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

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

doi:10.1007/s00431-024-05586-4

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

Eur J Pediatr. 2024 May 9. doi: 10.1007/s00431-024-05586-4. Online ahead of print.

Authors

Naama Schwartz^#^{1

2}, Ronit Ratzon^#^{3

4}, Itay Hazan³, Deena Rachel Zimmerman³, Shepherd Roee Singer^{3

5}, Janice Wasser³, Tunie Dweck³, Sharon Alroy-Preis³

Affiliations

¹ Public Health Services, Israel Ministry of Health, Jerusalem, Israel. Naama.stat@gmail.com.
² School of Public Health, University of Haifa, Haifa, Israel. Naama.stat@gmail.com.
³ Public Health Services, Israel Ministry of Health, Jerusalem, Israel.
⁴ Department of Public Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
⁵ Hadassah, Braun School of Public Health, Jerusalem, Israel.

^# Contributed equally.

PMID: 38724677
DOI: 10.1007/s00431-024-05586-4

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.

Keywords: COVID-19; Pediatric inflammatory multisystem syndrome; Vaccine.