Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health

GeroScience, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Abstract Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase infection, affecting approximately 10% to over 30% those infected. It presents a significant clinical challenge, notably due pronounced neurocognitive such brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing central role cerebromicrovascular dysfunction. This review investigates key pathophysiological contributing cerebrovascular dysfunction in long and their impacts on health. We discuss how endothelial tropism direct vascular trigger dysfunction, impaired neurovascular coupling, blood–brain barrier disruption, resulting compromised cerebral perfusion. Furthermore, appears induce mitochondrial enhancing oxidative stress inflammation within cells. Autoantibody formation following also potentially exacerbates injury, chronic ongoing compromise. These factors collectively contribute emergence white matter hyperintensities, promote amyloid pathology, may accelerate neurodegenerative processes, including Alzheimer’s disease. emphasizes critical advanced imaging techniques assessing health need for targeted interventions address complications. A deeper understanding essential advance treatments mitigate its long-term consequences.

Язык: Английский

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Possible Role of Cannabis in the Management of Neuroinflammation in Patients with Post-COVID Condition

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3805 - 3805

Опубликована: Март 29, 2024

The post-COVID condition (PCC) is a pathology stemming from COVID-19, and studying its pathophysiology, diagnosis, treatment crucial. Neuroinflammation causes the most common manifestations of this disease including headaches, fatigue, insomnia, depression, anxiety, among others. Currently, there are no specific management proposals; however, given that inflammatory component involves cytokines free radicals, these conditions must be treated to reduce current symptoms provide neuroprotection risk long-term neurodegenerative disease. It has been shown cannabis compounds with immunomodulatory antioxidant functions in other pathologies. Therefore, exploring approach could viable therapeutic option for PCC, which purpose review. This review involved an exhaustive search specialized databases PubMed, PubChem, ProQuest, EBSCO, Scopus, Science Direct, Web Science, Clinical Trials. Phytocannabinoids, cannabidiol (CBD), cannabigerol (CBG), Delta-9-tetrahydrocannabinol (THC), exhibit significant antioxidative anti-inflammatory properties have effective neuroinflammatory conditions. These promising adjuvants PCC alone or combination antioxidants therapies. presents challenges neurological health, neuroinflammation oxidative stress play central roles pathogenesis. Antioxidant therapy cannabinoid-based approaches represent areas research mitigating adverse effects, but further studies needed.

Язык: Английский

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Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses

Journal of Internal Medicine, Год журнала: 2024, Номер 296(1), С. 93 - 115

Опубликована: Май 1, 2024

Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease presenting with severe fatigue, post‐exertional malaise, and cognitive disturbances—among spectrum of symptoms—that collectively render the patient housebound or bedbound. Epigenetic studies in ME/CFS confirm alterations and/or malfunctions cellular organismal physiology associated immune responses, metabolism, cell death proliferation, neuronal endothelial function. The sudden onset follows major stress factor that, approximately 70% cases, involves viral infection, symptoms overlap those long COVID. Viruses primarily linked to pathology are symbiotic herpesviruses, which follow bivalent latent–lytic lifecycle. complex interaction between viruses hosts strategies from both sides: evasion persistence by viruses, activation clearance host. This dynamic imperative for herpesviruses that facilitate their through epigenetic regulation own host genome. In current article, we provide an overview signatures demonstrated focus on potential latent viruses—particularly Epstein–Barr virus—may employ long‐term reprograming ME/CFS. could aid elucidating relevant biological pathways impacted reflect physiological variations among patients stem environmental triggers, including exogenous altered activity.

