Long COVID: pathophysiological factors and abnormalities of coagulation

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(6), P. 321 - 344

Published: April 19, 2023

Acute COVID-19 infection is followed by prolonged symptoms in approximately one ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host (chronic inflammation, metabolic endocrine dysregulation, immune autoimmunity); downstream impacts (tissue damage from the initial infection, tissue hypoxia, dysbiosis, autonomic nervous system dysfunction). These mechanisms culminate long-term persistence disorder characterized a thrombotic endothelialitis, endothelial hyperactivated platelets, fibrinaloid microclots. abnormalities blood vessels coagulation affect every organ represent unifying pathway for various

Language: Английский

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Proteomics of fibrin amyloid microclots in long COVID/post-acute sequelae of COVID-19 (PASC) shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Sept. 21, 2022

Post-acute sequelae of COVID-19 (PASC), also now known as long COVID, has become a major global health and economic burden. Previously, we provided evidence that there is significant insoluble fibrin amyloid microclot load in the circulation individuals with these microclots entrap substantial number inflammatory molecules, including those might prevent clot breakdown. Scientifically, most challenging aspect this debilitating condition traditional pathology tests such serum CRP (C-reactive protein) may not show any abnormal markers, albeit measure only soluble molecules. Elevated, or biomarkers IL-6, D-Dimer fibrinogen indicate an increased risk for thrombosis host immune response COVID-19. The absence standard tests, result amount confusion patients clinicians, are extremely sick even bed-ridden but no regular identifiable reason their disease. Biomarkers currently available cannot detect molecules present identified therefore unable to confirm presence mechanisms drive formation.

Language: Английский

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Diagnosis and management of post-COVID (Long COVID) in children: a moving target

Current Opinion in Pediatrics, Journal Year: 2023, Volume and Issue: 35(2), P. 184 - 192

Published: Jan. 20, 2023

Purpose of review This describes recent findings about post-COVID condition (PCC, or Long COVID) in children, including current knowledge its epidemiology, clinical presentation, pathogenesis and care. Recent There is no internationally agreed definition PCC, although now most researchers agree that it a complex symptomatology persisting for at least 3 months after COVID-19, without an alternative diagnosis. are several uncertainties paediatric PCC. So far, available literature suggest 1–3% recognized children with Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) infection may develop Its unknown, there increasing evidence possible abnormalities the immune responses, cellular metabolism intestinal microbiota, along chronic endothelitis. Summary Management PCC require multidisciplinary approach, goal offering best care to support diagnostics, research, mental health access research projects.

Language: Английский

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Increased Levels of Inflammatory and Endothelial Biomarkers in Blood of Long COVID Patients Point to Thrombotic Endothelialitis

Seminars in Thrombosis and Hemostasis, Journal Year: 2023, Volume and Issue: 50(02), P. 288 - 294

Published: May 19, 2023

Abstract The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations von Willebrand factor (VWF), 4 (PF4), serum amyloid A (SAA), α-2 antiplasmin (α-2AP), endothelial-leukocyte adhesion molecule 1 (E-selectin), endothelial cell (PECAM-1) in soluble part blood. It was noteworthy that mean level exceeded upper limit laboratory reference range patients, other 5 were elevated patients as compared controls. This is alarming if take into consideration a significant amount total burden these molecules has previously shown be entrapped inside fibrinolysis-resistant (thus decreasing apparent molecules). We conclude presence microclotting, relatively high levels six biomarkers known key drivers clotting pathology, points thrombotic endothelialitis pathological process COVID.

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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Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses

Blood Reviews, Journal Year: 2023, Volume and Issue: 60, P. 101075 - 101075

Published: March 20, 2023

ME/CFS is a debilitating chronic condition that often develops after viral or bacterial infection. Insight from the study of Long COVID/Post Acute Sequelae COVID-19 (PASC), post-viral syndrome associated with SARS-CoV-2 infection, might prove to be useful for understanding pathophysiological mechanisms ME/CFS. Disease presentation similar between two conditions, and subset COVID patients meet diagnostic criteria Since characterized by significant vascular pathology – including endothelial dysfunction, coagulopathy, dysregulation question whether not same biological abnormalities are significance in arises. Cardiac have while now been documented cohorts, recent studies demonstrating major deficits cerebral blood flow, hence dysregulation. A growing body research accompanied platelet hyperactivation, anomalous clotting, procoagulant phenotype, dysfunction. Endothelial damage dysregulated clotting can impair substance exchange tissues, result hypoperfusion, which may contribute manifestation certain symptoms. Here we review literature summarize cardiovascular haematological findings condition, and, this context, briefly discuss potential role previously-implicated pathogens. Overall, cardiac present within cohorts. While atherosclerotic heart disease significantly ME/CFS, suboptimal function defined reduced output, impaired are, these do appear influenced deconditioning. Rather, dysfunction (autonomic) nervous system. Plenty recently published hyperactivity as well processes. It particular importance determine what extent symptom severity, if systems targeted therapeutic purposes. Viral reservoirs herpesviruses exist most likely directly indirectly. This highlights studying functioning, vasculature, coagulation system

