Pediatric multisystem inflammatory syndrome associated with COVID-19: Insights in pathogenesis and clinical management

Table 1 Case definition criteria for multisystemic inflammatory syndrome in children issued by the Royal College of Pediatrics and Child Health, World Health Organization and Centers for Disease Control and Prevention

Criteria	RCPCH[71]	WHO[72]	CDC[73]
Age	ND	< 21	< 19
Clinical	Persistent fever > 38.5 °C. Evidence of single or multi-organ dysfunction with additional features1	Fever ≥ 3 d; two of the following: (1) Mucocutaneous inflammation signs; (2) Hypotension or shock; (3) Cardiac issues2; (4) Evidence of coagulopathy; and (5) Acute gastrointestinal problems	Fever ≥ 38.0 °C for ≥ 24 h; multisystemic disease involving multiple (≥ 2) organs (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological). Requirement of hospitalization
Inflammatory markers	Neutrophilia, elevated CRP and lymphopenia	Elevated markers (such as ESR, CRP or procalcitonin)	Elevated CRP, ESR, fibrinogen, procalcitonin, d-dimer, ferritin, neutrophils, LDH, or IL-6 or reduced albumin and/or lymphocytes
COVID-19 test	Positive or negative SARS-CoV-2 RT-PCR test	Evidence of COVID-19 (via RT-PCR, antigen test, or serology) or probable contact with patients contaminated with SARS-CoV-2	RT-PCR, serology or antigen test positive for COVID-19 (currently or in recent period) or exposure to the virus within 4 wk prior to symptom onset
Exclusion factors	Exclusion of any other microbial cause	No other obvious etiology for the inflammation	Absence of other plausible alternative diagnoses

¹Additional features: Abdominal pain, confusion, conjunctivitis, cough, diarrhoea, headache, lymphadenopathy, mucus membrane changes, neck swelling, rash, resp symptons, sore throat, swollen hands and feet, syncope, vomiting.

²Cardiac issues: Myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP).

RCPCH: Royal College of Paediatrics and Child Health; WHO: World Health Organization; CDC: Centers for Disease Control and Prevention; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; LDH: Lactate dehydrogenase; IL-6: Interleukin 6; RT-PCR: Reverse transcription-polymerase chain reaction; ND: Not described; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus disease 2019.