Long COVID science, research and policy

Nature Medicine, Год журнала: 2024, Номер 30(8), С. 2148 - 2164

Опубликована: Авг. 1, 2024

Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system be severely disabling. The cumulative global incidence long around 400 million individuals, which estimated to have an annual economic impact approximately $1 trillion-equivalent about 1% economy. Several mechanistic pathways are implicated in COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement endothelial inflammation microbiome dysbiosis. devastating impacts on individual lives and, due its complexity prevalence, also has major ramifications for systems economies, even threatening progress toward achieving Sustainable Development Goals. Addressing challenge requires ambitious coordinated-but so far absent-global research policy response strategy. In this interdisciplinary review, we provide synthesis state scientific evidence assess human health, systems, economy metrics, forward-looking roadmap.

Язык: Английский

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Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

SLE and ME/CFS both present significant fatigue share immune dysregulation. The mechanisms underlying in these disorders remain unclear, there are no standardized treatments. This study aims to explore shared predict potential therapeutic drugs for ME/CFS. Genes associated with were collected from disease target clinical sample databases identify overlapping genes. Bioinformatics analyses, including GO, KEGG, PPI network construction, key identification, performed. ROC curve correlation analysis of targets, along single-cell clustering, conducted validate their expression different cell types. Additionally, an inflammation model was established using THP-1 cells simulate monocyte activation diseases vitro, RT-qPCR used the targets. A TF-mRNA-miRNA co-regulatory constructed, followed by drug prediction molecular docking. Fifty-eight genes identified, mainly involved innate immunity inflammation. Five targets identified (IL1β, CCL2, TLR2, STAT1, IFIH1). Single-cell sequencing revealed that monocytes enriched confirmed upregulation group. ten drugs, suloctidil, N-Acetyl-L-cysteine, simvastatin, ACMC-20mvek, camptothecin, predicted. Simvastatin camptothecin showed high affinity inflammatory pathways. predominantly at level, suggesting classical may be crucial linking fatigue. activated monocytes. provides a foundation future research, suggests N-Acetyl-L-cysteine as therapies.

Язык: Английский

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CBT and graded exercise therapy studies have proven that ME/CFS and long COVID are physical diseases, yet no one is aware of that

Frontiers in Human Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Янв. 29, 2025

The cognitive behavioral model (CBmodel) (1,2) has dominated the world of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) since 1990s. According to this model, a belief in an organic illness, known as dysfunctional beliefs, stops ME/CFS patients engaging normal activities, resulting avoidance behavior and deconditioning. deconditioning then leads further more CBmodel, symptoms are caused by not underlying illness. Cognitive therapy with graded activity (CBTplus) exercise (GET) were designed reverse lead recovery.As many runners know, if you beginner start exercising three times week, can run half marathon 12 weeks. In healthy sedentary person who doesn't do physical or work, that will take around 24 weeks (3). Let's keep mind have look at largest CBTplus GET trial for ME/CFS, PACE (n=641) (4), its group, particular. 160 participants group five days week up 30 minutes per day If there would be no disease, merely deconditioned, such regime very substantial improvement fitness. However, fitness did improve (5). same thing was seen group. Consequently, i.e. preventing that. It also means already their maximum when they joined study, which disproves assumption less than could due beliefs.Three Dutch studies (6)(7)(8) showed following: eight months adults, adolescents least 16 guided self-instructions based on CBTplus, objective (actometer) (9). A 12-week programme (10), 18-week combining severely affected (11) evaluation efficacy Belgium reference centers (12) fitness, according VO2peak, timed step test, "strongly reliably predicts maximal aerobic capacity VO2max" (p. ( 13)) VO2peak VO2max, respectively. This is only important patients, but those long Covid because 60% them fulfill criteria (14,15). But also, 400 million people conservative estimate (16).Moreover, ReCOVer found either (17,18).In all studies, one expected (very) increase activity/fitness didn't happen illness that, just like what trial. proved disease suffer from beliefs. study Covid.Some might say, simply down fact motivated follow treatments adhere them. above mentioned concluded effective implies adhered treatment. had treatment, concluded, we cannot conclude anything about our it. Or, treatment it / negatively Moreover, aforementioned (4) high rates acceptance satisfaction; 87% 85% adequately treated, adherence manual competent therapists good excellent (GET), dropout rate low (11%, 6%, GET).Additionally, (n=655) average 41 62 hours GET, spread over 6 8 months. (only 2.8%) "generally speaking…very therapy" 80 12)).The remaining question is, why aware that? Or put differently, none these report discovery? first possible answer conducted researchers originated devoted career CBmodel ME/CFS. As noted Ioannidis, "investigators working any field likely resist accepting whole spent careers 'null field.'" 0700, 19). second mainly mental health experts physiology. see own results showed. similar manner most us thrown away mold overgrown petri dish research Dr Alexander Fleming led discovery penicillin (20). needed someone him understand meaning it.CBT proven diseases. Yet involved built true outcomes invalidate model. Alternatively, instead

