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Journal article
Urinary phenotyping of SARS-CoV-2 infection connects clinical diagnostics with metabolomics and uncovers impaired NAD + pathway and SIRT1 activation
Clinical Chemistry and Laboratory Medicine, Vol.62(4), pp.770-788
2023
Abstract
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.
Details
- Title
- Urinary phenotyping of SARS-CoV-2 infection connects clinical diagnostics with metabolomics and uncovers impaired NAD + pathway and SIRT1 activation
- Authors/Creators
- Caterina Lonati - Center for Preclinical Research , Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico , Milan , Italy, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy , University Hospital Tübingen , Tübingen , GermanyGeorgy Berezhnoy - Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy , University Hospital Tübingen , Tübingen , GermanyNathan G Lawler - Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute , Murdoch University Perth , AustraliaReika Masuda - Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute , Murdoch University Perth , AustraliaAditi Kulkarni - Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy , University Hospital Tübingen , Tübingen , GermanySamuele Sala - Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute , Murdoch University Perth , AustraliaPhilipp Nitschke - Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute , Murdoch University Perth , AustraliaLaimdota Zizmare - Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy , University Hospital Tübingen , Tübingen , GermanyHartmut Schäfer - Bruker BioSpin GmbH, AIC Division , Ettlingen , GermanyYogesh Singh - Institute of Medical Genetics and Applied Genomics , University Hospital Tübingen , Tübingen , GermanyNicola Gray Dr - Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute , Murdoch University Perth , AustraliaSamantha Lodge - Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute , Murdoch University Perth , AustraliaJeremy K Nicholson - Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute , Murdoch University Perth , AustraliaUta Merle - Department of Internal Medicine IV , University Hospital Heidelberg , Heidelberg , GermanyJulien Wist - Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute , Murdoch University Perth , AustraliaChristoph Trautwein - Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy , University Hospital Tübingen , Tübingen , Germany
- Publication Details
- Clinical Chemistry and Laboratory Medicine, Vol.62(4), pp.770-788
- Publisher
- De Gruyter
- Identifiers
- 991005616670307891
- Copyright
- © 2023 the author(s)
- Murdoch Affiliation
- Australian National Phenome Centre; Centre for Computational and Systems Medicine; Health Futures Institute
- Language
- English
- Resource Type
- Journal article
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