Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study

Lancet Child Adolesc Health. 2021 May;5(5):323-331. doi: 10.1016/S2352-4642(21)00050-X. Epub 2021 Mar 10.


Background: Multisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes.

Methods: In this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities.

Findings: 1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]).

Interpretation: Identification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C.

Funding: None.

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • COVID-19 / complications*
  • COVID-19 / diagnosis
  • COVID-19 / epidemiology
  • COVID-19 / therapy*
  • Child
  • Child, Preschool
  • Critical Care
  • Early Diagnosis
  • Ethnicity
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Retrospective Studies
  • Risk Factors
  • Systemic Inflammatory Response Syndrome / complications*
  • Systemic Inflammatory Response Syndrome / diagnosis
  • Systemic Inflammatory Response Syndrome / epidemiology
  • Systemic Inflammatory Response Syndrome / therapy*
  • Time-to-Treatment
  • Treatment Outcome
  • United States
  • Young Adult


  • Biomarkers

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related