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.


  • Clinicians in the United Kingdom1, New York City and New York State have reported cases of children with multisystem inflammatory syndrome (many of whom tested positive for SARS-CoV-2 infection by RT-PCR or serologic assay).  Additional reports of children presenting with severe inflammatory syndrome with a laboratory-confirmed case of COVID-19 or an epidemiological link to a COVID-19 case have been reported by authorities in other countries2.
  • On May 14, 2020, the Centers for Disease Control and Prevention (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 syndrome3.
  • There is limited information currently available regarding the risk factors, pathogenesis, clinical course, and treatment for MIS-C3.

CDC Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C)3

  • 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 4 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 fulfill 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

  • All health care providers should maintain a high index of suspicion for MIS-C.
  • Suspected cases of MIS-C should be referred immediately to a tertiary care center with a pediatric intensive care unit (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 associated with COVID-19 case is suspected to be or is known to be (laboratory-confirmed case) the cause of death in an individual, this should be reported to the local health department.
  • Hospitals must submit pre-defined data elements on MIS-C patients through Illinois’ National Electronic Disease Surveillance System (I-NEDSS). NOTE: Electronic laboratory reporting alone will not suffice for this syndrome.
  • 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 INEDSS, providers should complete the MIS-C case report form when they suspect a case and submit it to their local health department.

Revisions and Updates

Interim Guidance developed

Essential Actions section, 2nd bullet - Added pediatric intensive care unit (PICU);
Testing section - Added 2 new bullets related to BNP and Troponin lab testing.

1 Royal College of Paediatrics and Child Health Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19,
2 Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, Bonanomi E, D’Anitga L. An outbreak of severe Kawasaki-like disease at the Italian epicenter of the SARS-CoV-2 Epidemic: an observational cohort study. Lancet. 2020. Advance online publication, doi: 10.1016/S0140-6736(20)31129-6
3 CDC Health Advisory, Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19), CDCHAN-0032, May 14, 2020