Acute respiratory distress syndrome (ARDS) in patients with Coronavirus disease 19 (COVID-19) is associated with an unusually high incidence of pulmonary embolism (PE) and microthrombotic disease, with evidence for reduced fibrinolysis. We describes even patients requiring invasive ventilation for COVID-19 ARDS with pulmonary thromboembolic disease, pulmonary hypertension ± severe right ventricular (RV) dysfunction on echocardiography, who were treated with alteplaseas fibrinolytic therapy. All patients were non-smokers, 6 (86%) were male and median age was 56.7 (50-64) years. They had failed approaches including therapeutic anticoagulation, prone ventilation (n=4), inhaled nitric oxide (n=5) and nebulised epoprostenol (n=2). The median duration of mechanical ventilation prior to thrombolysis was 7 (5-11) days.Systemic alteplase was administered to 6 patients (50mg or 90mg bolus over 120 minutes) at 16 (10-22) days after symptom onset. All received therapeutic heparin pre-and post-thrombolysis, without intracranial haemorrhageor other major bleeding. Alteplase improvedPaO2/FiO2(PF) ratio (from 97.0 (86.3-118.6) to 135.6 (100.7-171.4), p=0.03) and ventilatory ratio (from 2.76 (2.09 -3.49) to 2.36 (1.82 –3.05), p=0.011) at twenty-four hours.Echocardiographic parameters at 2 (1-3) days (n=6) showed RVSP was 63 (50.3-75) then 57 (49-66) mmHgpost-thrombolysis (p=0.26), TAPSE was unchanged (from 18.3 (11.9-24.5) to 20.5 (15.4-24.2) mm, p=0.56)and RV fractional area change (from 15.4 (11.1-35.6) to 31.2 (16.4-33.1) %, p=0.09). At7 (1-13) days after thrombolysis,using DECT imaging(n=3),average relative peripheral lung enhancement increased from 12.6 to 21.6% (p=0.06).Conclusion:Thrombolysis improved PF ratio and ventilatory ratio at 24h as rescue therapy in patients with RV dysfunction due to COVID-19 ARDS despite maximum therapy, as part of a multimodal approach, and requires further study.