ArticlePloS one2021
Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis.BMC infectious diseases · 2022Pooled it
- Integrative Multidimensional Profiling of Individuals Recovered from Mild COVID-19 Reveals Immune-Metabolic-Oxidative Network Interactions.International journal of molecular sciences · 2026Article
- MTHFR allele and one-carbon metabolic profile predict severity of COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CD103+ dendritic cell-fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis.JCI insight · 2025Article
- Metabolomic profile of severe COVID-19 and a signature predictive of progression towards severe disease status: a prospective cohort study (METCOVID).Scientific reports · 2025Article
- Multiplatform Metabolomics: Enhancing the Severity Risk Prognosis of SARS-CoV-2 Infection.ACS omega · 2024Article
- Metabolomic Insights into COVID-19 Severity: A Scoping Review.Metabolites · 2024Article
- Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients.International journal of molecular sciences · 2024Article
- Early Metabolomic and Immunologic Biomarkers as Prognostic Indicators for COVID-19.Metabolites · 2024Article
- Nucleotide, Phospholipid, and Kynurenine Metabolites Are Robustly Associated with COVID-19 Severity and Time of Plasma Sample Collection in a Prospective Cohort Study.International journal of molecular sciences · 2023Article
- Developing A Baseline Metabolomic Signature Associated with COVID-19 Severity: Insights from Prospective Trials Encompassing 13 U.S. Centers.Metabolites · 2023Article
- Integrative Plasma Metabolic and Lipidomic Modelling of SARS-CoV-2 Infection in Relation to Clinical Severity and Early Mortality Prediction.International journal of molecular sciences · 2023Article
- Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19.Frontiers in molecular biosciences · 2023Review
- Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia.Biomedicines · 2022Review
- Validation of a simple risk stratification tool for COVID-19 mortality.Frontiers in medicine · 2022Article
- Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.
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Registered trials
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