Urinary phenotyping of SARS-CoV-2 infection connects clinical diagnostics with metabolomics and uncovers impaired NAD+ pathway and SIRT1 activation

The stratification of individuals suffering from acute and post-acute SARS-CoV-2 infection remains a critical challenge. Notably, biomarkers able to specifically monitor viral progression, providing details about patient clinical status, are still not available. Herein, quantitative metabolomics is...

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Published inClinical chemistry and laboratory medicine Vol. 62; no. 4; pp. 770 - 788
Main Authors Lonati, Caterina, Berezhnoy, Georgy, Lawler, Nathan, Masuda, Reika, Kulkarni, Aditi, Sala, Samuele, Nitschke, Philipp, Zizmare, Laimdota, Bucci, Daniele, Cannet, Claire, Schäfer, Hartmut, Singh, Yogesh, Gray, Nicola, Lodge, Samantha, Nicholson, Jeremy, Merle, Uta, Wist, Julien, Trautwein, Christoph
Format Journal Article
LanguageEnglish
Published Germany De Gruyter 25.03.2024
Walter De Gruyter & Company
Subjects
Adenine
Antiviral Agents
Antiviral drugs
antiviral nucleosides
Biomarkers
Biomarkers - urine
Body mass index
Body size
COVID-19
COVID-19 - diagnosis
COVID-19 Testing
Genotype & phenotype
Humans
Immune response
kynurenine pathway
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Medical diagnosis
Metabolites
Metabolomics
Metabolomics - methods
NAD
Nicotinamide
NMR
NMR spectroscopy
Nuclear magnetic resonance
Nucleosides
Nucleotides
Phenotyping
precision diagnostics
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SIRT1 protein
Sirtuin 1
sirtuins
Spectrum analysis
Viral diseases
COVID-19
precision diagnostics
kynurenine pathway
sirtuins
antiviral nucleosides
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Abstract The stratification of individuals suffering from acute and post-acute SARS-CoV-2 infection remains a critical challenge. Notably, biomarkers able to specifically monitor viral progression, providing details about patient clinical status, are still not available. Herein, quantitative metabolomics is progressively recognized as a useful tool to describe the consequences of virus-host interactions considering also clinical metadata. The present study characterized the urinary metabolic profile of 243 infected individuals by quantitative nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography mass spectrometry (LC-MS). Results were compared with a historical cohort of noninfected subjects. Moreover, we assessed the concentration of recently identified antiviral nucleosides and their association with other metabolites and clinical data. Urinary metabolomics can stratify patients into classes of disease severity, with a discrimination ability comparable to that of clinical biomarkers. Kynurenines showed the highest fold change in clinically-deteriorated patients and higher-risk subjects. Unique metabolite clusters were also generated based on age, sex, and body mass index (BMI). Changes in the concentration of antiviral nucleosides were associated with either other metabolites or clinical variables. Increased kynurenines and reduced trigonelline excretion indicated a disrupted nicotinamide adenine nucleotide (NAD ) and sirtuin 1 (SIRT1) pathway. Our results confirm the potential of urinary metabolomics for noninvasive diagnostic/prognostic screening and show that the antiviral nucleosides could represent novel biomarkers linking viral load, immune response, and metabolism. Moreover, we established for the first time a casual link between kynurenine accumulation and deranged NAD /SIRT1, offering a novel mechanism through which SARS-CoV-2 manipulates host physiology.
AbstractList The stratification of individuals suffering from acute and post-acute SARS-CoV-2 infection remains a critical challenge. Notably, biomarkers able to specifically monitor viral progression, providing details about patient clinical status, are still not available. Herein, quantitative metabolomics is progressively recognized as a useful tool to describe the consequences of virus-host interactions considering also clinical metadata.The present study characterized the urinary metabolic profile of 243 infected individuals by quantitative nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography mass spectrometry (LC–MS). Results were compared with a historical cohort of noninfected subjects. Moreover, we assessed the concentration of recently identified antiviral nucleosides and their association with other metabolites and clinical data.Urinary metabolomics can stratify patients into classes of disease severity, with a discrimination ability comparable to that of clinical biomarkers. Kynurenines showed the highest fold change in clinically-deteriorated patients and higher-risk subjects. Unique metabolite clusters were also generated based on age, sex, and body mass index (BMI). Changes in the concentration of antiviral nucleosides were associated with either other metabolites or clinical variables. Increased kynurenines and reduced trigonelline excretion indicated a disrupted nicotinamide adenine nucleotide (NAD+) and sirtuin 1 (SIRT1) pathway.Our results confirm the potential of urinary metabolomics for noninvasive diagnostic/prognostic screening and show that the antiviral nucleosides could represent novel biomarkers linking viral load, immune response, and metabolism. Moreover, we established for the first time a casual link between kynurenine accumulation and deranged NAD+/SIRT1, offering a novel mechanism through which SARS-CoV-2 manipulates host physiology.
