Systemic perturbations in amine and kynurenine metabolism associated with acute SARS-CoV-2 infection and inflammatory cytokine responses
File(s)
Published version
Author(s)
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.
Date Issued
2021-05-07
Date Acceptance
2021-03-01
Citation
Journal of Proteome Research, 2021, 20 (5), pp.2796-2811
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.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000649269600055&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
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
Publication Status
Published
Date Publish Online
2021-03-16