COVID-19, Multisystem Inflammatory Syndrome (MIS-C, MIS-A)

by Editorial Board last updated 2021-01-21 18:09:07.546929-05:00

Clinical Setting

  • COVID-19 complication identified in children and adolescents under age 21 years. Median age 8
  • Similar presentation has been occasionally identified in young adults, referred to as Multisystem Inflammatory Syndrome in adults (MIS-A ) MMWR 2020;69:1450
  • Multisystem Inflammatory Syndrome in Children (MIS-C) (CDC HAN No, 432, 05/14/20). Also called Pediatric Multisystem Inflammatory Syndrome. Temporally associated with SARS-CoV-2 (PMIS-TS)
    • CDC Case definition:
      • Age <21 years, fever, lab evidence of inflammation, hospitalized severe illness, multi-organ (≥2) involvement: cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological + no alternate diagnosis + current / recent positive test for SARS CoV-2 or COVID-19 exposure within 4 weeks of symptom onset.
      • See also WHO and Royal College of Physicians definitions Lancet ID 2020;20:e276
    • Most common symptoms:
      • Shock, with cardiac involvement, gastrointestinal symptoms, and significantly elevated markers of inflammation and positive serology for SARS CoV-2. Similar to Kawasaki disease and toxic shock syndrome and can be difficult to distinguish. MMWR 7 Aug 2020 early release. N Engl J Med 2020;383:347; N Engl J Med 2020;383:334
      • Fever, abdominal pain, vomiting, diarrhea.
      • Other symptoms include rash, conjuctivitis, headache, cervical adenopathy, lip swelling
    • Most (60-80%) SARS-CoV-2 Ab positive, some (15-30%) PCR positive
    • Lab abnormaliites:
      • Lymphopenia, thrombocytopenia, elevated ferritin, d-dimer, CRP, ESR, soluble IL-2 receptor, transaminases
    • Many have cardiac involvement with elevated troponin, BNP, decreased function, conduction abnormalities.  Coronary artery dilation in a minority. Echocardiography  and EKG recommended
    • Clinical phenotype likely broader including shock syndrome with cardiac involvement, Kawasaki-like picture, and persistent fever with inflammation. Headache 
    • Alternative causes of symptoms must be excluded - many examples of cognitive bias with anchoring on a diagnosis of MIS-C when children present with unexplained fevers leading to delayed treatment
    • Lancet. 2020 Jun 6 2020; JAMA June 8 2020


  • SARS CoV-2

Primary Regimens

  • No definitive data or consensus on optimal therapy
  • IVIG 2 gm/kg and/or methylprednisolone 2 mg/kg usually first line therapy
  • Refractory cases: Consider anakinra or infliximab
  • Low dose ASA for all patients. Consider anti-coagulation with severe cardiac involvement

Alternative Regimens

  • Inotropic and vasopressor support up to and including ECMO may be needed


  • Prognosis is generally favorable.
  • Followup echocardiography indicated for those with cardiac involvement. Coronary aneurysms in < 10%
  • Studies of optimal treatment needed