Frontiers in Immunology (Oct 2020)

Increased Plasma Heparanase Activity in COVID-19 Patients

  • Baranca Buijsers,
  • Cansu Yanginlar,
  • Aline de Nooijer,
  • Inge Grondman,
  • Marissa L. Maciej-Hulme,
  • Inge Jonkman,
  • Nico A. F. Janssen,
  • Nils Rother,
  • Mark de Graaf,
  • Peter Pickkers,
  • Peter Pickkers,
  • Matthijs Kox,
  • Matthijs Kox,
  • Leo A. B. Joosten,
  • Tom Nijenhuis,
  • Mihai G. Netea,
  • Mihai G. Netea,
  • Luuk Hilbrands,
  • Frank L. van de Veerdonk,
  • Raphaël Duivenvoorden,
  • Raphaël Duivenvoorden,
  • Quirijn de Mast,
  • Johan van der Vlag

DOI
https://doi.org/10.3389/fimmu.2020.575047
Journal volume & issue
Vol. 11

Abstract

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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.

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