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Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers
François-Xavier Danlos, Claudia Grajeda-Iglesias, Sylvère Durand and 37 more
Cell Death & Disease · 2021 · CC BY
doi:10.1038/s41419-021-03540-y
Abstract
The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient’s plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
References 39
- 1.
Morens DM, Fauci AS. Emerging pandemic diseases: how we got to COVID-19. Cell. 2020;182:1077-1092.
Not in our library10.1016/j.cell.2020.08.021
- 2.
Ghinai I, et al. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lancet. 2020;395:1137-1144.
Not in our library10.1016/s0140-6736(20)30607-3
- 3.
Guan W-J, et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020;382:1708-1720.
Not in our library10.1056/nejmoa2002032
- 4.
Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. New Engl. J. Med. 2020;383:2451-2460.
Not in our library10.1056/nejmcp2009575
- 5.
Petersen E, et al. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect. Dis. 2020;20:e238-e244.
Not in our library10.1016/s1473-3099(20)30484-9
- 6.
Ellinghaus D, et al. Genomewide association study of severe Covid-19 with respiratory failure. N. Engl. J. Med. 2020;383:1522-1534.
Not in our library10.1056/nejmoa2020283
- 7.
Schulte-Schrepping J, et al. Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell. 2020;182:1419-1440.e23.
Not in our library10.1016/j.cell.2020.08.001
- 8.
Silvin, A. et al. Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell182, 1401–1418.e18 (2020).
Not in our library10.1016/j.cell.2020.08.002
- 9.
D’Alessandro A, et al. Serum proteomics in COVID-19 patients: altered coagulation and complement status as a function of IL-6 level. J. Proteome Res. 2020;19:4417-4427.
Not in our library10.1021/acs.jproteome.0c00365
- 10.
Shen B, et al. Proteomic and metabolomic characterization of COVID-19 patient sera. Cell. 2020;182:59-72.e15.
Not in our library10.1016/j.cell.2020.05.032
- 11.
Thomas T, et al. COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status. JCI insight. 2020;23:5.
Not in our library10.1172/jci.insight.140327
- 12.
Cai, Y. et al. Kynurenic acid underlies sex-specific immune responses to COVID-19. medRxiv10.1101/2020.09.06.20189159 (2020).
Not in our library
- 13.
Song J-W, et al. Omics-driven systems interrogation of metabolic dysregulation in COVID-19 pathogenesis. Cell Metab. 2020;32:188-202.e5.
Not in our library10.1016/j.cmet.2020.06.016
- 14.
Sapkota, D., Søland, T. M., Galtung, H. K., Sand, L. P., Giannecchini, S., To, KKW, et al. COVID-19 salivary signature: diagnostic and research opportunities. J. Clin. Pathol.10.1136/jclinpath-2020-206834 (2020).
Not in our library10.1136/jclinpath-2020-206834
- 15.
Steed AL, et al. The microbial metabolite desaminotyrosine protects from influenza through type I interferon. Science. 2017;357:498-502.
Not in our library10.1126/science.aam5336
- 16.
WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect. Dis. 2020;20:e192-e197.
Not in our library10.1016/s1473-3099(20)30483-7
- 17.
Platten M, Wick W, Van den Eynde BJ. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res. 2012;72:5435-5440.
Not in our library10.1158/0008-5472.can-12-0569
- 18.
Aslamkhan AG, et al. Characterization of indoleamine-2,3-dioxygenase 1, tryptophan-2,3-dioxygenase, and Ido1/Tdo2 knockout mice. Toxicol. Appl. Pharmacol. 2020;406:115216.
Not in our library10.1016/j.taap.2020.115216
- 19.
Platten M, et al. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science. 2005;310:850-855.
Not in our library10.1126/science.1117634
- 20.
Del Valle DM, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat. Med. 2020;26:1636-1643.
Not in our library10.1038/s41591-020-1051-9
- 21.
Grifoni E, et al. Interleukin-6 as prognosticator in patients with COVID-19. J. Infect. 2020;81:452-482.
