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Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers.

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.

SUBMITTER: Danlos FX

PROVIDER: S-EPMC7948172 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers.

Danlos François-Xavier FX Grajeda-Iglesias Claudia C Durand Sylvère S Sauvat Allan A Roumier Mathilde M Cantin Delphine D Colomba Emeline E Rohmer Julien J Pommeret Fanny F Baciarello Giulia G Willekens Christophe C Vasse Marc M Griscelli Frank F Fahrner Jean-Eudes JE Goubet Anne-Gaëlle AG Dubuisson Agathe A Derosa Lisa L Nirmalathasan Nitharsshini N Bredel Delphine D Mouraud Séverine S Pradon Caroline C Stoclin Annabelle A Rozenberg Flore F Duchemin Jérôme J Jourdi Georges G Ellouze Syrine S Levavasseur Françoise F Albigès Laurence L Soria Jean-Charles JC Barlesi Fabrice F Solary Eric E André Fabrice F Pène Frédéric F Ackerman Félix F Mouthon Luc L Zitvogel Laurence L Marabelle Aurélien A Michot Jean-Marie JM Fontenay Michaela M Kroemer Guido G

Cell death & disease 20210311 3

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 th ...[more]

PMID: 33707411

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Project description:Rationale & objectiveAcute kidney injury (AKI) is common in patients with coronavirus disease 2019 (COVID-19) and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. We investigated the association between urinary biomarkers and adverse kidney outcomes among patients hospitalized with COVID-19.Study designProspective cohort study.Setting & participantsPatients hospitalized with COVID-19 (n=153) at 2 academic medical centers between April and June 2020.Exposure19 urinary biomarkers of injury, inflammation, and repair.OutcomeComposite of KDIGO (Kidney Disease: Improving Global Outcomes) stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings.Analytical approachTime-varying Cox proportional hazards regression to associate biomarker level with composite outcome.ResultsOut of 153 patients, 24 (15.7%) experienced the primary outcome. Twofold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR, 1.34 [95% CI, 1.14-1.57]), monocyte chemoattractant protein (MCP-1) (HR, 1.42 [95% CI, 1.09-1.84]), and kidney injury molecule 1 (KIM-1) (HR, 2.03 [95% CI, 1.38-2.99]) were associated with highest risk of sustaining primary composite outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR, 0.61 [95% CI, 0.47-0.79]). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. The degree of kidney injury by biomarker level in COVID-19 was comparable to other settings of clinical AKI. There was evidence of subclinical AKI in COVID-19 patients based on elevated injury biomarker level in patients without clinical AKI defined by serum creatinine.LimitationsSmall sample size with low number of composite outcome events.ConclusionsUrinary biomarkers are associated with adverse kidney outcomes in patients hospitalized with COVID-19 and may provide valuable information to monitor kidney disease progression and recovery.

Project description:Cystinosis is a rare, devastating hereditary disease secondary to recessive CTNS gene mutations. The most commonly used diagnostic method is confirmation of an elevated leukocyte cystine level; however, this method is expensive and difficult to perform. This study aimed to identify candidate biomarkers for the diagnosis and follow-up of cystinosis based on multiomics studies. The study included three groups: newly-diagnosed cystinosis patients (patient group, n = 14); cystinosis patients under treatment (treatment group, n = 19); and healthy controls (control group, n = 30). Plasma metabolomics analysis identified 10 metabolites as candidate biomarkers that differed between the patient and control groups [L-serine, taurine, lyxose, 4-trimethylammoniobutanoic acid, orotic acid, glutathione, PE(O-18:1(9Z)/0:0), 2-hydroxyphenyl acetic acid, acetyl-N-formil-5-metoxikinuramine, 3-indoxyl sulphate]. As compared to the healthy control group, in the treatment group, hypotaurine, phosphatidylethanolamine, N-acetyl-d-mannosamine, 3-indolacetic acid, p-cresol, phenylethylamine, 5-aminovaleric acid, glycine, creatinine, and saccharic acid levels were significantly higher, and the metabolites quinic acid, capric acid, lenticin, xanthotoxin, glucose-6-phosphate, taurine, uric acid, glyceric acid, alpha-D-glucosamine phosphate, and serine levels were significantly lower. Urinary metabolomic analysis clearly differentiated the patient group from the control group by means of higher allo-inositol, talose, glucose, 2-hydroxybutiric acid, cystine, pyruvic acid, valine, and phenylalanine levels, and lower metabolite (N-acetyl-L-glutamic acid, 3-aminopropionitrile, ribitol, hydroquinone, glucuronic acid, 3-phosphoglycerate, xanthine, creatinine, and 5-aminovaleric acid) levels in the patient group. Urine metabolites were also found to be significantly different in the treatment group than in the control group. Thus, this study identified candidate biomarkers that could be used for the diagnosis and follow-up of cystinosis.

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Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers.

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Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers.

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