Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARS-CoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study

Ulrikka Nygaard*, Mette Holm, Ulla Birgitte Hartling, Jonathan Glenthøj, Lisbeth Samsø Schmidt, Sannie Brit Nordly, Astrid Thaarup Matthesen, Marie-Louise von Linstow, Laura Espenhain

*Corresponding author for this work
56 Citations (Scopus)

Abstract

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) occurs after infection with SARS-CoV-2 and its incidence is likely to depend on multiple factors, including the variant of the preceding SARS-CoV-2 infection and vaccine effectiveness. We aimed to estimate the incidence of MIS-C, and describe the clinical phenotype, following the delta variant of SARS-CoV-2 (B.1.617.2 and sublineages) according to vaccination status. We aimed to compare the incidence and clinical phenotype of MIS-C from our cohort during the pre-delta era.

METHODS: This prospective, population-based cohort study included patients aged 0-17 years hospitalised with MIS-C in Denmark, according to the US Centers for Disease Control and Prevention case definition, from Aug 1, 2021, to Feb 1, 2022, a period dominated by the delta variant. We identified MIS-C cases via a nationwide research collaboration involving real-time data collection from all 18 paediatric departments. Aggregated number of SARS-CoV-2 infections by vaccination status was obtained from the Danish COVID-19 surveillance registries. The incidence of MIS-C was calculated using the estimated number of infected individuals by vaccination status. We calculated the incidence of MIS-C per 1 000 000 vaccinated and unvaccinated person-years, and estimated vaccine effectiveness as 1-incidence rate ratio using Poisson regression. Incidence and phenotype of MIS-C were compared with MIS-C cases from the first year of the pandemic. This study is registered at ClinicalTrials.gov, NCT05186597.

FINDINGS: We identified 51 MIS-C cases among unvaccinated individuals and one in a fully vaccinated adolescent. The incidence of MIS-C was one in 3400 unvaccinated individuals (95% CI 2600-4600) with the delta variant and one in 9900 vaccinated individuals (95% CI 1800-390 000) with breakthrough infection. The estimated vaccine effectiveness against MIS-C after the delta variant was 94% (95% CI 55-99; p=0·0061) in individuals aged 5-17 years. The clinical phenotype during the delta wave was comparable to the pre-delta era.

INTERPRETATION: We found the incidence and phenotype of MIS-C in unvaccinated children during the delta wave to be similar to the incidence during the first year of the pandemic. We found vaccine effectiveness to be high against MIS-C, which we suggest was due to protection from infection and, possibly, a decreased incidence of MIS-C after breakthrough infection. Knowledge of the incidence of MIS-C after different SARS-CoV-2 variants and the effect of vaccination might contribute to the elucidation of the extent to which MIS-C is a vaccine-preventable disease.

FUNDING: National Ministry of Higher Education and Science and Innovation Fund Denmark.

Original languageEnglish
JournalThe Lancet Child & Adolescent Health
Volume6
Issue number7
Pages (from-to)459-465
Number of pages7
ISSN2352-4642
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Adolescent
  • COVID-19/complications
  • Child
  • Child, Preschool
  • Cohort Studies
  • Denmark/epidemiology
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Phenotype
  • Prospective Studies
  • SARS-CoV-2/genetics
  • Systemic Inflammatory Response Syndrome/epidemiology
  • Vaccination

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