Adaptive COVID-19 Treatment Trial 2 (ACTT-2)

Exclusion Criteria

• •1. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) \> 5 times the upper limit of normal.
• •2. Estimated glomerular filtration rate (eGFR) \< 30 ml/min or patient is receiving hemodialysis or hemofiltration at time of screening.
• •3. Neutropenia (absolute neutrophil count \<1000 cells/microliter) (\<1.0 x 103/microliter or \<1.0 GI/L).
• •4. Lymphopenia (absolute lymphocyte count \<200 cells/microliter) (\<0.20 x 103/microliter or \<0.20 GI/L)
• •5. Pregnancy or breast feeding.
• •6. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.
• •7. Allergy to any study medication.
• •8. Received three or more doses of remdesivir, including the loading dose, outside of the study under the EUA (or similar mechanism) for COVID-19.
• •9. Received convalescent plasma or intravenous immunoglobulin \[IVIg\]) for COVID-19, the current illness for which they are being enrolled.
• •10. Received small molecule tyrosine kinase inhibitors (e.g. baricitinib, imatibib, genfinitib), in the 1 week prior to screening
• •11. Received monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 \[IL-1\], anti-IL-6 \[tocilizumab or sarilumab\]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening.
• •12. Received monoclonal antibodies targeting B-cell (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
• •13. Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with baricitinib is larger than the risk of COVID-19.
• •14. Received \>/= 20 mg/day of prednisone or equivalent for \>/=14 consecutive days in the 4 weeks prior to screening.
• •15. Use of probenecid that cannot be discontinued at study enrollment.
• •16. Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
• •17. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.
• •18. Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects.
• •19. Have a history of VTE (deep vein thrombosis \[DVT\] or pulmonary embolism \[PE\]) within 12 weeks prior to screening or have a history of recurrent (\>1) VTE (DVT/PE).
• •20. Immunocompromised patients, patients with a chronic medical condition, or those taking a medication that cannot be discontinued at enrollment, who, in the judgment of PI, are at increased risk for serious infections or other safety concerns given the study products.