Objective: Multisystem Inflammatory Syndrome in Children (MIS-C) was identified as a rare
but serious hyperinflammatory condition temporally associated with SARS-CoV-2 infection.
Pediatric COVID-19 vaccination has been promoted based on the assumption that vaccination
reduces the risk of MIS-C; however, population-level evidence supporting this assumption
remains limited.
To assess whether pediatric COVID-19 vaccination was associated with reduced MIS-C
incidence.
Methods: Epidemiologic review across three periods: (1) pre–COVID-19 baseline Kawasaki
disease and Toxic Shock Syndrome (TSS), immunologically similar hyperinflammatory
condition to MIS-C (before March 2019); (2) pre-vaccine COVID-19 MIS-C incidence
(March 2019–May 2021); and (3) post–vaccine rollout MIS-C incidence (June 2021–
December 2022) was conducted.
Results: The baseline pre-pandemic Kawasaki disease (KD) and pediatric TSS incidence
ranged from 0.23 to 15.8 and from 0.15 to 0.25 per 100000 person-years, respectively. During
the pre-vaccine COVID-19 period, annualized MIS-C incidence ranged from 0.95 to 6.1 per
100,000 person-years, with substantial geographic and temporal variability. The incidence
of MIS-C after the enrollment of vaccines slightly declined but this may be attributed to
the emergence of Delta and later Omicron subvariants. Extrapolation from the Moderna’s
3d PSUR (Periodic Safety Update Report) suggests 42 MIS-C cases following Moderna
vaccination and 504 cases annually across all products in 2022.
Conclusion: Available data do not demonstrate a clear association between pediatric
COVID-19 vaccination and prevention of MIS-C at the population level. Interpretation is
limited by reliance on passive surveillance systems, inconsistent denominators, diagnostic
overlap, and restricted access to manufacturer safety data.
