Cited 82 times since 2020 (23 per year) source: EuropePMC Frontiers in immunology, Volume 11, 6 1 2020, Pages 575047 Increased Plasma Heparanase Activity in COVID-19 Patients. Buijsers B, Yanginlar C, de Nooijer A, Grondman I, Maciej-Hulme ML, Jonkman I, Janssen NAF, Rother N, de Graaf M, Pickkers P, Kox M, Joosten LAB, Nijenhuis T, Netea MG, Hilbrands L, van de Veerdonk FL, Duivenvoorden R, de Mast Q, van der Vlag J

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.

Front Immunol. 2020 10;11:575047