Metabolomics analysis identifies glutamic acid and cystine imbalances in COVID-19 patients without comorbid conditions. Implications on redox homeostasis and COVID-19 pathophysiology DOI Creative Commons

José C. Páez-Franco,

José Luis Maravillas‐Montero, Nancy R. Mejía‐Domínguez

et al.

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(9), P. e0274910 - e0274910

Published: Sept. 20, 2022

It is well known that the presence of comorbidities and age-related health issues may hide biochemical metabolic features triggered by SARS-CoV-2 infection other diseases associated to hypoxia, as they are themselves chronic inflammatory conditions potentially disturb homeostasis thereby negatively impact on COVID-19 progression. To unveil abnormalities inherent hypoxemia caused COVID-19, we here applied gas chromatography coupled mass spectrometry analyze main changes exhibited a population male patients less than 50 years age with mild/moderate severe without pre-existing predispose life-threatening complications from this infection. Several differences in serum levels particular metabolites between normal controls were identified. These included increased glutamic acid reduced glutamine, cystine, threonic acid, proline levels. In particular, using entire metabolomic fingerprint obtained, observed glutamine/glutamate metabolism was disease severity group presented lowest higher these amino acids, respectively. data highlight hypoxia-derived alterations provoked absence co-morbidities value determining reactive oxygen species recycling pathways, which when impaired lead oxidation proteins cell damage. They also provide insights new supportive therapies for disorders involve altered redox lower better outcomes severity.

Language: Английский

Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality DOI Creative Commons
Jeremy P. Gygi, Cole Maguire, Ravi K. Patel

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(9)

Published: April 30, 2024

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation molecular and cellular profiles the full course can link immune programs coordination progression heterogeneity.METHODSWe performed deep immunophenotyping conducted longitudinal multiomics modeling, integrating 10 assays 1,152 Immunophenotyping Assessment in a Cohort (IMPACC) study participants identifying several cascades were significant drivers differential outcomes.RESULTSIncreasing was driven by temporal pattern began early upregulation immunosuppressive metabolites then elevated levels inflammatory cytokines, signatures coagulation, formation neutrophil extracellular traps, T cell functional dysregulation. second cascade, predictive 28-day mortality among critically ill patients, characterized reduced total plasma Igs B cells dysregulated IFN responsiveness. We demonstrated balance disruption between IFN-stimulated genes inhibitors is crucial biomarker mortality, potentially contributing failure viral clearance patients fatal illness.CONCLUSIONOur profiling revealed across omics explain progression, providing insights inform targeted development therapies COVID-19, especially those who are ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, R01AI122220); National Science Foundation (DMS2310836).

Language: Английский

Citations

12
Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19 DOI Creative Commons
Morgan Essex, Belén Millet Pascual-Leone, Ulrike Löber

et al.

npj Biofilms and Microbiomes, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 1, 2024

Abstract The clinical course of COVID-19 is variable and often unpredictable. To test the hypothesis that disease progression inflammatory responses associate with alterations in microbiome metabolome, we analyzed metagenome, cytokine, transcriptome profiles repeated samples from hospitalized patients uninfected controls, leveraged information post-hoc confounder analysis. Severe was associated a depletion beneficial intestinal microbes, whereas oropharyngeal microbiota disturbance mainly linked to antibiotic use. severity also enhanced plasma concentrations kynurenine reduced levels several other tryptophan metabolites, lysophosphatidylcholines, secondary bile acids. Moreover, various metabolites were Faecalibacterium , decrease increase production cytokines. Collectively, our study identifies correlated metabolome as potential contributor dysregulation severe COVID-19.

Language: Английский

Citations

12
The roles of arginases and arginine in immunity DOI
Stefania Canè, Roger Geiger, Vincenzo Bronte

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 17, 2024

Language: Английский

Citations

11
Mesenchymal stem cell-based treatments for COVID-19: status and future perspectives for clinical applications DOI Open Access
Lijun Chen, Jingjing Qu, Farhin Shaheed Kalyani

et al.

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(3)

Published: Feb. 20, 2022

Language: Английский

Citations

33
Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity DOI Creative Commons

Chloé Loyer,

Arnaud Lapostolle, Tomas Urbina

et al.

Critical Care, Journal Year: 2022, Volume and Issue: 26(1)

Published: May 30, 2022

Abstract Background A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are components early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought decipher the role neutrophil phenotypes, functions, and homeostasis COVID-19 disease severity outcome. Methods By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 ICU patients with those 22 SARS-CoV-2-negative hospitalized for severe community-acquired pneumonia (CAP) 38 healthy controls. also assessed correlations between these phenotypic functional indicators markers endothelial damage well severity. Results At admission, circulating showed continuous basal hyperactivation seen CAP patients, associated higher levels soluble E- P-selectin, which reflect platelet activation. Furthermore, had expanded aged-angiogenic reverse transmigrated subsets—both involved dysfunction vascular Simultaneously, significantly lower oxidative burst bacterial formyl peptide. Moreover dying expansion subset greater impairment than survivors. Conclusions These data suggest that exhaustion may be pathogenesis identify angiogenic potentially harmful fatal Graphic

Language: Английский

Citations

31
An integrated analysis and comparison of serum, saliva and sebum for COVID-19 metabolomics DOI Creative Commons
Matt Spick, Holly-May Lewis,

Cécile Frampas

et al.

