PRE-VENT Study in Hospitalized Patients With Severe COVID-19 With or Without Cancer

Inclusion Criteria: 1. Hospitalized or will be hospitalized prior to randomization for the treatment of severe COVID-19 with SARS-CoV-2 infection confirmed by either a) a positive reverse transcriptase polymerase chain reaction (RT PCR) or b) an antigen-based test from any respiratory, nasopharyngeal, saliva, blood, or stool specimen at Screening or documented within 1 week prior to the start of Screening (Severe COVID-19 is defined as confirmed disease in patients who are hospitalized with hypoxia \[SpO2 ≤93% on room air\], respiratory rate \>30, PaO2/FiO2 \<300, but do not require IMV). 2. Age ≥ 18 years 3. Platelet count ≥ 50,000/µL 4. If fertile, willing to use effective birth control methods during the study 5. Provision of informed consent within 96 hours after hospitalization Exclusion Criteria: 1. In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments 2. Currently intubated or intubated between screening and randomization 3. Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID 19) 4. Prior allogenic hematopoietic stem cell transplantation 5. Active lung cancer or history of lung cancer within the past 12 months 6. Any active grade 2 or higher hemorrhage 7. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication 8. Uncontrolled intercurrent illness that, in the judgment of the treating physician, would limit compliance with study requirements 9. Known seropositivity for human immunodeficiency virus with cluster of differentiation 4 (CD4) count \< 200/mm3 within 3 months prior to randomization 10. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination 11. Concurrent enrollment in another interventional trial (investigational COVID-19 antiviral studies are permitted) 12. Serum creatinine \> 2.5 mg/dL 13. Total bilirubin \> 4× the upper limit of normal 14. QT corrected by the Fridericia method (QTcF) prolongation \> 480 msec 15. Known history of New York Heart Association Class II, III, or IV congestive heart failure prior to hospital admission 16. Known allergic reaction to any Janus kinase 2 (JAK2) inhibitor 17. Exposure to any JAK2 inhibitor within 28 days 18. Currently receiving a strong CYP3A4 inhibitor or strong P450 inducer (Appendix 1 and Appendix 2, respectively) and unable to stop the medication prior to the first dose of study drug and throughout the duration of study drug administration 19. Treatment with cytoreductive chemotherapy administered within 14 days prior to randomization 20. Administration of an IL 1 or IL 6 blocking immunomodulatory agent (such as tocilizumab, canakinumab, sarilumab, anakinra) within 48 hours prior to randomization 21. Currently receiving therapeutic anticoagulation or anti platelet medication and unable to stop the medication prior to randomization. Prophylactic anticoagulation therapy or aspirin (≤ 100mg) are permitted. 22. Unable to ingest capsules or tablets at randomization