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Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is centr...

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Autores principales: Boribong, Brittany P., LaSalle, Thomas J., Bartsch, Yannic C., Ellett, Felix, Loiselle, Maggie E., Davis, Jameson P., Gonye, Anna L.K., Sykes, David B., Hajizadeh, Soroush, Kreuzer, Johannes, Pillai, Shiv, Haas, Wilhelm, Edlow, Andrea G., Fasano, Alessio, Alter, Galit, Irimia, Daniel, Sade-Feldman, Moshe, Yonker, Lael M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676175/
https://www.ncbi.nlm.nih.gov/pubmed/36476388
http://dx.doi.org/10.1016/j.xcrm.2022.100848
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author Boribong, Brittany P.
LaSalle, Thomas J.
Bartsch, Yannic C.
Ellett, Felix
Loiselle, Maggie E.
Davis, Jameson P.
Gonye, Anna L.K.
Sykes, David B.
Hajizadeh, Soroush
Kreuzer, Johannes
Pillai, Shiv
Haas, Wilhelm
Edlow, Andrea G.
Fasano, Alessio
Alter, Galit
Irimia, Daniel
Sade-Feldman, Moshe
Yonker, Lael M.
author_facet Boribong, Brittany P.
LaSalle, Thomas J.
Bartsch, Yannic C.
Ellett, Felix
Loiselle, Maggie E.
Davis, Jameson P.
Gonye, Anna L.K.
Sykes, David B.
Hajizadeh, Soroush
Kreuzer, Johannes
Pillai, Shiv
Haas, Wilhelm
Edlow, Andrea G.
Fasano, Alessio
Alter, Galit
Irimia, Daniel
Sade-Feldman, Moshe
Yonker, Lael M.
author_sort Boribong, Brittany P.
collection PubMed
description Multisystem inflammatory syndrome in children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperinflammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism that is distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanistically, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature.
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spelling pubmed-96761752022-11-21 Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children Boribong, Brittany P. LaSalle, Thomas J. Bartsch, Yannic C. Ellett, Felix Loiselle, Maggie E. Davis, Jameson P. Gonye, Anna L.K. Sykes, David B. Hajizadeh, Soroush Kreuzer, Johannes Pillai, Shiv Haas, Wilhelm Edlow, Andrea G. Fasano, Alessio Alter, Galit Irimia, Daniel Sade-Feldman, Moshe Yonker, Lael M. Cell Rep Med Article Multisystem inflammatory syndrome in children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperinflammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism that is distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanistically, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature. Elsevier 2022-11-21 /pmc/articles/PMC9676175/ /pubmed/36476388 http://dx.doi.org/10.1016/j.xcrm.2022.100848 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Boribong, Brittany P.
LaSalle, Thomas J.
Bartsch, Yannic C.
Ellett, Felix
Loiselle, Maggie E.
Davis, Jameson P.
Gonye, Anna L.K.
Sykes, David B.
Hajizadeh, Soroush
Kreuzer, Johannes
Pillai, Shiv
Haas, Wilhelm
Edlow, Andrea G.
Fasano, Alessio
Alter, Galit
Irimia, Daniel
Sade-Feldman, Moshe
Yonker, Lael M.
Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children
title Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children
title_full Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children
title_fullStr Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children
title_full_unstemmed Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children
title_short Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children
title_sort neutrophil profiles of pediatric covid-19 and multisystem inflammatory syndrome in children
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676175/
https://www.ncbi.nlm.nih.gov/pubmed/36476388
http://dx.doi.org/10.1016/j.xcrm.2022.100848
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