Multisystem Inflammatory Syndrome in Children (MIS-C)

• Reporting criteria
• The disease and its epidemiology
• Case definition

• Laboratory testing
• Case investigation
• Disease control measures

• References
• Contact

What and how to report to the Colorado Department of Public Health and Environment (CDPHE) or local public health agency  

• Confirmed and probable MIS-C cases among people < 21 years of age.
• MIS-C cases should be reported within four days of diagnosis using the reportal, fax, encrypted email, or telephone to CDPHE. 

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Etiologic agent

Multisystem inflammatory syndrome in children (MIS-C) is a severe, delayed hyperinflammatory condition in children and adolescents (< 21 years of age) occurring 2-6 weeks after a SARS-CoV-2 infection (the virus that causes COVID-19). Several studies indicate that COVID-19 vaccination effectively reduces the risk of MIS-C.

Clinical description

The main risk factor for developing MIS-C is being infected with SARS-CoV-2, and many children with MIS-C had no or few symptoms of COVID-19. MIS-C is characterized by fever, elevated laboratory markers of systemic inflammation, and multiple organ system dysfunction, including cardiovascular, mucocutaneous, gastrointestinal, hematologic, neurologic, pulmonary, and renal involvement. Most children with MIS-C do not have any known underlying medical conditions, but of those who do, obesity is the most common. Patients with MIS-C usually present with fever and some combination of abdominal pain, vomiting, diarrhea, skin rash, and mucocutaneous lesions (i.e., conjunctivitis) approximately 2-6 weeks after a SARS-CoV-2 infection. In severe cases, children can present with hypotension and shock. The majority of patients with MIS-C require admission to an intensive care unit.

Hyperinflammation is a key feature of MIS-C. Patients with MIS-C have elevated laboratory markers of inflammation (e.g., C-reactive protein, ferritin), laboratory markers indicating damage to the heart (e.g., elevated troponin), and many have low platelet or absolute lymphocyte counts. Some patients develop cardiac dysfunction (e.g., decreased left ventricular function) and coronary artery dilatation or aneurysm. Gastrointestinal inflammation can manifest as abdominal pain, vomiting, and diarrhea. Neurological involvement is usually transient and presents as a headache or altered mental status. Other rare but severe neurologic manifestations may include encephalopathy, stroke, demyelination, and fulminant cerebral edema.

• Reservoirs

• Modes of transmission

• Incubation period

• Infectious period

Epidemiology   

MIS-C cases have been reported in all age groups less than 21 years of age, but the incidence is higher among younger children compared with older adolescents. Between 2020-2024, the median age of MIS-C cases in Colorado was 9 years, with a range of 5 months to 20 years. Between 2020 and 2023, trends in MIS-C cases generally followed trends in COVID-19 cases, with a sharp decline in the number of MIS-C cases reported in 2023 and 2024. During the first half of 2025, no MIS-C cases were identified in Colorado. Epidemiological data and disease statistics for MIS-C in Colorado are available on the Viral Respiratory Disease dashboard.

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Clinical description

An illness is characterized by all of the following in the absence of a more likely diagnosis: 

•  A subjective or documented fever (temperature ≥38.0⁰ C)
• Clinical severity requiring hospitalization or resulting in death
• Systemic inflammation indicated by C-reactive protein ≥3.0 mg/dL (30 mg/L)
• New onset manifestations in at least two of the following: shock and/or cardiac, mucocutaneous, gastrointestinal or hematologic involvement.  

Laboratory criteria for diagnosis

Confirmed

• Detection of SARS-CoV-2 RNA in a clinical specimen* up to 60 days prior to or during hospitalization, or in a post-mortem specimen using a diagnostic molecular amplification test (e.g., polymerase chain reaction [PCR]), OR
• Detection of SARS-CoV-2 antigen in a clinical specimen* up to 60 days prior to or during hospitalization, or in a post-mortem specimen, OR
• Detection of SARS-CoV-2 specific antibodies** in serum, plasma, or whole blood associated with current illness resulting in or during hospitalization. 

* Positive molecular or antigen results from self-administered testing using over-the-counter test kits meet laboratory criteria.

** Includes a positive serology test regardless of COVID-19 vaccination status. The detection of anti-nucleocapsid antibodies is indicative of SARS-CoV-2 infection; anti-spike protein antibodies may be induced by COVID-19 vaccination or SARS-CoV-2 infection.

Epidemiologic Linkage

• Close contact with a confirmed or probable case of COVID-19 disease in the 60 days prior to hospitalization, generally defined as being within six feet for at least 15 minutes (cumulative over a 24-hour period).

Case Classification

Confirmed

A person that is < 21 years of age that meets the clinical criteria AND is laboratory confirmed. 

Probable

A person that is < 21 years of age that meets the clinical AND epidemiologic linkage criteria.

Suspect

A person < 21 years of age whose death certificate lists MIS-C or multisystem inflammatory syndrome as an underlying cause of death or a significant condition contributing to death.

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CDPHE does not perform testing specific for MIS-C.  For more information about testing for SARS-CoV-2 RNA, antigen or antibody, visit the CDPHE information page about COVID-19 laboratory testing in Colorado. 

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CDPHE reviews medical records for all reported MIS-C cases. No additional case investigation is recommended for MIS-C cases.  

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Treatment

Persons diagnosed with MIS-C may receive anti-inflammatory drugs such as steroid therapy or intravenous immunoglobulin (IVIG). 

Prophylaxis

No prophylactic treatment of close contacts is recommended.

Education

• MIS-C is a rare but serious condition, and it is important to consult with a medical provider as soon as a person shows symptoms of MIS-C.
  • How to Recognize Multisystem Inflammatory Syndrome in Children (MIS-C) (English)
  • Cómo reconocer el síndrome inflamatorio multisistémico en niños (MIS-C) (Spanish)
• MIS-C is a condition associated with a SARS-CoV-2 infection. The best way to prevent MIS-C is to avoid infection with SARS-CoV-2, including Staying Up to Date with COVID-19 Vaccines for persons 6 months and older.

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MIS-C Clinical Overview: https://www.cdc.gov/mis/about/index.html 

MIS-C Case Definitions and Reporting: https://ndc.services.cdc.gov/case-definitions/multisystem-inflammatory-syndrome-in-children-mis-c-2023/ 

Clinical Treatment of MIS-C: https://www.cdc.gov/mis/hcp/clinical-care-treatment/index.html 

Signs and Symptoms of MIS-C: https://www.cdc.gov/mis/signs-symptoms/index.html 

Multisystemic inflammatory syndrome in children and the BNT162b2 vaccine: a nationwide cohort study | European Journal of Pediatrics. Available from URL: https://link.springer.com/article/10.1007/s00431-024-05586-4

Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARS-CoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study - The Lancet Child & Adolescent Health. Available from URL: https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(22)00100-6/fulltext

BNT162b2 mRNA Vaccination Against Coronavirus Disease 2019 is Associated With a Decreased Likelihood of Multisystem Inflammatory Syndrome in Children Aged 5-18 Years-United States, July 2021 - April 2022 - PubMed (nih.gov). Available from URL: https://pubmed.ncbi.nlm.nih.gov/35924406/

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CDPHE Communicable Disease Branch

• Phone: 303-692-2700 or 800-866-2759
• Fax: 303-782-0338
• After hours: 303-370-9395

CDPHE Lab Coordinators: 

• Email (preferred): cdphe_labcoordinators@state.co.us  
• Phone: 303-692-3480

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