Language: Английский

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease

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

Published: June 3, 2024

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by wide range of symptoms that severely impact all aspects life. Despite its significant prevalence, ME/CFS remains one the most understudied and misunderstood conditions in modern medicine. lacks standardised diagnostic criteria owing to variations both inclusion exclusion across different guidelines, furthermore, there are currently no effective treatments available. Moving beyond traditional fragmented perspectives have limited our understanding management disease, analysis current information on represents paradigm shift synthesising disease’s multifactorial origins into cohesive model. We discuss how emerges from an intricate web genetic vulnerabilities environmental triggers, notably viral infections, leading complex series pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, metabolic disturbances. This comprehensive model not only advances ME/CFS’s pathophysiology but also opens new avenues for research potential therapeutic strategies. By integrating these disparate elements, work emphasises necessity holistic approach diagnosing, researching, treating ME/CFS, urging scientific community reconsider complexity multifaceted required study management.

Language: Английский

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Treatment of Long COVID symptoms with triple anticoagulant therapy

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: March 21, 2023

Abstract Background: Fibrin(ogen) amyloid microclots and platelet hyperactivation are key pathological findings in patients with acute COVID-19 infection also those Long COVID/Post-Acute Sequelae of (PASC). These pathologies may represent a suitable target for pharmacological treatment COVID. Methods: Here we report on the symptoms displayed by cohort 91 South African COVID at baseline after clinician-initiated anticoagulant regime was completed. For laboratory analysis, provided blood sample before treatment. Fibrinaloid microclot presence studied adding thioflavin T to poor plasma (PPP), whilst using two markers- PAC1 CD62P (P-selectin). The included dual antiplatelet therapy (DAPT- Clopidogrel 75mg + Aspirin 75mg) once day, direct oral (DOAC- Apixaban) 5mg twice day. A proton pump inhibitor (PPI) pantoprazole 40 mg/day prescribed gastric protection. Each treated cases reported their main symptoms, whether resolved following or not. Results: In our most participants did not any comorbidities infection. Hypertension dyslipidaemia were commonest underlying illnesses, commonly fatigue, cognitive dysfunction, shortness breath, joint muscle pains. Following completion treatment, each different majority patients. This reflected where decrease severity fibrin microclotting degree pathology noted. No serious adverse bleeding events reported. Conclusions: Fibrin microclots, hyperactivation/ aggregation, widespread endothelialitis inhibit transport oxygen capillary/cellular level. provides ready explanation By normalizing failed clotting physiology reversal endothelialitis, triple represents promising option that appears be highly efficacious, warrants controlled clinical studies. We caution such must only followed under expert medical supervision view risk bleeding.

Language: Английский

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Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(2), P. 170 - 170

Published: Jan. 31, 2024

Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of variety chronic, inflammatory diseases, including long COVID, as are small, insoluble, 'fibrinaloid' microclots. We here develop the argument, with accompanying evidence, that fibrinaloid microclots, through their ability to block flow blood microcapillaries and thus cause tissue hypoxia, not simply correlated but in fact, by preceding it, may be chief intermediary POTS, which body's exaggerated 'physiological' response hypoxia. Similar reasoning accounts for symptoms bundled under term 'fatigue'. Amyloids known membrane disruptors, when targets nerve membranes, this can explain neurotoxicity hence autonomic nervous system dysfunction contributes POTS. Taken together view, we indicate microclots serve link POTS fatigue COVID manner at once both mechanistic explanatory. This has clear implications treatment such diseases.

Language: Английский

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Interdisziplinäres, kollaboratives D-A-CH Konsensus-Statement zur Diagnostik und Behandlung von Myalgischer Enzephalomyelitis/Chronischem Fatigue-Syndrom

Wiener klinische Wochenschrift, Journal Year: 2024, Volume and Issue: 136(S5), P. 103 - 123

Published: May 1, 2024

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, chronic multisystemic disease which, depending on its severity, can lead to considerable physical and cognitive impairment, loss of ability work the need for nursing care including artificial nutrition and, in very severe cases, even death.The aim this D-A-CH (Germany, Austria, Switzerland) consensus statement 1) summarize current state knowledge ME/CFS, 2) highlight Canadian Consensus Criteria (CCC) as clinical criteria diagnostics with focus leading symptom post-exertional malaise (PEM) 3) provide an overview options possible future developments, particularly regard therapy. The intended support physicians, therapists valuer diagnosing patients suspected ME/CFS by means adequate anamnesis clinical-physical examinations well recommended CCC, using questionnaires other examination methods presented. two pillars therapy pacing symptom-relieving options, not only orientation physicians therapists, but also decision-makers from healthcare policy insurance companies determining which should already be reimbursable them at point time indication ME/CFS.

Language: Английский

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