ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: June 2, 2023

Some patients remain unwell for months after "recovering" from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance other symptoms that greatly interfere with their ability to function can leave some people housebound disabled. The illness (Long COVID) is similar myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well persisting illnesses follow a wide variety of infectious agents following major traumatic injury. Together, these are projected cost the U.S. trillions dollars. In this review, we first compare ME/CFS Long COVID, noting considerable similarities few differences. We then in extensive detail underlying pathophysiology two conditions, focusing on abnormalities central autonomic nervous system, lungs, heart, vasculature, immune gut microbiome, energy metabolism redox balance. This comparison highlights how strong evidence each abnormality, illness, helps set priorities future investigation. review provides current road map literature biology both illnesses.

Language: Английский

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Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: a link with diabetes mellitus

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Feb. 20, 2024

Abstract Early since the onset of COVID-19 pandemic, medical and scientific community were aware extra respiratory actions SARS-CoV-2 infection. Endothelitis, hypercoagulation, hypofibrinolysis identified in patients as subsequent responses endothelial dysfunction. Activation barrier may increase severity disease contribute to long-COVID syndrome post-COVID sequelae. Besides, it cause alterations primary, secondary, tertiary hemostasis. Importantly, these have been highly decisive evolution infected also diagnosed with diabetes mellitus (DM), who showed previous In this review, we provide an overview potential triggers activation related under diabetic milieu. Several mechanisms are induced by both viral particle itself immune-defensive response (i.e., NF-κB/NLRP3 inflammasome pathway, vasoactive peptides, cytokine storm, NETosis, complement system). Alterations coagulation mediators such factor VIII, fibrin, tissue factor, von Willebrand factor: ADAMST-13 ratio, kallikrein-kinin or plasminogen-plasmin systems reported. Moreover, imbalance thrombotic thrombolytic (tPA, PAI-I, fibrinogen) factors favors hypercoagulation hypofibrinolysis. context DM, can be exacerbated leading higher loss However, a series therapeutic strategies targeting activated endothelium specific antibodies inhibitors against thrombin, key cytokines, X, system, system might represent new opportunities address hypercoagulable state present DM. Antidiabetics ameliorate dysfunction, inflammation, platelet aggregation. By improving microvascular pathology subjects, associated comorbidities risk mortality could reduced.

Language: Английский

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Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10458 - 10458

Published: June 21, 2023

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low-grade inflammatory response; immune dysregulation defective reactivation latent viruses; autoimmunity; persistent endothelial dysfunction coagulopathy; gut dysbiosis; hormonal metabolic dysregulation; mitochondrial dysfunction; autonomic nervous system dysfunction. There are no specific tests for diagnosis LC, clinical features laboratory findings biomarkers not specifically relate to LC. Therefore, is paramount importance develop validate that can employed prediction, prognosis its therapeutic response, although this effort hampered challenges pertaining non-specific nature majority manifestations in spectrum, small sample sizes relevant studies other methodological issues. Promising candidate found some patients markers systemic inflammation, acute phase proteins, cytokines chemokines; reflecting persistence, herpesviruses endotheliopathy, coagulation fibrinolysis; microbiota alterations; diverse proteins metabolites; biomarkers; cerebrospinal fluid biomarkers. At present, there only two reviews summarizing they do cover entire umbrella current biomarkers, their link etiopathogenetic mechanisms or diagnostic work-up comprehensive manner. Herein, we aim appraise synopsize available evidence on typical classification based pathogenetic main symptomatology frame epidemiological aspects syndrome furthermore assess limitations as well potential implications interventions.

Language: Английский

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COVID-19 and Long COVID: Disruption of the Neurovascular Unit, Blood-Brain Barrier, and Tight Junctions

The Neuroscientist, Journal Year: 2023, Volume and Issue: 30(4), P. 421 - 439

Published: Sept. 11, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), could affect brain structure and function. SARS-CoV-2 can enter through different routes, including olfactory, trigeminal, vagus nerves, blood immunocytes. may also from peripheral a disrupted blood-brain barrier (BBB). The neurovascular unit in brain, composed neurons, astrocytes, endothelial cells, pericytes, protects parenchyma by regulating entry substances blood. astrocytes highly express angiotensin converting enzyme (ACE2), indicating that BBB be disturbed lead to derangements tight junction adherens proteins. This leads increased permeability, leakage components, movement immune cells into parenchyma. cross microvascular an ACE2 receptor–associated pathway. exact mechanism dysregulation COVID-19/neuro-COVID is not clearly known, nor development long COVID. Various biomarkers indicate severity neurologic complications COVID-19 help objectively diagnose those developing review highlights importance disruption, as well some potentially useful COVID-19, COVID/neuro-COVID.

Language: Английский

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COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: May 28, 2024

The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It over 2.47 million deaths through various syndromes such as distress, hypercoagulability, and multiple organ failure. viral invasion proceeds the ACE2 receptor, expressed in cell types, some patients serious damage to tissues, organs, immune cells, microbes that colonize gastrointestinal tract (GIT). Some who survived SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae COVID-19 (PASC). Diagnosis these revealed biological effects, none which are mutually exclusive. However, severity also depends on numerous comorbidities obesity, age, diabetes, hypertension care must be taken with respect other morbidities, host immunity. Gut microbiota relation immunopathology is considered evolve progression via mechanisms biochemical metabolism, exacerbation inflammation, intestinal mucosal secretion, cytokine storm, immunity regulation. Therefore, modulation gut microbiome equilibrium food supplements probiotics remains a hot topic current research debate. In this review, we discuss complications physio-pathological effects infection, GIT response, therapeutic pharmacological strategies. We summarize targets probiotics, their limitations, efficacy preclinical clinical drugs effectively inhibit spread SARS-CoV-2.

