inclusion criteria: 1. signed informed consent obtained prior to initiation of any study-specific procedures and study treatment. 2. documented diagnosis of sars-cov-2 infection, determined by either qualitative polymerase chain reaction (pcr), antigen test by local laboratory, or any other validated method approved by the local health authority, from appropriate biological samples collected no more than 72 hours prior to study treatment on day 1. 3. patient meets category 5 on the 11-point who clinical progression scale: requires hospitalisation and oxygen by mask or nasal prongs/cannula. 4. a maximum of 14 days from onset of covid-19 symptoms to initiation of study treatment on day 1. 5. male or female aged ≥18 years. 6. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: * absolute neutrophil count ≥500/mm\^3 (0.5 x 10\^9/l). * platelet count ≥75,000/mm\^3 (75 x 10\^9/l). * alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln). * serum bilirubin ≤1 x uln (or direct bilirubin \<1 x uln when total bilirubin is above uln). * calculated creatinine clearance ≥30 ml/min (cockcroft-gault equation). * creatine phosphokinase (cpk) ≤2.5 x uln except if the patient has had recent (i.e., in the last week) shivering episodes or trauma. in that case, the level of cpk should be ≤5 x uln. 7. agree not to participate in another interventional clinical trial through day 31. 8. females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating. 9. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. patients in the control arm must use effective contraception during the time indicated in the approved product information (summary of product characteristics \[smpc\] or leaflet). if no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

inclusion criteria: 1. signed informed consent obtained prior to initiation of any study-specific procedures and study treatment. 2. documented diagnosis of sars-cov-2 infection, determined by either qualitative polymerase chain reaction (pcr), antigen test by local laboratory, or any other validated method approved by the local health authority, from appropriate biological samples collected no more than 72 hours prior to study treatment on day 1. 3. patient meets category 5 on the 11-point who clinical progression scale: requires hospitalisation and oxygen by mask or nasal prongs/cannula. 4. a maximum of 14 days from onset of covid-19 symptoms to initiation of study treatment on day 1. 5. male or female aged ≥18 years. 6. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: * absolute neutrophil count ≥500/mm\^3 (0.5 x 10\^9/l). * platelet count ≥75,000/mm\^3 (75 x 10\^9/l). * alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln). * serum bilirubin ≤1 x uln (or direct bilirubin \<1 x uln when total bilirubin is above uln). * calculated creatinine clearance ≥30 ml/min (cockcroft-gault equation). * creatine phosphokinase (cpk) ≤2.5 x uln except if the patient has had recent (i.e., in the last week) shivering episodes or trauma. in that case, the level of cpk should be ≤5 x uln. 7. agree not to participate in another interventional clinical trial through day 31. 8. females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating. 9. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. patients in the control arm must use effective contraception during the time indicated in the approved product information (summary of product characteristics \[smpc\] or leaflet). if no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

inclusion criteria: signed informed consent obtained prior to initiation of any study-specific procedures and study treatment. documented diagnosis of sars-cov-2 infection, determined by either qualitative polymerase chain reaction (pcr), antigen test by local laboratory, or any other validated method approved by the local health authority, from appropriate biological samples collected no more than 72 hours prior to study treatment on day 1. patient meets category 5 on the 11-point who clinical progression scale: requires hospitalisation and oxygen by mask or nasal prongs/cannula. a maximum of 14 days from onset of covid-19 symptoms to initiation of study treatment on day 1. male or female aged ≥18 years. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: absolute neutrophil count ≥500/mm^3 (0.5 x 10^9/l). platelet count ≥75,000/mm^3 (75 x 10^9/l). alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln). serum bilirubin ≤1 x uln (or direct bilirubin <1 x uln when total bilirubin is above uln). calculated creatinine clearance ≥30 ml/min (cockcroft-gault equation). creatine phosphokinase (cpk) ≤2.5 x uln except if the patient has had recent (i.e., in the last week) shivering episodes or trauma. in that case, the level of cpk should be ≤5 x uln. agree not to participate in another interventional clinical trial through day 31. females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. patients in the control arm must use effective contraception during the time indicated in the approved product information (summary of product characteristics [smpc] or leaflet). if no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

