Clinical Treatment of Multisystem Inflammatory Syndrome in Children

What to know

  • Children diagnosed with multisystem inflammatory syndrome (MIS-C), are hospitalized and may receive care from a variety of specialists.
  • Some children will need to be in the intensive care unit (ICU) to closely monitor signs and symptoms.
Three health care providers discussing interventions

Treatment timeline

During hospitalization

  • Depending on the child's illness severity and clinical features, multiple specialists (e.g., cardiologists, critical care specialists, hematologists, infectious disease specialists, and rheumatologists) may participate in management.
  • It is important to evaluate children with suspected MIS-C for alternative diagnoses, particularly as MIS-C clinical features overlap with those of other conditions. Testing to evaluate for other potential diagnoses should be directed by patient signs and symptoms.
  • Alternate diagnoses to consider include:
    • Acute viral infection (e.g., SARS-CoV-2, influenza virus, adenovirus)
    • Myocarditis associated with acute viral infection (e.g., influenza virus, enteroviruses)
    • Kawasaki disease
    • Rickettsial infections (e.g., typhus)
  • Laboratory testing for inflammatory markers (e.g., C-reactive protein) should be performed and may be repeated over the course of hospitalization to monitor response to treatment. Other laboratory markers may be followed depending on MIS-C organ involvement (e.g., cardiac enzymes, liver enzymes, platelets, absolute lymphocyte count).
  • Children with MIS-C and evidence of cardiac involvement (i.e., elevated cardiac enzymes or shock) will likely have at least one echocardiogram performed during their hospitalization and may have follow-up echocardiograms depending on findings.
  • Treatment generally involves intravenous immunoglobulin (IVIG) and steroids, both of which treat the overactive immune response.1
  • Prolonged duration of outpatient steroids should be avoided.2 The use of anti-inflammatory medications (e.g., anakinra) and the use of anti-coagulation medications have been variable, and data are limited regarding treatment benefit.
  • Aspirin has commonly been used because of concerns for coronary artery involvement, and antibiotics are routinely used to treat potential sepsis while awaiting results from bacterial cultures. Thrombotic prophylaxis is often used given the hypercoagulable state typically associated with MIS-C.

Safety alert

Keep in mind: Aspirin or aspirin-containing products should not be given to children to treat a viral infection unless instructed to do so by a healthcare provider because of the risk of Reye's syndrome, a very serious but rare illness that can harm the liver and brain. Aspirin use after MIS-C diagnosis should be only as specifically recommended by a child's healthcare provider.

After hospitalization

  • Evaluation and testing after hospitalization are based on the presentation and clinical course of each patient with MIS-C.
  • Cardiology follow-up with repeat echocardiogram is generally recommended for patients with MIS-C cardiac manifestations.
  • Exercise, sports, and strenuous activity are generally limited for patients with MIS-C cardiac manifestations until cleared by a cardiologist.

Keep in mind

Follow-up with the patient's primary care provider is important. A conversation between the patient, their guardian(s), and the clinical team or a specialist should occur to assist with decisions about COVID-19 vaccination after MIS-C.
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Long-term outcomes

Most MIS-C patients recover from MIS-C without any long-term effects. Fewer adults with MIS (also known as MIS-A) have been reported, and longer-term complications in adult populations have not been well-characterized.

Most signs and symptoms of MIS-C, including elevated laboratory markers of inflammation and abnormal heart function, resolve within 6 months. A small number of children can have persistent symptoms such as fatigue, sleep-disturbance, anxiety, and emotional difficulties.

Some children may have abnormalities on neuropsychological testing, especially after severe illness, but most resolve within 2 years.

Patients who experience persistent signs or symptoms can learn more about the long-term effects of COVID-19.

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Content Source:
National Center for Immunization and Respiratory Diseases; Coronavirus and Other Respiratory Viruses Division (CORVD)
  1. https://www.cdc.gov/mis/hcp/clinical-overview/index.html#cdcreference_11
  2. https://ww.cdc.gov/mis/hcp/clinical-overview/index.html#cdcreference_12
  • American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 3
  • Truong DT, et al. MUSIC Study Investigators. Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study. JAMA Pediatr. 2025 Mar 1;179(3):293-301. doi: 10.1001/jamapediatrics.2024.5466. PMID: 39804656; PMCID: PMC11877180.
  • Rollins CK, Calderon J, Wypij D, et al. Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children. JAMA Netw Open. 2023;6(7):e2324369. doi:10.1001/jamanetworkopen.2023.24369
  • Kaltman J, Keesari R, Madani R, Jaggi P, Oster ME. Six-month cardiac outcomes in children with multisystem inflammatory syndrome in children. Cardiol Young. 2023 Dec;33(12):2632-2638. doi: 10.1017/S1047951123000793. Epub 2023 Apr 28. PMID: 37114296.
  • Yasuhara J, Masuda K, Watanabe K, Shirasu T, Takagi H, Sumitomo N, Lee S, Kuno T. Longitudinal Cardiac Outcomes of Multisystem Inflammatory Syndrome in Children: A Systematic Review and Meta-Analysis. Pediatr Cardiol. 2023 Apr;44(4):892-907. doi: 10.1007/s00246-022-03052-2. Epub 2022 Nov 22. PMID: 36416893; PMCID: PMC9684941.