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Medical research: Severe multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection

Nature Medicine

August 18, 2020

Immunological profiling and detailed clinical characterization of 25 children with multisystem inflammatory syndrome in children (MIS-C) is reported in Nature Medicine. The findings suggest that MIS-C is an immunopathogenic illness, distinct from COVID-19 but associated with prior SARS-CoV-2 infection. Further research is needed to understand the mechanisms underpinning the immune response in MIS-C.

Recent reports have highlighted this new clinical syndrome in children related to SARS-CoV-2, characterized by multiorgan dysfunction and systematic inflammation. Manu Shankar-Hari and colleagues studied 25 children (15 boys and 10 girls) with MIS-C, aged 7–14 years. The authors found that 17 children were seropositive for SARS-CoV-2 antibodies. Of the 8 children who tested seronegative, 6 had previously had symptoms of SARS-CoV-2 infection, had been in close contact with people with confirmed cases of COVID-19 or had a parent who was a healthcare worker. Eighteen of the cohort reported gastrointestinal symptoms and 7 had radiological evidence of pneumonia. A further 7 had coronary artery dilatation or aneurysm. The authors found that seropositive status was associated with a greater prevalence of gastrointestinal symptoms, and coronary artery dilation or aneurysm was observed only in children who were seropositive.

The authors defined three clinical stages of the disease: acute (worst illness, within 72 hours of admission), resolution (clinical improvement) and convalescent (first outpatient appointment). They analysed blood samples from 23, 14 and 10 children, respectively, at these stages and compared the results to those of 7 healthy age-matched children. The authors found that in the acute phase of disease, patients had raised levels of cytokines ― signalling proteins released by immune cells — as has been observed in adults with COVID-19. They also found that during the acute stage the numbers of total B cells and different types of T cells decreased. Similar declines have been observed in the immune responses of adults with COVID-19. These populations returned to normal by the convalescent phase. They suggest that the immune responses in MIS-C patients and adult COVID-19 patients share some similarities but differ in other respects, such as numbers of neutrophils, another type of immune cell.

The authors conclude that MIS-C appears distinct from Kawasaki disease — another paediatric inflammatory syndrome. They caution that the cohort is small and that more research is needed to understand the activation mechanism of MIS-C and its associated immune response.

doi: 10.1038/s41591-020-1054-6

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