UCLA

Introduction

In COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB₂ ≫ PGE₂ > PGD₂ in the lungs, and 11-dehydro-TxB₂, a TxA₂ metabolite, in the systemic circulation. While TxA₂ stimulates thromboxane prostanoid (TP) receptors, 11-dehydro-TxB₂ is a full agonist of DP2 (formerly known as the CRTh2) receptors for PGD₂. Anecdotal experience of using ramatroban, a dual receptor antagonist of the TxA₂/TP and PGD₂/DP2 receptors, demonstrated rapid symptomatic relief from acute respiratory distress and hypoxemia while avoiding hospitalization.

Areas covered

Evidence supporting the role of TxA₂/TP receptors and PGD₂/DP2 receptors in causing rapidly progressive lung injury associated with hypoxemia, a maladaptive immune response and thromboinflammation is discussed. An innovative perspective on the dual antagonism of TxA₂/TP and PGD₂/DP2 receptor signaling as a therapeutic approach in COVID-19 is presented. This paper examines ramatroban an anti-platelet, immunomodulator, and antifibrotic agent for acute and long-haul COVID-19.

Expert opinion

Ramatroban, a dual blocker of TP and DP2 receptors, has demonstrated efficacy in animal models of respiratory dysfunction, atherosclerosis, thrombosis, and sepsis, as well as preliminary evidence for rapid relief from dyspnea and hypoxemia in COVID-19 pneumonia. Ramatroban merits investigation as a promising antithrombotic and immunomodulatory agent for chemoprophylaxis and treatment.