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Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses

Lawler, N.G., Gray, N., Kimhofer, T., Boughton, B.ORCID: 0000-0001-6342-9814, Gay, M., Yang, R.ORCID: 0000-0003-2563-2015, Morillon, A-C, Chin, S-T, Ryan, M., Begum, S., Bong, S.H., Coudert, J.D., Edgar, D., Raby, E., Pettersson, S., Richards, T., Holmes, E., Whiley, L.ORCID: 0000-0002-9088-4799 and Nicholson, J.K. (2021) Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses. Journal of Proteome Research .

Link to Published Version: https://doi.org/10.1021/acs.jproteome.1c00052
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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.

Item Type: Journal Article
Murdoch Affiliation(s): Australian National Phenome Center
Centre for Molecular Medicine and Innovative Therapeutics (CMMIT)
Health Futures Institute
Publisher: American Chemical Society
Copyright: © 2021 The Authors.
URI: http://researchrepository.murdoch.edu.au/id/eprint/60338
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