the second dose were reported by 43.8% of participants who received two 10-μg doses of BNT162b2, 31.3% of those who received two 20-μg doses, and 50.0% of those who received two 30-μg doses.

    “Adverse events from the first dose through 1 month after the second dose were reported by 43.8% of participants who received two 10-μg doses of BNT162b2, 31.3% of those who received two 20-μg doses, and 50.0% of those who received two 30-μg doses (Table S6).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Injection-site pain was the most common local reaction, occurring in 71 to 74% of BNT162b2 recipients.

    “Injection-site pain was the most common local reaction, occurring in 71 to 74% of BNT162b2 recipients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    No myocarditis, pericarditis, hypersensitivity, or anaphylaxis in BNT162b2 recipients was reported.

    “No myocarditis, pericarditis, hypersensitivity, or anaphylaxis in BNT162b2 recipients was reported.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Serum-neutralizing GMTs 1 month after the second dose of BNT162b2 were 1198 in 5-to-11-year-olds and 1147 in 16-to-25-year-olds; corresponding GMTs among placebo recipients were 11 and 10.

    “Serum-neutralizing GMTs 1 month after the second dose of BNT162b2 were 1198 in 5-to-11-year-olds and 1147 in 16-to-25-year-olds (Fig. S3); corresponding GMTs among placebo recipients were 11 and 10.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Most local reactions in phase 1 were mild to moderate, and all were transient.

    “Most local reactions were mild to moderate, and all were transient (Fig. S1A and Table S4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among all participants with data that could be evaluated, regardless of evidence of previous SARS-CoV-2 infection, no additional Covid-19 cases were reported, and observed vaccine efficacy was 90.7% (95% CI, 67.4 to 98.3).

    “Among all participants with data that could be evaluated, regardless of evidence of previous SARS-CoV-2 infection, no additional cases were reported; the observed vaccine efficacy was 90.7% (95% CI, 67.4 to 98.3) (Figure 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Four rashes in BNT162b2 recipients were considered related to vaccination; they were mild and self-limiting, with onset typically 7 days or more after vaccination.

    “Four rashes in BNT162b2 recipients (observed on the arm, torso, face, or body, with no consistent pattern) were considered to be related to vaccination; the rashes were mild and self-limiting, and onset was typically 7 days or more after vaccination.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Geometric mean fold rises from baseline to 1 month after the second dose were 118.2 in 5-to-11-year-olds and 111.4 in 16-to-25-year-olds; corresponding geometric mean fold rises among placebo recipients were 1.1 and 1.0.

    “Geometric mean fold rises from baseline to 1 month after the second dose were 118.2 in 5-to-11-year-olds and 111.4 in 16-to-25-year-olds; corresponding geometric mean fold rises among placebo recipients were 1.1 and 1.0.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Severe fatigue (0.9%), headache (0.3%), chills (0.1%), and muscle pain (0.1%) were reported after the first or second dose of BNT162b2.

    “Severe fatigue (0.9%), headache (0.3%), chills (0.1%), and muscle pain (0.1%) were also reported after the first or second dose of BNT162b2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The difference between the percentage of 5-to-11-year-olds who achieved seroresponse and the percentage in 16-to-25-year-olds was 0.0 percentage points (95% CI, -2.0 to 2.2), which met an immunobridging criterion.

    “The difference between the percentage of 5-to-11-year-olds who achieved seroresponse and the percentage in 16-to-25-year-olds was 0.0 percentage points (95% CI, –2.0 to 2.2), which also met an immunobridging criterion.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Neutralizing antibody titers are a valid surrogate for protection against Covid-19, such that immunobridging from 16-to-25-year-olds can infer vaccine efficacy in 5-to-11-year-olds.

  • May combine two claims.

    Findingcitation

    Lymphadenopathy was reported in 0.9% of 5-to-11-year-old BNT162b2 recipients, an incidence similar to that in 12-to-15-year-olds (0.8%) but higher than that observed in adults (0.3%).

    “Lymphadenopathy was reported in 0.9% of 5-to-11-year-old BNT162b2 recipients, an incidence similar to that in 12-to-15-year-olds (0.8%) but higher than that observed in adults (0.3%).3,4”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [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. 33301246 PMC7745181 source

      Not checked in the free run.

    • cites [4] 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. 34043894 PMC8174030 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Four potentially vaccine-related rashes were reported, too few to determine whether the pattern was similar to that observed in adult BNT162b2 recipients.

