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Differential Functional Responses of Neutrophil Subsets in Severe COVID-19 Patients.
McLeish, Kenneth R; Shrestha, Rejeena; Vashishta, Aruna; Rane, Madhavi J; Barati, Michelle T; Brier, Michael E; Lau, Mario Gutierrez; Hu, Xiaoling; Chen, Oscar; Wessel, Caitlin R; Spalding, Travis; Bush, Sarah E; Ijemere, Kenechi; Hopkins, C Danielle; Cooke, Elizabeth A; Tandon, Shweta; Manning, Terri; Uriarte, Silvia M; Huang, Jiapeng; Yan, Jun.
  • McLeish KR; Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, KY, United States.
  • Shrestha R; Department of Microbiology and Immunology, University of Louisville, KY, United States.
  • Vashishta A; Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, KY, United States.
  • Rane MJ; Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, KY, United States.
  • Barati MT; Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, KY, United States.
  • Brier ME; Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, KY, United States.
  • Lau MG; Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, KY, United States.
  • Hu X; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville, Louisville, KY, United States.
  • Chen O; Department of Anesthesiology and Perioperative Medicine, University of Louisville, KY, United States.
  • Wessel CR; Department of Anesthesiology and Perioperative Medicine, University of Louisville, KY, United States.
  • Spalding T; Department of Anesthesiology and Perioperative Medicine, University of Louisville, KY, United States.
  • Bush SE; Department of Anesthesiology and Perioperative Medicine, University of Louisville, KY, United States.
  • Ijemere K; Department of Anesthesiology and Perioperative Medicine, University of Louisville, KY, United States.
  • Hopkins CD; Department of Anesthesiology and Perioperative Medicine, University of Louisville, KY, United States.
  • Cooke EA; Department of Anesthesiology and Perioperative Medicine, University of Louisville, KY, United States.
  • Tandon S; Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, KY, United States.
  • Manning T; Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, KY, United States.
  • Uriarte SM; Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, KY, United States.
  • Huang J; Department of Anesthesiology and Perioperative Medicine, University of Louisville, KY, United States.
  • Yan J; Department of Microbiology and Immunology, University of Louisville, KY, United States.
Front Immunol ; 13: 879686, 2022.
Article in English | MEDLINE | ID: covidwho-1903014
ABSTRACT
Neutrophils play a significant role in determining disease severity following SARS-CoV-2 infection. Gene and protein expression defines several neutrophil clusters in COVID-19, including the emergence of low density neutrophils (LDN) that are associated with severe disease. The functional capabilities of these neutrophil clusters and correlation with gene and protein expression are unknown. To define host defense and immunosuppressive functions of normal density neutrophils (NDN) and LDN from COVID-19 patients, we recruited 64 patients with severe COVID-19 and 26 healthy donors (HD). Phagocytosis, respiratory burst activity, degranulation, neutrophil extracellular trap (NET) formation, and T-cell suppression in those neutrophil subsets were measured. NDN from severe/critical COVID-19 patients showed evidence of priming with enhanced phagocytosis, respiratory burst activity, and degranulation of secretory vesicles and gelatinase and specific granules, while NET formation was similar to HD NDN. COVID LDN response was impaired except for enhanced NET formation. A subset of COVID LDN with intermediate CD16 expression (CD16Int LDN) promoted T cell proliferation to a level similar to HD NDN, while COVID NDN and the CD16Hi LDN failed to stimulate T-cell activation. All 3 COVID-19 neutrophil populations suppressed stimulation of IFN-γ production, compared to HD NDN. We conclude that NDN and LDN from COVID-19 patients possess complementary functional capabilities that may act cooperatively to determine disease severity. We predict that global neutrophil responses that induce COVID-19 ARDS will vary depending on the proportion of neutrophil subsets.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Extracellular Traps / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.879686

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Extracellular Traps / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.879686