Phase II 1. Oxygenation index at time of enrollment (PaO2 / FiO2) < 100 or > 250 in supine position 2. Intubated > 48h at time point of enrollment 3. Patients who demonstrate an improvement in past 24h prior to enrollment in oxygenation and ventilation / support parameters which indicate an expected resolution of lung dysfunction in the next 24h without additional intervention according to judgment of the investigator with one or more of the following parameters present: 4. Improvement in oxygenation index of > 30% relative to previous measure (last 24h in supine position) 5. Extubation if intubated before 6. Known history of chronic obstructive pulmonary disease (COPD) (GOLD category C or D) 7. Known history of chronic dialysis OR received renal replacement therapy in past 14 days 8. Received new other biologic treatment attempt for COVID-19 in the past 14 days 9. Received treatment with a viral replication inhibitor in past 3 days 10. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 11. Known pregnancy 12. Received organ or bone marrow transplantation in past 3 months 13. Known mechanically resuscitation in past 14 days 14. Patient moribund or expected to die in next 12h according to the judgment of the investigator 15. Patients otherwise considered restricted from receiving full supportive care (including ICU support) 16. Existing diagnosis of progressed cancer or other life-limiting disease with life expectancy < 6 months 17. Known to have received anti-cancer therapy for oncological disease in past 4 weeks 18. Known severe congestive heart failure (New York Heart Association [NYHA] Class III-IV, see Appendix 8) Phase III 1. Intubated > 48h at time point of randomization 2. Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator 3. Known history of chronic dialysis OR received renal replacement therapy in past 14 days OR anticipated to receive renal replacement therapy within 24h after randomization 4. Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months 5. Treatment of COVID-19 with investigational antibody treatment(s) which are not approved or not included in locally adopted treatment guidelines (e.g., WHO guidance, National Institutes of Health [NIH] COVID-19 treatment guidelines) for this indication in the past 7 days (Note: Antibody treatment[s] given within past 7 days for pre-existing diseases, other than COVID-19, are allowed.) 6. At time point of randomization, treatment of COVID-19 with investigational treatments which are not approved or not included in locally adopted treatment guidelines for this indication (e.g., WHO guidance, NIH COVID-19 treatment guidelines), including SARS-CoV-2 multiplication inhibitor(s) or immunomodulator(s). (Note: If a locally adopted treatment guideline recommends drugs such as remdesivir, dexamethasone, or anticoagulation, this would be allowed. Adopted guidelines and updates must be documented at study initiation and throughout the conduct of the study.) 7. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 8. Serum or urine pregnancy test positive before randomization (required for women of childbearing potential) 9. Received organ or bone marrow transplantation in past 3 months 10. Known cardio-pulmonary mechanical resuscitation in past 14 days 11. Received cytokine adsorption therapy in past 3 days 12. Patient moribund or expected to die in next 24h according to the judgment of the investigator 13. Known to have received anti-cancer therapy for hemato-oncological disease in past 4 weeks OR known to have active malignant disease at time point of randomization 14. Known severe congestive heart failure (NYHA Class III-IV, see Appendix 8) 15. Known history of chronic liver disease (Child-Pugh B or C, see Appendix 9) 16. Participating in or has participated in other investigational interventional studies (drug or device) within the last 7 days before randomization

Phase II 1. Oxygenation index at time of enrollment (PaO2 / FiO2) < 100 or > 250 in supine position 2. Intubated > 48h at time point of enrollment 3. Patients who demonstrate an improvement in past 24h prior to enrollment in oxygenation and ventilation / support parameters which indicate an expected resolution of lung dysfunction in the next 24h without additional intervention according to judgment of the investigator with one or more of the following parameters present: 4. Improvement in oxygenation index of > 30% relative to previous measure (last 24h in supine position) 5. Extubation if intubated before 6. Known history of chronic obstructive pulmonary disease (COPD) (GOLD category C or D) 7. Known history of chronic dialysis OR received renal replacement therapy in past 14 days 8. Received new other biologic treatment attempt for COVID-19 in the past 14 days 9. Received treatment with a viral replication inhibitor in past 3 days 10. