Table 2.

Case definitions for multisystem inflammatory syndrome during the COVID-19 pandemic.

	World Health Organization29	Royal College of Paediatrics and Child Health (UK)12	Centers for Disease Control and Prevention (USA)50
Denomination	Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19.	Pediatric multisystem inflammatory syndrome temporally associated with COVID-19.	Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19).
Age	0–19 years	Children	<21 years
Fever	>3 days	≥38.5 °C; persistent	Fever >38.0 for ≥24 h or reports of subjective fever lasting ≥24 h
Clinical findings	AND two of the following five: 1. Rash or bilateral nonpurulent conjunctivitis or mucocutaneous inflammation signs (oral, hands, or feet). 2. Hypotension or shock. 3. Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain).	Evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, gastrointestinal, or neurological disorder, kidney). Most patients hypotension and oxygen supplementary needing. Some patients: abdominal pain, confusion, conjunctivitis, cough, diarrhea, headache, edema, lymphadenomegaly, changes in mucous membranes, cervical rash, respiratory symptoms, odynophagia, hand and foot edema, syncope and vomiting.	Evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, kidney, respiratory, hematologic, gastrointestinal, dermatologic, or neurological)
Laboratory changes	4. Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated troponin/NT-proBNP). 5. Evidence of coagulopathy (by PT, APTT, elevated D-dimers). AND Elevated markers of inflammation such as ESR, CRP, or procalcitonin. AND No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or treptococcal shock syndromes.	Inflammation signs. All patients: elevated CRP, ferritin and D-Dimer, abnormal fibrinogen, hypoalbuminemia and neutrophilia. Some patients: anemia, kidney failure, coagulopathy, neutrophilia, proteinuria, increased CPK, LDH, troponin, transaminases, triglycerides, thrombocytopenia, increased IL-6 (if available) and IL-10 (if available)	Laboratory evidence including, but not limited to, ≥1 of the following: an elevated CRP level, ESR, fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase, or IL-6; elevated neutrophils; reduced lymphocytes; and low albumin
Evidence of SARS-CoV-2 infection	AND Evidence of COVID-19 (RT-PCR, antigen test, or serology positive), or likely contact with patients with COVID-19.	SARS-CoV-2 PCR test results may be positive or negative	AND Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms
Exclusion criteria	Another obvious cause of infection or inflammation.	Exclusion of any other microbial cause, including bacterial sepsis, staphylococcal or streptococcal shock syndromes, infections associated with myocarditis such as enterovirus (waiting for results of these investigations should not delay seeking expert advice)	AND No alternative plausible diagnoses.
Considerations	Consider this syndrome in children with features of typical or atypical Kawasaki disease or toxic shock syndrome	Include children fulfilling full or partial criteria for Kawasaki disease	Some individuals may meet the full or partial criteria for Kawasaki disease, but should be reported if they meet the case definition for MIS-C. Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection

ECHO, echocardiography; NT-proBNP, N-terminal pro-B-type natriuretic peptide; PT, prothrombin time; APTT, activated partial thromboplastin time; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; RT-PCR, reverse transcription – polymerase chain reaction; CPK, creatine phosphokinase; LDH, lactate dehydrogenase; IL, interleukin; MIS-C, multisystem inflammatory syndrome in children.

Source: Whittaker et al.⁴¹ with modifications.