Muscle abnormalities worsen after post-exertional malaise in long COVID

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 4, 2024

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. distinctive symptom long COVID is post-exertional malaise, which associated a worsening fatigue- and pain-related symptoms acute mental or physical exercise, but its underlying pathophysiology unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the malaise in COVID. We show that skeletal muscle structure lower exercise capacity patients, local systemic metabolic disturbances, severe exercise-induced myopathy tissue infiltration amyloid-containing deposits muscles worsen induction malaise. This highlights novel pathways help to understand suffering from other post-infectious diseases.

Язык: Английский

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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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COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences

Pathology - Research and Practice, Год журнала: 2023, Номер 246, С. 154497 - 154497

Опубликована: Май 3, 2023

Worldwide there have been over 760 million confirmed coronavirus disease 2019 (COVID-19) cases, and 13 billion COVID-19 vaccine doses administered as of April 2023, according to the World Health Organization. An infection with severe acute respiratory syndrome 2 (SARS-CoV-2) can lead an disease, i.e. COVID-19, but also a post-acute (PACS, "long COVID"). Currently, side effects vaccines are increasingly being noted studied. Here, we summarise currently available indications discuss our conclusions that (i) these specific similarities differences PACS, (ii) new term should be used refer (post-COVID-19 vaccination syndrome, PCVS, colloquially "post-COVIDvac-syndrome"), (iii) is need distinguish between (ACVS) (PACVS) - in analogy PACS ("long Moreover, address mixed forms caused by natural SARS-CoV-2 vaccination. We explain why it important for medical diagnosis, care research use terms (PCVS, ACVS PACVS) order avoid confusion misinterpretation underlying causes enable optimal therapy. do not recommend "Post-Vac-Syndrome" imprecise. The article serves current problem "medical gaslighting" relation PCVS raising awareness among professionals supplying appropriate terminology disease.

Язык: Английский

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Pathophysiological, immunological, and inflammatory features of long COVID

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 28, 2024

The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social economic burdens on nations. While most of the attention therapeutic efforts have concentrated acute phase disease, a notable proportion survivors experience persistent symptoms post-infection clearance. This diverse set symptoms, loosely categorized as long COVID, presents potential additional public health crisis. It is estimated that 1 5 exhibit clinical manifestations consistent with COVID. Despite this prevalence, mechanisms pathophysiology COVID remain poorly understood. Alarmingly, evidence suggests cases within condition develop debilitating or disabling symptoms. Hence, urgent priority should be given further studies equip systems for its management. review provides an overview available information emerging condition, focusing affected individuals’ epidemiology, pathophysiological mechanisms, immunological inflammatory profiles.

Язык: Английский

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Long COVID clinical evaluation, research and impact on society: a global expert consensus

Annals of Clinical Microbiology and Antimicrobials, Год журнала: 2025, Номер 24(1)

Опубликована: Апрель 20, 2025

Abstract Background Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation management of patients COVID. More research into the pathology, cellular, molecular mechanisms COVID, treatments needed. The goal this work disseminate essential information about recommendations definition, diagnosis, treatment, social issues physicians, researchers, policy makers address escalating global health crisis. Methods A 3-round modified Delphi consensus methodology was distributed internationally 179 healthcare professionals, persons lived experience in 28 countries. Statements were combined specific areas: research, society. Results survey resulted 187 comprehensive statements reaching strongest areas being diagnosis assessment, general research. We establish conditions different subgroups within umbrella. Clear reached that impacts COVID-19 infection on children should be priority, additionally need determine effects societies economies. it affects nervous system other organs not likely observed initial symptoms. note, biomarkers critically needed these issues. Conclusions This forms guidance spectrum as disease reinforces translational large-scale treatment trials protocols.