Язык: Английский

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IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry

Medicina, Год журнала: 2024, Номер 60(1), С. 161 - 161

Опубликована: Янв. 15, 2024

Background and Objectives: The diagnosis pathology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain under debate. However, there is a growing body evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) other viral infections. Materials Methods: In this work, we analyzed large public dataset on IgG antibodies to 3054 EBV peptides understand whether these immune responses could help diagnose patients trigger pathological autoimmunity; used healthy controls (HCs) as comparator cohort. Subsequently, aimed at predicting disease status study participants using super learner algorithm targeting accuracy 85% when splitting data into train test datasets. Results: When compared all or subgroup those with non-infectious unknown triggers HC, not find antibody-based classifier that would meet desired dataset. identify 26-antibody distinguish infectious from HCs 100% 90% accuracies sets, respectively. We finally performed bioinformatic analysis associated 26 antibodies. found no correlation between importance metric selected maximal sequence homology human proteins each peptide recognized Conclusions: conclusion, against have effective potential subset patients. are less likely induce B-cell explain pathogenesis ME/CFS.

Язык: Английский

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Treatment of Acute and Long-COVID, Diabetes, Myocardial Infarction, and Alzheimer’s Disease: The Potential Role of a Novel Nano-Compound – the Transdermal Glutathione-Cyclodextrin Complex

Опубликована: Июнь 26, 2024

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants – primarily endogenous glutathione (GSH). There are many illnesses, acute and post-COVID-19, diabetes, myocardial infarction, to Alzheimer’s disease, that associated with OS. These dissimilar illnesses in order, viral infection, metabolic disorder, an ischemic event, neurodegenerative disorder. OS may be early initiator significant promotor their progressive pathophysiologic processes. Consequently, addressing initial OS-related pathology avoid subsequent severe irreversible complications. Early intervention would modulate multiple factors, including cytokine stimulation, complement dysregulation, immuno-thrombosis, fibrosis, autoimmunity. Past clinical studies addressed have had equivocal results. It due the use ineffective antioxidants, untimely delay use, inefficient delivery system. Experimental used not available for trials. Although GSH can significantly reduce OS, its exogenous is hampered by lack effective By incorporating into cyclodextrin (CD) through nanotechnology, there recent evidence delivered more effectively prevent mitigate injury [1]. Future using GSH/cyclodextrin (GC) complex will needed confirm effectiveness and, hopefully, offer path treat sub-optimally managed currently untreatable illnesses.

Язык: Английский

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Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 9, 2024

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine show similarities in their pathophysiology clinical manifestations. These disorders are related to viral adjuvant persistence, immunological alterations, autoimmune diseases hormonal imbalances. A developmental model is postulated that involves the interaction between immune hyperactivation, hypophysitis pituitary hypophysitis, depletion. This process might begin with a deficient CD4 T-cell response infections genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled CD8 hyperactivation elevated antibody production, some of which may be directed against autoantigens, can trigger direct damage pituitary, resulting decreased production hormones, such as ACTH. As disease progresses, prolonged exposure antigens lead exhaustion system, exacerbating symptoms pathology. It suggested these could included autoimmune/adjuvant-induced inflammatory (ASIA) because similar manifestations possible relationship genetic factors, polymorphisms HLA-DRB1 gene. In addition, it proposed treatment antivirals, corticosteroids/ginseng, antioxidants, metabolic precursors improve modulating response, function, inflammation oxidative stress. Therefore, purpose this review suggest origin adenohypophysis improvement after corticosteroid replacement therapy.

Язык: Английский

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Human herpesvirus reactivation and its potential role in the pathogenesis of post-acute sequelae of SARS-CoV-2 infection

GeroScience, Год журнала: 2024, Номер unknown

Опубликована: Авг. 29, 2024

The emergence of SARS-CoV-2 has precipitated a global pandemic with substantial long-term health implications, including the condition known as post-acute sequelae infection (PASC), commonly referred to Long COVID. PASC is marked by persistent symptoms such fatigue, neurological issues, and autonomic dysfunction that persist for months beyond acute phase COVID-19. This review examines potential role herpesvirus reactivation, specifically Epstein-Barr virus (EBV) cytomegalovirus (CMV), in pathogenesis PASC. Elevated antibody titers specific T cell responses suggest recent reactivation some patients, although viremia not consistently detected. exhibits endothelial trophism, directly affecting vascular endothelium contributing microvascular pathologies. These pathologies are significant PASC, where may underlie various chronic symptoms. Similarly, herpesviruses like CMV also exhibit which exacerbate damage when reactivated. Evidence suggests EBV could indirectly contribute immune dysregulation, immunosenescence, autoimmune observed Additionally, play genesis through creating mitochondrial dysfunction, though direct confirmation remains elusive. reviewed evidence while their indirect effects, especially context involvement, warrant further investigation.

