The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

C.R. Consiglio, N. Cotugno, F. Sardh, C. Pou, D. Amodio, L. Rodriguez, Z. Tan, S. Zicari, A. Ruggiero, G.R. Pascucci, V. Santilli, T. Campbell, Y. Bryceson, D. Eriksson, J. Wang, A. Marchesi, T. Lakshmikanth, A. Campana, A. Villani, P. RossiN. Landegren, P. Palma, P. Brodin, the CACTUS Study Team

Research output: Contribution to journalArticlepeer-review

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4–6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C. © 2020 The Author(s) A systems immunology approach describes how multisystem inflammatory syndrome in children (MIS-C) is distinct from Kawasaki disease as well as the cytokine storm associated with severe COVID-19 in terms of its molecular and immune profiles. © 2020 The Author(s)
Original languageEnglish
Pages (from-to)968
JournalCell
Volume183
Issue number4
DOIs
Publication statusPublished - 2020

Keywords

  • autoantibodies
  • COVID-19
  • hyperinflammation in children
  • IL-17A
  • Kawasaki disease
  • MIS-C
  • multisystem inflammatory syndrome in children
  • SARS-CoV-2
  • systems immunology
  • autoantibody
  • chemokine receptor CXCR5
  • gamma interferon
  • interleukin 17
  • cytokine
  • proteome
  • Article
  • child
  • clinical feature
  • controlled study
  • coronavirus disease 2019
  • cytokine storm
  • disease severity
  • enzyme linked immunosorbent assay
  • female
  • flow cytometry
  • human
  • human cell
  • humoral immunity
  • immunocompetent cell
  • immunology
  • immunomodulation
  • major clinical study
  • male
  • mucocutaneous lymph node syndrome
  • pathogenesis
  • pediatric patient
  • priority journal
  • proteomics
  • Severe acute respiratory syndrome coronavirus 2
  • systemic inflammatory response syndrome
  • T lymphocyte subpopulation
  • Betacoronavirus
  • blood
  • complication
  • Coronavirus infection
  • cytology
  • infant
  • isolation and purification
  • metabolism
  • pandemic
  • pathology
  • preschool child
  • principal component analysis
  • severity of illness index
  • virology
  • virus pneumonia
  • Autoantibodies
  • Child
  • Child, Preschool
  • Coronavirus Infections
  • Cytokines
  • Female
  • Humans
  • Immunity, Humoral
  • Infant
  • Male
  • Mucocutaneous Lymph Node Syndrome
  • Pandemics
  • Pneumonia, Viral
  • Principal Component Analysis
  • Proteome
  • Severity of Illness Index
  • Systemic Inflammatory Response Syndrome
  • T-Lymphocyte Subsets

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