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CDC and WHO case definitions of multisystem inflammatory syndrome in children

CDC case definition

All 4 criteria must be met:

Age <21 years

Clinical presentation consistent with MIS-C, including all of the following:

Fever:
- Documented fever >38.0°C (100.4°F) for ≥24 hours
  - or
- Report of subjective fever lasting ≥24 hours

Laboratory evidence of inflammation
- Including, but not limited to, any of the following:
  - Elevated CRP
  - Elevated ESR
  - Elevated fibrinogen
  - Elevated procalcitonin
  - Elevated D-dimer
  - Elevated ferritin
  - Elevated LDH
  - Elevated IL-6 level
  - Neutrophilia
  - Lymphocytopenia
  - Hypoalbuminemia

Multisystem involvement
- 2 or more organ systems involved:
  - Cardiovascular (eg, shock, elevated troponin, elevated BNP, abnormal echocardiogram, arrhythmia)
  - Respiratory (eg, pneumonia, ARDS, pulmonary embolism)
  - Renal (eg, AKI, kidney failure)
  - Neurologic (eg, seizure, stroke, aseptic meningitis)
  - Hematologic (eg, coagulopathy)
  - Gastrointestinal (eg, abdominal pain, vomiting, diarrhea, elevated liver enzymes, ileus, gastrointestinal bleeding)
  - Dermatologic (eg, erythroderma, mucositis, other rash)

Severe illness requiring hospitalization

No alternative plausible diagnoses

Recent or current SARS-CoV-2 infection or exposure

Any of the following:
- Positive SARS-CoV-2 RT-PCR
- Positive serology
- Positive antigen test
- COVID-19 exposure within the 4 weeks prior to the onset of symptoms

WHO case definition

All 6 criteria must be met:

Age 0 to 19 years

Fever for ≥3 days

Clinical signs of multisystem involvement (at least 2 of the following):

Rash, bilateral nonpurulent conjunctivitis, or mucocutaneous inflammation signs (oral, hands, or feet)

Hypotension or shock

Cardiac dysfunction, pericarditis, valvulitis, or coronary abnormalities (including echocardiographic findings or elevated troponin/BNP)

Evidence of coagulopathy (prolonged PT or PTT; elevated D-dimer)

Acute gastrointestinal symptoms (diarrhea, vomiting, or abdominal pain)

Elevated markers of inflammation (eg, ESR, CRP, or procalcitonin)

No other obvious microbial cause of inflammation, including bacterial sepsis and staphylococcal/streptococcal toxic shock syndromes

Evidence of SARS-CoV-2 infection

Any of the following:
- Positive SARS-CoV-2 RT-PCR
- Positive serology
- Positive antigen test
- Contact with an individual with COVID-19

This table outlines the CDC's and WHO's case definitions of MIS-C. Patients who meet these criteria and who also fulfill full or partial criteria for Kawasaki disease should be considered to have MIS-C and should be reported. In addition, MIS-C should be considered in any pediatric death with evidence of SARS-CoV-2 infection.

CDC: Centers for Disease Control and Prevention; WHO: World Health Organization; MIS-C: multisystem inflammatory syndrome in children; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; LDH: lactate dehydrogenase; IL-6: interleukin 6; BNP: brain natriuretic peptide; ARDS: acute respiratory distress syndrome; AKI: acute kidney injury; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; RT-PCR: reverse transcription polymerase chain reaction; COVID-19: coronavirus disease 2019; PT: prothrombin time; PTT: partial prothrombin time.

References:

Centers for Disease Control and Prevention Health Alert Network (HAN). Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Available at: https://emergency.cdc.gov/han/2020/han00432.asp (Accessed on May 15, 2020).
World Health Organization. Multisystem inflammatory syndrome in children and adolescents with COVID-19: Scientific Brief. 2020. Available at: https://www.who.int/publications-detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19 (Accessed on May 17, 2020).

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