Language: Английский

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Reactivation of herpesvirus type 6 and IgA/IgM-mediated responses to activin-A underpin long COVID, including affective symptoms and chronic fatigue syndrome

Acta Neuropsychiatrica, Journal Year: 2024, Volume and Issue: 36(3), P. 172 - 184

Published: April 4, 2024

Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID.

Language: Английский

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Development and validation of a brain fog scale for coeliac disease

Alimentary Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 59(10), P. 1260 - 1270

Published: March 6, 2024

Summary Background Brain fog is a subjective cognitive impairment commonly reported in coeliac disease. A standardised tool to define and assess it an important unmet need. Aims To develop patient‐informed brain disease support clinical care, research drug development. Methods pilot online study defined patient descriptors of fog. second evaluated the factor structure performance scale across two‐time points (‘Now’ ‘Past week’). One month later, participants were invited repeat with two processing tests, Stroop task trail making test. Results Among adults treated disease, 37 (91.9% F) participated 510 (88.8% whom 99 repeated 1 later 51 completing testing. The most common ‘difficulty focusing’, thinking’ finding right words communicating’. 12‐item reflects ‘cognitive impairment’ ‘somatic affective experience’ demonstrates strong psychometric properties. It tracked patients report being present or absent points. did not significantly correlate tests. Conclusion assessment severity first outcomes measuring brief validated for time‐based formats. Further coupling biomarker discovery needed confirm its validity as predictor performance.

Language: Английский

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Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: Randomized Controlled Trial

Nutrients, Journal Year: 2025, Volume and Issue: 17(2), P. 304 - 304

Published: Jan. 16, 2025

Background: Long COVID (LC) is characterized by persistent symptoms at least 3 months after a SARS-COV-2 infection. LC has been associated with fungal translocation, gut dysfunction, and enhanced systemic inflammation. Currently, there no approved treatment for this condition. The anti-inflammatory effect of vitamins K2 D3 was shown to help attenuate the course acute COVID-19 Objective hypothesis: This trial aims investigate effects K2/D3 on symptoms, as well inflammatory markers, in people established long COVID. Our hypothesis that attenuating inflammation, will improve symptoms. Methods: single-site randomized controlled study enrolled adults experiencing ≥2 moderate RECOVER Research Index number type were considered. Participants 2:1 daily 240 µg (pure MK-7 form) 2000 UI vitamin or standard care (SOC) 24 weeks. endpoints changes symptomatology select inflammatory, metabolic, biomarkers Results: We 151 participants (n = 98 received vit 53 SOC). median age 46 years; 71% female 29% non-white. Baseline demographics balanced between groups. At weeks, active group only had sharp increase 25(OH) D, indicating good adherence. In arm, 7.1% decrease proportion who an ≥12 (vs. 7.2% SOC group; p 0.01). average remained stable arm but increased (p 0.03). Additionally, reductions oxidized LDL, markers sTNF-RI sCD163, translocation marker (1,3)-β-d-glucan observed compared < 0.01) over Conclusions: Vitamins improved Index, several markers. provide promising safe intervention suffering from

Language: Английский

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Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease

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

Published: Feb. 12, 2025

The emergence of the COVID-19 pandemic made it critical to understand immune and inflammatory responses SARS-CoV-2 virus. It became increasingly recognized that response was a key mediator illness severity its mechanisms needed be better understood. Early infection both tissue cells, such as macrophages, leading pyroptosis-mediated inflammasome production in an organ system for systemic oxygenation likely plays central role morbidity wrought by SARS-CoV-2. Delayed transcription Type I III interferons may lead early disinhibition viral replication. Cytokines interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor α (TNFα), some which produced through involving nuclear kappa B (NF-κB), contribute hyperinflammatory state patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) CD8+ T-cells, B-cells, can disease reflect direct cytopathic effects or end-organ sequestration. Direct activation endothelial cells mechanism systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation microthrombi development seen lungs other organs throughout body, heart, gut, brain. kidney most impacted extrapulmonary owing high concentration ACE2 exposure kidney, acute tubular injury, myofibroblast activation, collapsing glomerulopathy select populations account COVID-19-related AKI CKD development. COVID-19-associated nephropathy (COVAN), particular, mediated IL-6 signal transducer activator 3 (STAT3) signaling, suggesting connection between chronic disease. Chronic manifestations also include conditions like Multisystem Inflammatory Syndrome Children (MIS-C) Adults (MIS-A) post-acute sequelae (PASC), spectrum clinical presentations persistent dysregulation. lessons learned those undergoing continued study have broad implications understanding infections’ immunologic consequences beyond coronaviruses.

Language: Английский

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The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: May 9, 2022

Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a specific and distinctive profile of clinical features, the disease remains an enigma because causal explanation pathobiological matrix is lacking. Several potential mechanisms have been identified, including immune abnormalities, inflammatory activation, mitochondrial alterations, endothelial muscular disturbances, cardiovascular anomalies, dysfunction peripheral central nervous systems. Yet, it unclear whether how these pathways may be related orchestrated. Here we explore hypothesis that common denominator processes in ME/CFS system due to impaired or pathologically reactive neuroglia (astrocytes, microglia oligodendrocytes). We will test this by reviewing, reference current literature, two most salient widely accepted features ME/CFS, investigating might linked dysfunctional neuroglia. From review conclude multifaceted pathobiology attributable unifying manner neuroglial dysfunction. Because key – post exertional malaise decreased cerebral blood flow are also recognized subset patients with post-acute sequelae COVID, suggest our findings pertinent entity.

Language: Английский

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