Язык: Английский

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The Proteome Content of Blood Clots Observed Under Different Conditions: Successful Role in Predicting Clot Amyloid(ogenicity)

Molecules, Год журнала: 2025, Номер 30(3), С. 668 - 668

Опубликована: Фев. 3, 2025

A recent analysis compared the proteome of (i) blood clots seen in two diseases—sepsis and long COVID—when was known to have clotted into an amyloid microclot form (as judged by staining with fluorogenic stain thioflavin T) (ii) that those non-amyloid considered formed normally. Such fibrinaloid microclots are also relatively resistant fibrinolysis. The proteins contained differed markedly both from soluble typical plasma normal clots, between diseases studied (an acute syndrome sepsis ITU a chronic disease represented Long COVID). Many were low concentration effectively accumulated fibres, whereas many other abundant excluded. found associated tended be themselves amyloidogenic. We here ask inverse question. This is: can clot tell us whether particular observed uniquely (or highly over-represented) relative thus fact nature? answer is affirmative variety major coagulopathies, viz., venous thromboembolism, pulmonary embolism, deep vein thrombosis, various cardiac issues, ischaemic stroke. Galectin-3-binding protein thrombospondin-1 seem especially widely amyloid-type latter has indeed been shown incorporated growing fibrin fibres. These may consequently provide useful biomarkers mechanistic basis.

Язык: 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, Год журнала: 2023, Номер 50(02), С. 288 - 294

Опубликована: Май 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.

Язык: 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, Год журнала: 2023, Номер 24(13), С. 10458 - 10458

Опубликована: Июнь 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.

Язык: Английский

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Role of Endothelium in Cardiovascular Sequelae of Long COVID

Biomedicines, Год журнала: 2023, Номер 11(8), С. 2239 - 2239

Опубликована: Авг. 9, 2023

The global action against coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, shed light on endothelial dysfunction. Although primarily affects the pulmonary system, multiple studies have documented pan-vascular involvement in COVID-19. virus is able to penetrate barrier, damaging it directly or indirectly and causing endotheliitis multi-organ injury. Several mechanisms cooperate development of dysfunction, including cell injury pyroptosis, hyperinflammation cytokine storm syndrome, oxidative stress reduced nitric oxide bioavailability, glycocalyx disruption, hypercoagulability, thrombosis. After acute-phase some patients reported signs symptoms a systemic disorder known as long COVID, which broad range cardiovascular (CV) disorders emerged. To date, exact pathophysiology COVID remains unclear: addition persistence infection mechanisms, specific pathways CV damage been postulated, such persistent viral reservoirs heart an autoimmune response cardiac antigens through molecular mimicry. aim this review provide overview main patterns enduring activation following offer latest summary complications COVID.

Язык: Английский

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Interventions for the management of long covid (post-covid condition): living systematic review

BMJ, Год журнала: 2024, Номер unknown, С. e081318 - e081318

Опубликована: Ноя. 27, 2024

Abstract Objective To compare the effectiveness of interventions for management long covid (post-covid condition). Design Living systematic review. Data sources Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, Cochrane Central Register Controlled Trials from inception to December 2023. Eligibility criteria that randomised adults (≥18 years) with drug or non-drug interventions, placebo sham, usual care. Results 24 trials 3695 patients were eligible. Four (n=708 patients) investigated eight (n=985) physical activity rehabilitation, three (n=314) behavioural, four (n=794) dietary, (n=309) medical devices technologies, one (n=585) a combination exercise mental health rehabilitation. Moderate certainty evidence suggested that, compared care, an online programme cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference −8.4, 95% confidence interval (CI) −13.11 −3.69; Checklist Individual Strength subscale; range 8-56, higher scores indicate greater impairment) improves concentration −5.2, −7.97 −2.43; problems 4-28; impairment). online, supervised, combined rehabilitation leads improvement in overall health, estimated 161 more per 1000 (95% CI 61 292 more) experiencing meaningful recovery, symptoms depression −1.50, −2.41 −0.59; Hospital Anxiety Depression Scale 0-21; impairment), quality life (0.04, 0.00 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; −0.022-1; less intermittent aerobic 3-5 times weekly 4-6 weeks function continuous 3.8, 1.12 6.48; SF-36 component summary score; 0-100; No compelling was found support other including, among others, vortioxetine, leronlimab, probiotics-prebiotics, coenzyme Q10, amygdala insula retraining, L-arginine vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, mobile application providing education on covid. Conclusion suggests CBT improve Systematic review registration Open Science Framework https://osf.io/9h7zm/ . Readers’ note This article is living will be updated reflect emerging evidence. Updates may occur up two years date original publication.

Язык: Английский

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