Heliyon (Mar 2023)
Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections
- Lisa M. Bramer,
- Robert D. Hontz,
- Amie J. Eisfeld,
- Amy C. Sims,
- Young-Mo Kim,
- Kelly G. Stratton,
- Carrie D. Nicora,
- Marina A. Gritsenko,
- Athena A. 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,
- Vanessa L. Paurus,
- Ernesto S. Nakayasu,
- Isaac K. Attah,
- Andrew G. Letizia,
- Katrina M. Waters,
- Thomas O. Metz,
- Karen Corson,
- Yoshihiro Kawaoka,
- Vincent R. Gerbasi,
- Hiroshi Yotsuyanagi,
- Kiyoko Iwatsuki-Horimoto
Affiliations
- Lisa M. Bramer
- Pacific Northwest National Laboratory, Richland, WA, USA
- Robert D. Hontz
- U.S. Naval Medical Research Unit No. TWO (NAMRU-2), Singapore, Singapore
- Amie J. Eisfeld
- Department of Pathobiological Sciences, University of Wisconsin—Madison, Madison, WI, USA
- Amy C. Sims
- Pacific Northwest National Laboratory, Richland, WA, USA
- Young-Mo Kim
- Pacific Northwest National Laboratory, Richland, WA, USA
- Kelly G. Stratton
- Pacific Northwest National Laboratory, Richland, WA, USA
- Carrie D. Nicora
- Pacific Northwest National Laboratory, Richland, WA, USA
- Marina A. Gritsenko
- Pacific Northwest National Laboratory, Richland, WA, USA
- Athena A. Schepmoes
- Pacific Northwest National Laboratory, Richland, WA, USA
- Osamu Akasaka
- Emergency Medical Center, Fujisawa City Hospital 2-6-1 Fujisawa, Fujisawa, Japan
- Michiko Koga
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Takeya Tsutsumi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Morio Nakamura
- Department of Pulmonary Medicine, Tokyo Saiseikai Central, Tokyo, Japan
- Ichiro Nakachi
- Pulmonary Division, Department of Internal Medicine, Utsunomiya Hospital, Utsunomiya, Japan
- Rie Baba
- Pulmonary Division, Department of Internal Medicine, Utsunomiya Hospital, Utsunomiya, Japan
- Hiroki Tateno
- Department of Pulmonary Medicine, Saitama City Hospital, Saitama, Japan
- Shoji Suzuki
- Department of Pulmonary Medicine, Saitama City Hospital, Saitama, Japan
- Hideaki Nakajima
- Department of Hematology and Clinical Immunology, University School of Medicine, Yokohama, Japan
- Hideaki Kato
- Department of Hematology and Clinical Immunology, University School of Medicine, Yokohama, Japan
- Kazunari Ishida
- Kobe Kaisei Hospital, Kobe, Japan
- Makoto Ishii
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
- Yoshifumi Uwamino
- Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan
- Keiko Mitamura
- Division of Infection Control, Eiju General Hospital, Tokyo, Japan
- Vanessa L. Paurus
- Pacific Northwest National Laboratory, Richland, WA, USA
- Ernesto S. Nakayasu
- Pacific Northwest National Laboratory, Richland, WA, USA
- Isaac K. Attah
- Pacific Northwest National Laboratory, Richland, WA, USA
- Andrew G. Letizia
- U.S. Naval Medical Research Unit No. TWO (NAMRU-2), Singapore, Singapore
- Katrina M. Waters
- Pacific Northwest National Laboratory, Richland, WA, USA
- Thomas O. Metz
- Pacific Northwest National Laboratory, Richland, WA, USA
- Karen Corson
- U.S. Naval Medical Research Unit No. TWO (NAMRU-2), Singapore, Singapore
- Yoshihiro Kawaoka
- Department of Pathobiological Sciences, University of Wisconsin—Madison, Madison, WI, USA; Department of Microbiology and Immunology, Japan; International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Vincent R. Gerbasi
- Pacific Northwest National Laboratory, Richland, WA, USA; Corresponding author. 902 Battelle Blvd, Richland, WA, 99354, USA.
- Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo
- Kiyoko Iwatsuki-Horimoto
- Division of Virology, Institute of Medical Science, University of Tokyo, Japan
- Journal volume & issue
-
Vol. 9,
no. 3
p. e13795
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 and correlative analysis of an immunologically naïve SARS-CoV-2 clinical cohort from blood plasma of uninfected controls, mild, and severe infections. Consistent with previous observations, severe patient populations showed an elevation of pulmonary surfactant levels. Intriguingly, mild patients showed a statistically significant elevation in the carnosine dipeptidase modifying enzyme (CNDP1). Mild and severe patient populations showed a strong elevation in the metabolite L-cystine (oxidized form of the amino acid cysteine) and enzymes with roles in glutathione metabolism. Neutrophil extracellular traps (NETs) were observed in both mild and severe populations, and NET formation was higher in severe vs. mild samples. Our correlative analysis suggests a potential protective role for CNDP1 in suppressing PSPB release from the pulmonary space whereas NET formation correlates with increased PSPB levels and disease severity. In our discussion we put forward a possible model where NET formation drives pulmonary occlusions and CNDP1 promotes antioxidation, pleiotropic immune responses, and vasodilation by accelerating histamine synthesis.
