Striking Similarities of Multisystem Inflammatory Syndrome in Children and a Myocarditis-Like Syndrome in Adults

Abstract

uch remains uncertain about the pathophysiology of the various clinical presentations of coronavirus disease 2019 (COVID-19).Severe infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) most often manifests with a pulmonary syndrome that evolves from viral pneumonia to an inflammatory mediated acute respiratory distress syndrome.Two less common clinical presentations of COVID-19 include multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19 cardiovascular syndrome (ACovCS) in adults.These 2 syndromes are being reported as distinct entities, but they have several overlapping clinical features, which suggests that these conditions may be attributable to related pathophysiology in 2 different age groups.The incidence of severe COVID-19 in children is lower than in adults; however, MIS-C has been recognized worldwide during the past few months, challenging the paradigm that children are not severely affected by SARS-CoV-2.By definition, MIS-C only occurs in individuals younger than 21 years of age, but to our knowledge there has been no effort to explain why a firm dichotomous age threshold is appropriate.Case series 1,2 have described children with fever, abdominal pain, and mucocutaneous disease (rash, conjunctivitis, oral lesions), and many develop coronary artery dilation, similar to Kawasaki disease.Although both syndromes are associated with elevated inflammatory markers, there are several features that distinguish MIS-C from Kawasaki disease.A large proportion of children with MIS-C present with cardiac complications including elevated troponin, cardiogenic shock, and reduced biventricular function; in contrast, such cardiac complications are rare in Kawasaki disease.Nearly half of the reported patients with MIS-C are older than 10 years old, yet the median age for Kawasaki disease is 2 years old.Additionally, thrombocytopenia is more common in MIS-C, whereas thrombocytosis is typically seen in Kawasaki disease.Why some children develop MIS-C is presently unknown.Many children with MIS-C have no history of a symptomatic respiratory infection and test negative for SARS-CoV-2 by polymerase chain reaction, but have developed SARS-CoV-2-specific IgG antibodies, suggesting the initial infection occurred at least 2 weeks before the development of MIS-C.Epidemiological studies have demonstrated that higher regional incidences of MIS-C are associated with the larger COVID-19 outbreaks in Italy, the United Kingdom, and New York City; and regional peaks in MIS-C diagnoses occur approximately 4 weeks after COVID-19 diagnoses peak. 3These observations have led to the hypothesis that MIS-C is attributable to a postinfectious inflammatory state that occurs several weeks after a primary infection with SARS-CoV-2.Cardiovascular complications associated with SARS-CoV-2 infection have also been recognized in adults. 4There is a range of diverse cardiac manifestations from acute coronary syndrome to a viral myocarditis-like syndrome, which we

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