patients with ards or patients requiring mechanical ventilation at screening or randomisation. in the opinion of the investigator, the patient is unlikely to survive the following 7 days after randomisation due to a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock. patients who are unconscious or considered by the investigator unable to consent. other severe co-morbidity with life expectancy ≤3 months according to the investigator's assessment. critically ill patients who have an apache ii score ≥30. concomitant severe bacterial infection including blood stream infections, endocarditis, osteomyelitis, retroperitoneal abscess, septic arthritis, or meningitis diagnosed within 7 days prior to randomisation (bacterial pulmonary infection that may complicate covid-19 is not an exclusion criterion). any of the following signs of severe sepsis: shock or profound hypotension defined as systolic blood pressure ≤90 mm hg or a decrease of ≥40 mm hg from the value obtained during screening that is not responsive to fluid challenge. hypothermia (core temperature ≤ 35.6°c). disseminated intravascular coagulation (dic) as evidenced by pt, ptt 2 × upper limit of normal (uln), or platelets ≤ 50% of the lower limit of normal (lln). history of positive test for human immunodeficiency virus (hiv) including all patients currently on highly active antiretroviral therapy (haart) regardless of the cd4+ cell count. presence of immunodeficiency or an immunocompromised condition including neutropenia, haematologic malignancy, history of haematopoietic stem cell transplant, history of solid organ transplant, receiving immunosuppressive therapy and long term use of systemic corticosteroids. severe hepatic impairment at screening, as evidenced by alanine aminotransferase (alt) or aspartate aminotransferase (ast) ≥3 × uln or total bilirubin ≥2 × uln (except in case of known gilbert syndrome), or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy). acute hepatitis, cirrhosis (any child-pugh class), acute hepatic failure or acute decompensation of chronic hepatic failure. alkaline phosphatase ≥3.0 × uln. patients with values ≥3.0 × uln and ≤5.0 × uln are eligible if this value is documented to be acute and directly related to the infectious process being treated. severe renal impairment (creatinine-clearance ≤30 ml/min) or end-stage renal disease (esrd) requiring haemodialysis or peritoneal dialysis, according to cockcroft-gault. uncontrolled hypertension. uncontrolled thyroid function. history of known or suspected clostridium difficile infection. history of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures). acute co-morbidity within 7 days before inclusion such as myocardial infarction. a female who is pregnant or breastfeeding. documented hypersensitivity reaction or anaphylaxis to alisporivir, one of the non-active ingredients or any of the soc medications. receipt of any investigational medication in the 3 months prior to screening. anticipated transfer to another hospital that is not a study site during the first 4 days of treatment. patients previously treated with antivirals, immunomodulators (mabs in the 3 months prior to screening) and other medicines prohibited in this study in the 14 days prior to randomisation. ongoing or recent use of any other medication (including over the counter medication and herbal products) within 14 days before randomisation or within 5 drug half-lives of that medication (whichever is longer) that are known inhibitors/inducers of cytochrome p450 3a or p-glycoprotein (p-gp), or inhibitors of organic anion transporting polypeptides (oatps), multi resistance protein 2 (mrp2) or bile salt export pump (bsep). known need of concomitant treatment with the following medications during treatment with alisporivir and 14 days after the end of treatment: known inhibitors/inducers of cytochrome p450 3a or p-gp, or inhibitors of oatps, mrp2 or bsep; drugs with narrow therapeutic index that are known sensitive substrates of cytochrome p450 3a, or substrates of p-gp, oatps, mrp2 or bsep. any other condition or prior therapy, which, in the opinion of the investigator, would make the patient unsuitable for this study. patients with history of pancreatic disease. patients under legal protection. prisoners. patients participating in another interventional study.

