Acute massive or high-risk pulmonary embolism (PE), described as a lung arteries occlusion by an embolus, causes a significant compromise of hemodynamic stability and could lead to a lethal event. Systemic fibrinolytic therapy has been accepted as the standard reperfusion therapy in massive PE, except when there is an increased risk of bleeding. Catheter-based mechanical strategies (thrombofragmentation, thromboaspiration with catheter-guided thrombolysis) are described as options when there are absolute contraindications to systemic thrombolysis. We briefly reviewed clinical situations when patients with severe pneumonia due to COVID-19 are complicated by a high-risk saddle pulmonary embolism and underwent repeated pharmacomechanical thrombolysis and high-flow oxygen therapy. There are scarce reports of failed catheter-guided pharmacomechanical thrombolysis in patients with PE secondary to COVID-19. Re-administration of systemic thrombolysis and alteplase (15 mg dose) can show favorable results.