    “Four potentially vaccine-related rashes were reported, too few to determine whether the pattern was similar to that observed in adult BNT162b2 recipients.31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Grieco T, Maddalena P, Sernicola A, et al. Cutaneous adverse reactions after COVID-19 vaccines in a cohort of 2740 Italian subjects: an observational study. Dermatol Ther 2021 October 7 (Epub ahead of print). 34622531 PMC8646410 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    As compared with adults and adolescents in the pivotal trial, 5-to-11-year-olds reported a higher incidence of injection-site redness (15 to 19% vs. 5 to 7%) and swelling (10 to 15% vs. 5 to 8%), but a generally lower incidence of systemic events, including fever (3 to 7% vs. 1 to 20%) and chills (5 to 10% vs. 6 to 42%).

    “As compared with adults and adolescents in the pivotal trial, 5-to-11-year-olds reported a higher incidence of injection-site redness (15 to 19%, vs. 5 to 7%) and swelling (10 to 15%, vs. 5 to 8%), but a generally lower incidence of systemic events, including fever (3 to 7%, vs. 1 to 20%) and chills (5 to 10%, vs. 6 to 42%).3,4”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [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. 33301246 PMC7745181 source

      Not checked in the free run.

    • cites [4] 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. 34043894 PMC8174030 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    No MIS-C cases were reported, although surveillance continues.

    “No MIS-C cases were reported, although surveillance continues.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The 10-μg dose level was associated with mainly low-grade local and systemic adverse events lasting 1 to 2 days, and the frequency and severity of fever were low.

    “This dose level was associated with mainly low-grade local and systemic adverse events lasting 1 to 2 days; the frequency and severity of fever were low.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The BNT162b2 vaccine is a lipid nanoparticle formulation containing nucleoside-modified mRNA encoding the SARS-CoV-2 viral spike glycoprotein.

    “The BNT162b2 vaccine (Pfizer–BioNTech) is a lipid nanoparticle formulation containing nucleoside-modified mRNA encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral spike glycoprotein.1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Sahin U, Muik A, Vogler I, et al. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature 2021; 595: 572- 577. 34044428 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart is safe, immunogenic, and efficacious in children 5 to 11 years of age.

    “A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age.”
    • Also stated in: § Discussion · plain
      “Two 10-μg doses of the BNT162b2 vaccine administered 21 days apart were safe, immunogenic, and 90.7% effective against Covid-19 in 5-to-11-year-old children.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Neutralizing antibody titers are a valid surrogate for protection against Covid-19, such that immunobridging from 16-to-25-year-olds can infer vaccine efficacy in 5-to-11-year-olds.
    • Rests on an assumption: The safety profile observed over a median follow-up of 2.3 months is sufficient to conclude that the vaccine is safe in 5-to-11-year-olds.

  • May combine two claims.

    Premisecitation

    Vaccine efficacy against Covid-19 from 7 days to 6 months after the second dose was 91%, with similar estimated real-world effectiveness from 8 to 28 days after the second dose.

    “Vaccine efficacy against Covid-19 from 7 days to 6 months after the second dose was 91%,6 with a similar estimated real-world effectiveness from 8 to 28 days after the second dose.7”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] 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. 34525277 PMC8461570 source

      Not checked in the free run.

    • cites [7] Glatman-Freedman A, Hershkovitz Y, Kaufman Z, Dichtiar R, Keinan-Boker L, Bromberg M. Effectiveness of BNT162b2 vaccine in adolescents during outbreak of SARS-CoV-2 delta variant infection, Israel, 2021. Emerg Infect Dis 2021; 27: 2919- 2922. 34570694 PMC8544958 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    School-age children represent a high proportion of Covid-19 cases and may play an important role in transmission of SARS-CoV-2, including spread of the delta variant.

    “School-age children represent a high proportion of Covid-19 cases,10 and they may play an important role in the transmission of SARS-CoV-2,11,12 including spread of the highly transmissible B.1.617.2 (or delta) variant.13,14”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [10] American Academy of Pediatrics. Children and COVID-19: state-level data report. 2021 (https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/).

      Not checked in the free run.

    • cites [11] Rumain B, Schneiderman M, Geliebter A. Prevalence of COVID-19 in adolescents and youth compared with older adults in states experiencing surges. PLoS One 2021; 16(3): e0242587- e0242587. 33690600 PMC7946189 source

      Not checked in the free run.

