AUTHOR=Ogletree Martin L. , Chander Chiang Kate , Kulshrestha Rashmi , Agarwal Aditya , Agarwal Ashutosh , Gupta Ajay TITLE=Treatment of COVID-19 Pneumonia and Acute Respiratory Distress With Ramatroban, a Thromboxane A2 and Prostaglandin D2 Receptor Antagonist: A Four-Patient Case Series Report JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.904020 DOI=10.3389/fphar.2022.904020 ISSN=1663-9812 ABSTRACT=

Hypoxemia in COVID-19 pneumonia is associated with hospitalization, mechanical ventilation, and mortality. COVID-19 patients exhibit marked increases in fatty acid levels and inflammatory lipid mediators, predominantly arachidonic acid metabolites, notably thromboxane B2 >> prostaglandin E2 > prostaglandin D2. Thromboxane A2 increases pulmonary capillary pressure and microvascular permeability, leading to pulmonary edema, and causes bronchoconstriction contributing to ventilation/perfusion mismatch. Prostaglandin D2-stimulated IL-13 production is associated with respiratory failure, possibly due to hyaluronan accumulation in the lungs. Ramatroban is an orally bioavailable, dual thromboxane A2/TP and prostaglandin D2/DP2 receptor antagonist used in Japan for allergic rhinitis. Four consecutive outpatients with COVID-19 pneumonia treated with ramatroban exhibited rapid relief of dyspnea and hypoxemia within 12–36 h and complete resolution over 5 days, thereby avoiding hospitalization. Therefore, ramatroban as an antivasospastic, broncho-relaxant, antithrombotic, and immunomodulatory agent merits study in randomized clinical trials that might offer hope for a cost-effective pandemic treatment.