ArticleJCI insight2021
COVID-19 generates hyaluronan fragments that directly induce endothelial barrier dysfunction.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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.
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Who cites it
58 citing papers in PubMed, 86 citations in OpenAlex.
- The hyaluronan receptor CD44 drives COVID-19 severity through its regulation of neutrophil migration.PLoS pathogens · 2026Article
- The bone marrow niche and hematopoietic system are distinctly remodeled by CD45-targeted astatine-211 radioimmunotherapy.Blood advances · 2026Article
- Immune-endothelial-coagulation crosstalk as a driver of multi-organ dysfunction in severe viral pneumonia.Frontiers in immunology · 2026Review
- A nomogram for predicting ARDS progression and need for invasive ventilation in COVID-19 patients using plasma hyaluronic acid and clinical scores.Frontiers in cellular and infection microbiology · 2026Article
- Advancing understanding of long COVID pathophysiology through quantum walk-based network analysis.Bioinformatics advances · 2026Article
- Glycocalyx at the host-virus interface: a double-edged sword in virus infection and tissue damage.Frontiers in molecular biosciences · 2026Review
- Article
- The predictive value of hyaluronic acid for the severity and prognosis of COVID-19: a retrospective multicenter cohort study.Annals of medicine · 2025Article
- The hyaluronan receptor CD44 drives COVID-19 severity through its regulation of neutrophil migration.bioRxiv : the preprint server for biology · 2025Article
- Musculoskeletal Complications in COVID-19: Exploring the Role of Key Biomarkers.International journal of molecular sciences · 2025Review
- Hyaluronan Accumulates in Inflamed Lymph Nodes and Promotes B-Cell Activation.Proteoglycan research · 2025Article
- Platelet Hyaluronan Synthase 3 Regulates Thrombin Signaling and Adhesion to Fibrinogen Under Venous Shear.Proteoglycan research · 2025Article
- Associations between urinary glycosaminoglycans and onset of acute respiratory distress syndrome in sepsis patients: a prospective exploratory study.Scientific reports · 2025Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Thromboembolic Events in the Era of COVID-19: A Detailed Narrative Review.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2025Review
- Article
- Article
- Chemical modification of hyaluronan oligosaccharides differentially modulates hyaluronan-hyaladherin interactions.The Journal of biological chemistry · 2024Article
- Protecting the endothelial glycocalyx in COVID-19.PLoS pathogens · 2024Article
- Targeted Analysis of the Size Distribution of Heavy Chain-Modified Hyaluronan with Solid-State Nanopores.Analytical chemistry · 2024Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Vascular injury has emerged as a complication contributing to morbidity in coronavirus disease 2019 (COVID-19). The glycosaminoglycan hyaluronan (HA) is a major component of the glycocalyx, a protective layer of glycoconjugates that lines the vascular lumen and regulates key endothelial cell functions. During critical illness, as in the case of sepsis, enzymes degrade the glycocalyx, releasing fragments with pathologic activities into circulation and thereby exacerbating disease. Here, we analyzed levels of circulating glycosaminoglycans in 46 patients with COVID-19 ranging from moderate to severe clinical severity and measured activities of corresponding degradative enzymes. This report provides evidence that the glycocalyx becomes significantly damaged in patients with COVID-19 and corresponds with severity of disease. Circulating HA fragments and hyaluronidase, 2 signatures of glycocalyx injury, strongly associate with sequential organ failure assessment scores and with increased inflammatory cytokine levels in patients with COVID-19. Pulmonary microvascular endothelial cells exposed to COVID-19 milieu show dysregulated HA biosynthesis and degradation, leading to production of pathological HA fragments that are released into circulation. Finally, we show that HA fragments present at high levels in COVID-19 patient plasma can directly induce endothelial barrier dysfunction in a ROCK- and CD44-dependent manner, indicating a role for HA in the vascular pathology of COVID-19.
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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.