Exploring Hypercoagulability in Post-COVID Syndrome (PCS): An Attempt at Unraveling the Endothelial Dysfunction

Background: The lingering effects of SARS-CoV-2 infection, collectively known as post-COVID syndrome (PCS), affect a significant proportion of recovered patients, manifesting as persistent symptoms like fatigue, cognitive dysfunction, and exercise intolerance. Increasing evidence suggests that endothelial dysfunction and coagulation abnormalities play a central role in PCS pathophysiology. This study investigates hypercoagulability and endothelial dysfunction in PCS through thrombin generation and the von Willebrand factor (VWF)/ADAMTS13 axis. Methods: Plasma samples from 97 PCS patients recruited since October 2020 by the clinical research unit of the Brugmann University Hospital were analyzed. A thrombin generation test was performed on a St-Genesia^® analyzer (Stago) using the Thromboscreen kit; VWF antigen was determined on a CS-2500 analyzer (Siemens); and ADAMTS-13 activity was determined using an ELISA kit (Technozym^®) on an ElX808 plate reader. Results: Thrombin generation testing revealed elevated thrombin production in PCS patients, particularly when thrombomodulin was included. Although most PCS patients showed normalized VWF/ADAMTS13 ratios, 11.3% exhibited elevated ratios (≥1.5), associated with advanced age. Conclusions: Patients with PCS show a consistent pattern of prolonged thrombo-inflammatory dysregulation, highlighted by elevated in vitro thrombin generation and the persistence of abnormal VWF/ADAMTS-13 ratios in a subset of patients.