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The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19
Open accessPublished version of a preprint
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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“MIS-C has distinct immunological features different from the two with respect to circulating cytokine profiles and composition of the T cell compartment”
From COVID-19 and the human innate immune system (2021) · cites this paper as Consiglio et al., 2020
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- Anft, 2020, COVID-19 progression is potentially driven by T cell immunopathogenesis, medRxiv
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Metadata
- 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)
- 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
- 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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