patients with ards or patients requiring mechanical ventilation at screening or randomisation. in the opinion of the investigator, the patient is unlikely to survive the following 7 days after randomisation due to a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock. patients who are unconscious or considered by the investigator unable to consent. other severe co-morbidity with life expectancy ≤3 months according to the investigator's assessment. critically ill patients who have an apache ii score ≥30. concomitant severe bacterial infection including blood stream infections, endocarditis, osteomyelitis, retroperitoneal abscess, septic arthritis, or meningitis diagnosed within 7 days prior to randomisation (bacterial pulmonary infection that may complicate covid-19 is not an exclusion criterion). any of the following signs of severe sepsis: shock or profound hypotension defined as systolic blood pressure ≤90 mm hg or a decrease of ≥40 mm hg from the value obtained during screening that is not responsive to fluid challenge. hypothermia (core temperature ≤ 35.6°c). disseminated intravascular coagulation (dic) as evidenced by pt, ptt 2 × upper limit of normal (uln), or platelets ≤ 50% of the lower limit of normal (lln). history of positive test for human immunodeficiency virus (hiv) including all patients currently on highly active antiretroviral therapy (haart) regardless of the cd4+ cell count. presence of immunodeficiency or an immunocompromised condition including neutropenia, haematologic malignancy, history of haematopoietic stem cell transplant, history of solid organ transplant, receiving immunosuppressive therapy and long term use of systemic corticosteroids. severe hepatic impairment at screening, as evidenced by alanine aminotransferase (alt) or aspartate aminotransferase (ast) ≥3 × uln or total bilirubin ≥2 × uln (except in case of known gilbert syndrome), or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy). acute hepatitis, cirrhosis (any child-pugh class), acute hepatic failure or acute decompensation of chronic hepatic failure. alkaline phosphatase ≥3.0 × uln. patients with values ≥3.0 × uln and ≤5.0 × uln are eligible if this value is documented to be acute and directly related to the infectious process being treated. severe renal impairment (creatinine-clearance ≤30 ml/min) or end-stage renal disease (esrd) requiring haemodialysis or peritoneal dialysis, according to cockcroft-gault. uncontrolled hypertension. uncontrolled thyroid function. history of known or suspected clostridium difficile infection. history of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures). acute co-morbidity within 7 days before inclusion such as myocardial infarction. a female who is pregnant or breastfeeding. documented hypersensitivity reaction or anaphylaxis to alisporivir, one of the non-active ingredients or any of the soc medications. receipt of any investigational medication in the 3 months prior to screening. anticipated transfer to another hospital that is not a study site during the first 4 days of treatment. patients previously treated with antivirals, immunomodulators (mabs in the 3 months prior to screening) and other medicines prohibited in this study in the 14 days prior to randomisation. ongoing or recent use of any other medication (including over the counter medication and herbal products) within 14 days before randomisation or within 5 drug half-lives of that medication (whichever is longer) that are known inhibitors/inducers of cytochrome p450 3a or p-glycoprotein (p-gp), or inhibitors of organic anion transporting polypeptides (oatps), multi resistance protein 2 (mrp2) or bile salt export pump (bsep). known need of concomitant treatment with the following medications during treatment with alisporivir and 14 days after the end of treatment: known inhibitors/inducers of cytochrome p450 3a or p-gp, or inhibitors of oatps, mrp2 or bsep; drugs with narrow therapeutic index that are known sensitive substrates of cytochrome p450 3a, or substrates of p-gp, oatps, mrp2 or bsep. any other condition or prior therapy, which, in the opinion of the investigator, would make the patient unsuitable for this study. patients with history of pancreatic disease. patients under legal protection. prisoners. patients participating in another interventional study.

1. patients with ards or patients requiring mechanical ventilation at screening or randomisation. 2. in the opinion of the investigator, the patient is unlikely to survive the following 7 days after randomisation due to a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock. 3. patients who are unconscious or considered by the investigator unable to consent. 4. other severe co-morbidity with life expectancy ≤3 months according to the investigator's assessment. 5. critically ill patients who have an apache ii score ≥30. 6. concomitant severe bacterial infection including blood stream infections, endocarditis, osteomyelitis, retroperitoneal abscess, septic arthritis, or meningitis diagnosed within 7 days prior to randomisation (bacterial pulmonary infection that may complicate covid-19 is not an exclusion criterion). 7. any of the following signs of severe sepsis: 1. shock or profound hypotension defined as systolic blood pressure ≤90 mm hg or a decrease of ≥40 mm hg from the value obtained during screening that is not responsive to fluid challenge. 2. hypothermia (core temperature ≤ 35.6°c). 3. disseminated intravascular coagulation (dic) as evidenced by pt, ptt 2 × upper limit of normal (uln), or platelets ≤ 50% of the lower limit of normal (lln). 8. history of positive test for human immunodeficiency virus (hiv) including all patients currently on highly active antiretroviral therapy (haart) regardless of the cd4+ cell count. 9. presence of immunodeficiency or an immunocompromised condition including neutropenia, haematologic malignancy, history of haematopoietic stem cell transplant, history of solid organ transplant, receiving immunosuppressive therapy and long term use of systemic corticosteroids. 10. severe hepatic impairment at screening, as evidenced by alanine aminotransferase (alt) or aspartate aminotransferase (ast) ≥3 × uln or total bilirubin ≥2 × uln (except in case of known gilbert syndrome), or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy). 11. acute hepatitis, cirrhosis (any child-pugh class), acute hepatic failure or acute decompensation of chronic hepatic failure. 12. alkaline phosphatase ≥3.0 × uln. patients with values ≥3.0 × uln and ≤5.0 × uln are eligible if this value is documented to be acute and directly related to the infectious process being treated. 13. severe renal impairment (creatinine-clearance ≤30 ml/min) or end-stage renal disease (esrd) requiring haemodialysis or peritoneal dialysis, according to cockcroft-gault. 14. uncontrolled hypertension. 15. uncontrolled thyroid function. 16. history of known or suspected clostridium difficile infection. 17. history of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures). 18. acute co-morbidity within 7 days before inclusion such as myocardial infarction. 19. a female who is pregnant or breastfeeding. 20. documented hypersensitivity reaction or anaphylaxis to alisporivir, one of the non-active ingredients or any of the soc medications. 21. receipt of any investigational medication in the 3 months prior to screening. 22. anticipated transfer to another hospital that is not a study site during the first 4 days of treatment. 23. patients previously treated with antivirals, immunomodulators (mabs in the 3 months prior to screening) and other medicines prohibited in this study in the 14 days prior to randomisation. 24. ongoing or recent use of any other medication (including over the counter medication and herbal products) within 14 days before randomisation or within 5 drug half-lives of that medication (whichever is longer) that are known inhibitors/inducers of cytochrome p450 3a or p-glycoprotein (p-gp), or inhibitors of organic anion transporting polypeptides (oatps), multi resistance protein 2 (mrp2) or bile salt export pump (bsep). known need of concomitant treatment with the following medications during treatment with alisporivir and 14 days after the end of treatment: 1. known inhibitors/inducers of cytochrome p450 3a or p-gp, or inhibitors of oatps, mrp2 or bsep; 2. drugs with narrow therapeutic index that are known sensitive substrates of cytochrome p450 3a, or substrates of p-gp, oatps, mrp2 or bsep. 25. any other condition or prior therapy, which, in the opinion of the investigator, would make the patient unsuitable for this study. 26. patients with history of pancreatic disease. 27. patients under legal protection. 28. prisoners. 29. patients participating in another interventional study.

