Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 400 - 400

Published: Jan. 31, 2023

A novel syndrome called long-haul COVID or long is increasingly recognized in a significant percentage of individuals within few months after infection with SARS-CoV-2. This disorder characterized by wide range persisting, returning even new but related symptoms that involve different tissues and organs, including respiratory, cardiac, vascular, gastrointestinal, musculo-skeletal, neurological, endocrine systemic. Some overlapping symptomatologies exist between myalgic encephalomyelitis/chronic fatigue (ME/CFS). Very much like ME/CFS, infections herpes family viruses, immune dysregulation, the persistence inflammation have been reported as most common pattern for development COVID. review describes several factors determinants proposed, elaborating mainly on viral persistence, reactivation latent viruses such Epstein–Barr virus human herpesvirus 6 which are also associated pathology superantigen activation system, disturbance gut microbiome, multiple tissue damage autoimmunity. Based these factors, we propose diagnostic strategies measurement IgG IgM antibodies against SARS-CoV-2, EBV, HHV-6, superantigens, microbiota, biomarkers autoimmunity to better understand manage this multi-factorial continues affect millions people world.

Language: Английский

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Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: April 11, 2022

Nicotinamide mononucleotide (NNM) is an orally bioavailable NAD+ precursor that has demonstrated beneficial effects against aging and aging-associated diseases in animal models. NMN ultimately converted to NAD+, a redox cofactor mediates many metabolic enzymes. also serves as the substrate for poly(ADP-ribose) polymerase (PARP) sirtuins, regulates various biological processes, such metabolism, DNA repair, gene expression, stress responses. Previous mouse models showed administration can increase organs ameliorate aging-related diseases, obesity, diabetes, heart failure, stroke, kidney Alzheimer's disease through NAD+-mediated pathways. However, evidence of its effect on humans still scarce. In this study, we conducted placebo-controlled, randomized, double blind, parallel-group trial investigate safety administered efficacy levels thirty healthy subjects. Healthy volunteers received 250 mg/day (n = 15) or placebo 12 weeks, physiological laboratory tests were performed during period. addition, related metabolites whole blood examined. Oral supplementation weeks caused no abnormalities tests, obvious adverse observed. significantly increased after administration. We observed significant rise nicotinic acid (NAMN) levels, but not NMN. found amount was strongly correlated with pulse rate before These results suggest oral safe practical strategy boost humans. Clinical Trial Registration: JRCT [https://jrct.niph.go.jp/], identifier: [jRCTs041200034].

Language: Английский

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The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Biochemical Journal, Journal Year: 2022, Volume and Issue: 479(16), P. 1653 - 1708

Published: Aug. 31, 2022

Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety acute circumstances. We argue here that I-R injury also underpins elements pathology chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be fibrin amyloid microclot blockage capillaries, for instance as exercise started; reperfusion necessary corollary when it finishes. rehearse mechanistic evidence these occurrences here, terms their manifestation oxidative stress, hyperinflammation, mast cell activation, production marker metabolites related activities. Such microclot-based phenomena can explain both breathlessness/fatigue post-exertional malaise observed conditions, many other observables. The recognition processes implies, mechanistically, therapeutic benefit potentially to had from antioxidants, anti-inflammatories, iron chelators, suitable, safe fibrinolytics, and/or anti-clotting agents. review considerable existing consistent with this, biochemical mechanisms involved.

Language: Английский

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NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health

Current Nutrition Reports, Journal Year: 2023, Volume and Issue: 12(3), P. 445 - 464

Published: June 5, 2023

Language: Английский

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Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19

Brain Behavior & Immunity - Health, Journal Year: 2024, Volume and Issue: 36, P. 100733 - 100733

Published: Feb. 2, 2024

A subset of patients experiences persistent fatigue symptoms after COVID-19, and may develop long COVID, which is characterized by lasting systemic symptoms. No treatments for this condition have been validated are urgently warranted. In pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) supplementation NAD + through iontophoresis patches could improve quality life in 36 moderate/severe COVID-19. We detected a significant increase from baseline SF-36 survey scores 12 weeks (mean total score 36.5 [SD: 15.6] vs. 52.1 [24.8]; p < 0.0001), suggestive improvement life. Furthermore, participants scored significantly lower on the Chalder scale (baseline: 25.9 [4.6], weeks: 17.4 [9.7]; 0.0001). found 52 % to be responders treatment. Treatment was generally safe, mild adverse events previously reported LDN, managed dose adjustments. The were associated mild, short-lived skin irritation 25 patients. Our data suggest LDN NAD+ safe beneficial Larger randomized controlled trials will confirm our determine patient subpopulations might benefit most strategy.

