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Multisystemic inflammatory syndrome in children and the BNT162b2 vaccine: a nationwide cohort study

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Abstract

Multisystemic inflammatory syndrome in children (MIS-C) is a rare, severe, post-infectious hyperinflammatory condition that occurs after COVID-19 infection. In this study, we aimed to demonstrate the risk reduction of MIS-C and severe MIS-C after Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccination. This nationwide cohort study included 526,685 PCR-confirmed COVID-19 cases (age < 19 years), of whom 14,118 were fully vaccinated prior to COVID-19 infection. MIS-C cases were collected from all hospitals in Israel from April 2020 through November 2021. The MIS-C rates were calculated among two COVID-19 populations: positive PCR confirmed cases and estimated COVID-19 cases (PCR confirmed and presumed). Vaccination status was determined from Ministry of Health (MoH) records. The MIS-C risk difference (RD) and 95% confidence intervals (95%CI) between vaccinated and unvaccinated patients are presented. Overall, 233 MIS-C cases under the age of 19 years were diagnosed and hospitalized in Israel during the study period. Among the estimated COVID-19 cases, MIS-C RD realistically ranged between 2.1 [95%CI 0.7–3.4] and 1.0 [95%CI 0.4–1.7] per 10,000 COVID-19 cases. For severe MIS-C, RD realistically ranged between 1.6 [95%CI 1.3–1.9] and 0.8 [95%CI 0.7–1.0], per 10,000 COVID-19 cases. Sensitivity analysis was performed on a wide range of presumed COVID-19 rates, demonstrating significant RD for each of these rates.

Conclusion: This research demonstrates that vaccinating children and adolescents against COVID-19 has reduced the risk of MIS-C during the study period.

What is Known:

• Most of the published literature regarding vaccine effectiveness is based on case-control studies, which are limited due to small sample sizes and the inability to fully estimate the risk of MIS-C among vaccinated and unvaccinated children and adolescents.

• The known underestimation of COVID-19 diagnosis among children and adolescents is challenging, as they often have few to no symptoms.

What is New:

• Significant risk difference was found in favor of the vaccinated group, even after including extreme assumptions regarding the underdiagnosed COVID-19 rate.

• During this nationwide study period, it was found that vaccinating children and adolescents reduced the risk of MIS-C and its complications.

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Data availability

No datasets were generated or analyzed during the current study.

Abbreviations

CDC:

Centers for Disease Control

CI:

Confidence intervals

FDA:

Food and Drug Administration

HMO:

Health Maintenance Organizations

ICU:

Intensive care unit

MoH:

Ministry of Health

MIS-C:

Multisystemic inflammatory syndrome in children

RD:

Risk difference

STROBE:

Strengthening the Reporting of Observational Studies in Epidemiology

UK:

United Kingdom

US:

United States

VEU:

Vaccine emergency use

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Acknowledgements

We thank Mr. Nati Brooks for initial support of the data management, Aviva Uliel for her assistance in data collection, Dr. Michal Stein and Dr. Tal Brosh for their assistance in determining the clinical status of borderline cases, and Karina Slobodkin for her role in data collection and building the database.

Author information

Author notes

  1. Naama Schwartz and Ronit Ratzon contributed equally to this work.

Authors and Affiliations

  1. Public Health Services, Israel Ministry of Health, Jerusalem, Israel

    Naama Schwartz, Ronit Ratzon, Itay Hazan, Deena Rachel Zimmerman, Shepherd Roee Singer, Janice Wasser, Tunie Dweck & Sharon Alroy-Preis

  2. School of Public Health, University of Haifa, Haifa, Israel

    Naama Schwartz

  3. Department of Public Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel

    Ronit Ratzon

  4. Hadassah, Braun School of Public Health, Jerusalem, Israel

    Shepherd Roee Singer

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  1. Naama Schwartz
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Contributions

S.A.P., N.S., R.R., S.R.S., and I.H. contributed to the design and implementation of the research. D.R.Z., J.W., and T.D. carried out the MIS-C case collection and confirmation. Analysis and manuscript write-up were carried out by N.S. and R.R., and all the authors aided in interpreting the results and worked on the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Naama Schwartz.

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Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of the Israel Ministry of Health (protocol code 011-2022-MOH-COR). A waiver of informed consent form was granted as no identifiable patient data were mined and analyzed.

Competing interests

The authors declare no competing interests.

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Communicated by Gregorio Milani

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Schwartz, N., Ratzon, R., Hazan, I. et al. Multisystemic inflammatory syndrome in children and the BNT162b2 vaccine: a nationwide cohort study. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05586-4

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  • DOI: https://doi.org/10.1007/s00431-024-05586-4

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