Not in our library10.1016/j.jinf.2020.06.008
- 22.
- 23.
Laing AG, et al. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat. Med. 2020;26:1623-1635.
Not in our library10.1038/s41591-020-1038-6
- 24.
Carriche, G. M. et al. Regulating T-cell differentiation through the polyamine spermidine. J. Allergy Clin. Immunol.10.1016/j.jaci.2020.04.037 (2020).
Not in our library10.1016/j.jaci.2020.04.037
- 25.
Madeo, F., Eisenberg, T., Pietrocola, F. & Kroemer, G. Spermidine in health and disease. Science359, eaan2788 (2018).
Not in our library10.1126/science.aan2788
- 26.
Pietrocola F, et al. Caloric restriction mimetics enhance anticancer immunosurveillance. Cancer Cell. 2016;30:147-160.
Not in our library10.1016/j.ccell.2016.05.016
- 27.
- 28.
García-Alvarez F, et al. S-adenosylmethionine immunomodulator treatment in sepsis. Int. J. Surg. Investig. 2000;2:9-15.
Not in our library
- 29.
Mehdi A, et al. Enhanced anticancer effect of a combination of S-adenosylmethionine (SAM) and immune checkpoint inhibitor (ICPi) in a syngeneic mouse model of advanced melanoma. Front. Oncol. 2020;10:1361.
Not in our library10.3389/fonc.2020.01361
- 30.
Rosa FT, Freitas EC, Deminice R, Jordão AA, Marchini JS. Oxidative stress and inflammation in obesity after taurine supplementation: a double-blind, placebo-controlled study. Eur. J. Nutr. 2014;53:823-830.
Not in our library10.1007/s00394-013-0586-7
- 31.
Zhang J, Yu M, Tong S, Liu L-Y, Tang L-V. Predictive factors for disease progression in hospitalized patients with coronavirus disease 2019 in Wuhan. China J. Clin. Virol. 2020;127:104392.
Not in our library10.1016/j.jcv.2020.104392
- 32.
Steiner J, Bernstein H-G, Guest PC, Summergrad P, Oxenkrug G. Plasma leptin correlates with anthranilic acid in schizophrenia but not in major depressive disorder. Eur. Neuropsychopharmacol. 2020;41:167-168.
Not in our library10.1016/j.euroneuro.2020.08.001
- 33.
Oxenkrug G, van der Hart M, Summergrad P. Elevated anthranilic acid plasma concentrations in type 1 but not type 2 diabetes mellitus. Integr. Mol. Med. 2015;2:365-368.
Not in our library10.15761/imm.1000169
- 34.
Pawlak K, Kowalewska A, Mysliwiec M, Pawlak D. Kynurenine and its metabolites-kynurenic acid and anthranilic acid are associated with soluble endothelial adhesion molecules and oxidative status in patients with chronic kidney disease. Am. J. Med. Sci. 2009;338:293-300.
Not in our library10.1097/maj.0b013e3181aa30e6
- 35.
Le Naour J, Galluzzi L, Zitvogel L, Kroemer G, Vacchelli E. Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology. 2020;9:1777625.
Not in our library10.1080/2162402x.2020.1777625
- 36.
Liu Q, Hua S, Wang X, Chen F, Gou S. The introduction of immunosuppressor (TDO inhibitor) significantly improved the efficacy of irinotecan in treating hepatocellular carcinoma. Cancer Immunol. Immunother. 2021;70:497-508.
Not in our library10.1007/s00262-020-02697-3
- 37.
Pilotte L, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc. Natl Acad. Sci. USA. 2012;109:2497-2502.
Not in our library10.1073/pnas.1113873109
- 38.
Prendergast GC, Malachowski WP, DuHadaway JB, Muller AJ. Discovery of IDO1 inhibitors: from bench to bedside. Cancer Res. 2017;77:6795-6811.
Not in our library10.1158/0008-5472.can-17-2285
- 39.
Viltard M, et al. The metabolomic signature of extreme longevity: naked mole rats versus mice. Aging. 2019;11:4783-4800.
Not in our library10.18632/aging.102116
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