inclusion criteria: signed informed consent obtained prior to initiation of any study-specific procedures and study treatment. documented diagnosis of sars-cov-2 infection, determined by either qualitative polymerase chain reaction (pcr), antigen test by local laboratory, or any other validated method approved by the local health authority, from appropriate biological samples collected no more than 72 hours prior to study treatment on day 1. patient meets category 5 on the 11-point who clinical progression scale: requires hospitalisation and oxygen by mask or nasal prongs/cannula. a maximum of 14 days from onset of covid-19 symptoms to initiation of study treatment on day 1. male or female aged ≥18 years. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: absolute neutrophil count ≥500/mm^3 (0.5 x 10^9/l). platelet count ≥75,000/mm^3 (75 x 10^9/l). alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln). serum bilirubin ≤1 x uln (or direct bilirubin <1 x uln when total bilirubin is above uln). calculated creatinine clearance ≥30 ml/min (cockcroft-gault equation). creatine phosphokinase (cpk) ≤2.5 x uln except if the patient has had recent (i.e., in the last week) shivering episodes or trauma. in that case, the level of cpk should be ≤5 x uln. agree not to participate in another interventional clinical trial through day 31. females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. patients in the control arm must use effective contraception during the time indicated in the approved product information (summary of product characteristics [smpc] or leaflet). if no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

inclusion criteria: signed informed consent obtained prior to initiation of any study-specific procedures and study treatment documented diagnosis of sars-cov-2 infection, determined by either qualitative polymerase chain reaction (pcr) or antigen test by local laboratory, from oro nasopharyngeal exudate collected no more than 72 hours prior to study treatment on day 1 patient meets category 5 on the 11-point who clinical progression scale: requires hospitalization and oxygen by mask or nasal prongs/cannula a maximum of 10 days from onset of covid-19 symptoms to initiation of study treatment on day 1 male or female aged ≥18 years adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: absolute neutrophil count ≥1000/mm^3 (1.0 x 10^9/l) lymphocyte count ≥500/mm^3 (0.5 x 10^9/l) platelet count ≥100 000/mm^3 (100 x 10^9/l) haemoglobin >9.0 g/dl alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln) serum bilirubin ≤1 x uln calculated creatinine clearance ≥30 ml/min (cockcroft and gault formula) creatine phosphokinase ≤2.5 x uln except if the patient has had recent (ie, in the last week) shivering episodes or trauma. in that case, the level of creatine phosphokinase (cpk) should be ≤5 x uln). agree not to participate in another interventional clinical trial through day 31 females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. patients in the control arm must use effective contraception at the time indicated in the approved product information (summary of product characteristics [smpc] or leaflet). if no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

inclusion criteria: signed informed consent obtained prior to initiation of any study-specific procedures and study treatment documented diagnosis of sars-cov-2 infection, determined by either qualitative polymerase chain reaction (pcr) or antigen test by local laboratory, from oro nasopharyngeal exudate collected no more than 72 hours prior to study treatment on day 1 patient meets category 5 on the 11-point who clinical progression scale: requires hospitalization and oxygen by mask or nasal prongs/cannula a maximum of 10 days from onset of covid-19 symptoms to initiation of study treatment on day 1 male or female aged ≥18 years adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: absolute neutrophil count ≥1000/mm^3 (1.0 x 10^9/l) lymphocyte count ≥500/mm^3 (0.5 x 10^9/l) platelet count ≥100 000/mm^3 (100 x 10^9/l) haemoglobin >9.0 g/dl alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln) serum bilirubin ≤1 x uln calculated creatinine clearance ≥30 ml/min (cockcroft and gault formula) creatine phosphokinase ≤2.5 x uln except if the patient has had recent (ie, in the last week) shivering episodes or trauma. in that case, the level of creatine phosphokinase (cpk) should be ≤5 x uln). agree not to participate in another interventional clinical trial through day 31 females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. patients in the control arm must use effective contraception at the time indicated in the approved product information (summary of product characteristics [smpc] or leaflet). if no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

inclusion criteria: 1. signed informed consent obtained prior to initiation of any study-specific procedures and study treatment 2. documented diagnosis of sars-cov-2 infection, determined by either qualitative polymerase chain reaction (pcr) or antigen test by local laboratory, from oro nasopharyngeal exudate collected no more than 72 hours prior to study treatment on day 1 3. patient meets category 5 on the 11-point who clinical progression scale: requires hospitalization and oxygen by mask or nasal prongs/cannula 4. a maximum of 10 days from onset of covid-19 symptoms to initiation of study treatment on day 1 5. male or female aged ≥18 years 6. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: - absolute neutrophil count ≥1000/mm^3 (1.0 x 10^9/l) - lymphocyte count ≥500/mm^3 (0.5 x 10^9/l) - platelet count ≥100 000/mm^3 (100 x 10^9/l) - haemoglobin >9.0 g/dl - alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln) - serum bilirubin ≤1 x uln - calculated creatinine clearance ≥30 ml/min (cockcroft and gault formula) - creatine phosphokinase ≤2.5 x uln except if the patient has had recent (ie, in the last week) shivering episodes or trauma. in that case, the level of creatine phosphokinase (cpk) should be ≤5 x uln). 7. agree not to participate in another interventional clinical trial through day 31 8. females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating 9. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. patients in the control arm must use effective contraception at the time indicated in the approved product information (summary of product characteristics [smpc] or leaflet). if no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

