* orotracheal intubation or ecmo support * active solid / hematologic cancer (including invasive non-melanoma skin cancer) * hypersensitivity or contra-indications to one of the investigational agents (including history of deep vein thrombosis / pulmonary thromboembolism within 12 weeks prior to screening) * other active concurrent viral, fungal or bacterial infections (including active tuberculosis/latent tb treated for less than 4 weeks, hiv and hcv/hbv infections) * pregnancy/breastfeeding * incapability to provide a valid informed consent (including age \< 18 years old) * heart failure with nyha \>= 2 or any acute cardiac or vascular event requiring therapy in the previous 12 months * chronic renal failure (baseline gfr \< 45 ml/min\*1.73m2) * liver cirrhosis moderate / severe (child-pugh b or c) * chronic respiratory failure requiring o2 therapy or ventilation therapy at home * blood neutrophils \<1000/mcl, platelet \<50000/mcl, hb levels \<80 g/l * alt/ast \> 5 times unl * use of any biologic agent or small molecule inhibitor and other investigational drugs in the previous 4 weeks or 5 half-lives (whichever is longer). specific cut-offs for wash-out are required for the following therapies: * b-cell targeted therapies: 24 weeks or 5 half-lives (whichever is longer) * tnf-inhibitors: 2 weeks or 5 half-lives (whichever is longer) * jak-inhibitors: 1 week or 5 half-lives (whichever is longer) * use of other immunosuppressive agents in the last 3 months (chronic use of topical steroids and systemic steroids with a dose ≤5 mg of prednisone equivalents is allowed) * use of any other investigational therapy for covid-19 (including iv immunoglobulins, convalescent covid-19 plasma or monoclonal antibodies) * impossibility to discontinue strong inhibitors of oat3 (such as probenecid) at study entry * any other condition judged by the local investigator as a contra-indication to eligibility * subjects who have received live vaccines within 4 weeks before the study or are planned to receive live vaccine in the first months after study enrolment.

* orotracheal intubation or ecmo support * active solid / hematologic cancer (including invasive non-melanoma skin cancer) * hypersensitivity or contra-indications to one of the investigational agents (including history of deep vein thrombosis / pulmonary thromboembolism within 12 weeks prior to screening) * other active concurrent viral, fungal or bacterial infections (including active tuberculosis/latent tb treated for less than 4 weeks, hiv and hcv/hbv infections) * pregnancy/breastfeeding * incapability to provide a valid informed consent (including age \< 18 years old) * heart failure with nyha \>= 2 or any acute cardiac or vascular event requiring therapy in the previous 12 months * chronic renal failure (baseline gfr \< 45 ml/min\*1.73m2) * liver cirrhosis moderate / severe (child-pugh b or c) * chronic respiratory failure requiring o2 therapy or ventilation therapy at home * blood neutrophils \<1000/mcl, platelet \<50000/mcl, hb levels \<80 g/l * alt/ast \> 5 times unl * use of any biologic agent or small molecule inhibitor and other investigational drugs in the previous 4 weeks or 5 half-lives (whichever is longer). specific cut-offs for wash-out are required for the following therapies: * b-cell targeted therapies: 24 weeks or 5 half-lives (whichever is longer) * tnf-inhibitors: 2 weeks or 5 half-lives (whichever is longer) * jak-inhibitors: 1 week or 5 half-lives (whichever is longer) * use of other immunosuppressive agents in the last 3 months (chronic use of topical steroids and systemic steroids with a dose ≤5 mg of prednisone equivalents is allowed) * use of any other investigational therapy for covid-19 (including iv immunoglobulins, convalescent covid-19 plasma or monoclonal antibodies) * impossibility to discontinue strong inhibitors of oat3 (such as probenecid) at study entry * any other condition judged by the local investigator as a contra-indication to eligibility * subjects who have received live vaccines within 4 weeks before the study or are planned to receive live vaccine in the first months after study enrolment.

