Study: Developing MIS-C Remains Rare but Significantly More Likely for Unvaccinated Children


Study shows that 98% of cases of multi-system inflammatory syndrome in children (MIS-C) were unvaccinated, suggesting that vaccination reduces the chance of a child who had COVID-19 later developing MIS-C.

Since the FDA authorized use of the Pfizer-BioNTech COVID-19 vaccine for 5- to 11-year-olds in October 2021, more than 8 million children have received at least 1 dose.1 Vaccination has proven extremely effective in reducing hospital admissions for COVID-19 and analysis of other possible benefits is ongoing.

One area of interest is the rate of hospitalization for multi-system inflammatory syndrome in children (MIS-C). A recent Epic Research study showed that 98% of MIS-C patients were unvaccinated, suggesting that vaccination reduces the chance of a child who had COVID-19 later developing MIS-C.

First identified in early 2020, MIS-C is a delayed inflammatory reaction to the SARS-CoV-2 virus occurring about four weeks after infection. It affects mostly school age children, who experience fever, dizziness, confusion, rashes, abdominal pain, and other symptoms severe enough to require hospitalization. MIS-C is a rare complication and most children recover fully, but the CDC recommends that any children showing symptoms be seen by a physician.2

MIS-C occurs almost exclusively in children who have antibodies to the SARS-CoV-2 virus, indicating that they have been infected previously. Some children who develop MIS-C never experienced symptoms of COVID-19.3

Throughout the pandemic, Epic Research has analyzed the health record data of millions of patients to provide insights to both the medical community and general public. The MIS-C study’s dataset is limited to hospitalizations that occurred in 2021 after the COVID-19 vaccine became available for pediatric patients.

Of the 699 pediatric hospitalizations for COVID, 513 (73%) were for unvaccinated patients. Of the 1499 pediatric hospitalizations for MIS-C, 1474 (98%) were for unvaccinated patients. MIS-C cases also tend to peak after COVID cases peak, a relationship that was also reported by the CDC.4 These findings suggest that in addition to the known decrease in likelihood of vaccinated patients being hospitalized for COVID, vaccination may also play a role in decreasing the likelihood of developing MIS-C.

This study was completed using Cosmos, a HIPAA-defined limited data set that allows physicians to learn from thousands of other hospitals and clinics—and their patients—on a national scale. Cosmos was created by more than 145 health care organizations that use Epic’s electronic health record system and have consented to this information being used for medical research. The dataset used in this analysis represents more than 128 million patients across all 50 states and closely aligns with US census demographics.

About the Author

Sam Butler, MD, member of the Epic clinical informatics team.


  1. Tolbert J, Kates J, Rouw A. Update on COVID-19 vaccination of 5-11 year olds in the U.S. Kaiser Family Foundation. Published January 20, 2022. Accessed February 2, 2022.
  2. Information for healthcare providers about multisystem inflammatory syndrome in children (mis-C). Centers for Disease Control and Prevention. Published May 20, 2021. Accessed February 2, 2022.
  3. Sick-Samuels AC. MIS-C and COVID-19: Uncommon but serious inflammatory syndrome in kids and teens. Johns Hopkins Medicine. Published December 8, 2021. Accessed February 2, 2022.
  4. Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States. COVID Data Tracker. Accessed February 2, 2022.
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