Язык: Английский

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Unequal access to diagnosis of myalgic encephalomyelitis in England

BMC Public Health, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 21, 2025

Abstract Background People with Myalgic Encephalomyelitis (ME/CFS; sometimes referred to as chronic fatigue syndrome) experience poor health-related quality of life and only rarely recover. ME/CFS has no curative treatment, single diagnostic test. Public health policy decisions relevant require knowledge its prevalence barriers diagnosis. However, people report lengthy delays estimates vary greatly due uneven diagnosis misdiagnosis. Factors that influence could be revealed by stratifying a population gender, age ethnicity. Methods Hospital Episode Statistics data, routinely collected the NHS in England, was downloaded from Feasibility Self-Service DigiTrials. This used stratify individuals ICD-10 code best reflects symptoms (G93.3) according age, self-reported gender ethnicity, General Practice England Integrated Care Board (ICB). Results In all, 100,055 had been diagnosed (ICD-10:G93.3) between April 1 1989 October 7 2023, 0.16% all registered patients. Of these, 79,445 were females 20,590 males, female-to-male ratio 3.88:1. Female relative male peaked at about 6-to-1 individuals’ fourth fifth decades life. Prevalence varied widely across 42 ICBs: 0.086%-0.82% for 0.024%-0.21% males. White approximately fivefold more likely than others; Black, Asian or Chinese ethnicities are associated particularly low rates diagnoses. ethnicity bias is stronger other common diseases. Among active English GP practices, 176 (3%) Eight ICBs (19%) each contained fewer 8 other-than-white G93.3 despite their registers containing total 293,770 Conclusion Other-than-white ethnic groups, older (> 60y), males 80y), living areas multiple deprivation disproportionately undiagnosed ME/CFS. Lifetime may high 0.92% 0.25%, respectively, 404,000 UK overall (0.6%). improved estimate allows accurate assessment socioeconomic disease burden imposed

Язык: Английский

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Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome

The Journal of Immunology, Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex heterogeneous multiorgan disease that can have severe impact on individuals' quality of life. Diagnosis ME/CFS based symptom presentation, and significant goal for the field to establish meaningful subtypes. The heterogeneity in literature suggests individuals living with may suffer from overlapping but different underlying pathophysiological mechanisms. We enrolled 40 participants 41 matched healthy control subjects at Bragée Clinic Sweden. assessed plasma samples both cases groups cerebrospinal fluid (CSF) ME/CFS. investigated dysregulated pathways profiles through clinical questionnaires; multiplex analyses cytokines, hormones, matrix metalloproteinases; pathogen seroreactivity peptide display bacteria libraries; high-throughput microarray autoantibodies. All used were humans. show altered interaction patterns between circulating biological factors participants. Our analysis CSF revealed immunotypes disease. found 2 patient clusters metalloproteinases profiles. subgroups had similar presentation distinct exposure inflammatory findings shed light immune phenotypes generate hypotheses future research pathogenesis treatment development by exploring subgroups.

Язык: Английский

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Cognitive impairment in asthenic disorders

S S Korsakov Journal of Neurology and Psychiatry, Год журнала: 2025, Номер 125(3), С. 27 - 27

Опубликована: Апрель 8, 2025

The article presents a review of scientific publications devoted to cognitive aspects asthenic disorders. authors present different views on the etiology and basic mechanisms pathogenesis psychogenic asthenia chronic fatigue syndrome, current diagnostic criteria for these diseases. main attention is paid consideration neurocognitive deficit observed in mental syndrome. role control impairment development adaptation disorders formation conditions considered. results studies effectiveness pharmacological therapy are presented.

Язык: Английский

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Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Abstract Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogeneous, and systemic disease defined by suite of symptoms, including unexplained persistent fatigue, post-exertional malaise (PEM), cognitive impairment, myalgia, orthostatic intolerance, unrefreshing sleep. The mechanism ME/CFS unknown, with no effective curative treatments. In this study, we present multi-site whole-genome analysis, which powered novel deep learning framework, HEAL2. We show that HEAL2 not only has predictive value for based on personal rare variants, but also links genetic risk to various ME/CFS-associated symptoms. Model interpretation identifies 115 ME/CFS-risk genes exhibit significant intolerance loss-of-function (LoF) mutations. Transcriptome network analyses highlight the functional importance these across wide range tissues cell types, central nervous system (CNS) immune cells. Patient-derived multi-omics data implicate reduced expression within patients, in plasma proteome, transcriptomes B T cells, especially cytotoxic CD4 supporting their relevance. Pan-phenotype analysis further reveals correlation between other complex diseases traits, depression long COVID-19. Overall, provides candidate genetic-based diagnostic tool ME/CFS, our findings contribute comprehensive understanding genetic, molecular, cellular basis yielding insights into therapeutic targets. Our model offers potent, broadly applicable framework parallel variant prediction traits.

