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Multisystemic inflammatory syndrome in children and the BNT162b2 vaccine: a nationwide cohort study
Naama Schwartz1,2, Ronit Ratzon3,4, Itay Hazan3
1Public Health Services, Israel Ministry of Health, Jerusalem, Israel. Naama.stat@gmail.com.
Insights
COVID-19 vaccination for children and adolescents significantly reduced the risk of Multisystemic Inflammatory Syndrome in Children (MIS-C). This study confirms vaccine effectiveness in preventing severe post-infectious complications in pediatric populations.
Area of Science:
- Pediatric Infectious Diseases
- Vaccinology
- Public Health
Background:
- Multisystemic Inflammatory Syndrome in Children (MIS-C) is a rare but severe post-infectious hyperinflammatory condition following COVID-19 infection.
- Existing vaccine effectiveness literature often relies on small case-control studies, limiting comprehensive risk assessment for MIS-C in vaccinated versus unvaccinated children.
- Underdiagnosis of COVID-19 in children, who may present with mild or no symptoms, poses a challenge in accurately estimating MIS-C risk.
Purpose of the Study:
- To evaluate the risk reduction of MIS-C and severe MIS-C following Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccination in children and adolescents.
- To provide a nationwide assessment of vaccine effectiveness against MIS-C using a large cohort.
Main Methods:
- A nationwide cohort study in Israel included 526,685 PCR-confirmed COVID-19 cases in individuals under 19 years old, with 14,118 fully vaccinated before infection.
- MIS-C cases were identified from all Israeli hospitals between April 2020 and November 2021.
- MIS-C rates were calculated for estimated COVID-19 cases (PCR-confirmed and presumed), and risk differences (RD) between vaccinated and unvaccinated groups were analyzed, including sensitivity analyses for underdiagnosed COVID-19 rates.
Main Results:
- A total of 233 MIS-C cases were diagnosed in individuals under 19 during the study period.
- The estimated MIS-C risk difference ranged from 1.0 to 2.1 per 10,000 COVID-19 cases.
- For severe MIS-C, the risk difference ranged from 0.8 to 1.6 per 10,000 COVID-19 cases, with significant risk reduction observed in the vaccinated group across various assumptions of underdiagnosed COVID-19.
Conclusions:
- COVID-19 vaccination in children and adolescents significantly reduced the risk of developing MIS-C and severe MIS-C during the study period.
- The findings demonstrate a favorable risk difference for the vaccinated group, even when accounting for potential underdiagnosis of COVID-19.
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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