inclusion criteria: 1. signed informed consent obtained prior to initiation of any study-specific procedures and study treatment 2. documented diagnosis of sars-cov-2 infection, determined by either qualitative polymerase chain reaction (pcr) or antigen test by local laboratory, from oro nasopharyngeal exudate collected no more than 72 hours prior to study treatment on day 1 3. patient meets category 5 on the 11-point who clinical progression scale: requires hospitalization and oxygen by mask or nasal prongs/cannula 4. a maximum of 10 days from onset of covid-19 symptoms to initiation of study treatment on day 1 5. male or female aged ≥18 years 6. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: - absolute neutrophil count ≥1000/mm^3 (1.0 x 10^9/l) - lymphocyte count ≥500/mm^3 (0.5 x 10^9/l) - platelet count ≥100 000/mm^3 (100 x 10^9/l) - haemoglobin >9.0 g/dl - alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln) - serum bilirubin ≤1 x uln - calculated creatinine clearance ≥30 ml/min (cockcroft and gault formula) - creatine phosphokinase ≤2.5 x uln except if the patient has had recent (ie, in the last week) shivering episodes or trauma. in that case, the level of creatine phosphokinase (cpk) should be ≤5 x uln). 7. agree not to participate in another interventional clinical trial through day 31 8. females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating 9. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. patients in the control arm must use effective contraception at the time indicated in the approved product information (summary of product characteristics [smpc] or leaflet). if no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

inclusion criteria: 1. signed informed consent obtained prior to initiation of any study-specific procedures and study treatment 2. laboratory confirmed severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection as determined by qualitative polymerase chain reaction (pcr) by local laboratory from oro/nasopharyngeal exudate (or other respiratory specimen) collected no more than 24 hours prior to study treatment on day 1 3. admitted to hospital as clinically indicated for management of moderate sars-cov-2 (covid-19) infection, defined by the following criteria: - positive pcr test for sars-cov-2 - symptoms of moderate illness with covid-19, which could include any symptoms of mild illness or shortness of breath with exertion - clinical signs suggestive of moderate illness with covid-19 such as respiratory rate ≥20 but <30 breaths per minute, saturation of oxygen (spo2) >93% but <95% on room air at sea level, heart rate ≥90 but <125 beats per minute, and requiring o2 supplementation. if spo2 on room air is not possible to be measured, the ratio partial pressure of oxygen/fraction of inspired oxygen (pao2/fio2) should be ≥ 300 mm hg; in addition, if the site is located at high altitude over sea level (> 1000 m), the ratio pao2/fio2 should be adjusted - no clinical signs indicative of severe illness, which could include shortness of breath at rest or respiratory distress, or pao2/fio2 ratio < 300 mm hg (sea level) 4. onset of covid-19 symptoms no later than 6 days prior to initiation of study treatment on day 1 5. male or female aged ≥18 years 6. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: - absolute neutrophil count ≥1000/mm^3 (1.0 x 10^9/l) - lymphocyte count ≥500/mm^3 (0.5 x 10^9/l) - platelet count ≥100 000/mm^3 (100 x 10^9/l) - haemoglobin >9.0 g/dl - alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln) - serum bilirubin ≤1 x uln - calculated creatinine clearance ≥30 ml/min (cockcroft and gault formula) - creatine phosphokinase ≤2.5 x uln 7. agree not to participate in another interventional clinical trial through day 31 8. females of reproductive capacity must have a negative serum pregnancy test by local laboratory at study enrolment and must be non-lactating 9. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin.

