Montelukast inhibits platelet activation induced by plasma from COVID-19 patients

Leukotrienes are important proinflammatory lipid mediators derived from the arachidonic acid metabolism. In particular, cysteinyl leukotrienes, LTC₄, LTD₄ and LTE₄, are involved in many of the principal features of asthma, while more recently they have also been implicated in cardiovascular diseases. COVID-19 is characterized by an overwhelming state of inflammation, sometimes resulting in an acute respiratory distress syndrome. Furthermore, severe COVID-19 patients present an endothelial cell damage characterized by an hyperinflammatory/procoagulant state and a widespread thrombotic disease. Leukotriene receptor antagonists, such as montelukast, have long been proven to have an efficacy in asthma, while more recently they have been suggested to have a protective role also in cardiovascular diseases. As elevated levels of LTE₄ have been detected in bronchoalveolar lavage of COVID-19 patients, and montelukast, in addition to its anti-inflammatory properties, has been suggested to have a protective role in cardiovascular diseases, we decided to investigate whether this drug could also affect platelet activation characteristic of COVID-19 syndrome. In this contribution we demonstrate that montelukast inhibits platelet activation induced by plasma from COVID-19 patients by preventing the surface expression of tissue factor (TF) and P-selectin, reducing the formation of circulating monocyte- and granulocyte-platelet aggregates, and, finally, in completely inhibiting the release of TF^pos circulating microvescicles. These data suggest the use of montelukast as a possible innovative treatment for COVID-19 syndrome.