AUTHOR=Buijsers Baranca , Yanginlar Cansu , de Nooijer Aline , Grondman Inge , Maciej-Hulme Marissa L. , Jonkman Inge , Janssen Nico A. F. , Rother Nils , de Graaf Mark , Pickkers Peter , Kox Matthijs , Joosten Leo A. B. , Nijenhuis Tom , Netea Mihai G. , Hilbrands Luuk , van de Veerdonk Frank L. , Duivenvoorden Raphaël , de Mast Quirijn , van der Vlag Johan TITLE=Increased Plasma Heparanase Activity in COVID-19 Patients JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.575047 DOI=10.3389/fimmu.2020.575047 ISSN=1664-3224 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. To test this hypothesis, 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 was associated with disease severity including the need for intensive care, 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.