Importance Hypoxemia in COVID-19 pneumonia is dispositive for hospitalization and mechanical ventilation and contributes to mortality. Other than oxygen supplementation, there is no treatment that resolves hypoxemia in COVID-19 pneumonia. Objective COVID-19 pneumonia sustains a massive increase in lipid mediators, especially thromboxane A2 >> PGE2 > PGD2. Thromboxane A2 induces pulmonary venoconstriction, increases pulmonary capillary pressure and contributes to pulmonary edema. High thromboxane A2 metabolite levels are strongly associated with respiratory failure and mortality in hospitalized COVID-19 patients. Ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) is an inexpensive, orally bioavailable, thromboxane A2 receptor antagonist. Ramatroban was administered to patients with COVID-19 pneumonia and hypoxemia to explore the effect of thromboxane A2 antagonism on clinical symptoms and outcomes. Design, Setting, and Participants A retrospective case series comprising 4 consecutive outpatients, 22 to 87 years of age, with COVID-19 pneumonia and hypoxemia treated with ramatroban between April and July 2021 in India. Main Outcomes and Measures The primary outcome measure was blood oxygen saturation using pulse oximetry (SpO2). Secondary outcome measures were respiratory distress and need for hospitalization. Results Four COVID-19 outpatients had developed progressive respiratory distress and hypoxemia. Within 12-36 hours of the first dose of ramatroban, all four patients experienced increase in SpO2 and decrease in respiratory distress, which obviated hospitalization. Continued treatment for 5 days was associated with complete resolution of respiratory distress and hypoxemia. Conclusions and Relevance There is an unmet medical need for drugs that target the hemodynamic, prothrombotic, and maladaptive immune responses that lead to pneumonia and respiratory failure following SARS-CoV-2 infection. As an anti-vasospastic, broncho-relaxant, anti-thrombotic and immunomodulatory agent, ramatroban addresses the fundamental host response mechanisms underlying respiratory and critical organ failure in COVID-19. Ramatroban merits study in randomized clinical trials that might offer hope for a cost-effective pandemic treatment.

COVID-19 associated pneumonia and acute respiratory distress syndrome are characterized by a lipid mediator storm with massive increases in lung and systemic thromboxane A2 >> prostaglandin D2. Thromboxane A2 is a potent vasoconstrictor of pulmonary veins >> arteries, and thereby promotes an increase in pulmonary capillary pressures, transudation of fluid into the alveolar space, pulmonary edema and ARDS. Thromboxane A2 also increases vascular permeability, contracts bronchial smooth muscle, triggers and amplifies platelet activation, and promotes a prothrombotic state. PGD2 promotes a Th2 immune response that is atypical for viral infections and inhibits antiviral defense by suppressing interferon λ expression. D-dimers, urinary 11-dehydro-TxB2, and IL-13, a Th2 cytokine, have emerged as key biomarkers of severity and organ failure in COVID-19. Ramatroban is an orally bioavailable, potent, dual antagonist of the thromboxane A2 (TPr) and PGD2 (DPr2) receptors. We report use of ramatroban in 4 COVID-19 outpatients, 22 to 87 years of age, with acute onset / worsening of respiratory distress and hypoxemia. All four patients experienced decrease in respiratory distress and increase in SpO2, within hours of the first dose and thereby avoided hospitalization. By the 5th day all 4 patients had complete resolution of respiratory distress and hypoxemia. Ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) has an established safety profile, having been indicated in Japan for the treatment of allergic rhinitis for over 20 years. As a broncho-relaxant, anti-vasospastic, anti-thrombotic and immunomodulator, ramatroban addresses the fundamental pathophysiologic mechanisms underlying respiratory and critical organ failure in COVID-19, and therefore merits urgent clinical trials that might impact the ongoing pandemic.