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 11. Known pregnancy 12. Received organ or bone marrow transplantation in past 3 months 13. Known mechanically resuscitation in past 14 days 14. Patient moribund or expected to die in next 12h according to the judgment of the investigator 15. Patients otherwise considered restricted from receiving full supportive care (including ICU support) 16. Existing diagnosis of progressed cancer or other life-limiting disease with life expectancy < 6 months 17. Known to have received anti-cancer therapy for oncological disease in past 4 weeks 18. Known severe congestive heart failure (New York Heart Association [NYHA] Class III-IV, see Appendix 8) Phase III 1. Intubated > 48h at time point of randomization 2. Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator 3. Known history of chronic dialysis OR received renal replacement therapy in past 14 days OR anticipated to receive renal replacement therapy within 24h after randomization 4. Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months 5. Treatment of COVID-19 with investigational antibody treatment(s) which are not approved or not included in locally adopted treatment guidelines (e.g., WHO guidance, National Institutes of Health [NIH] COVID-19 treatment guidelines) for this indication in the past 7 days (Note: Antibody treatment[s] given within past 7 days for pre-existing diseases, other than COVID-19, are allowed.) 6. At time point of randomization, treatment of COVID-19 with investigational treatments which are not approved or not included in locally adopted treatment guidelines for this indication (e.g., WHO guidance, NIH COVID-19 treatment guidelines), including SARS-CoV-2 multiplication inhibitor(s) or immunomodulator(s). (Note: If a locally adopted treatment guideline recommends drugs such as remdesivir, dexamethasone, or anticoagulation, this would be allowed. Adopted guidelines and updates must be documented at study initiation and throughout the conduct of the study.) 7. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 8. Serum or urine pregnancy test positive before randomization (required for women of childbearing potential) 9. Received organ or bone marrow transplantation in past 3 months 10. Known cardio-pulmonary mechanical resuscitation in past 14 days 11. Received cytokine adsorption therapy in past 3 days 12. Patient moribund or expected to die in next 24h according to the judgment of the investigator 13. Known to have received anti-cancer therapy for hemato-oncological disease in past 4 weeks OR known to have active malignant disease at time point of randomization 14. Known severe congestive heart failure (NYHA Class III-IV, see Appendix 8) 15. Known history of chronic liver disease (Child-Pugh B or C, see Appendix 9) 16. Participating in or has participated in other investigational interventional studies (drug or device) within the last 7 days before randomization

Phase II 1. Oxygenation index at time of enrollment (PaO2 / FiO2) < 100 or > 250 in supine position 2. Intubated > 48h at time point of enrollment 3. Patients who demonstrate an improvement in past 24h prior to enrollment in oxygenation and ventilation / support parameters which indicate an expected resolution of lung dysfunction in the next 24h without additional intervention according to judgment of the investigator with one or more of the following parameters present: 4. Improvement in oxygenation index of > 30% relative to previous measure (last 24h in supine position) 5. Extubation if intubated before 6. Known history of chronic obstructive pulmonary disease (COPD) (GOLD category C or D) 7. Known history of chronic dialysis OR received renal replacement therapy in past 14 days 8. Received new other biologic treatment attempt for COVID-19 in the past 14 days 9. Received treatment with a viral replication inhibitor in past 3 days 10. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 11. Known pregnancy 12. Received organ or bone marrow transplantation in past 3 months 13. Known mechanically resuscitation in past 14 days 14. Patient moribund or expected to die in next 12h according to the judgment of the investigator 15. Patients otherwise considered restricted from receiving full supportive care (including ICU support) 16. Existing diagnosis of progressed cancer or other life-limiting disease with life expectancy < 6 months 17. Known to have received anti-cancer therapy for oncological disease in past 4 weeks 18. Known severe congestive heart failure (New York Heart Association [NYHA] Class III-IV, see Appendix 8) Phase III 1. Intubated > 48h at time point of first IMP randomization 2. Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator 3. Known history of chronic dialysis OR received renal replacement therapy in past 14 days OR anticipated to receive renal replacement therapy within 24h after randomization 4. Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months 5. Treatment of COVID-19 with investigational antibody treatment(s) which are not approved or not included in locally adopted treatment guidelines (e.g., WHO guidance, National Institutes of Health [NIH] COVID-19 treatment guidelines) for this indication in the past 7 days (Note: Antibody treatment[s] given within past 7 days for pre-existing diseases, other than COVID-19, are allowed.) 6. At time point of randomization, treatment of COVID-19 with investigational treatments which are not approved or not included in locally adopted treatment guidelines for this indication (e.g., WHO guidance, NIH COVID-19 treatment guidelines), including SARS-CoV-2 multiplication inhibitor(s) or immunomodulator(s). (Note: If a locally adopted treatment guideline recommends drugs such as remdesivir, dexamethasone, or anticoagulation, this would be allowed. Adopted guidelines and updates must be documented at study initiation and throughout the conduct of the study.) 7. Received cytokine adsorption therapy in past 3 days 8. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 9. Serum or urine pregnancy test positive before randomization (required for women of childbearing potential) 10. Received organ or bone marrow transplantation in past 3 months 11. Known cardio-pulmonary mechanical resuscitation in past 14 days 12. Patient moribund or expected to die in next 24h according to the judgment of the investigator 13. Known to have received anti-cancer therapy for hemato-oncological disease in past 4 weeks OR known to have active malignant disease at time point of randomization 14. Known severe congestive heart failure (corresponding to e.g. NYHA Class III-IV, left ventricular ejection fraction <40%, see Appendix 8) 15. Known history of chronic liver disease (Child-Pugh B or C, see Appendix 11) 16. Participating in or has participated in other investigational interventional studies (drug or device) within the last 7 days before randomization

Phase II 1. Oxygenation index at time of enrollment (PaO2 / FiO2) < 100 or > 250 in supine position 2. Intubated > 48h at time point of enrollment 3. Patients who demonstrate an improvement in past 24h prior to enrollment in oxygenation and ventilation / support parameters which indicate an expected resolution of lung dysfunction in the next 24h without additional intervention according to judgment of the investigator with one or more of the following parameters present: 4. Improvement in oxygenation index of > 30% relative to previous measure (last 24h in supine position) 5. Extubation if intubated before 6. Known history of chronic obstructive pulmonary disease (COPD) (GOLD category C or D) 7. Known history of chronic dialysis OR received renal replacement therapy in past 14 days 8. Received new other biologic treatment attempt for COVID-19 in the past 14 days 9. Received treatment with a viral replication inhibitor in past 3 days 10. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 11. Known pregnancy 12. Received organ or bone marrow transplantation in past 3 months 13. Known mechanically resuscitation in past 14 days 14. Patient moribund or expected to die in next 12h according to the judgment of the investigator 15. Patients otherwise considered restricted from receiving full supportive care (including ICU support) 16. Existing diagnosis of progressed cancer or other life-limiting disease with life expectancy < 6 months 17. Known to have received anti-cancer therapy for oncological disease in past 4 weeks 18. Known severe congestive heart failure (New York Heart Association [NYHA] Class III-IV, see Appendix 8) Phase III 1. Intubated > 48h at time point of first IMP randomization 2. Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator 3. Known history of chronic dialysis OR received renal replacement therapy in past 14 days OR anticipated to receive renal replacement therapy within 24h after randomization 4. Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months 5. Treatment of COVID-19 with investigational antibody treatment(s) which are not approved or not included in locally adopted treatment guidelines (e.g., WHO guidance, National Institutes of Health [NIH] COVID-19 treatment guidelines) for this indication in the past 7 days (Note: Antibody treatment[s] given within past 7 days for pre-existing diseases, other than COVID-19, are allowed.) 