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Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells.
Dean, Matthew J; Ochoa, Juan B; Sanchez-Pino, Maria Dulfary; Zabaleta, Jovanny; Garai, Jone; Del Valle, Luis; Wyczechowska, Dorota; Baiamonte, Lyndsey Buckner; Philbrook, Phaethon; Majumder, Rinku; Vander Heide, Richard S; Dunkenberger, Logan; Thylur, Ramesh Puttalingaiah; Nossaman, Bobby; Roberts, W Mark; Chapple, Andrew G; Wu, Jiande; Hicks, Chindo; Collins, Jack; Luke, Brian; Johnson, Randall; Koul, Hari K; Rees, Chris A; Morris, Claudia R; Garcia-Diaz, Julia; Ochoa, Augusto C.
  • Dean MJ; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Ochoa JB; Department of Surgery, Ochsner Medical Center, New Orleans, LA, United States.
  • Sanchez-Pino MD; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Zabaleta J; Department of Genetics, LSU Health, New Orleans, LA, United States.
  • Garai J; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Del Valle L; Department of Pediatrics, LSU Health, New Orleans, LA, United States.
  • Wyczechowska D; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Baiamonte LB; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Philbrook P; Department of Pathology LSU Health, New Orleans, LA, United States.
  • Majumder R; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Vander Heide RS; Tissue Biorepository, Ochsner Medical Center, New Orleans, LA, United States.
  • Dunkenberger L; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Thylur RP; Department of Genetics, LSU Health, New Orleans, LA, United States.
  • Nossaman B; Department of Biochemistry, LSU Health, New Orleans, LA, United States.
  • Roberts WM; Department of Pathology LSU Health, New Orleans, LA, United States.
  • Chapple AG; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Wu J; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Hicks C; Department of Surgery, Ochsner Medical Center, New Orleans, LA, United States.
  • Collins J; Department of Internal Medicine, Ochsner Medical Center, New Orleans, LA, United States.
  • Luke B; Louisiana State University Cancer Center, New Orleans, LA, United States.
  • Johnson R; School of Public Health, LSU Health, New Orleans, LA, United States.
  • Koul HK; Department of Genetics, LSU Health, New Orleans, LA, United States.
  • Rees CA; Department of Genetics, LSU Health, New Orleans, LA, United States.
  • Morris CR; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
  • Garcia-Diaz J; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
  • Ochoa AC; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
Front Immunol ; 12: 695972, 2021.
Article in English | MEDLINE | ID: covidwho-1339498
ABSTRACT
COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Myeloid-Derived Suppressor Cells / SARS-CoV-2 / COVID-19 / Granulocytes Type of study: Diagnostic study / Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.695972

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Myeloid-Derived Suppressor Cells / SARS-CoV-2 / COVID-19 / Granulocytes Type of study: Diagnostic study / Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.695972