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

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

Journal: Journal of proteome research 2021;20(5):2796-2811

PMID: 33724837

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Plain Language Summary

Understanding the action of Covid-19 and the host response is paramount to developing personalised treatments and improving recovery rates. This cohort study of 64 individuals aimed to determine underlying biological signatures of individuals with severe and mild Covid-19, to potentially risk stratify patients and provide targeted treatments. The results showed that several biological signatures were disrupted with infection, some increased and some decreased and indicated possible liver, brain, and inflammatory disruptions. There was also evidence of a time-based pattern of biological disruptions, which may be of significance when looking at “long Covid” syndrome. It was concluded that identifying the hosts biological response to the virus offers insights into the viral action on the body. The action of Covid-19 on processes in the brain may indicate a secondary effect of the virus. Using biological markers to predict recovery of individuals suffering from “long Covid” may also be a possibility. This study could be used by healthcare professionals to understand which biological processes may be disrupted during Covid-19 infection, with the view to testing to understand who may be at risk of long-term complications post recovery.

Abstract

We performed quantitative metabolic phenotyping of blood plasma in parallel with cytokine/chemokine analysis from participants who were either SARS-CoV-2 (+) ( = 10) or SARS-CoV-2 (-) ( = 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; < 0.05), while four metabolites were lower in infection (tryptophan, histidine, indole-3-acetic acid, and citrulline; < 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.

Address: Australian National Phenome Centre, Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth, WA 6150, Australia.; Bruker Pty Ltd., Preston, VIC 3072, Australia.; Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, U.K.; Centre for Molecular Medicine & Innovative Therapeutics, Murdoch University, Perth, WA 6150, Australia.; State Adult Burn Unit, Fiona Stanley Hospital, Murdoch, WA 6150, Australia.; Burn Injury Research Node, The University of Notre Dame, Fremantle, WA 6160, Australia.; Fiona Wood Foundation, Murdoch, WA 6150, Australia.; Department of Microbiology, PathWest Laboratory Medicine, Perth, WA 6009, Australia.; Department of Infectious Diseases, Fiona Stanley Hospital, Perth, WA 6150, Australia.; Singapore National Neuro Science Centre, Singapore Mandalay Road, Singapore 308232, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Mandalay Road, Singapore 308232, Singapore.; Department of Life Science Centre, Sunway University, 55100 Kuala Lumpur, Malaysia.; Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Nedlands, WA 6009, Australia.; Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia.; Institute of Global Health Innovation, Imperial College London, Level 1, Faculty Building South Kensington Campus, London SW7 2AZ, U.K.

DOI: 10.1021/acs.jproteome.1c00052