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. On 2 June, news emerged of a first case of MIS-C diagnosed in Peru. In Brazil, cases of MIS-C have been reported in São Paulo, and in the context of a prospective study in Pará; more children with severe late manifestations of COVID-19 were being admitted to paediatric intensive care units in the region. In Chile, 42 confirmed cases of MIS-C had been recorded nationally by June 28, including 27 in the capital, Santiago. In Russia, 13 children had been treated (5 with intensive care) by mid-June for a multisystem inflammatory syndrome at the Morozov Childrens Hospital in Moscow, including a 2-year-old girl with the COVID-19 infection who died on 23 May following an initial diagnosis of suspected Kawasaki disease. In Iran, a case report (first submitted in May) described severe MIS-C in a 5-year-old girl who had presented with shock and was initially diagnosed with Kawasaki disease, and further cases of the new syndrome have been recorded. In India, a case of suspected MIS-C was reported in late May regarding a child who had presented in a COVID-19 hotspot in Kerala.
Misclassification of cases of Kawasaki disease and of other inflammatory and infectious diseases of childhood whose case definitions overlap with MIS-C could skew understanding of the new entity, such as the frequency of coronary artery aneurysms. Another concern is that clinically less severe cases of the new entity may be missed, and that the actual spectrum of disease severity could be broader, especially given the reliance on early observations of severe disease for provisional case definition. Some statistical modeling has been used to explore possible subdivision of cases satisfying the CDCs case definition into three distinct subgroups based on underlying clinical similarities: Class 1, characterized by pronounced multiorgan involvement, with little overlap with Kawasaki disease or acute COVID-19; Class 2, more predominantly characterized by respiratory symptoms typical of acute COVID-19; Class 3, a clinically less severe grouping, where rashes and mucosal symptoms are prevalent, with less multiorgan involvement, and generally greater overlap with Kawasaki disease. A suggestion that research into the biology of the disease might benefit from considering cases of Kawasaki disease and of the provisionally defined entity in conjunction is debated. In adults
There has been uncertainty as to whether the condition is confined to children, and the appropriateness of excluding adults from case definitions has been questioned. Sporadic reports exist of a similar life-threatening condition, denominated  multisystem inflammatory syndrome in adults (MIS-A), which also usually requires intensive care.