medRxiv · 2020 · 17 citations · 42 references
Veterinary MedicineBiochemistryInfectious DiseasesGlycobiologyHemostasisInflammationEndothelial ActivationEndothelial DysfunctionInflammatory MediatorsPlasma ProteinsEndothelial Glycocalyx FunctionHeparan Sulfate DegradationHeparin AnticoagulationHeparin-mediated AnticoagulationHeparin-protein InteractionsLow-molecular-weight Heparin ProphylaxisLow-molecular-weight Heparin TherapyVascular Endothelial Dysfunction
Abstract 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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