tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 Sep 26;100779.
doi: 10.1016/j.xcrm.2022.100779. Online ahead of print.
Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients
Thomas J LaSalle[SUP] 1 [/SUP], Anna L K Gonye[SUP] 2 [/SUP], Samuel S Freeman[SUP] 3 [/SUP], Paulina Kaplonek[SUP] 4 [/SUP], Irena Gushterova[SUP] 2 [/SUP], Kyle R Kays[SUP] 5 [/SUP], Kasidet Manakongtreecheep[SUP] 6 [/SUP], Jessica Tantivit[SUP] 6 [/SUP], Maricarmen Rojas-Lopez[SUP] 7 [/SUP], Brian C Russo[SUP] 7 [/SUP], Nihaarika Sharma[SUP] 8 [/SUP], Molly F Thomas[SUP] 9 [/SUP], Kendall M Lavin-Parsons[SUP] 5 [/SUP], Brendan M Lilly[SUP] 5 [/SUP], Brenna N Mckaig[SUP] 5 [/SUP], Nicole C Charland[SUP] 5 [/SUP], Hargun K Khanna[SUP] 5 [/SUP], Carl L Lodenstein[SUP] 5 [/SUP], Justin D Margolin[SUP] 5 [/SUP], Emily M Blaum[SUP] 2 [/SUP], Paola B Lirofonis[SUP] 8 [/SUP], Or-Yam Revach[SUP] 10 [/SUP], Arnav Mehta[SUP] 11 [/SUP], Abraham Sonny[SUP] 12 [/SUP], Roby P Bhattacharyya[SUP] 13 [/SUP], Blair Alden Parry[SUP] 5 [/SUP], Marcia B Goldberg[SUP] 14 [/SUP], Galit Alter[SUP] 4 [/SUP], Michael R Filbin[SUP] 15 [/SUP], Alexandra-Chloé Villani[SUP] 16 [/SUP], Nir Hacohen[SUP] 17 [/SUP], Moshe Sade-Feldman[SUP] 18 [/SUP]
Affiliations
Abstract
Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19[SUP]+[/SUP] patients and 86 controls and perform bulk RNA sequencing of enriched neutrophils, plasma proteomics, and high-throughput antibody profiling to investigate relationships between neutrophil states and disease severity. We identify dynamic switches between six distinct neutrophil subtypes. At days 3 and 7 post-hospitalization, patients with severe disease display a granulocytic myeloid-derived suppressor cell-like gene expression signature, while patients with resolving disease show a neutrophil progenitor-like signature. Humoral responses are identified as potential drivers of neutrophil effector functions, with elevated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G1 (IgG1)-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirm that while patient-derived IgG antibodies induce phagocytosis in healthy donor neutrophils, IgA antibodies predominantly induce neutrophil cell death. Overall, our study demonstrates a dysregulated myelopoietic response in severe COVID-19 and a potential role for IgA-dominant responses contributing to mortality.
Keywords: COVID-19; G-MDSC; IgA; NETosis; SARS-CoV-2; degranulation; neutrophil; transcriptomics.
. 2022 Sep 26;100779.
doi: 10.1016/j.xcrm.2022.100779. Online ahead of print.
Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients
Thomas J LaSalle[SUP] 1 [/SUP], Anna L K Gonye[SUP] 2 [/SUP], Samuel S Freeman[SUP] 3 [/SUP], Paulina Kaplonek[SUP] 4 [/SUP], Irena Gushterova[SUP] 2 [/SUP], Kyle R Kays[SUP] 5 [/SUP], Kasidet Manakongtreecheep[SUP] 6 [/SUP], Jessica Tantivit[SUP] 6 [/SUP], Maricarmen Rojas-Lopez[SUP] 7 [/SUP], Brian C Russo[SUP] 7 [/SUP], Nihaarika Sharma[SUP] 8 [/SUP], Molly F Thomas[SUP] 9 [/SUP], Kendall M Lavin-Parsons[SUP] 5 [/SUP], Brendan M Lilly[SUP] 5 [/SUP], Brenna N Mckaig[SUP] 5 [/SUP], Nicole C Charland[SUP] 5 [/SUP], Hargun K Khanna[SUP] 5 [/SUP], Carl L Lodenstein[SUP] 5 [/SUP], Justin D Margolin[SUP] 5 [/SUP], Emily M Blaum[SUP] 2 [/SUP], Paola B Lirofonis[SUP] 8 [/SUP], Or-Yam Revach[SUP] 10 [/SUP], Arnav Mehta[SUP] 11 [/SUP], Abraham Sonny[SUP] 12 [/SUP], Roby P Bhattacharyya[SUP] 13 [/SUP], Blair Alden Parry[SUP] 5 [/SUP], Marcia B Goldberg[SUP] 14 [/SUP], Galit Alter[SUP] 4 [/SUP], Michael R Filbin[SUP] 15 [/SUP], Alexandra-Chloé Villani[SUP] 16 [/SUP], Nir Hacohen[SUP] 17 [/SUP], Moshe Sade-Feldman[SUP] 18 [/SUP]
Affiliations
- PMID: 36208629
- DOI: 10.1016/j.xcrm.2022.100779
Abstract
Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19[SUP]+[/SUP] patients and 86 controls and perform bulk RNA sequencing of enriched neutrophils, plasma proteomics, and high-throughput antibody profiling to investigate relationships between neutrophil states and disease severity. We identify dynamic switches between six distinct neutrophil subtypes. At days 3 and 7 post-hospitalization, patients with severe disease display a granulocytic myeloid-derived suppressor cell-like gene expression signature, while patients with resolving disease show a neutrophil progenitor-like signature. Humoral responses are identified as potential drivers of neutrophil effector functions, with elevated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G1 (IgG1)-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirm that while patient-derived IgG antibodies induce phagocytosis in healthy donor neutrophils, IgA antibodies predominantly induce neutrophil cell death. Overall, our study demonstrates a dysregulated myelopoietic response in severe COVID-19 and a potential role for IgA-dominant responses contributing to mortality.
Keywords: COVID-19; G-MDSC; IgA; NETosis; SARS-CoV-2; degranulation; neutrophil; transcriptomics.