Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)

Cell. 2020 Nov 12;183(4):982-995.e14. doi: 10.1016/j.cell.2020.09.034. Epub 2020 Sep 14.


Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1), and mucosal immune dysregulation (IL-17A, CCL20, and CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK and T lymphocytes, suggesting extravasation to affected tissues. Finally, profiling the autoantigen reactivity of MIS-C plasma revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal, and immune-cell antigens. All patients were treated with anti-IL-6R antibody and/or IVIG, which led to rapid disease resolution.

Keywords: COVID-19; Kawasaki-like; MIS-C; PIMS; SARS-CoV-2; autoimmunity; dysfunction; immune; pediatrics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood
  • Autoantibodies / blood
  • Betacoronavirus / immunology
  • Betacoronavirus / isolation & purification
  • COVID-19
  • Chemokine CCL3 / metabolism
  • Child
  • Child, Preschool
  • Coronavirus Infections / complications
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Female
  • Humans
  • Immunity, Humoral
  • Infant
  • Infant, Newborn
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Interleukin-17 / metabolism
  • Interleukin-18 / metabolism
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / metabolism
  • Male
  • Pandemics
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Systemic Inflammatory Response Syndrome / immunology
  • Systemic Inflammatory Response Syndrome / metabolism
  • Systemic Inflammatory Response Syndrome / pathology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism
  • Young Adult


  • Antibodies, Viral
  • Autoantibodies
  • Chemokine CCL3
  • Interleukin-17
  • Interleukin-18

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related