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Background. Fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT) rapidly improves hemodynamic parameters and reverses right ventricular dysfunction caused by acute pulmonary embolism (PE). The effectiveness of USAT for acute PE associated with coronavirus disease 2019 (COVID-19) is unknown. Methods and results. The study population of this cohort study consisted of 36 patients with an intermediate-high- or high-risk acute PE treated with a fixed low-dose USAT protocol (r-tPA 10–20 mg/15 h). Of these, 9 patients tested positive for COVID-19 and were age–sex-matched to 27 patients without COVID-19. The USAT protocol included, beyond the infusion of recombinant tissue plasminogen activator, anti-Xa-activity-adjusted unfractionated heparin therapy (target 0.3–0.7 U/mL). The study outcomes were the invasively measured mean pulmonary arterial pressure (mPAP) before and at completion of USAT, and the National Early Warning Score (NEWS), according to which more points indicate more severe hemodynamic impairment. Twenty-four (66.7%) patients were men; the mean age was 67 ± 14 years. Mean  ±  standard deviation mPAP decreased from 32.3 ± 8.3 to 22.4 ± 7.0 mmHg among COVID-19 patients and from 35.4 ± 9.7 to 24.6 ± 7.0 mmHg among unexposed, with no difference in the relative improvement between groups (p = 0.84). Within 12 h of USAT start, the median NEWS decreased from six (Q1–Q3: 4–8) to three (Q1–Q3: 2–4) points among COVID-19 patients and from four (Q1–Q3: 2–6) to two (Q1–Q3: 2–3) points among unexposed (p = 0.29). One COVID-19 patient died due to COVID-19-related complications 14 days after acute PE. No major bleeding events occurred. Conclusions. Among patients with COVID-19-associated acute PE, mPAP rapidly decreased during USAT with a concomitant progressive improvement of the NEWS. The magnitude of mPAP reduction was similar in patients with and without COVID-19.

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