tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 Nov 21;100848.
doi: 10.1016/j.xcrm.2022.100848. Online ahead of print.
Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children
Brittany P Boribong[SUP] 1 [/SUP], Thomas J LaSalle[SUP] 2 [/SUP], Yannic C Bartsch[SUP] 3 [/SUP], Felix Ellett[SUP] 4 [/SUP], Maggie E Loiselle[SUP] 5 [/SUP], Jameson P Davis[SUP] 5 [/SUP], Anna L K Gonye[SUP] 6 [/SUP], David B Sykes[SUP] 7 [/SUP], Soroush Hajizadeh[SUP] 8 [/SUP], Johannes Kreuzer[SUP] 9 [/SUP], Shiv Pillai[SUP] 3 [/SUP], Wilhelm Haas[SUP] 9 [/SUP], Andrea G Edlow[SUP] 10 [/SUP], Alessio Fasano[SUP] 1 [/SUP], Galit Alter[SUP] 3 [/SUP], Daniel Irimia[SUP] 4 [/SUP], Moshe Sade-Feldman[SUP] 11 [/SUP], Lael M Yonker[SUP] 12 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; RNA sequencing; multisystem inflammatory syndrome in children; neutrophil; neutrophil extracellular traps; pediatrics.
. 2022 Nov 21;100848.
doi: 10.1016/j.xcrm.2022.100848. Online ahead of print.
Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children
Brittany P Boribong[SUP] 1 [/SUP], Thomas J LaSalle[SUP] 2 [/SUP], Yannic C Bartsch[SUP] 3 [/SUP], Felix Ellett[SUP] 4 [/SUP], Maggie E Loiselle[SUP] 5 [/SUP], Jameson P Davis[SUP] 5 [/SUP], Anna L K Gonye[SUP] 6 [/SUP], David B Sykes[SUP] 7 [/SUP], Soroush Hajizadeh[SUP] 8 [/SUP], Johannes Kreuzer[SUP] 9 [/SUP], Shiv Pillai[SUP] 3 [/SUP], Wilhelm Haas[SUP] 9 [/SUP], Andrea G Edlow[SUP] 10 [/SUP], Alessio Fasano[SUP] 1 [/SUP], Galit Alter[SUP] 3 [/SUP], Daniel Irimia[SUP] 4 [/SUP], Moshe Sade-Feldman[SUP] 11 [/SUP], Lael M Yonker[SUP] 12 [/SUP]
Affiliations
- PMID: 36476388
- DOI: 10.1016/j.xcrm.2022.100848
Abstract
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.
Keywords: COVID-19; RNA sequencing; multisystem inflammatory syndrome in children; neutrophil; neutrophil extracellular traps; pediatrics.