Plasma small extracellular vesicles (SEVs) from critically ill patients with COVID-19 are enriched in ultra-large VWF multimers, mostly of endothelial origin, enhance platelet adhesion and thrombus formation under arterial shear, and promote endothelial activation, suggesting VWF-positive SEVs may contribute to the prothrombotic milieu and serve as biomarkers of disease severity.
SEVs from critically ill patients with COVID-19 markedly enhanced platelet adhesion and thrombus formation under arterial shear conditions.
SEVs from patients with severe COVID-19 promoted endothelial activation, shown by increased release of ICAM-1 and VCAM-1.
SEVs from patients with COVID-19 were highly enriched in ultra-large VWF multimers, with significantly elevated high-to-low molecular weight VWF ratios compared with controls.
Circulating SEVs derived from leukocytes, platelets, and endothelial cells were increased in severe COVID-19.
VWF-positive SEVs predominantly originated from endothelial cells.
Enrichment of VWF-SEVs was independent of gender and diabetes status, suggesting a primary association with disease severity.
The authors conclude that SEVs rich in endothelial-derived VWF are associated with platelet activation and may contribute to the prothrombotic milieu in COVID-19, and may be biomarkers of severity.
This study looked at tiny membrane-bound particles called small extracellular vesicles that cells release into the blood. The researchers collected them from hospitalized COVID-19 patients and tested how they affect blood clotting. Particles from critically ill patients made platelets stick more and form more clots under conditions that mimic blood flow in arteries. They also caused blood vessel lining cells to release more inflammatory adhesion molecules (ICAM-1 and VCAM-1). The particles from severely ill patients carried large amounts of ultra-large von Willebrand factor (VWF), a sticky protein that helps platelets attach to vessel walls. Most of the VWF-carrying particles came from endothelial cells, which line blood vessels. Levels of particles from white blood cells, platelets, and endothelial cells were all higher in severe disease. The VWF enrichment did not depend on gender or diabetes, pointing toward disease severity as the main factor. This research suggests that VWF-carrying vesicles may help drive the abnormal clotting seen in severe COVID-19 and could someday serve as markers of how sick a patient is. The findings show an association rather than proof of cause, and further studies are needed before any clinical use.
Chen L, Mahajan A, Kumar Ram A, Chalise P, Zhang Q, Dong H, et al.. (2026). Characterization of von Willebrand factor-enriched extracellular vesicles and their association with platelet adhesion in COVID-19.. American journal of physiology. Cell physiology. https://doi.org/10.1152/ajpcell.00374.2026