ArticleJournal of thrombosis and haemostasis : JTH2021
Persistent endotheliopathy in the pathogenesis of long COVID syndrome.
Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05668039 (Enhanced External Counterpulsation), which is not on this map. Cited by 209 papers, 6 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Enhanced External Counterpulsation (EECP/ECPT) to Treat Long-COVID-19 Fatigue - a Randomized Controlled Trial
Who cites it
209 citing papers in PubMed, 6 syntheses or guidelines pooled it, 327 citations in OpenAlex.
- The immunopathological spectrum of COVID-19: from cytokine storm to autoimmunity-a systematic review.Frontiers in medicine · 2026Pooled it
- Vascular Complications of Long COVID-From Endothelial Dysfunction to Systemic Thrombosis: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review.International journal of environmental research and public health · 2024Pooled it
- Endotheliopathy in Acute COVID-19 and Long COVID.International journal of molecular sciences · 2023Pooled it
- Biomarkers in long COVID-19: A systematic review.Frontiers in medicine · 2023Pooled it
- Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis.Thrombosis research · 2022Pooled it
- Acupressure and Qigong in post-infectious fatigue with impaired physical function: a randomized clinical trial.Frontiers in medicine · 2026Trial
- Brief Outpatient Rehabilitation Program for Post-COVID-19 Condition: A Randomized Clinical Trial.JAMA network open · 2024Trial
- Trial
- Pulmonary Dysfunction after Pediatric COVID-19.Radiology · 2023Trial
- Long COVID-19 in Spain: A Phenomenological Exploration of Health, Support, and Systemic Challenges.Healthcare (Basel, Switzerland) · 2026Article
- Long-term angiogenic and thromboinflammatory signatures in post-COVID-19 syndrome.Angiogenesis · 2026Article
- Retinal microvascular alterations consistent with endothelial dysregulation in paediatric post-COVID-19 syndrome: A prospective matched-cohort study.Scientific reports · 2026Article
- Understanding the long-term neurological effects of SARS-CoV-2 infection.Nature reviews. Neurology · 2026Review
- Endothelial dysfunction and metabolic biomarkers in post-COVID-19 syndrome.Scientific reports · 2026Article
- Clinical relevance of circulating blood microaggregates and reactivation of Epstein Barr Virus in long-term Post-CoVID syndrome patients.Scientific reports · 2026Article
- Algorithm dependence of patient phenotypes in Long COVID: a patient-led, multi-method clustering of 6031 patients using 162 self-reported symptoms.Oxford open immunology · 2026Article
- Commentary: Internal medicine at the crossroads of long COVID diagnosis and management.Frontiers in medicine · 2026Article
- Unraveling the cardiovascular burden of long COVID: symptom profiles, underlying mechanisms, and clinical management insights.Frontiers in cardiovascular medicine · 2026Review
- CD169Frontiers in cellular and infection microbiology · 2026Article
149 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPersistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this "long COVID" syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID-19.
objectivesTo assess whether endothelial cell activation may be sustained in convalescent COVID-19 patients and contribute to long COVID pathogenesis. PATIENTS AND
methodsFifty patients were reviewed at a median of 68 days following SARS-CoV-2 infection. In addition to clinical workup, acute phase markers, endothelial cell (EC) activation and NETosis parameters and thrombin generation were assessed.
resultsThrombin generation assays revealed significantly shorter lag times (p < .0001, 95% CI -2.57 to -1.02 min), increased endogenous thrombin potential (p = .04, 95% CI 15-416 nM/min), and peak thrombin (p < .0001, 95% CI 39-93 nM) in convalescent COVID-19 patients. These prothrombotic changes were independent of ongoing acute phase response or active NETosis. Importantly, EC biomarkers including von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID-19 compared with controls (p = .004, 95% CI 0.09-0.57 IU/ml; p = .009, 95% CI 0.06-0.5 IU/ml; p = .04, 95% CI 0.03-0.44 IU/ml, respectively). In addition, plasma soluble thrombomodulin levels were significantly elevated in convalescent COVID-19 (p = .02, 95% CI 0.01-2.7 ng/ml). Sustained endotheliopathy was more frequent in older, comorbid patients, and those requiring hospitalization. Finally, both plasma VWF:Ag and VWFpp levels correlated inversely with 6-min walk tests.
conclusionsCollectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID-19 and raise the intriguing possibility that this may contribute to long COVID pathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.