SARS-CoV-2 pathogenesis

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 20(5), P. 270 - 284

Published: March 30, 2022

Language: Английский

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The plasma metabolome of long COVID patients two years after infection

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Aug. 1, 2023

Abstract One of the major challenges currently faced by global health systems is prolonged COVID-19 syndrome (also known as “long COVID”) which has emerged a consequence SARS-CoV-2 epidemic. It estimated that at least 30% patients who have had will develop long COVID. In this study, our goal was to assess plasma metabolome in total 100 samples collected from healthy controls, patients, and COVID recruited Mexico between 2020 2022. A targeted metabolomics approach using combination LC–MS/MS FIA MS/MS performed quantify 108 metabolites. IL-17 leptin were measured immunoenzymatic assay. The comparison paired COVID-19/long revealed 53 metabolites statistically different. Compared 27 remained dysregulated even after two years. Post-COVID-19 displayed heterogeneous metabolic profile. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline arginine identified most relevant for distinguishing with more complicated evolution. Additionally, levels significantly increased these patients. Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, chronic immune dysregulation are likely be main hallmarks years acute infection.

Language: Английский

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MetaboAnalystR 4.0: a unified LC-MS workflow for global metabolomics

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 1, 2024

Abstract The wide applications of liquid chromatography - mass spectrometry (LC-MS) in untargeted metabolomics demand an easy-to-use, comprehensive computational workflow to support efficient and reproducible data analysis. However, current tools were primarily developed perform specific tasks LC-MS based Here we introduce MetaboAnalystR 4.0 as a streamlined pipeline covering raw spectra processing, compound identification, statistical analysis, functional interpretation. key features includes auto-optimized feature detection quantification algorithm for LC-MS1 MS2 deconvolution identification data-dependent or data-independent acquisition, more accurate interpretation through integrated spectral annotation. Comprehensive validation studies using obtained from standards mixtures, dilution series clinical samples have shown its excellent performance across range common such peak picking, deconvolution, with good computing efficiency. Together existing analysis utilities, represents significant step toward unified, end-to-end global the open-source R environment.

Language: Английский

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COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2414 - 2414

Published: Feb. 22, 2022

Omics-based technologies have been largely adopted during this unprecedented global COVID-19 pandemic, allowing the scientific community to perform research on a large scale understand pathobiology of SARS-CoV-2 infection and its replication into human cells. The application omics techniques has addressed every level application, from detection mutations, methods diagnosis or monitoring, drug target discovery, vaccine generation, basic definition pathophysiological processes biochemical mechanisms behind spread SARS-CoV-2. Thus, term COVIDomics wants include those efforts provided by omics-scale investigations with current research. This review summarizes diverse pieces knowledge acquired techniques, main focus proteomics metabolomics studies, in order capture common signature terms proteins, metabolites, pathways dysregulated disease. Exploring multiomics perspective concurrent data integration may provide new suitable therapeutic solutions combat pandemic.

Language: Английский

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Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(10), P. 100779 - 100779

Published: Sept. 26, 2022

Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19+ patients and 86 controls perform bulk RNA sequencing enriched neutrophils, plasma proteomics, high-throughput antibody profiling to investigate relationships between states severity. We identify dynamic switches six distinct subtypes. At days 3 7 post-hospitalization, with display a granulocytic myeloid-derived suppressor cell-like gene expression signature, while resolving show progenitor-like signature. Humoral responses are identified as potential drivers effector functions, elevated acute respiratory syndrome 2 (SARS-CoV-2)-specific immunoglobulin G1 (IgG1)-to-IgA1 ratios who survived. In vitro experiments confirm that patient-derived IgG antibodies induce phagocytosis healthy donor IgA predominantly cell death. Overall, our study demonstrates dysregulated myelopoietic response COVID-19 role for IgA-dominant contributing mortality.

