Multisystem Inflammatory Syndrome in Children

This document aims to ensure that clinicians are aware of current guidance regarding Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19), including the case definition and guidance on reporting to local health departments.

Current Illinois MIS-C Data

Illinois has received 172 reports of MIS-C from clinicians with many other cases currently under investigation. The 172 cases have been submitted to the Centers for Disease Control and Prevention (CDC) for further reporting and review. The CDC has determined four reports are considered not to be a case. Additional cases being investigated will be counted and reported as soon as all necessary data are received and reviewed. Below is a graph depicting the reported cases by the onset month of their reported MIS-C illness. IDPH anticipates additional reports will be received as reporting for these cases can lag as the critical task of treating these patients becomes the clinicians’ priority.

Reported MIS-C Cases by Onset Month in Illinois, 2020-2021



  • In spring 2020, clinicians in the United Kingdom1, New York City, and New York State reported cases of children with multisystem inflammatory syndrome (many of whom tested positive for SARS-CoV-2 infection by RT-PCR or serologic assay).
  • On May 14, 2020, CDC issued a Health Advisory regarding a multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19), along with a case definition for this syndrome2 (see below).
  • Most cases of MIS-C have features of shock, with cardiac involvement; gastrointestinal symptoms; and significantly elevated markers of inflammation, with positive laboratory test results for SARS-CoV-23. A recent prospective study found that ethnicity seemed to be a factor in both critical care admission and MIS-C and identified additional clinical characteristics of MIS-C versus acute COVID patients4. The literature continues to evolve regarding the pathogenesis and the clinical course of MIS-C5.

CDC Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C)2

  • An individual aged <21 years presenting with feveri, laboratory evidence of inflammationii, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological); AND
  • no alternative plausible diagnoses; AND
  • positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the four weeks prior to the onset of symptoms.

iFever >38.0oC for >24 hours, or report of subjective fever lasting >24 hours,
iiincluding, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes, and low albumin.

Additional comments

  • Some individuals may meet full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C
  • Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection

Essential Actions

  • Health care providers should maintain a high index of suspicion for MIS-C
  • Refer to the attached two-page "Multisystem Inflammatory Syndrome in Children (MIS-C) Clinical Pathway - Emergency Department (ED), Inpatient Unit, Pediatric Intensive Care Unit (PICU)" document, developed by the Illinois MIS-C Workgroup
  • Suspected cases of MIS-C should be referred immediately to a tertiary care center with a PICU
  • Tertiary care centers are asked to consider a collaborative approach in the management of these patients by convening a multispecialty committee (comprised of pediatric critical care, cardiology, hematology, infectious disease, and rheumatology/immunology) that provides coordinated clinical care guidance for each patient while (1) confirming patients meet the case definition, and (2) ensuring that appropriate diagnostic and treatment resources are readily available for this patient population
  • Hospital infection preventionists should be notified immediately upon recognition of patients meeting case definition to initiate public health reporting


  • In suspected cases of MIS-C, strongly recommend the following additional laboratory testing due to the potential for myocardial involvement: BNP and Troponin
  • If the BNP and/or Troponin levels are elevated, initiate transfer to a tertiary care center with a PICU
  • Hospitals must assess for current or recent SARS-COV-2 infection by performing a combination of RT-PCR, antigen test, and/or serology (as available) in patients who are under 21 years of age and present with symptoms compatible with MIS-C associated with COVID-19


  • Health care providers and laboratories are required by the Control of Communicable Disease Code to report suspected or known MIS-C associated with COVID-19 cases to the local health department
  • When an MIS-C case associated with COVID-19 is suspected to be or is known to be the cause of death in an individual (laboratory-confirmed case), this should be reported to the local health department
  • Hospitals must submit pre-defined data elements on MIS-C patients through the Illinois National Electronic Disease Surveillance System (I-NEDSS). NOTE: Electronic laboratory reporting alone will not suffice for this syndrome. IMPORTANT REMINDER: When reporting these cases in I-NEDSS, select “Multisystem Inflammatory Syndrome” as the condition
  • Hospitals should ensure complete reporting of co-morbidities and details of previous outpatient, inpatient, or emergency department visits through I-NEDSS, as applicable
  • In addition to reporting through I-NEDSS, providers should complete the MIS-C Case Report Form (CRF) when they suspect a case and submit it to their local health department

Follow the steps below to ensure appropriate completion of the reporting process:

  • Identify suspected MIS-C case
  • Promptly report the case to the local health department thru I-NEDSS
    • Choose ”Multisystem Inflammatory Syndrome” as the condition.
  • Submit a completed MIS-C Case Report Form (CRF) to the local health department.
  • NOTE: Local health departments submit the CRF forms to IDPH to determine if MIS-C classification is met, prior to submission to the CDC.

1 Royal College of Paediatrics and Child Health Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19, May 2020.
2 CDC Health Advisory, Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19), CDCHAN-0032, May 14, 2020
3 Godfred-Cato S, Bryant B, Leung J, et al. COVID-19-Associated Multisystem Inflammatory Syndrome in Children – United States, March-July 2020. MMWR Morb Mortal Wkly Rep 2020; 69: 1074-1080. doi:
4 Swann O, Holden K, Turtle L, et al. Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicenter observational cohort study. BMJ 2020; 370: m3249. doi:
5Consiglio C, Cotugno N, Sardh F, et al. The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. Cell 183, 968-981. November 12, 2020. doi:

Last Updated: 06/01/2021