Multisystem Inflammatory Syndrome in Children-United States, February 2020-July 2021

Clin Infect Dis. 2022 Aug 24;75(1):e1165-e1175. doi: 10.1093/cid/ciab1007.


Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory condition in persons aged <21 years associated with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to describe MIS-C cases reported to Centers for Disease Control and Prevention's (CDC's) national surveillance since the coronavirus disease 2019 (COVID-19) pandemic began.

Methods: We included patients meeting the MIS-C case definition with onset date from 19 February 2020 through 31 July 2021, using CDC's MIS-C case report form, which collects information on demographics, clinical presentation, and laboratory results. Trends over time across 3 MIS-C pandemic waves were assessed using Cochran-Armitage test for categorical and Jonckheere-Terpstra test for continuous variables.

Results: Of 4901 reported cases, 4470 met inclusion criteria. Median patient age increased over time (P < .001), with a median of 9 years (interquartile range, 5-13 years) during the most recent (third) wave. Male predominance also increased (62% in third wave, P < .001). A significant (P < .001) increase in severe hematologic and gastrointestinal involvement was observed across the study period. Frequency of several cardiovascular complications (ie, cardiac dysfunction, myocarditis, and shock/vasopressor receipt) and renal failure declined (P < .001). Provision of critical care including mechanical ventilation (P < .001) and extracorporeal membrane oxygenation (ECMO; P = .046) decreased, as did duration of hospitalization and mortality (each P < .001).

Conclusions: Over the first 3 pandemic waves of MIS-C in the United States, cardiovascular complications and clinical outcomes including length of hospitalization, receipt of ECMO, and death decreased over time. These data serve as a baseline for monitoring future trends associated with SARS-CoV-2 B.1.617.2 (Delta) or other variants and increased COVID-19 vaccination among children.

Keywords: COVID-19; child; epidemiology; multisystem inflammatory syndrome in children.

Publication types

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

MeSH terms

  • COVID-19 Vaccines
  • COVID-19* / complications
  • COVID-19* / epidemiology
  • COVID-19* / therapy
  • Child
  • Connective Tissue Diseases*
  • Female
  • Humans
  • Male
  • SARS-CoV-2
  • Systemic Inflammatory Response Syndrome / epidemiology
  • Systemic Inflammatory Response Syndrome / therapy
  • United States / epidemiology


  • COVID-19 Vaccines

Supplementary concepts

  • SARS-CoV-2 variants
  • pediatric multisystem inflammatory disease, COVID-19 related

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