    • cites [12] Szablewski CM, Chang KT, Brown MM, et al. SARS-CoV-2 transmission and infection among attendees of an overnight camp — Georgia, June 2020. MMWR Morb Mortal Wkly Rep 2020; 69: 1023- 1025. 32759921 PMC7454898 source

      Not checked in the free run.

    • cites [13] Centers for Disease Control and Prevention. COVID data tracker. 2021 (https://covid.cdc.gov/covid-data-tracker/#datatracker-home).

      Not checked in the free run.

    • cites [14] Lam-Hine T, McCurdy SA, Santora L, et al. Outbreak associated with SARS-CoV-2 B.1.617.2 (delta) variant in an elementary school — Marin County, California, May–June 2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1214- 1219. 34473683 PMC8422870 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although Covid-19 is generally milder in children than in adults, severe illness and long-term complications, including MIS-C, can occur after primary infection.

    “Although Covid-19 is generally milder in children than in adults, severe illness and long-term complications, including multisystem inflammatory syndrome in children (MIS-C), can occur after the primary infection.8,9”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] Tsabouri S, Makis A, Kosmeri C, Siomou E. Risk factors for severity in children with coronavirus disease 2019: a comprehensive literature review. Pediatr Clin North Am 2021; 68: 321- 338. 33228941 PMC7392074 source

      Not checked in the free run.

    • cites [9] Centers for Disease Control and Prevention. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). 2021 (https://www.cdc.gov/mis/hcp/index.html).

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The sample size for phase 1 and the total sample size for phase 2-3 were not based on statistical hypothesis testing.

    “The sample size for phase 1 and the total sample size for phase 2–3 were not based on statistical hypothesis testing.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    A sample size of 225 BNT162b2 recipients with data that could be evaluated in both age groups provided 90.4% and 92.6% power to demonstrate immunobridging on the basis of the geometric mean ratio and the difference in seroresponse, respectively.

    “A sample size of 225 BNT162b2 recipients with data that could be evaluated in both age groups provided 90.4% and 92.6% power to demonstrate immunobridging on the basis of the geometric mean ratio and the difference in seroresponse, respectively.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Serum samples from 5-to-11-year-olds and 16-to-25-year-olds were assayed in parallel to ensure comparability of titers.

    “Serum samples collected from 5-to-11-year-olds and 16-to-25-year-olds in this study were assayed in parallel to ensure comparability of titers.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    In phase 2-3, participants were randomly assigned in a 2:1 ratio to receive two doses, 21 days apart, of either BNT162b2 at the phase 1-selected dose of 10 μg or saline placebo.

    “Through the use of an interactive Web-based system, participants were randomly assigned in a 2:1 ratio to receive two doses, 21 days apart, of either BNT162b2 at the dose level selected during phase 1 (10 μg) or saline placebo.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    In phase 2-3, all participants and study personnel, except those preparing or administering injections, were unaware of group assignments.

    “In phase 2–3, all participants and study personnel, with the exception of those preparing or administering the injections, were unaware of group assignments.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    More than 99% of participants received a second dose.

    “More than 99% of participants received a second dose.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The pandemic has interrupted education and adversely affected children's social and emotional development and mental health.

    “The pandemic has also interrupted education and has adversely affected children’s social and emotional development and mental health.16-19”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [16] McKune SL, Acosta D, Diaz N, et al. Psychosocial health of school-aged children during the initial COVID-19 safer-at-home school mandates in Florida: a cross-sectional study. BMC Public Health 2021; 21: 603- 603. 33781220 PMC8006116 source

      Not checked in the free run.

    • cites [17] Engzell P, Frey A, Verhagen MD. Learning loss due to school closures during the COVID-19 pandemic. Proc Natl Acad Sci U S A 2021; 118(17): e2022376118- e2022376118. 33827987 PMC8092566 source

      Not checked in the free run.

    • cites [18] López-Bueno R, López-Sánchez GF, Casajús JA, Calatayud J, Tully MA, Smith L. Potential health-related behaviors for pre-school and school-aged children during COVID-19 lockdown: a narrative review. Prev Med 2021; 143: 106349- 106349. 33271236 PMC7701882 source

      Not checked in the free run.

    • cites [19] UNICEF. COVID-19 and children. 2020 (https://data.unicef.org/covid-19-and-children/).

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Direct benefits of preventing SARS-CoV-2 infection in children include protection against severe disease, hospitalizations, and severe or long-term complications such as MIS-C.