6. At time point of randomization, treatment of COVID-19 with investigational treatments which are not approved or not included in locally adopted treatment guidelines for this indication (e.g., WHO guidance, NIH COVID-19 treatment guidelines), including SARS-CoV-2 multiplication inhibitor(s) or immunomodulator(s). (Note: If a locally adopted treatment guideline recommends drugs such as remdesivir, dexamethasone, or anticoagulation, this would be allowed. Adopted guidelines and updates must be documented at study initiation and throughout the conduct of the study.) 7. Received cytokine adsorption therapy in past 3 days 8. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 9. Serum or urine pregnancy test positive before randomization (required for women of childbearing potential) 10. Received organ or bone marrow transplantation in past 3 months 11. Known cardio-pulmonary mechanical resuscitation in past 14 days 12. Patient moribund or expected to die in next 24h according to the judgment of the investigator 13. Known to have received anti-cancer therapy for hemato-oncological disease in past 4 weeks OR known to have active malignant disease at time point of randomization 14. Known severe congestive heart failure (corresponding to e.g. NYHA Class III-IV, left ventricular ejection fraction <40%, see Appendix 8) 15. Known history of chronic liver disease (Child-Pugh B or C, see Appendix 11) 16. Participating in or has participated in other investigational interventional studies (drug or device) within the last 7 days before randomization

Phase II 1. Oxygenation index at time of enrollment (PaO2 / FiO2) < 100 or > 250 in supine position 2. Intubated > 48h at time point of enrollment 3. Patients who demonstrate an improvement in past 24h prior to enrollment in oxygenation and ventilation / support parameters which indicate an expected resolution of lung dysfunction in the next 24h without additional intervention according to judgment of the investigator with one or more of the following parameters present: 4. Improvement in oxygenation index of > 30% relative to previous measure (last 24h in supine position) 5. Extubation if intubated before 6. Known history of chronic obstructive pulmonary disease (COPD) (GOLD category C or D) 7. Known history of chronic dialysis OR received renal replacement therapy in past 14 days 8. Received new other biologic treatment attempt for COVID-19 in the past 14 days 9. Received treatment with a viral replication inhibitor in past 3 days 10. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 11. Known pregnancy 12. Received organ or bone marrow transplantation in past 3 months 13. Known mechanically resuscitation in past 14 days 14. Patient moribund or expected to die in next 12h according to the judgment of the investigator 15. Patients otherwise considered restricted from receiving full supportive care (including ICU support) 16. Existing diagnosis of progressed cancer or other life-limiting disease with life expectancy < 6 months 17. Known to have received anti-cancer therapy for oncological disease in past 4 weeks 18. Known severe congestive heart failure (New York Heart Association [NYHA] Class III-IV, see Appendix 8) Phase III 1. Intubated > 48h at time point of randomization 2. Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator 3. Known history of chronic dialysis OR received renal replacement therapy in past 14 days OR anticipated to receive renal replacement therapy within 24h after randomization 4. Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months 5. Treatment of COVID-19 with investigational antibody treatment(s) which are not approved or not included in locally adopted treatment guidelines (e.g., WHO guidance, National Institutes of Health [NIH] COVID-19 treatment guidelines) for this indication in the past 7 days (Note: Antibody treatment[s] given within past 7 days for pre-existing diseases, other than COVID-19, are allowed.) 6. At time point of randomization, treatment of COVID-19 with investigational treatments which are not approved or not included in locally adopted treatment guidelines for this indication (e.g., WHO guidance, NIH COVID-19 treatment guidelines), including SARS-CoV-2 multiplication inhibitor(s) or immunomodulator(s). (Note: If a locally adopted treatment guideline recommends drugs such as remdesivir, dexamethasone, or anticoagulation, this would be allowed. Adopted guidelines and updates must be documented at study initiation and throughout the conduct of the study.) 7. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 8. Serum or urine pregnancy test positive before randomization (required for women of childbearing potential) 9. Received organ or bone marrow transplantation in past 3 months 10. Known cardio-pulmonary mechanical resuscitation in past 14 days 11. Received cytokine adsorption therapy in past 3 days 12. Patient moribund or expected to die in next 24h according to the judgment of the investigator 13. Known to have received anti-cancer therapy for hemato-oncological disease in past 4 weeks OR known to have active malignant disease at time point of randomization 14. Known severe congestive heart failure (NYHA Class III-IV, see Appendix 8) 15. Known history of chronic liver disease (Child-Pugh B or C, see Appendix 9) 16. Participating in or has participated in other investigational interventional studies (drug or device) within the last 7 days before randomization

Phase II 1. Oxygenation index at time of enrollment (PaO2 / FiO2) < 100 or > 250 in supine position 2. Intubated > 48h at time point of enrollment 3. Patients who demonstrate an improvement in past 24h prior to enrollment in oxygenation and ventilation / support parameters which indicate an expected resolution of lung dysfunction in the next 24h without additional intervention according to judgment of the investigator with one or more of the following parameters present: 4. Improvement in oxygenation index of > 30% relative to previous measure (last 24h in supine position) 5. Extubation if intubated before 6. Known history of chronic obstructive pulmonary disease (COPD) (GOLD category C or D) 7. Known history of chronic dialysis OR received renal replacement therapy in past 14 days 8. Received new other biologic treatment attempt for COVID-19 in the past 14 days 9. Received treatment with a viral replication inhibitor in past 3 days 10. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 11. Known pregnancy 12. Received organ or bone marrow transplantation in past 3 months 13. Known mechanically resuscitation in past 14 days 14. Patient moribund or expected to die in next 12h according to the judgment of the investigator 15. Patients otherwise considered restricted from receiving full supportive care (including ICU support) 16. Existing diagnosis of progressed cancer or other life-limiting disease with life expectancy < 6 months 17. Known to have received anti-cancer therapy for oncological disease in past 4 weeks 18. Known severe congestive heart failure (New York Heart Association [NYHA] Class III-IV, see Appendix 8) Phase III 1. Intubated > 48h at time point of randomization 2. Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator 3. Known history of chronic dialysis OR received renal replacement therapy in past 14 days OR anticipated to receive renal replacement therapy within 24h after randomization 4. Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months 5. Treatment of COVID-19 with investigational antibody treatment(s) which are not approved or not included in locally adopted treatment guidelines (e.g., WHO guidance, National Institutes of Health [NIH] COVID-19 treatment guidelines) for this indication in the past 7 days (Note: Antibody treatment[s] given within past 7 days for pre-existing diseases, other than COVID-19, are allowed.) 6. At time point of randomization, treatment of COVID-19 with investigational treatments which are not approved or not included in locally adopted treatment guidelines for this indication (e.g., WHO guidance, NIH COVID-19 treatment guidelines), including SARS-CoV-2 multiplication inhibitor(s) or immunomodulator(s). (Note: If a locally adopted treatment guideline recommends drugs such as remdesivir, dexamethasone, or anticoagulation, this would be allowed. Adopted guidelines and updates must be documented at study initiation and throughout the conduct of the study.) 7. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 8. Serum or urine pregnancy test positive before randomization (required for women of childbearing potential) 9. Received organ or bone marrow transplantation in past 3 months 10. Known cardio-pulmonary mechanical resuscitation in past 14 days 11. Received cytokine adsorption therapy in past 3 days 12. Patient moribund or expected to die in next 24h according to the judgment of the investigator 13. Known to have received anti-cancer therapy for hemato-oncological disease in past 4 weeks OR known to have active malignant disease at time point of randomization 14. Known severe congestive heart failure (NYHA Class III-IV, see Appendix 8) 15. Known history of chronic liver disease (Child-Pugh B or C, see Appendix 9) 16. Participating in or has participated in other investigational interventional studies (drug or device) within the last 7 days before randomization