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: July 13, 2022

The majority of metabolomics studies to date have utilised blood serum or plasma, biofluids that do not necessarily address the full range patient pathologies. Here, correlations between metabolites, salivary metabolites and sebum lipids are studied for first time. 83 COVID-19 positive negative hospitalised participants provided alongside saliva samples analysis by liquid chromatography mass spectrometry. Widespread alterations serum-sebum lipid relationships were observed in versus controls. There was also a marked correlation immunostimulatory hormone dehydroepiandrosterone sulphate cohort. analysed herein compared terms their ability differentiate from controls; performed best multivariate (sensitivity specificity 0.97), with dominant changes triglyceride bile acid levels, concordant other identifying dyslipidemia as hallmark infection. Sebum well 0.92; 0.84), performing worst 0.78; 0.83). These findings show skin profiles coincide dyslipidaemia serum. work signposts potential integrated biofluid analyses provide insight into whole-body atlas pathophysiological conditions.

Language: Английский

Citations

30
Neutrophil extracellular traps and long COVID DOI Creative Commons
Areez Shafqat, Mohamed H. Omer, Ibrahem Albalkhi

et al.

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

Published: Sept. 27, 2023

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by significant number survivors. The underlying pathophysiology COVID has become topic intense research discussion. While chronic inflammation in received considerable attention, the role neutrophils, which are most abundant all immune cells and primary responders to inflammation, been unfortunately overlooked, perhaps due their short lifespan. In this review, we discuss emerging neutrophil extracellular traps (NETs) persistent inflammatory response observed patients. We present early evidence linking persistence NETs pulmonary fibrosis, cardiovascular abnormalities, neurological dysfunction COVID. Several uncertainties require investigation future studies. These include mechanisms SARS-CoV-2 brings about sustained activation phenotypes after infection resolution; whether heterogeneity neutrophils seen acute persists into phase; presence autoantibodies can induce protect them from degradation; exert differential, organ-specific effects; specifically NET components contribute pathologies, such fibrosis; senescent drive formation through pro-inflammatory secretome Answering these questions may pave way for development clinically applicable strategies targeting NETs, providing relief health crisis.

Language: Английский

Citations

23
Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19 DOI Creative Commons

Samuel Druzak,

Elizabeth Iffrig,

Blaine R. Roberts

et al.

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

Published: April 4, 2023

Abstract The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways critically ill adults compared to non-COVID using a multiomics approach. Mechanistic in-vitro studies, microvasculature-on-chip devices, reveal that plasma from induces fibrinogen-dependent red blood cell aggregation mechanically damages glycocalyx. This mechanism appears unique COVID-19, sepsis patients demonstrates greater membrane stiffness but less significant overall rheology. Multiomics analyses pediatric or post-infectious multi-inflammatory syndrome children (MIS-C) demonstrate little overlap cytokine metabolite changes adult patients. Instead, MIS-C strongly upregulation. These findings link high fibrinogen endotheliopathy highlight differences key mediators between populations.

Language: Английский

Citations

21
Applications of liquid chromatography-mass spectrometry based metabolomics in predictive and personalized medicine DOI Creative Commons
Juntuo Zhou, Lijun Zhong

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 3, 2022

Metabolomics is a fast-developing technique used in biomedical researches focusing on pathological mechanism illustration or novel biomarker development for diseases. The ability of simultaneously quantifying thousands metabolites samples makes metabolomics promising predictive personalized medicine-oriented and applications. Liquid chromatography-mass spectrometry the most widely employed analytical strategy metabolomics. In this current mini-review, we provide brief update recent developments applications LC-MS based medicine sector, such as early diagnosis, molecular phenotyping prognostic evaluation. COVID-19 related metabolomic studies are also summarized. We discuss prospects precision researches, well critical issues that need to be addressed when employing clinical

Language: Английский

Citations

28
Targeting Arginine in COVID-19-Induced Immunopathology and Vasculopathy DOI Creative Commons
William Durante

Metabolites, Journal Year: 2022, Volume and Issue: 12(3), P. 240 - 240

Published: March 11, 2022

Coronavirus disease 2019 (COVID-19) represents a major public health crisis that has caused the death of nearly six million people worldwide. Emerging data have identified deficiency circulating arginine in patients with COVID-19. Arginine is semi-essential amino acid serves as key regulator immune and vascular cell function. metabolized by nitric oxide (NO) synthase to NO which plays pivotal role host defense health, whereas catabolism arginase ornithine contributes suppression disease. Notably, activity upregulated COVID-19 disease-dependent fashion, favoring production its metabolites from over synthesis NO. This rewiring metabolism promotes endothelial dysfunction, smooth muscle proliferation migration, inflammation, vasoconstriction, thrombosis, arterial thickening, fibrosis, stiffening, can lead occlusion, muti-organ failure, death. Strategies restore plasma concentration arginine, inhibit activity, and/or enhance bioavailability potency represent promising therapeutic approaches may preserve function prevent development severe

Language: Английский

Citations

27