Study To antagOnize Plasminogen Activator Inhibitor-1 in Severe COVID-19

Inclusion Criteria:

1. Adults ≥65 years old or < 65 years old AND at least one major cardiometabolic comorbidity (diabetes, hypertension, or cardiovascular disease)
2. Established diagnosis of COVID-19 as evidenced by a positive nasopharyngeal or bronchoalveolar lavage viral PCR for SARS-CoV2
3. Requiring supplemental oxygen

Exclusion Criteria:

1. Age <18 years old

2. Pregnancy or breast-feeding

3. Known contraindication to tissue plasminogen activator (tPA), including

   1. Active internal bleeding
   2. History of cerebrovascular accident
   3. Recent intracranial or intraspinal surgery or trauma
   4. Intracranial neoplasm, arteriovenous malformation or aneurysm
   5. Known bleeding diathesis
   6. Severe uncontrolled hypertension (SBP>200 persistently >12 hours)

4. Currently receiving therapeutic dose anticoagulation (specifically will exclude those with potential drug-drug interaction such as heparin, apixaban, warfarin)

5. Platelets <50,000

6. Hematocrit <30%

7. Not hemodynamically stable in the preceding 4 hours (symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements)

8. Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary care physician could interfere with the conduct of the study including outcome assessment

9. Other patient characteristics (not thought to be related to COVID-19) that portend a very poor prognosis (e.g., severe liver failure, metastatic malignancy)

10. Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Patients in observational, natural history or epidemiological studies not involving an intervention are eligible.

11. Participant's responsible attending physician believes it is not appropriate for participant to participate in the study.

12. Inability or unwillingness to provide written informed consent

13. Involvement in the planning and/or conduct of the study

14. Previous randomization in the present study

15. Unable to complete study procedures.

16. Patients with active venothromboembolic disease

17. Patients who are receiving other investigational agents for COVID-19.