Cardiovascular impact of COVID-19 with a focus on children: A systematic review

Table 3 Different case-definitiosns for the novel hyperinflammatory syndrome described during coronavirus disease-2019 pandemic

Royal College of Pediatrics and Child Health (United Kingdom)	World Health Organization	Centers for Disease Control and Prevention (United States)
A child presenting with persistent fever, inflammation (neutrophilia, elevated CRP, and lymphopenia) and evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, kidney, gastrointestinal, or neurological disorder) with additional clinical features, including children fulfilling full or partial criteria for Kawasaki disease 2	Children and adolescents 0-19 yr of age with fever > 3 d AND 2 of the following: (1) Rash or bilateral nonpurulent conjunctivitis or mucocutaneous inflammation signs (oral, hands, or feet); (2) Hypotension or shock; (3) Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated troponin/NT-proBNP); (4) Evidence of coagulopathy (by PT, APTT, elevated D-dimers); (5) Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain). 1Consider this syndrome in children with features of typical or atypical Kawasaki disease or toxic shock syndrome	An individual aged < 21 yr presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (> 2) organ involvement (cardiac, kidney, respiratory, hematologic, gastrointestinal, dermatologic, or neurological). 1Fever > 38.0 °C for ≥ 24 h or report of subjective fever lasting ≥ 24 h. 1Laboratory 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
And 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 elevated markers of inflammation such as ESR, CRP, or procalcitonin.	And no alternative plausible diagnoses
And SARS-CoV-2 PCR test results may be positive or negative	And no other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes	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
	And evidence of COVID-19 (RT-PCR, antigen test, or serology positive), or likely contact with patients with COVID-19	Additionally, 1some individuals may fulfil full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C. 1Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection

Reproduced from references[50-52]. COVID-19: Coronavirus disease-2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; APTT: Activated partial thromboplastin time; 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.

¹Criteria for Kawasaki disease include persistent fever and 4 of 5 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. Incomplete KD can be diagnosed if there are only 2 or 3 of these criteria.