Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection

M. Carter, M. Fish, Aislinn Jennings, K. Doores, P. Wellman, J. Seow, S. Acors, C. Graham, E. Timms, J. Kenny, S. Neil, M. Malim, S. Tibby, M. Shankar-Hari

Nature Medicine, 2020

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 inflammation 2 – 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 infections 14 , 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 illness 1 and appears distinct from Kawasaki disease. Characterization of a cohort of children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection provides insights into the immunopathogenic features of the disease.

Cited by 102 publications.

Field of study: Medicine

10.1038/s41591-020-1054-6