1. patients with ards or patients requiring mechanical ventilation at screening or randomisation. 2. in the opinion of the investigator, the patient is unlikely to survive the following 7 days after randomisation due to a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock. 3. patients who are unconscious or considered by the investigator unable to consent. 4. other severe co-morbidity with life expectancy ≤3 months according to the investigator's assessment. 5. critically ill patients who have an apache ii score ≥30. 6. concomitant severe bacterial infection including blood stream infections, endocarditis, osteomyelitis, retroperitoneal abscess, septic arthritis, or meningitis diagnosed within 7 days prior to randomisation (bacterial pulmonary infection that may complicate covid-19 is not an exclusion criterion). 7. any of the following signs of severe sepsis: 1. shock or profound hypotension defined as systolic blood pressure ≤90 mm hg or a decrease of ≥40 mm hg from the value obtained during screening that is not responsive to fluid challenge. 2. hypothermia (core temperature ≤ 35.6°c). 3. disseminated intravascular coagulation (dic) as evidenced by pt, ptt 2 × upper limit of normal (uln), or platelets ≤ 50% of the lower limit of normal (lln). 8. history of positive test for human immunodeficiency virus (hiv) including all patients currently on highly active antiretroviral therapy (haart) regardless of the cd4+ cell count. 9. presence of immunodeficiency or an immunocompromised condition including neutropenia, haematologic malignancy, history of haematopoietic stem cell transplant, history of solid organ transplant, receiving immunosuppressive therapy and long term use of systemic corticosteroids. 10. severe hepatic impairment at screening, as evidenced by alanine aminotransferase (alt) or aspartate aminotransferase (ast) ≥3 × uln or total bilirubin ≥2 × uln (except in case of known gilbert syndrome), or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy). 11. acute hepatitis, cirrhosis (any child-pugh class), acute hepatic failure or acute decompensation of chronic hepatic failure. 12. alkaline phosphatase ≥3.0 × uln. patients with values ≥3.0 × uln and ≤5.0 × uln are eligible if this value is documented to be acute and directly related to the infectious process being treated. 13. severe renal impairment (creatinine-clearance ≤30 ml/min) or end-stage renal disease (esrd) requiring haemodialysis or peritoneal dialysis, according to cockcroft-gault. 14. uncontrolled hypertension. 15. uncontrolled thyroid function. 16. history of known or suspected clostridium difficile infection. 17. history of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures). 18. acute co-morbidity within 7 days before inclusion such as myocardial infarction. 19. a female who is pregnant or breastfeeding. 20. documented hypersensitivity reaction or anaphylaxis to alisporivir, one of the non-active ingredients or any of the soc medications. 21. receipt of any investigational medication in the 3 months prior to screening. 22. anticipated transfer to another hospital that is not a study site during the first 4 days of treatment. 23. patients previously treated with antivirals, immunomodulators (mabs in the 3 months prior to screening) and other medicines prohibited in this study in the 14 days prior to randomisation. 24. ongoing or recent use of any other medication (including over the counter medication and herbal products) within 14 days before randomisation or within 5 drug half-lives of that medication (whichever is longer) that are known inhibitors/inducers of cytochrome p450 3a or p-glycoprotein (p-gp), or inhibitors of organic anion transporting polypeptides (oatps), multi resistance protein 2 (mrp2) or bile salt export pump (bsep). known need of concomitant treatment with the following medications during treatment with alisporivir and 14 days after the end of treatment: 1. known inhibitors/inducers of cytochrome p450 3a or p-gp, or inhibitors of oatps, mrp2 or bsep; 2. drugs with narrow therapeutic index that are known sensitive substrates of cytochrome p450 3a, or substrates of p-gp, oatps, mrp2 or bsep. 25. any other condition or prior therapy, which, in the opinion of the investigator, would make the patient unsuitable for this study. 26. patients with history of pancreatic disease. 27. patients under legal protection. 28. prisoners. 29. patients participating in another interventional study.