- orotracheal intubation or ecmo support - active solid / hematologic cancer (including invasive non-melanoma skin cancer) - hypersensitivity or contra-indications to one of the investigational agents (including history of deep vein thrombosis / pulmonary thromboembolism within 12 weeks prior to screening) - other active concurrent viral, fungal or bacterial infections (including active tuberculosis/latent tb treated for less than 4 weeks, hiv and hcv/hbv infections) - pregnancy/breastfeeding - incapability to provide a valid informed consent (including age < 18 years old) - heart failure with nyha >= 2 or any acute cardiac or vascular event requiring therapy in the previous 12 months - chronic renal failure (baseline gfr < 45 ml/min*1.73m2) - liver cirrhosis moderate / severe (child-pugh b or c) - chronic respiratory failure requiring o2 therapy or ventilation therapy at home - blood neutrophils <1000/mcl, platelet <50000/mcl, hb levels <80 g/l - alt/ast > 5 times unl - use of any biologic agent or small molecule inhibitor and other investigational drugs in the previous 4 weeks or 5 half-lives (whichever is longer). specific cut-offs for wash-out are required for the following therapies: - b-cell targeted therapies: 24 weeks or 5 half-lives (whichever is longer) - tnf-inhibitors: 2 weeks or 5 half-lives (whichever is longer) - jak-inhibitors: 1 week or 5 half-lives (whichever is longer) - use of other immunosuppressive agents in the last 3 months (chronic use of topical steroids and systemic steroids with a dose ≤5 mg of prednisone equivalents is allowed) - use of any other investigational therapy for covid-19 (including iv immunoglobulins, convalescent covid-19 plasma or monoclonal antibodies) - impossibility to discontinue strong inhibitors of oat3 (such as probenecid) at study entry - any other condition judged by the local investigator as a contra-indication to eligibility - subjects who have received live vaccines within 4 weeks before the study or are planned to receive live vaccine in the first months after study enrolment.

- orotracheal intubation or ecmo support - active solid / hematologic cancer (including invasive non-melanoma skin cancer) - hypersensitivity or contra-indications to one of the investigational agents (including history of deep vein thrombosis / pulmonary thromboembolism within 12 weeks prior to screening) - other active concurrent viral, fungal or bacterial infections (including active tuberculosis/latent tb treated for less than 4 weeks, hiv and hcv/hbv infections) - pregnancy/breastfeeding - incapability to provide a valid informed consent (including age < 18 years old) - heart failure with nyha >= 2 or any acute cardiac or vascular event requiring therapy in the previous 12 months - chronic renal failure (baseline gfr < 45 ml/min*1.73m2) - liver cirrhosis moderate / severe (child-pugh b or c) - chronic respiratory failure requiring o2 therapy or ventilation therapy at home - blood neutrophils <1000/mcl, platelet <50000/mcl, hb levels <80 g/l - alt/ast > 5 times unl - use of any biologic agent or small molecule inhibitor and other investigational drugs in the previous 4 weeks or 5 half-lives (whichever is longer). specific cut-offs for wash-out are required for the following therapies: - b-cell targeted therapies: 24 weeks or 5 half-lives (whichever is longer) - tnf-inhibitors: 2 weeks or 5 half-lives (whichever is longer) - jak-inhibitors: 1 week or 5 half-lives (whichever is longer) - use of other immunosuppressive agents in the last 3 months (chronic use of topical steroids and systemic steroids with a dose ≤5 mg of prednisone equivalents is allowed) - use of any other investigational therapy for covid-19 (including iv immunoglobulins, convalescent covid-19 plasma or monoclonal antibodies) - impossibility to discontinue strong inhibitors of oat3 (such as probenecid) at study entry - any other condition judged by the local investigator as a contra-indication to eligibility - subjects who have received live vaccines within 4 weeks before the study or are planned to receive live vaccine in the first months after study enrolment.