Язык: Английский

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Immunological Avalanches in Renal Immune Diseases

Biomedicines, Год журнала: 2025, Номер 13(4), С. 1003 - 1003

Опубликована: Апрель 21, 2025

The complex nature of immune system behavior in both autoimmune diseases and transplant rejection can be understood through the lens avalanche dynamics critical-point systems. This paper introduces concept “immunological avalanche” as a framework for understanding unpredictable patterns activity contexts. Just avalanches represent sudden releases accumulated potential energy, responses exhibit periods apparent stability followed by explosive flares triggered seemingly minor stimuli. model presented here draws parallels between other systems such earthquakes, forest fires, neuronal activity, where localized events propagate into large-scale disruptions. In conditions like systemic lupus erythematosus (SLE), which affects multiple organ including kidneys approximately 50% patients, these manifest alternating remission flares. Similarly, recipients, exhibits metastable under constant allograft stimulation. is characterized threshold-dependent activation, positive feedback loops, dynamic non-linearity. diseases, triggers UV light exposure, infections, or stress initiate cascading responses. longitudinal analysis reveals how monitoring oscillatory blood parameters biological age markers predict risk. preliminary study on kidney transplant, all measured variables showed temporal instability. Proteinuria exhibited precise log–log linearity power law analysis, confirming near-critical-point behavior. Two distinct emerged: large oscillations eGFR, proteinuria, predicted declining function, while small indicated stability. During events, increased dramatically, with partial reversal leaving persistent elevation after acute episodes. Understanding has important implications therapeutic approaches Key findings suggest that parameter oscillations, rather than absolute values, better indicates instability events. Additionally, calculations provide valuable prognostic information, proteinuria measurements offer efficient sampling assessment. conceptual provides unifying pathogenesis transplant-related responses, potentially leading to new perspectives disease management prediction.

Язык: Английский

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The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Май 11, 2025

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective this review was to synthesize qualitative quantitative data from research examining microbiota composition, inflammatory markers, therapeutic outcomes interventions targeting microbiome context ME/CFS. collection involved detailed search peer-reviewed English literature January 1995 2025, focusing on studies related This comprehensive utilized databases such as PubMed, Scopus, Web Science, keywords including "ME/CFS," "Gut-Brain Axis," "Gut Health," "Intestinal Dysbiosis," "Microbiome "Pathophysiology," "Therapeutic Approaches." Where possible, insights clinical trials observational were included enrich findings. A narrative synthesis method also employed effectively organize present these study found notable changes diversity composition ME/CFS patients, contributing systemic inflammation worsening physical impairments. As result, various like probiotics, prebiotics, specific diets, supplements, fecal transplantation, pharmacological interventions, improved sleep, moderate exercise training are potential strategies that merit further exploration. Interventions gut-brain axis may help reduce neuropsychiatric symptoms utilizing benefits microbiome. Therefore, identifying beneficial elements incorporating their assessments into practice can enhance patient care through personalized treatments. Due complexity ME/CFS, which involves genetic, environmental, microbial factors, multidisciplinary approach necessary. Since current lacks how might aid treatment, standardized diagnostics longitudinal could foster innovative therapies, potentially improving quality life symptom management for those affected.

Язык: Английский

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A Direct Relationship Between ‘Blood Stasis’ and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment

Pharmaceuticals, Год журнала: 2025, Номер 18(5), С. 712 - 712

Опубликована: Май 12, 2025

'Blood stasis' (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it known as Xue Yu (). Similar concepts exist Korean ('Eohyul') and Japanese Kampo medicine (Oketsu). Blood stasis considered to underpin large variety of inflammatory diseases, though an exact equivalent Western systems yet be described. Some time ago we discovered that blood can clot into anomalous amyloid form, creating what have referred fibrinaloid microclots. These microclots occur great many chronic, diseases are comparatively resistant fibrinolysis, thus the ability block microcapillaries hence lower oxygen transfer tissues, with multiple pathological consequences. We here develop idea precisely relate to, largely mechanistically responsible for, traditional (a term also used by Virchow). First, associated all stasis. Secondly, blocking red cell transport, provide simple mechanistic explanation for physical slowing down ('stasis') flow. Thirdly, herbal formulae proposed treat these especially Fu Zhu its derivatives, anticoagulatory anti-inflammatory, consistent they actually helping levels microclots, plausibly part catalysis polymerization fibrinogen form. rehearse some actions constituent herbs specific bioactive molecules contain. Consequently, such formulations (and their components), which little science medicine, would seem offer opportunity novel, safe, useful treatments chronic display including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, even ischemic stroke.

Язык: Английский

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