1. Systemic perturbations in amine and kynurenine metabolism associated with acute SARS-CoV-2 infection and inflammatory cytokine responses
- Author
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Sven Pettersson, Monique Ryan, Nathan G. Lawler, Toby Richards, Edward Raby, Berin A. Boughton, Torben Kimhofer, Aude-Claire Morillon, Sze-How Bong, Dale W. Edgar, Rongchang Yang, Sofina Begum, Sung Tong Chin, Luke Whiley, Jerome D Coudert, Nicola Gray, Jeremy K. Nicholson, and Elaine Holmes
- Subjects
0301 basic medicine ,Chemokine ,Taurine ,Metabolite ,NICOTINIC-ACID ,Biochemistry ,DISEASE ,chemistry.chemical_compound ,GLUTAMATE ,Aspartic acid ,host response ,IMMUNE-RESPONSE ,phenoconversion ,OXIDATIVE STRESS ,Amines ,Kynurenine ,biology ,PLASMA ,FALSE DISCOVERY RATE ,HEPATIC-ENCEPHALOPATHY ,03 Chemical Sciences ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Biochemistry & Molecular Biology ,metabolic phenotyping ,biogenic amines ,Article ,Biochemical Research Methods ,Proinflammatory cytokine ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,tryptophan ,Science & Technology ,030102 biochemistry & molecular biology ,INTERFERON-GAMMA ,SARS-CoV-2 ,COVID-19 ,General Chemistry ,Glutamic acid ,06 Biological Sciences ,cytokines ,030104 developmental biology ,Endocrinology ,chemistry ,CELLS ,biology.protein ,Quinolinic acid - 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.
- Published
- 2021