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

Leukotrienes are important pro-inflammatory lipid mediators derived from the arachidonic
acid metabolism. In particular, cysteinyl leukotrienes, namely 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 a 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 the
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 TFpos-circulating
microvesicles. These data suggest the repurposing of montelukast as a possible
auxiliary treatment for COVID-19 syndrome.