A Study in Patients With COVID-19 and Respiratory Distress Not Requiring Mechanical Ventilation, to Compare Standard-of-care With Anakinra and Tocilizumab Treatment The Immunomodulation-CoV Assessment (ImmCoVA) Study

1. Pregnancy or breast feeding.

2. Ongoing or completed mechanical ventilation.

3. In the opinion of the investigator, unlikely to survive for \>48 hours from screening.

4. In the opinion of the investigator, expected overall survival due to other comorbidities less than 3 months.

5. Severe renal dysfunction eGFR \< 30 ml/min.

6. Medical history including chronic liver disease with inflammation, fibrosis or cirrhosis including underlying diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, chronic viral hepatitis, alcoholic liver disease, autoimmune liver disease, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cholangitis, or carcinoma.

7. Uncontrolled hypertension Systolic BP \>180 mm Hg, Diastolic BP \> 110 mm Hg.

8. History of hypersensitivity to the study drugs

9. Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 2 x 109/L, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN), platelets \<100 x 109/L

10. Treatment with anakinra, anti-IL 6, anti-IL-6R antagonists, Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period

11. Current treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents

12. Use of chronic oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 10 mg or equivalent per day. Ongoing acute treatment for COVID-19 with any peroral or iv steroid is permitted for up to five days before inclusion. Chronic or acute treatment with inhaled steroids is also permitted

13. History of, or current autoimmune or inflammatory systemic or localized disease(s) other than rheumatoid arthritis

14. Acute systemic infection; verified by blood cultures systemic bacterial infection, systemic fungi-infection or prosthesis-related infection

15. History of stem-cell or solid organ transplantation

16. Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections

17. Diagnosis of, or suspicion of HIV infection, acute hepatitis A and/or chronic hepatitis B and/or C

18. Previous history of gastrointestinal ulceration or diverticulitis.

19. Patients who have received immunosuppressive antibody therapy within the past 3 months, including intravenous immunoglobulin or plans to receive during the study period

20. Participation in any clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit. The use of remdesivir is permitted.

21. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study

What this study is about