Although data on the incidence and severity of new coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection showed more significant disease among adults and the elderly, a clinical manifestation characterized by a multisystem inflammatory syndrome was described in children (MIS-C). It was initially thought to be specific to children, but recent reports have shown that it can also occur in adults. MIS-C is characterized by a number of multisystemic manifestations resembling other known previously described illnesses, mainly Kawasaki disease, especially in cases with shock, toxic shock syndrome, and macrophage activation syndrome. Available literature shows that our knowledge of MIS-C is largely incomplete. Its development in strict relation with SARS-CoV-2 infection seems documented and, in most cases, can be considered a post-infectious manifestation secondary to an abnormal immune response for some aspects, similar to that seen in adults several days after SARS-CoV-2 infection. However, in a minority of cases, a clinical picture with symptoms fulfilling criteria for MIS-C diagnosis develops during the acute phase of SARS-CoV-2 infection. It is highly likely that the criteria currently used to diagnose MIS-C are too broad, meaning that children with different diseases are included. As clarity on the pathogenesis of MIS-C is lacking, different therapeutic approaches have been used, but no specific therapy is currently available. Further studies are urgently needed to improve our definition of MIS-C, to define the real impact on child health, and to elucidate the best clinical and therapeutic approach and true prognosis.
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