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Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients.
LaSalle, Thomas J; Gonye, Anna L K; Freeman, Samuel S; Kaplonek, Paulina; Gushterova, Irena; Kays, Kyle R; Manakongtreecheep, Kasidet; Tantivit, Jessica; Rojas-Lopez, Maricarmen; Russo, Brian C; Sharma, Nihaarika; Thomas, Molly F; Lavin-Parsons, Kendall M; Lilly, Brendan M; Mckaig, Brenna N; Charland, Nicole C; Khanna, Hargun K; Lodenstein, Carl L; Margolin, Justin D; Blaum, Emily M; Lirofonis, Paola B; Revach, Or-Yam; Mehta, Arnav; Sonny, Abraham; Bhattacharyya, Roby P; Parry, Blair Alden; Goldberg, Marcia B; Alter, Galit; Filbin, Michael R; Villani, Alexandra-Chloé; Hacohen, Nir; Sade-Feldman, Moshe.
  • LaSalle TJ; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Program in Health Sciences and Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA, USA. Electronic addr
  • Gonye ALK; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Freeman SS; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • Kaplonek P; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Gushterova I; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kays KR; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Manakongtreecheep K; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Tantivit J; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Rojas-Lopez M; Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
  • Russo BC; Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
  • Sharma N; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Thomas MF; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Medicin
  • Lavin-Parsons KM; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Lilly BM; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Mckaig BN; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Charland NC; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Khanna HK; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Lodenstein CL; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Margolin JD; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Blaum EM; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lirofonis PB; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Revach OY; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Mehta A; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Sonny A; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Bhattacharyya RP; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Parry BA; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Goldberg MB; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Microbiology, Harvard Medical School, Boston, MA, USA; Harv
  • Alter G; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Filbin MR; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
  • Villani AC; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Medicin
  • Hacohen N; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA. Electronic address: nhacohen@mgh.harvard.edu.
  • Sade-Feldman M; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA. Electronic address: msade-feldman@mgh.harvard.edu.
Cell Rep Med ; 3(10): 100779, 2022 10 18.
Article in English | MEDLINE | ID: covidwho-2096146
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+ 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Rep Med Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Rep Med Year: 2022 Document Type: Article