Immunological profiling and detailed clinical characterisation of 25 children with multi-system inflammatory syndrome in children (MIS-C) is reported by researchers at Kings College London. The findings suggest that MIS-C is an immuno-pathogenic 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, characterised by multi-organ 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 sero-positive for SARS-CoV-2 antibodies. Of the 8 children who tested sero-negative, 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 sero-positive 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.
Abstract
Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1—multisystem inflammatory syndrome in children (MIS-C)—which comprises multiorgan dysfunction and systemic inflammation2,3,4,5,6,7,8,9,10,11,12,13. We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections14,15, and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-17, interferon-γ and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on γδ and CD4+CCR7+ T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness1 and appears distinct from Kawasaki disease.
Authors
Michael J Carter, Matthew Fish, Aislinn Jennings, Katie J Doores, Paul Wellman, Jeffrey Seow, Sam Acors, Carl Graham, Emma Timms, Julia Kenny, Stuart Neil, Michael H Malim, Shane M Tibby, Manu Shankar-Hari
[link url="https://www.nature.com/articles/s41591-020-1054-6"]Nature Medicine abstract[/link]