Language: Английский

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Metabolomic analysis reveals potential biomarkers and the underlying pathogenesis involved in Mycoplasma pneumoniae pneumonia

Emerging Microbes & Infections, Journal Year: 2022, Volume and Issue: 11(1), P. 593 - 605

Published: Jan. 31, 2022

Although previous studies have reported the use of metabolomics for infectious diseases, little is known about potential function plasma metabolites in children infected with Mycoplasma pneumoniae (MP). Here, a combination liquid chromatography-quadrupole time-of-flight mass spectrometry and random forest-based classification model was used to provide broader range applications MP diagnosis. In training cohort, from 63 pneumonia (MPPs), 37 healthy controls (HC) 29 disease (IDC) collected. After multivariate analyses, 357 were identified be differentially expressed among MPP, HC IDC groups, 3 (568.5661, 459.3493 411.3208) had high diagnostic values. an independent cohort 57 blinded subjects, samples successfully classified into different demonstrating reliability these biomarkers distinguishing MPPs controls. A metabolomic signature analysis major classes glycerophospholipids, sphingolipids fatty acyls increased MPPs. These markedly altered are mainly involved glycerophospholipid sphingolipid metabolism. As ubiquitous building blocks eukaryotic cell membranes, dysregulated lipid metabolism indicates damage cellular membrane activation immunity Moreover, metabolites, between severe mild MPPs, correlated markers extrapulmonary complications, suggesting that they may MPP severity. findings offer new insights biomarker selection pathogenesis children.

Language: Английский

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Immunosenescence and inflamm-ageing in COVID-19

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 84, P. 101818 - 101818

Published: Dec. 11, 2022

Language: Английский

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Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 15, 2023

COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at respiratory track, it is clear that pathophysiology has a systemic ultimately affecting many organs. This feature enables possibility investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or nuclear magnetic resonance (NMR) spectroscopy. Here we review extensive literature on metabolomics in COVID-19, unraveled aspects disease including: characteristic metabotipic signature associated discrimination patients according severity, effect drugs and vaccination treatments characterization natural history metabolic evolution disease, from full recovery long-term long sequelae COVID.

Language: Английский

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Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 5, 2023

Severe COVID-19 is characterized by an increase in the number and changes function of innate immune cells including neutrophils. However, it not known how metabolome patients with COVID-19. To address these questions, we analyzed neutrophils from severe or mild healthy controls. We identified widespread dysregulation neutrophil metabolism disease progression amino acid, redox, central carbon metabolism. Metabolic were consistent reduced activity glycolytic enzyme GAPDH. Inhibition GAPDH blocked glycolysis promoted pentose phosphate pathway but blunted respiratory burst. was sufficient to cause extracellular trap (NET) formation which required elastase activity. inhibition increased pH, blocking this prevented cell death NET formation. These findings indicate that have aberrant can contribute their dysfunction. Our work also shows formation, a pathogenic feature many inflammatory diseases, actively suppressed cell-intrinsic mechanism controlled

Language: Английский

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

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 9, 2023

Background Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity clinical symptoms potential biomarkers for disease 2019 (COVID-19). Several studies described the role small as well complex molecules such metabolites, cytokines, chemokines lipoproteins during in recovered patients. In fact, after SARS-CoV-2 viral almost 10-20% experience persistent post 12 weeks recovery defined long-term COVID-19 (LTCS) or long post-acute (PACS). Emerging evidence revealed that dysregulated immune system persisting inflammation could be one key drivers LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, clear understanding parameters within integrated fashion predict course would help to stratify LTCS This even allow elucidation mechanistic course. Methods study comprised subjects (n=7; longitudinal), (n=33), Recov (n=12), no history positive testing (n=73). 1 H-NMR-based metabolomics IVDr standard operating procedures verified phenotyped all blood samples by quantifying 38 metabolites 112 lipoprotein properties. Univariate multivariate statistics identified NMR-based cytokine changes. Results Here, we report on analysis serum/plasma NMR spectroscopy flow cytometry-based cytokines/chemokines quantification We lactate pyruvate were significantly different either healthy controls (HC) Subsequently, correlation group only among cytokines amino acids histidine glutamine uniquely attributed mainly pro-inflammatory cytokines. Of note, triglycerides several (apolipoproteins Apo-A1 A2) demonstrate COVID-19-like alterations compared HC. Interestingly, distinguished mostly their phenylalanine, 3-hydroxybutyrate (3-HB) glucose concentrations, illustrating imbalanced energy metabolism. Most present at low levels HC except IL-18 chemokine, which tended higher Conclusion The identification plasma will better other diseases ongoing severity

Language: Английский

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