inclusion criteria: 1. signed informed consent obtained prior to initiation of any study-specific procedures and study treatment 2. laboratory confirmed severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection as determined by qualitative polymerase chain reaction (pcr) by local laboratory from oro/nasopharyngeal exudate (or other respiratory specimen) collected no more than 24 hours prior to study treatment on day 1 3. admitted to hospital as clinically indicated for management of moderate sars-cov-2 (covid-19) infection, defined by the following criteria: - positive pcr test for sars-cov-2 - symptoms of moderate illness with covid-19, which could include any symptoms of mild illness or shortness of breath with exertion - clinical signs suggestive of moderate illness with covid-19 such as respiratory rate ≥20 but <30 breaths per minute, saturation of oxygen (spo2) >93% but <95% on room air at sea level, heart rate ≥90 but <125 beats per minute, and requiring o2 supplementation. if spo2 on room air is not possible to be measured, the ratio partial pressure of oxygen/fraction of inspired oxygen (pao2/fio2) should be ≥ 300 mm hg; in addition, if the site is located at high altitude over sea level (> 1000 m), the ratio pao2/fio2 should be adjusted - no clinical signs indicative of severe illness, which could include shortness of breath at rest or respiratory distress, or pao2/fio2 ratio < 300 mm hg (sea level) 4. onset of covid-19 symptoms no later than 6 days prior to initiation of study treatment on day 1 5. male or female aged ≥18 years 6. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: - absolute neutrophil count ≥1000/mm^3 (1.0 x 10^9/l) - lymphocyte count ≥500/mm^3 (0.5 x 10^9/l) - platelet count ≥100 000/mm^3 (100 x 10^9/l) - haemoglobin >9.0 g/dl - alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln) - serum bilirubin ≤1 x uln - calculated creatinine clearance ≥30 ml/min (cockcroft and gault formula) - creatine phosphokinase ≤2.5 x uln 7. agree not to participate in another interventional clinical trial through day 31 8. females of reproductive capacity must have a negative serum pregnancy test by local laboratory at study enrolment and must be non-lactating 9. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin.

inclusion criteria: 1. signed informed consent obtained prior to initiation of any study-specific procedures and study treatment 2. laboratory confirmed sars-cov-2 infection as determined by qualitative polymerase chain reaction (pcr) by local laboratory from oro/nasopharyngeal exudate (or other respiratory specimen) collected no more than 48 hours prior to study treatment on day 1 3. admitted to hospital as clinically indicated for management of moderate sars-cov-2 (covid-19) infection, defined by the following criteria: - positive pcr test for sars-cov-2 - symptoms of moderate illness with covid-19, which could include any symptoms of mild illness or shortness of breath with exertion - clinical signs suggestive of moderate illness with covid-19 such as respiratory rate ≥20 breaths but <30 breaths per minute, spo2 >93% but <95% on room air at sea level, heart rate ≥90 but <125 beats per minute, and requiring o2 supplementation - no clinical signs indicative of severe illness, which could include shortness of breath at rest or respiratory distress 4. onset of covid-19 symptoms no later than 6 days prior to initiation of study treatment on day 1 5. male or female aged ≥18 years 6. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: • absolute neutrophil count ≥1000/mm3 (1.0 x 109/l) • lymphocyte count ≥500/mm3 (0.5 x 109/l) - platelet count ≥100 000/mm3 (100 x 109/l) • haemoglobin >9.0 g/dl - alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln) • serum bilirubin ≤1 x uln • calculated creatinine clearance ≥30 ml/min (cockcroft and gault formula) • creatine phosphokinase ≤2.5 x uln 7. agree not to participate in another interventional clinical trial through day 31 8. females of reproductive capacity must have a negative serum pregnancy test by local laboratory at study enrolment and must be non-lactating 9. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin.

inclusion criteria: 1. signed informed consent obtained prior to initiation of any study-specific procedures and study treatment 2. laboratory confirmed sars-cov-2 infection as determined by qualitative polymerase chain reaction (pcr) by local laboratory from oro/nasopharyngeal exudate (or other respiratory specimen) collected no more than 48 hours prior to study treatment on day 1 3. admitted to hospital as clinically indicated for management of moderate sars-cov-2 (covid-19) infection, defined by the following criteria: - positive pcr test for sars-cov-2 - symptoms of moderate illness with covid-19, which could include any symptoms of mild illness or shortness of breath with exertion - clinical signs suggestive of moderate illness with covid-19 such as respiratory rate ≥20 breaths but <30 breaths per minute, spo2 >93% but <95% on room air at sea level, heart rate ≥90 but <125 beats per minute, and requiring o2 supplementation - no clinical signs indicative of severe illness, which could include shortness of breath at rest or respiratory distress 4. onset of covid-19 symptoms no later than 6 days prior to initiation of study treatment on day 1 5. male or female aged ≥18 years 6. adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: • absolute neutrophil count ≥1000/mm3 (1.0 x 109/l) • lymphocyte count ≥500/mm3 (0.5 x 109/l) - platelet count ≥100 000/mm3 (100 x 109/l) • haemoglobin >9.0 g/dl - alanine transaminase (alt), aspartate transaminase (ast) ≤3 x upper limit of normal (uln) • serum bilirubin ≤1 x uln • calculated creatinine clearance ≥30 ml/min (cockcroft and gault formula) • creatine phosphokinase ≤2.5 x uln 7. agree not to participate in another interventional clinical trial through day 31 8. females of reproductive capacity must have a negative serum pregnancy test by local laboratory at study enrolment and must be non-lactating 9. females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin.