Long COVID science, research and policy

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(8), P. 2148 - 2164

Published: Aug. 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.

Language: Английский

---

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

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 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.

Language: Английский

---

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, Journal Year: 2025, Volume and Issue: 19

Published: Jan. 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

Language: Английский

---

Cognitive impairment in asthenic disorders

S S Korsakov Journal of Neurology and Psychiatry, Journal Year: 2025, Volume and Issue: 125(3), P. 27 - 27

Published: April 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.

Language: Английский

---

Immunological Avalanches in Renal Immune Diseases

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 1003 - 1003

Published: April 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.

Language: Английский

---

Unequal access to diagnosis of myalgic encephalomyelitis in England

BMC Public Health, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 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

Language: Английский

---

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

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 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.

Language: Английский

---

Long COVID and hypermobility spectrum disorders have shared pathophysiology

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 5, 2024

Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are the most common joint hypermobility conditions encountered by physicians, with classical EDS accounting for >90% of all cases. has been detected in up to 30-57% patients myalgic encephalomyelitis/chronic fatigue (ME/CFS), fibromyalgia, postural orthostatic tachycardia (POTS), long COVID (LC) compared general population. Extrapulmonary symptoms, including musculoskeletal pain, dysautonomia disorders, cognitive fatigue, seen both LC HSD. Additionally, ME/CFS overlapping symptoms those Mast cell activation degranulation occurring may result hyperinflammation damage connective tissue these patients, thereby inducing hypermobility. Persistent inflammation development or worsening Hence, screening other related POTS, ME/CFS, chronic pain conditions, myalgia is essential individuals experiencing LC. Pharmacological treatments should be symptom-focused geared a patient's presentation. Paced exercise, massage, yoga, meditation also provide benefits.

Language: Английский

---

The relation between FT3 and long-term fatigue in patients with COVID-19

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 23, 2024

Background Under the current pandemic of Corona Virus Disease 2019 (COVID-19), The relationship between fatigue and COVID-19 has been found. Infection with is associated long after acute phase COVID-19. Understanding association thyroid hormones levels post-COVID condition, such as fatigue, necessary to improve quality life. Methods This population-based cohort study was conducted in Dalian, China, from December 2022, March 2023, using a Yidu Core platform First Affiliated Hospital Dalian Medical University, that integrates medical records, laboratory tests, all diagnosis treatment information based on patients hospital. Eligible individuals were 40 COVID-19, Divided them into group non-fatigue following up by telephone FS-14 scale 6 months. primary outcomes diagnoses fatigue. assessed logistic regression analysis. Results Compared group, FT 3 level lower ( p <0.05). negatively correlated months OR 0.257, After adjusting for confounding factors age gender, low risk factor 0.225, And less than 2.47 mol/L, it best critical value predicting long-term sensitivity 92.3% specificity 48.1%. Conclusions Most people still have infection. serves important index predict should be closely monitored during

Language: Английский

---

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

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 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

Language: Английский

---