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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.
Affiliation
  • Boribong BP; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
  • LaSalle TJ; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Health Sciences and Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, US
  • Bartsch YC; Harvard Medical School, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Ellett F; Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Loiselle ME; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Davis JP; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Gonye ALK; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Sykes DB; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
  • Hajizadeh S; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Kreuzer J; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Pillai S; Harvard Medical School, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Haas W; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Edlow AG; Harvard Medical School, Boston, MA 02115, USA; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Boston, MA 02114, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Fasano A; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Alter G; Harvard Medical School, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Irimia D; Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Sade-Feldman M; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: msade-feldman@mgh.harvard.edu.
  • Yonker LM; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: lyonker@mgh.harvard.edu.
Cell Rep Med ; 3(12): 100848, 2022 12 20.
Article in En | MEDLINE | ID: mdl-36476388
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: COVID-19 / Neutrophils Type of study: Diagnostic_studies / Prognostic_studies Limits: Child / Humans Language: En Journal: Cell Rep Med Year: 2022 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: COVID-19 / Neutrophils Type of study: Diagnostic_studies / Prognostic_studies Limits: Child / Humans Language: En Journal: Cell Rep Med Year: 2022 Type: Article Affiliation country: United States