Table 3.

Multisystemic inflammatory syndrome (MIS-C) classifications.

World Health Organization (WHO)	Royal College of Pediatrics and Child Health (RCPCH)	Center for Disease Control and Prevention (CDC)
Child or adolescent aged 0–19 years with fever >3 days and 2 of the following characteristics: rash or non-purulent conjunctivitis or signs of mucocutaneous inflammation (oral cavity, hands or feet) hypotension or shock signs of myocardial dysfunction, pericarditis, valvulitis or coronary abnormalities (including ultrasound alterations or troponin elevation /NT-proBNP) evidence of coagulopathy (PT, APTT, D-dimer elevation) acute gastrointestinal problems AND Elevation of inflammation indices such as CRP, PCT or ESR AND Exclusion of other microbiological causes of inflammation including bacterial sepsis, staphylococcal or streptococcal toxic shock syndrome: AND Evidence of SARS-CoV-2 infection (antigenic test or positive serology) or contact with COVID-19 patient Consider MIS-C in patients with typical/atypical Kawasaki disease or toxic shock syndrome	Patient with persistent fever (>38.5 °C), systemic inflammation (neutrophilia, PCR elevation and lymphopenia) and evidence of single or multiple organ dysfunction (shock, heart, kidney, gastrointestinal or neurological disorders) with additional characteristics * Patients with symptomatology partially or wholly meeting the criteria of Kawasaki’s disease may be included Exclusion of any other microbiological cause including bacterial sepsis, staphylococcal or streptococcal toxic shock syndrome, other infectious causes of myocarditis Searching for SARS-CoV-2 using PCR can be positive or negative* Additional features: Clinical: Many: O2 request, hypotension Some: abdominal pain, confusion, conjunctivitis, cough, diarrhea, headache, lymphadenopathy, changes in the mucous membranes, nuchal stiffness, rash, respiratory symptoms, pharyngitis, edema of the feet and hands, syncope, vomiting Laboratory: All: alteration of fibrinogen, high D-dimer, high ferritin, hypoalbuminemia Many: acute kidney damage, anemia, thrombocytopenia, coagulopathy, elevation IL- 10, -6, proteinuria, CK and LDH elevation, triglyceride elevation, troponin and liver transaminases Imaging: Echocardiography and ECG: myocarditis, valvulitis, pericardial effusion, dilation of the coronary arteries Radiography: Symmetrical pulmonary infiltrations, pleural effusion Abdomen echo: colitis, ileitis, lymphadenopathy, ascites, hepatosplenomegaly Pulmonary CT with contrast may show coronary aneurysms	Patients aged <21 years who have fever, laboratory evidence of inflammation and clinical evidence of severe prostration that requires hospitalization and the presence of two or more affected organs/apparatuses (heart, kidney, respiratory system, hematopoietic, gastrointestinal, dermatological or neurological) Fever >38 °C for ≥24 h or subjective fever reported for more than 24 h Laboratory positivity of more than 1 of the following indices: CRP, ESR, PCT, fibrinogen, D-dimer, ferritin, LDH or IL-6; neutrophilia, lymphopenia and hypoalbuminemia AND No other plausible diagnoses AND Laboratory positivity for recent or ongoing infection for SARS-CoV-2 (positivity of molecular, antigenic or serological investigations or contact with a certain case of COVID-19 in the previous 4 weeks) Comment Patients who partially or wholly meet the criteria of Kawasaki’s disease should be reported if they meet the MIS-C criteria Consider MIS-C in pediatric death cases with evidence of SARS-CoV-2 infection

APTT, activated partial thromboplastin time; CRP, C reactive protein; CT, computed tomography; ECG, electrocardiogram; ESR, erythrocyte sedimentation rate; IL, interleukin; LDH, lactate dehydrogenase; MIS-C, multisystemic inflammatory syndrome; NT-proBNT, N-terminal pro b-type natriuretic peptide; PCT, procalcitonin; PT, prothrombin time.