The stratification of individuals suffering from acute and post-acute SARS-CoV-2 infection remains a critical challenge. Notably, biomarkers able to specifically monitor viral progression, providing details about patient clinical status, are still not available. Herein, quantitative metabolomics is progressively recognized as a useful tool to describe the consequences of virus-host interactions considering also clinical metadata.OBJECTIVESThe stratification of individuals suffering from acute and post-acute SARS-CoV-2 infection remains a critical challenge. Notably, biomarkers able to specifically monitor viral progression, providing details about patient clinical status, are still not available. Herein, quantitative metabolomics is progressively recognized as a useful tool to describe the consequences of virus-host interactions considering also clinical metadata.The present study characterized the urinary metabolic profile of 243 infected individuals by quantitative nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography mass spectrometry (LC-MS). Results were compared with a historical cohort of noninfected subjects. Moreover, we assessed the concentration of recently identified antiviral nucleosides and their association with other metabolites and clinical data.METHODSThe present study characterized the urinary metabolic profile of 243 infected individuals by quantitative nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography mass spectrometry (LC-MS). Results were compared with a historical cohort of noninfected subjects. Moreover, we assessed the concentration of recently identified antiviral nucleosides and their association with other metabolites and clinical data.Urinary metabolomics can stratify patients into classes of disease severity, with a discrimination ability comparable to that of clinical biomarkers. Kynurenines showed the highest fold change in clinically-deteriorated patients and higher-risk subjects. Unique metabolite clusters were also generated based on age, sex, and body mass index (BMI). Changes in the concentration of antiviral nucleosides were associated with either other metabolites or clinical variables. Increased kynurenines and reduced trigonelline excretion indicated a disrupted nicotinamide adenine nucleotide (NAD+) and sirtuin 1 (SIRT1) pathway.RESULTSUrinary metabolomics can stratify patients into classes of disease severity, with a discrimination ability comparable to that of clinical biomarkers. Kynurenines showed the highest fold change in clinically-deteriorated patients and higher-risk subjects. Unique metabolite clusters were also generated based on age, sex, and body mass index (BMI). Changes in the concentration of antiviral nucleosides were associated with either other metabolites or clinical variables. Increased kynurenines and reduced trigonelline excretion indicated a disrupted nicotinamide adenine nucleotide (NAD+) and sirtuin 1 (SIRT1) pathway.Our results confirm the potential of urinary metabolomics for noninvasive diagnostic/prognostic screening and show that the antiviral nucleosides could represent novel biomarkers linking viral load, immune response, and metabolism. Moreover, we established for the first time a casual link between kynurenine accumulation and deranged NAD+/SIRT1, offering a novel mechanism through which SARS-CoV-2 manipulates host physiology.CONCLUSIONSOur results confirm the potential of urinary metabolomics for noninvasive diagnostic/prognostic screening and show that the antiviral nucleosides could represent novel biomarkers linking viral load, immune response, and metabolism. Moreover, we established for the first time a casual link between kynurenine accumulation and deranged NAD+/SIRT1, offering a novel mechanism through which SARS-CoV-2 manipulates host physiology.
The stratification of individuals suffering from acute and post-acute SARS-CoV-2 infection remains a critical challenge. Notably, biomarkers able to specifically monitor viral progression, providing details about patient clinical status, are still not available. Herein, quantitative metabolomics is progressively recognized as a useful tool to describe the consequences of virus-host interactions considering also clinical metadata. The present study characterized the urinary metabolic profile of 243 infected individuals by quantitative nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography mass spectrometry (LC-MS). Results were compared with a historical cohort of noninfected subjects. Moreover, we assessed the concentration of recently identified antiviral nucleosides and their association with other metabolites and clinical data. Urinary metabolomics can stratify patients into classes of disease severity, with a discrimination ability comparable to that of clinical biomarkers. Kynurenines showed the highest fold change in clinically-deteriorated patients and higher-risk subjects. Unique metabolite clusters were also generated based on age, sex, and body mass index (BMI). Changes in the concentration of antiviral nucleosides were associated with either other metabolites or clinical variables. Increased kynurenines and reduced trigonelline excretion indicated a disrupted nicotinamide adenine nucleotide (NAD ) and sirtuin 1 (SIRT1) pathway. Our results confirm the potential of urinary metabolomics for noninvasive diagnostic/prognostic screening and show that the antiviral nucleosides could represent novel biomarkers linking viral load, immune response, and metabolism. Moreover, we established for the first time a casual link between kynurenine accumulation and deranged NAD /SIRT1, offering a novel mechanism through which SARS-CoV-2 manipulates host physiology.
Author Schäfer, Hartmut
Lonati, Caterina
Gray, Nicola
Merle, Uta
Kulkarni, Aditi
Wist, Julien
Trautwein, Christoph
Singh, Yogesh
Nicholson, Jeremy
Zizmare, Laimdota
Lodge, Samantha
Cannet, Claire
Sala, Samuele
Bucci, Daniele
Masuda, Reika
Nitschke, Philipp
Berezhnoy, Georgy
Lawler, Nathan
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Issue 4
Keywords COVID-19
precision diagnostics
kynurenine pathway
sirtuins
antiviral nucleosides
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Snippet The stratification of individuals suffering from acute and post-acute SARS-CoV-2 infection remains a critical challenge. Notably, biomarkers able to...
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walterdegruyter
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SubjectTerms Adenine
Antiviral Agents
Antiviral drugs
antiviral nucleosides
Biomarkers
Biomarkers - urine
Body mass index
Body size
COVID-19
COVID-19 - diagnosis
COVID-19 Testing
Genotype & phenotype
Humans
Immune response
kynurenine pathway
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Medical diagnosis
Metabolites
Metabolomics
Metabolomics - methods
NAD
Nicotinamide
NMR
NMR spectroscopy
Nuclear magnetic resonance
Nucleosides
Nucleotides
Phenotyping
precision diagnostics
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SIRT1 protein
Sirtuin 1
sirtuins
Spectrum analysis
Viral diseases
Title Urinary phenotyping of SARS-CoV-2 infection connects clinical diagnostics with metabolomics and uncovers impaired NAD+ pathway and SIRT1 activation
URI https://www.degruyter.com/doi/10.1515/cclm-2023-1017
https://www.ncbi.nlm.nih.gov/pubmed/37955280
https://www.proquest.com/docview/2931539095
https://www.proquest.com/docview/2889588447
Volume 62
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