. 2021 Mar 6;36(4):404–415. doi: 10.1007/s12291-021-00963-4

Table 1.

Paediatric Case Definitions for Emerging Inflammatory Condition During COVID-19 Pandemic From the World Health Organization, Royal College of Paediatrics and Child Health, and Centers for Disease Control and Prevention

World Health Organization [27]	Royal College of Paediatrics and Child Health (United Kingdom) [28]	Centers for Disease Control and Prevention (United States) [29]
Age ≤ 19 y with fever > 3 d AND Two of the following: Rash or bilateral nonpurulent conjunctivitis or mucocutaneous inflammation signs (oral, hands, or feet) Hypotension or shock Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (ECHO findings or elevated troponin/ NT-proBNP) Proof of coagulopathy (PT, APTT, elevated D-dimers) Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain) AND Elevated inflammation markers (ESR, CRP, or procalcitonin) AND No evidence of microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes AND Evidence of COVID-19 (RT-PCR, antigen test, or serology positive), or likely contact with patients with COVID-19 (children with features of typical or atypical Kawasaki disease or toxic shock syndrome)	A child presenting with Persistent fever, Inflammation (neutrophilia, elevated CRP, and lymphopenia) Evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, kidney, gastrointestinal, or neurological disorder) with Additional features include fulfilling full or partial criteria for Kawasaki disease^a Exclusion of any other microbial cause, including bacterial sepsis, staphylococcal or streptococcal shock syndromes, infections associated with myocarditis such as enterovirus SARS-CoV-2 PCR test results may be positive or negative	Individual aged < 21 y presenting with fever, Fever > 38.0 °C for ≥ 24 h or report of subjective fever lasting ≥ 24 h Laboratory evidence of inflammation, as well ≥ 1 of the following: (elevated CRP level, ESR, fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase, or IL-6; elevated neutrophils; reduced lymphocytes; and low albumin) Evidence of clinically severe illness with multisystem (> 2) organ involvement (cardiac, kidney, respiratory, hematologic, gastrointestinal, dermatologic, or neurological) AND No alternative plausible diagnoses AND Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 wk prior to the onset of symptoms Some individuals may fulfill full or partial criteria for Kawasaki disease

World Health Organization [27]

Royal College of Paediatrics and Child Health (United Kingdom) [28]

Centers for Disease Control and Prevention (United States) [29]

Age ≤ 19 y with fever > 3 d

AND

Two of the following:

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

Hypotension or shock

Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (ECHO findings or elevated troponin/ NT-proBNP)

Proof of coagulopathy

(PT, APTT, elevated D-dimers)

Acute gastrointestinal problems

(diarrhea, vomiting, or abdominal pain)

AND

Elevated inflammation markers (ESR, CRP, or procalcitonin)

AND

No evidence of microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes

AND

Evidence of COVID-19 (RT-PCR, antigen test, or serology positive), or likely contact with patients with COVID-19 (children with features of typical or atypical Kawasaki disease or toxic shock syndrome)

A child presenting with

Persistent fever,

Inflammation (neutrophilia, elevated CRP, and lymphopenia)

Evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, kidney, gastrointestinal, or neurological disorder) with

Additional features include fulfilling full or partial criteria for Kawasaki disease^a

Exclusion of any other microbial cause, including bacterial sepsis, staphylococcal or streptococcal shock syndromes, infections associated with myocarditis such as enterovirus

SARS-CoV-2 PCR test results may be positive or negative

Individual aged < 21 y

presenting with fever,

Fever > 38.0 °C for ≥ 24 h or report of subjective

fever lasting ≥ 24 h

Laboratory evidence of inflammation, as well

≥ 1 of the following:

(elevated CRP level, ESR, fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase, or IL-6; elevated neutrophils;

reduced lymphocytes; and low albumin)

Evidence of clinically severe illness with multisystem (> 2) organ involvement (cardiac,

kidney, respiratory, hematologic, gastrointestinal,

dermatologic, or neurological)

AND

No alternative plausible diagnoses

AND

Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 wk prior to the onset of symptoms

Some individuals may fulfill full or partial criteria for Kawasaki disease

APTT activated partial thromboplastin time; COVID-19 coronavirus disease 2019; CRP C-reactive protein; ECHO echocardiography; ESR erythrocyte sedimentation rate; MIS-C multisystem inflammatory syndrome in children; NT-proBNP N-terminal pro–B-type natriuretic peptide; PT prothrombin time; RT-PCR reverse transcriptase–polymerase chain reaction; SARS-CoV-2 severe acute respiratory syndrome coronavirus 2

^aCriteria for Kawasaki disease include persistent fever and four of five principal clinical features: erythema and cracking of lips, strawberry tongue, and/or erythema of oral and pharyngeal mucosa; bilateral bulbar conjunctival injection without exudate; rash (maculopapular, diffuse erythroderma); erythema and edema of the hands and feet and/or periungual desquamation; and cervical lymphadenopathy