BMJ Quality & Safety · 2006 · 1.1K citations · 5 references
Veterinary MedicineInfectious DiseasesPharmacologyClinical PharmacologyGlycobiologyInflammationEndothelial ActivationEndothelial DysfunctionInflammatory MediatorsPlasma ProteinsCreatinine-based BiomarkersEndothelial Glycocalyx FunctionHeparin AnticoagulationHeparin-protein InteractionsInflammation-induced Endothelial DysfunctionLow-molecular-weight Heparin ProphylaxisLow-molecular-weight Heparin TherapyVascular Endothelial Dysfunction
Endothelial dysfunction and loss of glycocalyx integrity, mediated by the enzyme heparanase, contribute to vascular leakage and inflammation in COVID‑19, and low‑molecular‑weight heparins can inhibit heparanase. The study aims to test whether heparanase drives COVID‑19 pathology and whether low‑molecular‑weight heparins can inhibit it, suggesting a therapeutic role. Plasma heparanase activity and heparan sulfate levels were quantified in 10 healthy controls and 48 COVID‑19 patients. COVID‑19 patients showed markedly higher plasma heparanase activity and heparan sulfate, which correlated with disease severity and were lowered by prophylactic LMWH in non‑ICU patients.
<h3>Abstract</h3> Reports suggest a role of endothelial dysfunction and loss of endothelial barrier function in COVID-19. It is well established that the endothelial glycocalyx-degrading enzyme heparanase contributes to vascular leakage and inflammation. Low molecular weight heparins (LMWH) serve as an inhibitor of heparanase. We hypothesize that heparanase contributes to the pathogenesis of COVID-19, and that heparanase may be inhibited by LMWH. Heparanase activity and heparan sulfate levels were measured in plasma of healthy controls (n=10) and COVID-19 patients (n=48). Plasma heparanase activity and heparan sulfate levels were significantly elevated in COVID-19 patients. Heparanase activity associated with disease severity including the need for intensive care and mechanical ventilation, lactate dehydrogenase levels and creatinine levels. Use of prophylactic LMWH in non-ICU patients was associated with a reduced heparanase activity. Since there is no other clinically applied heparanase inhibitor currently available, therapeutic treatment of COVID-19 patients with low molecular weight heparins should be explored.
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