{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Barrett CD"],"funding":["NHLBI NIH HHS"],"pagination":["e12669"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8935535"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(2)"],"pubmed_abstract":["<h4>Background</h4>Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure.<h4>Methods</h4>A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO<sub>2</sub>/FiO<sub>2</sub> ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis.<h4>Results</h4>tPA was associated with significant PaO<sub>2</sub>/FiO<sub>2</sub> improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term <i>p </i>< 0.00). tPA administration was also associated with improved National Early Warning Score 2 scores at 24, 48, and 72 h after receiving tPA (interaction term <i>p </i>= 0.00). D-dimer was significantly elevated immediately after tPA, consistent with lysis of formed clot. Patients with declining respiratory status preceding tPA administration had more marked improvement in PaO<sub>2</sub>/FiO<sub>2</sub> ratios than those who had poor but stable (not declining) respiratory status. There was one intracranial hemorrhage, which occurred within 24 h following tPA administration.<h4>Conclusions</h4>These data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population."],"journal":["Research and practice in thrombosis and haemostasis"],"pubmed_title":["MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID-19 severe respiratory failure (MUST COVID): A retrospective cohort study."],"pmcid":["PMC8935535"],"funding_grant_id":["R00 HL151887"],"pubmed_authors":["Barrett CD","Shaefi S","Wright FL","Yaffe MB","Yacoub M","Moore EE","Jhunjhunwala R","Banner-Goodspeed V","Wang J","Ramdeo R","Hajizadeh N","Capers K","Nemec H","Moore HB","Hussain S","Moore PK","Nonnemacher C","Baedorf-Kassis EN","Sauaia A","Moraco A","Bull T","McIntyre R","Hattar L","Talmor DS","Benjamin Christie D","Espinal A","Rajcooar N","Orfanos S","Anez-Bustillos L","Guevara A","Thomas Buchanan J","Al-Shammaa A"],"additional_accession":[]},"is_claimable":false,"name":"MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID-19 severe respiratory failure (MUST COVID): A retrospective cohort study.","description":"<h4>Background</h4>Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure.<h4>Methods</h4>A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO<sub>2</sub>/FiO<sub>2</sub> ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis.<h4>Results</h4>tPA was associated with significant PaO<sub>2</sub>/FiO<sub>2</sub> improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term <i>p </i>< 0.00). tPA administration was also associated with improved National Early Warning Score 2 scores at 24, 48, and 72 h after receiving tPA (interaction term <i>p </i>= 0.00). D-dimer was significantly elevated immediately after tPA, consistent with lysis of formed clot. Patients with declining respiratory status preceding tPA administration had more marked improvement in PaO<sub>2</sub>/FiO<sub>2</sub> ratios than those who had poor but stable (not declining) respiratory status. There was one intracranial hemorrhage, which occurred within 24 h following tPA administration.<h4>Conclusions</h4>These data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2026-04-08T17:23:24.314Z","creation":"2025-04-19T22:38:23.173Z"},"accession":"S-EPMC8935535","cross_references":{"pubmed":["35341072"],"doi":["10.1002/rth2.12669"]}}