Language: Английский

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Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19

Brain Communications, Journal Year: 2024, Volume and Issue: 6(2)

Published: Jan. 1, 2024

Abstract Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g. ischaemia, microbleeds infection) alter cellular physiologic processes within the neurovascular unit contribute cognitive dysfunction. COVID-19 has posed significant complications during acute convalescent stages in multiple organ systems, including brain. Cognitive impairment is prevalent complication patients, irrespective of severity SARS-CoV-2 infection. Moreover, overwhelming evidence from vitro, preclinical clinical studies reported SARS-CoV-2-induced pathologies components are associated with impairment. Neurovascular disruption alters coupling response, critical mechanism regulates cerebromicrovascular blood flow meet energetic demands locally active neurons. Normal processing achieved through response involves coordinated action cells (i.e. neurons glia) cell types endothelia, smooth muscle pericytes). However, current work on COVID-19-induced yet investigate as causal factor. Hence, this review, we aim describe SARS-CoV-2's effects how they can impact decline disease. Additionally, explore potential therapeutic interventions mitigate Given great both individuals public health, necessity effort fundamental scientific research application becomes imperative. This integrated endeavour crucial mitigating deficits induced by its subsequent burden especially vulnerable population.

Language: Английский

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NAD+ metabolism-based immunoregulation and therapeutic potential

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 10, 2023

Abstract Nicotinamide adenine dinucleotide (NAD + ) is a critical metabolite that acts as cofactor in energy metabolism, and serves cosubstrate for non-redox NAD -dependent enzymes, including sirtuins, CD38 poly(ADP-ribose) polymerases. metabolism can regulate functionality attributes of innate adaptive immune cells contribute to inflammatory responses. Thus, the manipulation bioavailability reshape courses immunological diseases. Here, we review basics biochemistry its roles response, discuss current challenges future translational potential research development therapeutics diseases, such COVID-19.

Language: Английский

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Redox Regulation and Metabolic Dependency of Zika Virus Replication: Inhibition by Nrf2-Antioxidant Response and NAD(H) Antimetabolites

Journal of Virology, Journal Year: 2023, Volume and Issue: 97(2)

Published: Jan. 23, 2023

Zika virus (ZIKV) is a major public health concern of international proportions. While the incidence ZIKV infections has declined substantially in recent years, potential for reemergence or reintroduction remains high.

Language: Английский

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Promoting healthy cardiovascular aging: emerging topics

The Journal of Cardiovascular Aging, Journal Year: 2022, Volume and Issue: 2(4), P. 43 - 43

Published: Jan. 1, 2022

The development of age-related cardiovascular (CV) dysfunction increases the risk CV disease as well other chronic age-associated disorders, including kidney disease, and Alzheimer's related dementias. Major manifestations that increase are vascular dysfunction, primarily endothelial arterial stiffening, elevated systolic blood pressure. Declines in nitric oxide bioavailability secondary to increased oxidative stress inflammation established mechanisms with aging. Moreover, fundamental aging, termed "hallmarks aging" extend system and, such, may be considered aging". These represent viable therapeutic targets for treating Healthy lifestyle behaviors, such regular aerobic exercise certain dietary patterns, "first-line" strategies prevent and/or treat dysfunction. Despite well-established benefits these strategies, many older adults do not meet recommended guidelines or consume a healthy diet. Therefore, it is important establish alternative complementary evidence-based approaches reverse Targeting aging interventions time-efficient training, food-derived molecules, nutraceuticals, select synthetic pharmacological agents represents promising approach. In present review, we will highlight emerging topics field specific focus on how exercise, nutrition/dietary nutraceuticals compounds promote part, by targeting hallmarks

Language: Английский

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Study of Albumin Oxidation in COVID-19 Pneumonia Patients: Possible Mechanisms and Consequences

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10103 - 10103

Published: Sept. 3, 2022

Oxidative stress induced by neutrophils and hypoxia in COVID-19 pneumonia leads to albumin modification. This may result elevated levels of advanced oxidation protein products (AOPPs) lipoxidation end-products (ALEs) that trigger oxidative bursts thus participate cytokine storms, accelerating endothelial lung cell injury, leading respiratory distress. In this study, sixty-six hospitalized patients with symptoms were studied. AOPPs-HSA was produced vitro treating human serum (HSA) chloramine T. The interaction malondialdehyde HSA studied using time-resolved fluorescence spectroscopy. findings revealed a significantly level AOPPs on admission the hospital one week later as long they acute phase infection when compared values recorded for same 6- 12-months post-infection. Significant negative correlations positive with, e.g., procalcitonin, D-dimers, lactate dehydrogenase, aspartate transaminase, radiological scores computed tomography (HRCT), observed. AOPPs/albumin ratio found be strongly correlated D-dimers. We suggest oxidized could involved pathophysiology. Some possible clinical consequences modification are also discussed.

Language: Английский

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