    “Direct benefits of preventing SARS-CoV-2 infection in children include protection against severe disease, hospitalizations, and severe or long-term complications, such as MIS-C.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    With prioritization of older age groups for vaccination, school-age children now account for an increasing proportion of cases and hospitalizations compared with their proportion early in the pandemic, and school outbreaks are occurring.

    “With the prioritization of older age groups for vaccination, school-age children now account for an increasing proportion of cases and hospitalizations as compared with their proportion early in the pandemic,10,22,23,24 and school outbreaks are occurring.14,25”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [10] American Academy of Pediatrics. Children and COVID-19: state-level data report. 2021 (https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/).

      Not checked in the free run.

    • cites [22] Delahoy MJ, Ujamaa D, Whitaker M, et al. Hospitalizations associated with COVID-19 among children and adolescents — COVID-NET, 14 states, March 1, 2020–August 14, 2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1255- 1260. 34499627 PMC8437052 source

      Not checked in the free run.

    • cites [23] Preston LE, Chevinsky JR, Kompaniyets L, et al. Characteristics and disease severity of US children and adolescents diagnosed with COVID-19. JAMA Netw Open 2021; 4(4): e215298- e215298. 33835179 PMC8035649 source

      Not checked in the free run.

    • cites [24] Siegel DA, Reses HE, Cool AJ, et al. Trends in COVID-19 cases, emergency department visits, and hospital admissions among children and adolescents aged 0–17 years — United States, August 2020–August 2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1249- 1254. 34499628 PMC8437056 source

      Not checked in the free run.

    • cites [14] Lam-Hine T, McCurdy SA, Santora L, et al. Outbreak associated with SARS-CoV-2 B.1.617.2 (delta) variant in an elementary school — Marin County, California, May–June 2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1214- 1219. 34473683 PMC8422870 source

      Not checked in the free run.

    • cites [25] Jehn M, McCullough JM, Dale AP, et al. Association between K–12 school mask policies and school-associated COVID-19 outbreaks — Maricopa and Pima Counties, Arizona, July–August 2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1372- 1373. 34591830 PMC8486387 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Neither myocarditis nor pericarditis was observed, a finding consistent with the low frequency of these adverse events with real-world use of BNT162b2 in other age groups.

    “Neither myocarditis nor pericarditis was observed, a finding consistent with the low frequency of these adverse events with real-world use of BNT162b2 in other age groups.32”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Cai C, Peng Y, Shen E, et al. A comprehensive analysis of the efficacy and safety of COVID-19 vaccines. Mol Ther 2021; 29: 2794- 2805. 34365034 PMC8342868 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The robust virus-neutralizing response observed in 5-to-11-year-olds was similar to that seen in 16-to-25-year-olds from the pivotal trial, which demonstrated 95% vaccine efficacy among persons at least 16 years of age from 7 days to approximately 2 months after the second dose.

    “The robust virus-neutralizing response observed in 5-to-11-year-olds was similar to that seen in 16-to-25-year-olds from the pivotal trial, which demonstrated 95% vaccine efficacy among persons at least 16 years of age from 7 days to approximately 2 months after the second dose.3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [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. 33301246 PMC7745181 source

      Not checked in the free run.

    • Rests on an assumption: Neutralizing antibody titers are a valid surrogate for protection against Covid-19, such that immunobridging from 16-to-25-year-olds can infer vaccine efficacy in 5-to-11-year-olds.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Further limitations are that concomitant administration of BNT162b2 with other vaccines was not assessed, and cell-mediated responses to immunization are not yet available.

    “Further limitations are that concomitant administration of BNT162b2 with other vaccines was not assessed, and cell-mediated responses to immunization are not yet available.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Indirect benefits of vaccination include the likelihood of reduced transmission in the home and school settings, including transmission affecting vulnerable persons, and safer in-person learning.

    “Indirect benefits include the likelihood of reduced transmission in the home and in school settings, including transmission affecting vulnerable persons, and safer in-person learning.26-29”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [26] Anderson EJ, Campbell JD, Creech CB, et al. Warp speed for coronavirus disease 2019 (COVID-19) vaccines: why are children stuck in neutral? Clin Infect Dis 2021; 73: 336- 340. 32945335 PMC7543330 source

      Not checked in the free run.

    • cites [27] Klass P, Ratner AJ. Vaccinating children against Covid-19 — the lessons of measles. N Engl J Med 2021; 384: 589- 591. 33471977 source

      Not checked in the free run.