COVID-19 associated pneumonia and acute respiratory distress syndrome are accompanied by a massive and sustained increase in lung and systemic thromboxane (Tx) A2. TxA2 is a short-lived, potent vasoconstrictor of pulmonary veins > arteries, and thereby selectively increases pulmonary venous resistance, promoting an increase in pulmonary capillary pressure. TxA2 also increases vascular permeability which, in the lungs, exaggerates pressure-mediated transudation into the alveolar space, causing pulmonary edema and ARDS. Also relevant to COVID-19 pathophysiology, TxA2 contracts bronchial smooth muscle, triggers and amplifies platelet activation, mediates apoptosis of immature thymocytes, and promotes a procoagulant state, all of which are mediated by TxA2 receptor (TPr) activation. The stable TxA2 metabolite, 11-dehydro-TxB2, is elevated in direct proportion to COVID-19 severity. Though inactive at TPr, 11-dehydro-TxB2 activates PGD2 / DP2 receptors (DPr2) which promote a Th2 immune response that is atypical for viral infections and inhibits antiviral defense by suppressing interferon λ expression. Ramatroban is an orally bioavailable, potent, dual antagonist of TPr and DPr2 receptors. We report use of ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) in 4 COVID-19 outpatients, 22 to 87 years of age, with acute onset / worsening of respiratory distress and hypoxemia. All four patients experienced a decrease in respiratory distress and increase in SpO2, within hours of the first dose of ramatroban and, thereby, avoided hospitalization. By the 5th day all 4 patients had complete resolution of respiratory distress and hypoxemia. Ramatroban has an established safety profile, having been indicated in Japan for the treatment of allergic rhinitis for over 20 years. As an anti-vasospastic, broncho-relaxant, anti-thrombotic and immunomodulator, ramatroban addresses the fundamental host response mechanisms underlying respiratory and critical organ failure in COVID-19, and merits urgent clinical trials that might impact the ongoing pandemic.

COVID-19 associated pneumonia and acute respiratory distress syndrome are characterized by a lipid mediator storm with massive increases in lung and systemic thromboxane A2 >> prostaglandin D2. Thromboxane A2 is a potent vasoconstrictor of pulmonary veins >> arteries, and thereby promotes an increase in pulmonary capillary pressures, transudation of fluid into the alveolar space, pulmonary edema and ARDS. Thromboxane A2 also increases vascular permeability, contracts bronchial smooth muscle, triggers and amplifies platelet activation, and promotes a prothrombotic state. PGD2 promotes a Th2 immune response that is atypical for viral infections and inhibits antiviral defense by suppressing interferon λ expression. D-dimers, urinary 11-dehydro-TxB2, and IL-13, a Th2 cytokine, have emerged as key biomarkers of severity and organ failure in COVID-19. Ramatroban is an orally bioavailable, potent, dual antagonist of the thromboxane A2 (TPr) and PGD2 (DPr2) receptors. We report use of ramatroban in 4 COVID-19 outpatients, 22 to 87 years of age, with acute onset / worsening of respiratory distress and hypoxemia. All four patients experienced decrease in respiratory distress and increase in SpO2, within hours of the first dose and thereby avoided hospitalization. By the 5th day all 4 patients had complete resolution of respiratory distress and hypoxemia. Ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) has an established safety profile, having been indicated in Japan for the treatment of allergic rhinitis for over 20 years. As a broncho-relaxant, anti-vasospastic, anti-thrombotic and immunomodulator, ramatroban addresses the fundamental pathophysiologic mechanisms underlying respiratory and critical organ failure in COVID-19, and therefore merits urgent clinical trials that might impact the ongoing pandemic.

Importance Hypoxemia in COVID-19 pneumonia is dispositive for hospitalization and mechanical ventilation and contributes to mortality. Other than oxygen supplementation, there is no treatment that resolves hypoxemia in COVID-19 pneumonia. Objective COVID-19 pneumonia sustains a massive increase in lipid mediators, especially thromboxane A2 >> PGE2 > PGD2. Thromboxane A2 induces pulmonary venoconstriction, increases pulmonary capillary pressure and contributes to pulmonary edema. High thromboxane A2 metabolite levels are strongly associated with respiratory failure and mortality in hospitalized COVID-19 patients. Ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) is an inexpensive, orally bioavailable, thromboxane A2 receptor antagonist. Ramatroban was administered to patients with COVID-19 pneumonia and hypoxemia to explore the effect of thromboxane A2 antagonism on clinical symptoms and outcomes. Design, Setting, and Participants A retrospective case series comprising 4 consecutive outpatients, 22 to 87 years of age, with COVID-19 pneumonia and hypoxemia treated with ramatroban between April and July 2021 in India. Main Outcomes and Measures The primary outcome measure was blood oxygen saturation using pulse oximetry (SpO2). Secondary outcome measures were respiratory distress and need for hospitalization. Results Four COVID-19 outpatients had developed progressive respiratory distress and hypoxemia. Within 12-36 hours of the first dose of ramatroban, all four patients experienced increase in SpO2 and decrease in respiratory distress, which obviated hospitalization. Continued treatment for 5 days was associated with complete resolution of respiratory distress and hypoxemia. Conclusions and Relevance There is an unmet medical need for drugs that target the hemodynamic, prothrombotic, and maladaptive immune responses that lead to pneumonia and respiratory failure following SARS-CoV-2 infection. As an anti-vasospastic, broncho-relaxant, anti-thrombotic and immunomodulatory agent, ramatroban addresses the fundamental host response mechanisms underlying respiratory and critical organ failure in COVID-19. Ramatroban merits study in randomized clinical trials that might offer hope for a cost-effective pandemic treatment.