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Systemic perturbations in amine and kynurenine metabolism associated with acute SARS-CoV-2 infection and inflammatory cytokine responses

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Title: Systemic perturbations in amine and kynurenine metabolism associated with acute SARS-CoV-2 infection and inflammatory cytokine responses
Authors: Lawler, NG
Gray, N
Kimhofer, T
Boughton, B
Gay, M
Yang, R
Morillon, A-C
Chin, S-T
Ryan, M
Begum, S
Bong, SH
Coudert, JD
Edgar, D
Raby, E
Pettersson, S
Richards, T
Holmes, E
Whiley, L
Nicholson, JK
Item Type: Journal Article
Abstract: We performed quantitative metabolic phenotyping of blood plasma in parallel with cytokine/chemokine analysis from participants who were either SARS-CoV-2 (+) (n = 10) or SARS-CoV-2 (-) (n = 49). SARS-CoV-2 positivity was associated with a unique metabolic phenotype and demonstrated a complex systemic response to infection, including severe perturbations in amino acid and kynurenine metabolic pathways. Nine metabolites were elevated in plasma and strongly associated with infection (quinolinic acid, glutamic acid, nicotinic acid, aspartic acid, neopterin, kynurenine, phenylalanine, 3-hydroxykynurenine, and taurine; p < 0.05), while four metabolites were lower in infection (tryptophan, histidine, indole-3-acetic acid, and citrulline; p < 0.05). This signature supports a systemic metabolic phenoconversion following infection, indicating possible neurotoxicity and neurological disruption (elevations of 3-hydroxykynurenine and quinolinic acid) and liver dysfunction (reduction in Fischer’s ratio and elevation of taurine). Finally, we report correlations between the key metabolite changes observed in the disease with concentrations of proinflammatory cytokines and chemokines showing strong immunometabolic disorder in response to SARS-CoV-2 infection.
Issue Date: 7-May-2021
Date of Acceptance: 1-Mar-2021
URI: http://hdl.handle.net/10044/1/91210
DOI: 10.1021/acs.jproteome.1c00052
ISSN: 1535-3893
Publisher: American Chemical Society
Start Page: 2796
End Page: 2811
Journal / Book Title: Journal of Proteome Research
Volume: 20
Issue: 5
Copyright Statement: © 2021 The Authors. Published by American Chemical Society. This work is published under CC BY-NC-ND license.
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemical Research Methods
Biochemistry & Molecular Biology
biogenic amines
tryptophan
kynurenine
cytokines
host response
SARS-CoV-2
COVID-19
metabolic phenotyping
phenoconversion
FALSE DISCOVERY RATE
HEPATIC-ENCEPHALOPATHY
OXIDATIVE STRESS
INTERFERON-GAMMA
IMMUNE-RESPONSE
NICOTINIC-ACID
PLASMA
GLUTAMATE
DISEASE
CELLS
COVID-19
SARS-CoV-2
biogenic amines
cytokines
host response
kynurenine
metabolic phenotyping
phenoconversion
tryptophan
Amines
COVID-19
Cytokines
Humans
Kynurenine
SARS-CoV-2
Humans
Amines
Kynurenine
Cytokines
COVID-19
SARS-CoV-2
Science & Technology
Life Sciences & Biomedicine
Biochemical Research Methods
Biochemistry & Molecular Biology
biogenic amines
tryptophan
kynurenine
cytokines
host response
SARS-CoV-2
COVID-19
metabolic phenotyping
phenoconversion
FALSE DISCOVERY RATE
HEPATIC-ENCEPHALOPATHY
OXIDATIVE STRESS
INTERFERON-GAMMA
IMMUNE-RESPONSE
NICOTINIC-ACID
PLASMA
GLUTAMATE
DISEASE
CELLS
Biochemistry & Molecular Biology
03 Chemical Sciences
06 Biological Sciences
Publication Status: Published
Online Publication Date: 2021-03-16
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Imperial College London COVID-19



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