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Multi-omics Characterization of Neutrophil Extracellular Trap Formation in Severe and Mild COVID-19 Infections
Lisa Bramer; Robert Hontz; Amie Eisfeld; Amy Sims; Young-Mo Kim; Kelly Stratton; Carrie Nicora; Marina Gritsenko; Athena Schepmoes; Osamu Akasaka; Michiko Koga; Takeya Tsutsumi; Morio Nakamura; Ichiro Nakachi; Rie Baba; Hiroki Tateno; Shoji Suzuki; Hideaki Nakajima; Hideaki Kato; Kazunari Ishida; Makoto Ishii; Yoshifumi Uwamino; Keiko Mitamura; Venessa Paurus; Ernesto Nakayasu; Isaac Attah; Andrew G Letizia; Katrina Waters; Tom Metz; Karen Corson; Yoshihiro Kawaoka; Vincent R Gerbasi.
  • Lisa Bramer; Pacific Northwest National Laboratory
  • Robert Hontz; U.S. Naval Medical Research Unit No. TWO
  • Amie Eisfeld; Department of Pathobiological Sciences, University of Wisconsin
  • Amy Sims; Pacific Northwest National Laboratory
  • Young-Mo Kim; Pacific Northwest National Laboratory
  • Kelly Stratton; Pacific Northwest National Labs
  • Carrie Nicora; Pacific Northwest National Labs
  • Marina Gritsenko; Pacific Northwest National Labs
  • Athena Schepmoes; Pacific Northwest National Labs
  • Osamu Akasaka; Emergency Medical Center, Fujisawa City Hospital
  • Michiko Koga; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo
  • Takeya Tsutsumi; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo
  • Morio Nakamura; Department of Pulmonary Medicine, Tokyo Saiseikai Central Hospital
  • Ichiro Nakachi; Pulmonary division, Department of Internal Medicine, Saiseikai Utsunomiya Hospital
  • Rie Baba; Pulmonary division, Department of Internal Medicine, Saiseikai Utsunomiya Hospital
  • Hiroki Tateno; Department of Pulmonary Medicine, Saitama City Hospital
  • Shoji Suzuki; Department of Pulmonary Medicine, Saitama City Hospital
  • Hideaki Nakajima; Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine
  • Hideaki Kato; Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine
  • Kazunari Ishida; Kobe Kaisei Hospital
  • Makoto Ishii; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine
  • Yoshifumi Uwamino; Keio University School of Medicine
  • Keiko Mitamura; Division of Infection Control, Eiju General Hospital
  • Venessa Paurus; Pacific Northwest National Labs
  • Ernesto Nakayasu; Pacific Northwest National Labs
  • Isaac Attah; Pacific Northwest National Labs
  • Andrew G Letizia; U.S. Naval Medical Research Unit No. TWO
  • Katrina Waters; Pacific Northwest National Labs
  • Tom Metz; Pacific Northwest National Labs
  • Karen Corson; U.S. Naval Medical Research Unit No. TWO
  • Yoshihiro Kawaoka; Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, J
  • Vincent R Gerbasi; Pacific Northwest National Labs
Preprint in English | medRxiv | ID: ppmedrxiv-22274196
ABSTRACT
The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics analysis of an immunologically naive SARS-CoV-2 clinical cohort from the plasma of uninfected controls, mild, and severe infections. A comparison of healthy controls and patient samples showed activation of neutrophil degranulation pathways and formation of neutrophil extracellular trap (NET) complexes that were activated in a subset of the mild infections and more prevalent in severe infections (containing multiple NET proteins in individual patient samples). As a potential mechanism to suppress NET formation, multiple redox enzymes were elevated in the mild and severe symptom population. Analysis of metabolites from the same cohort showed a 24- and 60-fold elevation in plasma L-cystine, the oxidized form of cysteine, which is a substrate of the powerful antioxidant glutathione, in mild and severe patients, respectively. Unique to patients with mild infections, the carnosine dipeptidase modifying enzyme (CNDP1) was up-regulated. The strong protein and metabolite oxidation signatures suggest multiple compensatory pathways working to suppress oxidation and NET formation in SARS-CoV-2 infections.
Full text: Available Collection: Preprints Database: medRxiv Language: English Year: 2022 Document Type: Preprint

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Full text: Available Collection: Preprints Database: medRxiv Language: English Year: 2022 Document Type: Preprint