Horizons of Heparin Therapy in COVID-19 and Pandemic-Related Diseases

Abstract

The disease caused by the coronavirus SARS-CoV-2, named COVID-19, has been spread around the world at a high transmission rate. It was initially considered to be an acute respiratory distress syndrome. Recent clinical data has highlighted that COVID-19 is characterized by a vascular dysfunction and thrombosis, which are not typical for many other acute respiratory diseases. Thrombotic complications are markers of severe COVID-19 and are associated with multiple organ failure and increased mortality. The application of unfractionated and/or low-molecular-weight heparins as anticoagulant medications, significantly reduced the severity of the disease and COVID-19-induced mortality, since heparin is a multifunctional agent. The goal of this review is to summarize the literature data on the pathogenic mechanisms of SARS-CoV-2 and to characterize the properties of heparin, which allow inhibiting these mechanisms at any stage of pathogenesis. We proposed a vicious circle hypothesis of SARS-CoV-2 pathogenesis, as well as an original approach to low-dose heparin therapy beyond its anticoagulant properties. The analysis of a wide range of effects and mechanisms of action of heparin will help create an idea of current possibilities and future potential of applying this drug.

Keywords: COVID-19; coagulopathy; complexing; endothelial glycocalyx; heparin; inflammatory response syndrome; post-traumatic stress disorder.

Fig. 1.

SARS-CoV-2 binds to the surface of endothelial cells via the host receptors. Heparin blocks the receptor-binding domain of the virus.

Fig. 2.

SARS-CoV-2 thrombogenic action and antithrombogenic heparin effects. ROS—reactive oxygen species, SOD—superoxide dismutase, dotted lines—inhibition, solid lines—activation, —proinflammatory cells.

Fig. 3.

Changes in the blood coagulation system in COVID-19. ROS—Reactive oxygen species.