Complications, Adverse Drug Events, High Costs, and Disparities in Multisystem Inflammatory Syndrome in Children vs COVID-19

JAMA Netw Open. 2023 Jan 3;6(1):e2244975. doi: 10.1001/jamanetworkopen.2022.44975.


Importance: Multisystem inflammatory syndrome in children (MIS-C) causes severe inflammation of multiple organ systems after SARS-CoV-2 infection. During the pandemic, surveillance reporting of MIS-C was voluntary, with likely underreporting. For a rare syndrome like MIS-C, numerous data are needed to explore the disease in greater detail.

Objective: To use large all-payer billing data and the new International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification (ICD-10-CM) code for MIS-C to compare outcomes across MIS-C and COVID-19 over all 4057 hospitals in 31 states.

Design, setting, and participants: A retrospective cross-sectional study of all COVID-19 and MIS-C hospitalizations in individuals younger than 21 years from 31 states was conducted, using Agency for Healthcare Research and Quality 2021 Healthcare Cost and Utilization Project data. Analyses were conducted from February 1 to October 20, 2022.

Main outcomes and measures: Fifty complications, adverse medication events, costs, and the Social Vulnerability Index.

Results: There were 4107 individuals with MIS-C (median age, 9 [IQR, 5-13] years; 2443 [59.5%] male; 1384 [38.1%] White) and 23 686 individuals with COVID-19 without MIS-C (median age, 15 [IQR, 5-18] years; 12 878 [54.4%] female; 4605 [44.1%] White), with 1.48 (95% CI, 1.35-1.62) MIS-C hospitalizations per 100 000 children per month, ranging from 0.97 hospitalizations per 100 children for White and 1.99 hospitalizations per 100 children for Black children. Outcomes worsened as the number of organ system dysfunctions increased from 2 to 8 organs. Deaths associated with MIS-C increased from less than 1% to 5.8% (95% CI, 3.3%-8.4%) and from less than 1% to 17.2% (95% CI, 11.7%-22.7%) for COVID-19 (P = .001). Adverse medication events associated with MIS-C increased from 4.9% (95% CI, 3.8%-6.0%) to 17.8% (95% CI, 13.7%-22.0%) and from 1.2% (95% CI, 1.0%-1.3%) to 13.4% (95% CI, 8.4%-18.3%) for COVID-19. The median length of stay for MIS-C increased from 4 (IQR, 2-5) to 8 (IQR, 5-12) days and from 3 (IQR, 2-5) to 16 (IQR, 7-23) days for COVID-19. Median costs for MIS-C increased from $16 225 (IQR, $9244-$26 822) to $53 359 (IQR, $35 920-$86 882) and from $6474 (IQR, $3741-$12 103) to $98 643 (IQR, $30 675-$204 956) for COVID-19. The percentage of MIS-C cases that were in Black children doubled from 16.2% to 31.7% (P = .001) as organ dysfunction increased, remaining unchanged with COVID-19. Hospital stays for MIS-C increased by 1 day (P = .01) for Black patients compared with White patients, with Black patients moving from the bottom to top quartile of socioeconomic vulnerability, with no disparity with COVID-19.

Conclusions and relevance: In this cross-sectional study, MIS-C was more common and severe than previously reported, with more racial disparities in outcomes than were seen in patients with COVID-19. The findings of this study suggest that relying on mean outcomes for MIS-C from past studies can be misleading, since outcomes and disparities varied widely with the number of multiorgan dysfunctions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • COVID-19* / epidemiology
  • Child
  • Connective Tissue Diseases*
  • Cross-Sectional Studies
  • Drug-Related Side Effects and Adverse Reactions*
  • Female
  • Humans
  • Male
  • Retrospective Studies
  • SARS-CoV-2

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related