    • cites [28] Parks SE, Zviedrite N, Budzyn SE, et al. COVID-19-related school closures and learning modality changes — United States, August 1–September 17, 2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1374- 1376. 34591828 PMC8486392 source

      Not checked in the free run.

    • cites [29] Paul LA, Daneman N, Schwartz KL, et al. Association of age and pediatric household transmission of SARS-CoV-2 infection. JAMA Pediatr 2021: 175; 1151- 1158. 34398179 PMC8369380 source

      Not checked in the free run.

43 of 43

  • The paper relies on this without support.

    Neutralizing antibody titers are a valid surrogate for protection against Covid-19, such that immunobridging from 16-to-25-year-olds can infer vaccine efficacy in 5-to-11-year-olds.

    “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 demonstrated4), with formal noninferiority hypothesis testing.”
    “The observed high efficacy of BNT162b2 in 5-to-11-year-olds is consistent with the immunobridging results and the high efficacy demonstrated in the pivotal trial.3,4,6”

  • The paper relies on this without support.

    The 16-to-25-year-old immunobridging control group from the earlier trial is sufficiently comparable to the 5-to-11-year-old group for valid immunobridging.

    “A random sample of 350 participants 16 to 25 years of age from an earlier study4 (300 in the 30-μg BNT162b2 group and 50 in the placebo group [included for blinding purposes]) was selected with the use of a simple random-sample selection procedure as the immunobridging control age group.”
    “Apart from younger age and a lower percentage of Black and Hispanic or Latinx 5-to-11-year-olds (6% and 18%, respectively) than 16-to-25-year-olds (12% and 36%, respectively), demographic characteristics were similar among the 5-to-11-year-old and 16-to-25-year-old BNT162b2 recipients who were included in the immunobridging subset (Table S3).”

  • The paper relies on this without support.

    The safety profile observed over a median follow-up of 2.3 months is sufficient to conclude that the vaccine is safe in 5-to-11-year-olds.

    “In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile.”
    “This study was also not powered to detect potential rare side effects of BNT162b2 in 5-to-11-year-olds.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The FDA granted BNT162b2 emergency approval for use in children and adolescents aged 5 to 11 on October 29, 2021.

    “The FDA granted BNT162b2 emergency approval for use in children and adolescents aged 5 to 11 on October 29, 2021.103,106”

    From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [103]

  • In 5- to 11-year-olds, two 10 μg doses of BNT162b2 were found to give rise to 90.7% vaccine efficacy.

    “Recently, as a part of the clinical trial examining BNT162b2 in 5- to 11-year-olds (NCT04816643), two 10 μg doses of BNT162b2 were found to give rise to 90.7% vaccine efficacy (prevention of COVID-19).108”

    From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [108]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting counts of randomized children

    Minor

    The abstract says 2268 children were randomly assigned, but the Results section says 2285 underwent randomization and 2268 received injections. The abstract appears to give the injected count as the randomized count.

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Authors
Walter, E. B., Talaat, K. R., Sabharwal, C., Gurtman, A., Lockhart, S., Paulsen, G. C., Barnett, E. D., Muñoz, F. M., Maldonado, Y., Pahud, B. A., Domachowske, J. B., Simões, E. A. F., Sarwar, U. N., Kitchin, N., Cunliffe, L., Rojo, P., Kuchar, E., Rämet, M., Munjal, I., Perez, J. L., Frenck, R. W., Lagkadinou, E., Swanson, K. A., Ma, H., Xu, X., Koury, K., Mather, S., Belanger, T. J., Cooper, D., Türeci, Ö., Dormitzer, P. R., Şahin, U., Jansen, K. U., & Gruber, W. C.
Affiliations
Johns Hopkins University (US)
Corresponding author
Gurtman, Alejandra
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2022-01-06
Volume
386
Issue
1
Pages
35-46
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2116298
PMC
PMC8609605
OpenAlex
W3212487860
Semantic Scholar
04a28d2ec63e63743ca66479b3ffa62e537c98fd
Cited by
593
References
26
Citations by year
2026: 19 · 2025: 50 · 2024: 74 · 2023: 141 · 2022: 292 · 2021: 14
FWCI
41.33
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Pfizer
  • BioNTech
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Social Sciences › Health › Vaccine Coverage and Hesitancy
Keywords
BNT162b2, COVID-19 vaccines, childhood immunization, children aged 5-11, SARS-CoV-2, vaccine safety, immunogenicity, neutralizing antibodies, vaccine efficacy, dose selection, reactogenicity, age-stratified analysis, vaccine hesitancy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

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