Язык: Английский

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Metformin in Antiviral Therapy: Evidence and Perspectives

Viruses, Год журнала: 2024, Номер 16(12), С. 1938 - 1938

Опубликована: Дек. 18, 2024

Metformin, a widely used antidiabetic medication, has emerged as promising broad-spectrum antiviral agent due to its ability modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes energy reserves that viruses rely on, effectively limiting the replication of pathogens such influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting mTOR pathway, crucial protein synthesis reactivation, is particularly significant managing infections caused by CMV, EBV. Furthermore, reduces oxidative stress reactive oxygen species (ROS), which are critical replicating arboviruses Zika dengue. The drug also regulates immune responses, differentiation, inflammation, disrupting life cycle HPV potentially other viruses. These diverse mechanisms suppress replication, enhance system functionality, contribute better clinical outcomes. This multifaceted approach highlights metformin’s potential an adjunctive therapy treating wide range infections.

Язык: Английский

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Treatment of Acute and Long-COVID, Diabetes, Myocardial Infarction, and Alzheimer’s Disease: The Potential Role of a Novel Nano-Compound—The Transdermal Glutathione–Cyclodextrin Complex

Antioxidants, Год журнала: 2024, Номер 13(9), С. 1106 - 1106

Опубликована: Сен. 12, 2024

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants—primarily endogenous glutathione (GSH). There are many illnesses, acute and post-COVID-19, diabetes, myocardial infarction to Alzheimer’s disease, that associated with OS. These dissimilar illnesses are, in order, viral infections, metabolic disorders, ischemic events, neurodegenerative disorders. Evidence is presented (1) OS an early initiator significant promotor their progressive pathophysiologic processes, (2) reduction may prevent later serious irreversible complications, (3) GSH OS, (4) can likely reduce restore adaptive physiology, (5) effective administration be accomplished novel nano-product, the GSH/cyclodextrin (GC) complex. overlooked pathological process illnesses. Significantly, complex, therapeutic now available Finally, rigorous prospective studies needed confirm efficacy this approach.

Язык: Английский

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Immunometabolic changes and potential biomarkers in CFS peripheral immune cells revealed by single-cell RNA sequencing

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Окт. 11, 2024

The pathogenesis of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains unclear, though increasing evidence suggests inflammatory processes play key roles. In this study, single-cell RNA sequencing (scRNA-seq) peripheral blood mononuclear cells (PBMCs) was used to decipher the immunometabolic profile in 4 ME/CFS patients and heathy controls. We analyzed changes composition major PBMC subpopulations observed an increased frequency total T a significant reduction NKs, monocytes, cDCs pDCs. Further investigation revealed even more complex proportions cell within each subpopulation. Gene expression patterns upregulated transcription factors related immune regulation, as well genes associated with viral infections neurodegenerative diseases.CD4+ CD8+ show different differentiation states altered trajectories, indicating possible suppression differentiation. Memory B are found early pseudotime, unique subtype specific ME/CFS, plasma suggesting overactivity. NK exhibit reduced cytotoxicity impaired responses, perforin CD107a upon stimulation. Pseudotime analysis showed abnormal development adaptive enhanced cell-cell communication network converging on monocytes particular. Our also identified estrogen-related receptor alpha (ESRRA)-APP-CD74 signaling pathway potential biomarker for blood. addition, data from GSE214284 database confirmed higher ESRRA monocyte types male patients. These results suggest link between neurological symptoms. support disease model dysfunction ranging autoimmunity immunodeficiency point amyloidotic pathways ME/CFS. While study provides important insights, limitations include modest sample size evaluation only. findings highlight targets diagnostic biomarkers therapeutic interventions. research is needed validate these explore their clinical applications managing

Язык: Английский

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