Cited by 919Kawasaki Disease and Coronary ComplicationsCOVID-19 Clinical Research StudiesAutoimmune and Inflammatory Disorders Research

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

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Consiglio, Camila Rosat, Cotugno, Nicola, Sardh, Fabian, Pou, Christian, Amodio, Donato, Rodriguez, Lucie, Tan, Ziyang, Zicari, Sonia, Ruggiero, Alessandra, Pascucci, Giuseppe Rubens, Santilli, Veronica, Campbell, Tessa, Bryceson, Yenan, Eriksson, Daniel, Wang, Jun, Marchesi, Alessandra, Lakshmikanth, Tadepally, Campana, Andrea, Villani, Alberto, Rossi, Paolo, Landegren, Nils, Palma, Paolo, Brodin, Petter·2020·Cell

DOI 10.1016/j.cell.2020.09.016PMC PMC7474869

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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.

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Authors: Consiglio, C. R., Cotugno, N., Sardh, F., Pou, C., Amodio, D., Rodriguez, L., Tan, Z., Zicari, S., Ruggiero, A., Pascucci, G. R., Santilli, V., Campbell, T., Bryceson, Y., Eriksson, D., Wang, J., Marchesi, A., Lakshmikanth, T., Campana, A., Villani, A., Rossi, P., Landegren, N., Palma, P., & Brodin, P.
Affiliations: Science for Life Laboratory (SE)
University of Rome Tor Vergata (IT)
Karolinska University Hospital (SE)
Bambino Gesù Children's Hospital (IT)
Karolinska Institutet (SE)
Uppsala University (SE)
Corresponding author: Rossi, Paolo
Landegren, Nils
Brodin, Petter
ORCID: Consiglio, Camila Rosat
Cotugno, Nicola
Pou, Christian
Amodio, Donato
Rodriguez, Lucie
Tan, Ziyang
Zicari, Sonia
Ruggiero, Alessandra
Pascucci, Giuseppe Rubens
Santilli, Veronica
Campbell, Tessa
Bryceson, Yenan
Eriksson, Daniel
Wang, Jun
Marchesi, Alessandra
Lakshmikanth, Tadepally
Campana, Andrea
Villani, Alberto
Rossi, Paolo
Landegren, Nils
Palma, Paolo
Brodin, Petter
Venue: Cell
Publisher: Elsevier BV
Published: 2020-11
Volume: 183
Issue: 4
Pages: 968-981.e7
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2020.09.016
PMC: PMC7474869
OpenAlex: W3083424448
Cited by: 919
References: 58
Citations by year: 2026: 30 · 2025: 46 · 2024: 89 · 2023: 185 · 2022: 218 · 2021: 311 · 2020: 36
FWCI: 171.26
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Cell (publishedVersion, cc-by)
medRxiv (acceptedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, cc-by)
Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
Funders: Knut och Alice Wallenbergs Stiftelse
Topics: Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Kawasaki Disease and Coronary Complications
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Keywords: multisystem inflammatory syndrome in children, COVID-19 pandemic, SARS-CoV-2, Kawasaki disease, vasculitis, autoimmunity, cytokine storm, T cell subsets, IL-17A, autoantibodies, pediatric immunology, blood immune cells
MeSH terms: Betacoronavirus, COVID-19, SARS-CoV-2, Autoantibodies, Child, Child, Preschool, Female, Humans, Infant, Male, Mucocutaneous Lymph Node Syndrome, Pneumonia, Viral, Severity of Illness Index, T-Lymphocyte Subsets, Cytokines, Coronavirus Infections, Systemic Inflammatory Response Syndrome, Proteome, Principal Component Analysis, Immunity, Humoral, Pandemics

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