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COVID-19

Multisystem inflammatory syndrome in children: getting to the heart of the matter

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Two preprint studies by Gruber et al. and Consiglio et al. explore the immune landscape underlying the devastating multisystem inflammatory syndrome in children (MIS-C) seen following SARS-CoV-2 infection. Parallels have been drawn between MIS-C and other paediatric vasculitides, such as Kawasaki disease. Consiglio et al. initially compared a small group of patients with MIS-C with healthy controls, paediatric patients with SARS-CoV-2 and patients with Kawasaki disease. Distinct cytokine profiles in MIS-C and Kawasaki disease were demonstrated, with IL-17A levels higher in Kawasaki disease than in MIS-C or in patients with SARS-CoV-2. Gruber et al. compared eight patients with MIS-C to healthy controls, patients with COVID-19 or convalescent individuals, and identified enhanced expression of pro-inflammatory cytokines and chemokines in MIS-C. Patients with MIS-C also had reduced numbers of immune cell types such as monocytes and T cells in peripheral blood, likely due to migration of these cells to inflamed sites. Both studies showed that autoantibodies targeting the heart and blood vessels are prominent in MIS-C. Autoantibody targets in the heart including endoglin and RBPJ were identified by Consiglio et al., whereas Gruber et al. found autoantibodies targeting not only cardiac but also gastrointestinal antigens. These results are consistent with the vasculitis-like symptoms observed in MIS-C. Importantly, a number of treatment strategies were employed in the two studies, including anti-IL-6R, intravenous immunoglobulin therapy, recombinant IL-1RA and corticosteroids. These findings provide significant insight into the disease mechanisms and relevant treatment options for MIS-C.

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Original articles

  1. Gruber, C. et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Preprint at medRxiv https://doi.org/10.1101/2020.07.04.20142752 (2020)

    Article  PubMed  PubMed Central  Google Scholar 

  2. Consiglio, C. R. et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Preprint at medRxiv https://doi.org/10.1101/2020.07.08.20148353 (2020)

    Article  Google Scholar 

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Correspondence to Athena Cavounidis or Jennifer Alderson or Max Quastel.

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The authors declare no competing interests.

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Cavounidis, A., Alderson, J. & Quastel, M. Multisystem inflammatory syndrome in children: getting to the heart of the matter. Nat Rev Immunol 20, 520 (2020). https://doi.org/10.1038/s41577-020-0409-z

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