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

Nathan G. Lawler, Nicola Gray, Torben Kimhofer, Berin Boughton, Melvin Gay, Rongchang Yang, Aude Claire Morillon, Sung Tong Chin, Monique Ryan, Sofina Begum, Sze How Bong, Jerome D. Coudert, Dale Edgar, Edward Raby, Sven Pettersson, Toby Richards, Elaine Holmes, Jeremy K. Nicholson

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2796-2811
Number of pages16
JournalJournal of Proteome Research
Volume20
Issue number5
Early online date16 Mar 2021
DOIs
Publication statusPublished - 7 May 2021

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