[15] Clinical complications can include damage to the heart muscle, respiratory distress, acute kidney injury, and increased blood coagulation.

[33][37] In April 2020, a small group of children with evidence of SARS-CoV-2 infection or exposure to COVID-19 were found to display clinical features corresponding to the diagnostic criteria of Kawasaki disease, sometimes accompanied by shock.

[3] Recovery typically occurs spontaneously, though some children later develop mid-sized or giant coronary artery aneurysms in the heart – a potentially fatal complication.

[3][44] While the exact cause of Kawasaki disease is unknown, one plausible explanation is that it may stem from an infection triggering an autoimmune and/or autoinflammatory response in children who are genetically predisposed.

[45][46] No specific diagnostic test exists for Kawasaki disease, and its recognition is based on various combinations of clinical and laboratory findings (including persistent fever, widespread rashes, enlarged lymph nodes, conjunctivitis, changes to the mucous membranes, and swollen hands and feet).

[3][40][47] MIS-C / PIMS-TS is a systemic disorder involving persistent fever, extreme[7] inflammation (hyperinflammation), and organ dysfunction, which is temporally associated with exposure to COVID-19.

[14] Some children display features of a cytokine storm,[14] including extremely high serum interleukin-6 (IL-6) levels,[22] and need inotropic support to maintain cardiac output.

[15] Pronounced biological markers of inflammation generally include strongly raised erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),[57] procalcitonin, ferritin, and IL6.

[7] In addition to respiratory distress, major complications that may need aggressive supportive care can include myocardial damage, acute kidney injury, and coagulopathy (thrombophilia).

[59] A set of guidelines proposed by Western New York recommends also evaluating children with clinical features that overlap with the MIS-C case definition, but who have been screened with mild illness and laboratory abnormalities, and who do not have an alternative diagnosis.

[21] It is essential to exclude alternative non-infectious[14] and infectious causes of the inflammatory condition, including bacterial sepsis, staphylococcal and streptococcal shock, and infections associated with myocarditis, such as enterovirus.

"[65] Due to the limited information available on this rare new diagnosis, clinical management has been largely based on expert opinion, including knowledge acquired from treating Kawasaki disease and other systemic inflammatory disorders of childhood, in addition to experience with COVID-19 in adults.

[45] As with Kawasaki disease, antibody-dependent enhancement, whereby development of antibodies could facilitate viral entry into host cells, has been proposed as a potential mechanism.

[16] Association of Kawasaki-like disease with COVID-19 could support the view that SARS-CoV-2 can cause systemic vasculitis by targeting endothelial tissue via angiotensin-converting enzyme 2 (ACE2), the protein which the virus uses to gain access to cells.

[74] While the initial infection is known to be capable of causing acute myocardial damage, occurrence of myocarditis could also plausibly be linked to systemic hyperinflammation triggered by a disorderly post-infectious immune response.

[48] Another key question is whether the molecular mechanisms that trigger autoimmune/autoinflammatory responses in children with PMIS and adults with severe COVID-19 (including the induction of high concentrations of IL-6) are similar or distinct.

[5] In MIS-C, such a scenario could lead to a clinical picture similar to STING-associated vasculopathy with onset in infancy (also known as SAVI) – a condition characterized by fever, lung injury, vascular inflammation, myositis, skin lesions (occasionally acral necrosis), and arterial aneurysms.

[77] Frequent presentation without prominent respiratory symptoms in children who do not appear to have ongoing SARS-CoV-2 infection but who have already developed antibodies suggests that the disease may be driven by a delayed, post-infectious mechanism.

[7] Regarding ethnicity, reports from France and the UK raised the possibility that children of Afro-Caribbean descent may be at greater risk, plausibly due to a genetic predisposition.

[84] As regards geographical distribution, there has been uncertainty as to whether the initial reports of cases in Europe and North America reflected a true pattern, or whether the condition had gone unrecognized elsewhere.

[76] Concerns have been raised regarding the potential for missed or delayed diagnosis of Kawasaki disease due to heightened diagnostic suspicion for the new entity.

[110] Sporadic reports exist of a similar life-threatening condition, denominated 'multisystem inflammatory syndrome in adults' (MIS-A), which also usually requires intensive care.

[3] In Bergamo, at the heart of the COVID-19 epidemic in Lombardy, a cluster of 20 cases of Kawasaki disease appeared to be roughly equivalent to the number commonly recorded there over the course of three years.

[13][38] Two weeks later, on 15 May, two further preliminary case definitions were published separately by the WHO[24] and by the CDC,[1] while the ECDC released a 'rapid risk assessment' of the condition on behalf of the European Union.

[85][140][141] The absence of documented cases in China and other Asian countries that had already experienced a COVID-19 epidemic led to conjectures regarding the possibility of a significant evolution of the virus, or variations in susceptibility in different populations.

[142][143] In Brazil, cases of MIS-C have been reported in São Paulo,[144] and in the context of a prospective study in Pará;[145] more children with severe late manifestations of COVID-19 were being admitted to paediatric intensive care units in the region.

[92] An editorial commentary urged clinicians to have a high level of diagnostic suspicion and follow WHO and CDC definitions to facilitate timely identification and treatment of cases.

[154] In Costa Rica, a national public health organization announced towards the end of August that three children had been diagnosed with MIS-C.[155] Cases of MIS-C had also been recorded in many other Latin American countries, including Argentina, Bolivia, Colombia, Cuba, the Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Uruguay, and Venezuela, as well as in Puerto Rico.

[110][29][157] In June, an adult case of a Kawasaki-like multisystem inflammatory syndrome following SARS-CoV-2 infection was described in a 54-year-old woman from Israel with no history of autoimmune disease, who experienced uveitis in both eyes.

[161] A case report published in The Lancet regarding a 45-year-old Hispanic man who presented in New York with features strongly resembling MIS-C called for awareness of "a potential MIS-C-like condition in adults.