Advantages of Metabolomics-Based Multivariate Machine Learning to Predict Disease Severity: Example of COVID

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12199 - 12199

Published: Nov. 13, 2024

The COVID-19 outbreak caused saturations of hospitals, highlighting the importance early patient triage to optimize resource prioritization. Herein, our objective was test if high definition metabolomics, combined with ML, can improve prognostication and performance over standard clinical parameters using COVID infection as an example. Using resolution mass spectrometry, we obtained metabolomics profiles patients them design machine learning (ML) algorithms predicting severity (herein determined need for mechanical ventilation during care). A total 64 PCR-positive at Poitiers CHU were recruited. Clinical investigations conducted 8 days after onset symptoms. We show that could predict good (AUC ROC curve: 0.85), SpO2, first respiratory rate, Horowitz quotient age most important variables. However, prediction substantially improved by use = 0.92). Our small-scale study demonstrates diagnosis prognosis algorithms, thus be a key player in future discovery new biological signals. This technique is easily deployable clinic, learning, it help mathematical models needed advance towards personalized medicine.

Language: Английский

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Macrophage-Induced Exacerbation of Nasopharyngeal Inflammatory Lymphocytes in COVID-19 Disease

COVID, Journal Year: 2023, Volume and Issue: 3(4), P. 567 - 591

Published: April 13, 2023

The nasal microenvironment plays a crucial role in the transmission, modulation, and clinical progression of COVID-19; however, immune responses at site viral entry remain poorly understood. We deciphered link between nasopharyngeal (NP) inflammatory response that triggers cytokine/chemokine storms route COVID-19-positive patients. used RT-PCR, multiplex ELISA, flow cytometry, LC-MS/MS to decipher perturbations associated with severe COVID-19. In addition, we performed vitro assays using cultured human monocytes-derived macrophages trained both presence absence SARS-CoV-2 trimeric spike protein(s) co-cultured without autologous peripheral blood mononuclear cells (hPBMCs)/total T-cells/CD8 T-cells. were examined by cytometry assays. Our findings confirm orchestrate NP highlight increased CD8+T-cells along Tregs, Th1, Th17.1 T-helper cells. observed correlation macrophages, profoundly M2c, differentially promote surfactome on CD8 T-cells, including ITGAM, LGALS3, CD38, TKT, LRPAP1, SSBP1. this study conclude lymphocyte within nasopharynx COVID-19 patients may enforce homeostasis during SARS-CoV-2-infection contribute pathology. This explored therapeutic target proteins could facilitate development new medications, which allow for immediate treatment possible emerging infections.

Language: Английский

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The metabolic footprint of Vero E6 cells highlights the key metabolic routes associated with SARS-CoV-2 infection and response to drug combinations

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 4, 2024

SARS-CoV-2 burdens healthcare systems worldwide, yet specific drug-based treatments are still unavailable. Understanding the effects of on host molecular pathways is critical for providing full descriptions and optimizing therapeutic targets. The present study used Nuclear Magnetic Resonance-based metabolic footprinting to characterize secreted cellular metabolite levels (exometabolomes) Vero E6 cells in response infection two candidate drugs (Remdesivir, RDV, Azithromycin, AZI), either alone or combination. appears force VE6 have increased glucose concentrations from extra-cellular medium altered energetic metabolism. RDV AZI, combination, can modify glycolic-gluconeogenesis pathway cell, thus impairing mitochondrial oxidative damage caused by primary phase. treatment be associated with a shift toward TCA cycle. Our findings reveal reprogramming produced studied pharmacological that protects against virus-induced damage, an emphasis glycolytic-gluconeogenetic pathway. These may help researchers better understand relevant biological mechanisms involved viral infection, as well creation mechanistic hypotheses such drugs, thereby opening up new possibilities therapy.

Language: Английский

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Biomarkers of invasive mechanical ventilation in obesity and metabolic syndrome in patients with COVID-19

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 587 - 599

Published: Jan. 1, 2024

Language: Английский

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Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome (LTCS) patients

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 17, 2023

Abstract Deep metabolomic, proteomic and immunologic phenotyping of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients have matched a wide diversity clinical symptoms with potential biomarkers for disease 2019 (COVID-19). Within here, several studies described the role metabolites, lipoproteins inflammation markers during infection in recovered patients. In fact, after SARS-CoV-2 viral almost 20-30% experience persistent even 12 weeks recovery which has been defined as long-term COVID-19 (LTCS). Emerging evidence revealed that dysregulated immune system persisting could be one key drivers LTCS. However, how these small biomolecules such lipoprotein, cytokines chemokines altogether govern pathophysiology is largely underexplored. Thus, clear understanding parameters into an integrated fashion predict course may help to stratify LTCS from or specimen would elucidate mechanistic course. Here, we report analysis blood serum plasma by vitro diagnostics research NMR spectroscopy flow cytometry-based cytokine quantification total 125 individuals (healthy controls (HC; n=73), (n=12), (n=7) (n=33)). We identified lactate pyruvate were significantly different either healthy Further correlational metabolites indicated creatine, glutamine, high-density lipoprotein (HDL) phospholipids distributed differentially amongst individuals. Of note, triglycerides (apolipoproteins Apo-A1 A2) demonstrate COVID-19-like alterations compared HC. Interestingly, samples distinguished mostly their creatinine, phenylalanine, succinate, 3-hydroxybutyrate (3-HB) glucose concentrations, illustrating imbalanced energy metabolism. Most present at low levels HC except IL-18 chemokine, tended higher correlated positively amino acids (creatine, histidine, leucine, valine), (lactate 3-HB) lipoproteins. The identification will better other diseases ongoing severity Graphical abstract Layman summary & significance Almost infected virus regardless hospitalization status It devasting millions worldwide hardly anything known about why some people 3 months phase. this, attempted understand whether metabolism contributing factors Total Cory cycle pyruvate) higher, (Apo-A1 drastically lower controls. Correlation age gender are (citrate, glutamate, 3-hydroxybutyrate, glucose) (Apo-A1, HDL Apo-A1, LDL triglycerides) Several also thus, dysregulation contributory factor symptoms.

Language: Английский

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Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: March 31, 2023

Abstract Background COVID-19 could develop severe respiratory symptoms in certain infected patients, especially the patients with immune disorders. Gut microbiome and plasma metabolome act important immunological modulators human body contribute to responses impacting progression of COVID-19. Methods Based on two-sample Mendelian randomization framework, causal effects 131 microbiota genus or species level 452 metabolites are estimated. Single nucleotide polymorphisms (SNPs) strongly associated abundance intestinal bacteria gut concentration have been utilized as instrument variables infer whether they factors In addition, mediation analysis is conducted find potential link between metabolite which identified by polygenic analysis, while colocalization has performed validate relationships cis -Mendelian analysis. Results support 13 53 metabolites, significantly association Mediation 11 mediated relations, such myo-inositol, 2-stearoylglycerophosphocholine alpha-glutamyltyrosine, appeared mediate Howardella Ruminiclostridium 6 respectively, Butyrivibrio Ruminococcus gnavus myo-inositol N-acetylalanine respectively. torques was colocalized (PP.H4 = 0.77) colon expression permeability related protein RASIP1 0.95). Conclusions Our study results highlight for COVID-19, promise be served clinical biomarkers risk stratification prognostication, novel basis unravel pathophysiological mechanisms

Language: Английский

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