Signatures of Mitochondrial Dysfunction and Impaired Fatty Acid Metabolism in Plasma of Patients with Post-Acute Sequelae of COVID-19 (PASC)

Metabolites, Journal Year: 2022, Volume and Issue: 12(11), P. 1026 - 1026

Published: Oct. 26, 2022

Exercise intolerance is a major manifestation of post-acute sequelae severe acute respiratory syndrome coronavirus infection (PASC, or "long-COVID"). in PASC associated with higher arterial blood lactate accumulation and lower fatty acid oxidation rates during graded exercise tests to volitional exertion, suggesting altered metabolism mitochondrial dysfunction. It remains unclear whether the profound disturbances that have been identified plasma from patients suffering disease 2019 (COVID-19) are also present PASC. To bridge this gap, individuals history previous COVID-19 did not require hospitalization were enrolled at National Jewish Health (Denver, CO, USA) grouped into those developed (n = 29) fully recovered 16). Plasma samples two groups analyzed via mass spectrometry-based untargeted metabolomics compared against metabolic profiles healthy control 30). Observational demographic clinical data retrospectively abstracted medical record. Compared controls who COVID-19, exhibited significantly free- carnitine-conjugated mono-, poly-, highly unsaturated acids, accompanied by markedly levels di- tricarboxylates (pyruvate, lactate, citrate, succinate, malate), polyamines (spermine) taurine. an intermediary phenotype, milder spermine Of note, depletion tryptophan-a hallmark severity COVID-19-is normalized patients, despite normalization kynurenine levels-a tryptophan metabolite predicts mortality hospitalized patients. In conclusion, metabolites indicative dysfunctional mitochondria-dependent lipid catabolism. These obtained rest consistent previously reported dysfunction exercise, may pave way for therapeutic intervention focused on restoring fat-burning capacity.

Language: Английский

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Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways

International Journal of Environmental Research and Public Health, Journal Year: 2022, Volume and Issue: 19(16), P. 10362 - 10362

Published: Aug. 19, 2022

The physio-affective phenome of Long COVID-19 is predicted by (a) immune-inflammatory biomarkers the acute infectious phase, including peak body temperature (PBT) and oxygen saturation (SpO2), (b) subsequent activation immune oxidative stress pathways during COVID. purpose this study was to delineate effects PBT SpO2 infection, as well increased neurotoxicity on physical, psychological, social environmental domains health-related quality life (HR-QoL) in people with We recruited 86 participants COVID 39 normal controls, assessed WHO-QoL-BREF (World Health Organization Quality Life Instrument-Abridged Version, Geneva, Switzerland) (comprising depression, anxiety fibromyalgia-fatigue rating scales) measured (NT, comprising serum interleukin (IL)-1β, IL-18 caspase-1, advanced oxidation protein products myeloperoxidase, calcium insulin resistance) found that 70.3% variance HR-QoL explained regression phenome, lowered NT, whilst 61.5% calcium, PBT, SpO2, female sex vaccination AstraZeneca Pfizer. were mediated NT yielding severity which largely affects HR-QoL. In conclusion, HR-Qol neuro-immune neuro-oxidative

Language: Английский

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Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 23, 2022

In patients with SARS-CoV-2, innate immunity is playing a central role, depicted by hyperinflammation and longer lasting inflammatory response. Reliable markers that cover both acute long-lasting COVID-19 monitoring are still lacking. Thus, we investigated one specific marker involved as key player of the immune system, kynurenine (Kyn), its use for diagnosis/detection Long-/Post-COVID syndrome in comparison to currently used serum saliva samples.

Language: Английский

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Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in long COVID

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: June 2, 2023

Critical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production neuroactive catabolites (TRYCATs), including kynurenine (KYN). The TRYCAT pathway has not been studied extensively association with the physiosomatic affective symptoms Long COVID. In present study, we measured serum TRY, TRYCATs, insulin resistance (using Homeostatic Model Assessment Index 2-insulin resistance, HOMA2-IR), C-reactive protein (CRP), physiosomatic, depression, anxiety 90 COVID patients, 3-10 months after remission acute infection. We were able to construct an endophenotypic class severe (22% patients) very low TRY oxygen saturation (SpO2, during infection), increased kynurenine, KYN/TRY ratio, CRP, high ratings on all symptom domains. One factor could be extracted from (including chronic fatigue-fibromyalgia), symptoms, indicating that domains are manifestations common physio-affective phenome. Three biomarkers (CRP, KYN/TRY, IR) explained around 40% variance latter ratio significantly predicted peak body temperature (PBT) lowered SpO2 validated latent vector three a composite based IR (Long COVID), PBT (acute COVID-19). conclusion, phenome manifestation inflammatory responses COVID, may contribute these effects.

Language: Английский

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Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: A systematic review and meta-analysis

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 113, P. 374 - 388

Published: Aug. 8, 2023

Language: Английский

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Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to Long COVID: A precision nomothetic approach

Acta Neuropsychiatrica, Journal Year: 2022, Volume and Issue: 35(2), P. 76 - 87

Published: Sept. 22, 2022

Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology the affective, fatigue and physiosomatic symptoms (labelled as "physio-affective phenome") LC has remained elusive.The current study aims to delineate effects oxygen saturation (SpO2) body temperature during phase on physio-affective phenome LC.We recruited 120 patients 36 controls. For all participants, we assessed lowest SpO2 peak COVID-19, Hamilton Depression Anxiety Rating Scale (HAMD/HAMA) Fibro Fatigue (FF) scales 3-4 months later.Lowered increased female sex predict 60.7% variance in LC. Using unsupervised learning techniques, were able new endophenotype class, which comprises around 26.7% characterised by very low high temperature, depression, anxiety, fatigue, autonomic gastro-intestinal scores. Single latent vectors could be extracted from both biomarkers, anxiety FF or insomnia, symptoms.The newly constructed class pathway phenotypes indicate that at least part consequence namely combined lowered SpO2, associated immune-inflammatory processes lung lesions.

Language: Английский

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The tryptophan catabolite or kynurenine pathway in major depressive and bipolar disorder: A systematic review and meta-analysis

Brain Behavior & Immunity - Health, Journal Year: 2022, Volume and Issue: 26, P. 100537 - 100537

Published: Oct. 21, 2022

There is now evidence that affective disorders including major depressive disorder (MDD) and bipolar (BD) are mediated by immune-inflammatory nitro-oxidative pathways. Activation of these pathways may be associated with activation the tryptophan catabolite (TRYCAT) pathway inducing indoleamine 2,3-dioxygenase (IDO, rate-limiting enzyme) leading to depletion (TRP) increases in catabolites (TRYCATs). To systematically review meta-analyze central peripheral (free total) TRP levels, its competing amino-acids (CAAs) TRYCATs MDD BD. This searched PubMed, Google Scholar SciFinder included 121 full-text articles 15470 individuals, 8024 MDD/BD patients 7446 healthy controls. levels (either free TRP/CAAs ratio were significantly decreased (p < 0.0001) as compared controls a moderate effect size (standardized mean difference for TRP: SMD = −0.513, 95% confidence interval, CI: −0.611; −0.414; TRP/CAAs: −0.558, −0.758; −0.358). Kynurenine (KYN) small 0.0001, −0.213, 95%CI: −0.295; −0.131). These differences significant plasma −0.304, −0.415, −0.194) but not serum 0.054) or nervous system (CNS, p 0.771). The KYN/TRP ratio, frequently used an index IDO activity, neurotoxicity indices based on downstream unaltered even lowered MDD/BD. Our findings suggest BD accompanied without TRYCAT activation. Lowered availability probably consequence albumin during inflammatory response disorders.

Language: Английский

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Association between Gut Microbiota and SARS-CoV-2 Infection and Vaccine Immunogenicity

Microorganisms, Journal Year: 2023, Volume and Issue: 11(2), P. 452 - 452

Published: Feb. 10, 2023

Gut microbiota is increasingly recognized to play a pivotal role in various human physiological functions and diseases. Amidst the COVID-19 pandemic, research has suggested that dysbiosis of gut also involved development severity symptoms by regulating SARS-CoV-2 entry modulating inflammation. Previous studies have their metabolites could immunomodulatory effects on vaccine immunogenicity, including influenza vaccines oral rotavirus vaccines. In light these observations, it possible plays influencing immune responses vaccinations via similar mechanisms lipopolysaccharides, flagellin, peptidoglycan, short-chain fatty acids. this review, we give an overview current understanding manifestations immunogenicity. We then discuss limitations currently published associations between outcomes. Future directions shall be focused microbiota-based interventions improving response infection vaccinations.

Language: Английский

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The kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy

Bioscience Reports, Journal Year: 2023, Volume and Issue: 43(8)

Published: July 24, 2023

Abstract SARS-CoV-2 (COVID-19) exerts profound changes in the kynurenine (Kyn) pathway (KP) of tryptophan (Trp) metabolism that may underpin its pathophysiology. The KP is main source vital cellular effector NAD+ and intermediate metabolites modulate immune neuronal functions. Trp top influenced by COVID-19. Sixteen studies established virus-induced activation mediated mainly induction indoleamine 2,3-dioxygenase (IDO1) most affected tissues IDO2 lung increased release proinflammatory cytokines but could additionally involve flux plasma free (TDO) cortisol. major Kyn metabolite targeted COVID-19 kynurenic acid (KA), with greatest affinity for aryl hydrocarbon receptor (AhR), which also activated AhR initiates two important series events: a vicious circle involving IDO1 induction, KA accumulation further activation, poly (ADP-ribose) polymerase (PARP) leading to depletion cell death. virus deprives host inhibiting biosynthetic from quinolinic acid, while simultaneously acquiring promoting synthesis nicotinamide salvage pathway. Additionally, protective effects sirtuin 1 are minimised PARP activation. dysfunction mood neurological disorders acutely during ‘long COVID’. More potential vaccination therapy on required exploration therapeutic strategies modulation proposed.

Language: Английский

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The Multisystem Impact of Long COVID: A Comprehensive Review

Diagnostics, Journal Year: 2024, Volume and Issue: 14(3), P. 244 - 244

Published: Jan. 24, 2024

(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: recent literature systematically analyzed to categorize examine symptomatology pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, endocrinological aspects. (3) Results: The review outlines diverse multiple emphasizing its complexity challenges diagnosis treatment. Factors such pre-existing conditions, initial severity, vaccination status, gender, age were identified influential manifestation persistence symptoms. This condition is highlighted disease capable enduring an period presenting new symptoms time. (4) Conclusions: emerges with intricate multi-systemic involvement, complicating findings underscore necessity nuanced understanding effectively manage address evolving nature this

Language: Английский

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