Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care (NEREIDA)

Inclusion Criteria: * Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment. * Participant aged ≥18 years. * Participant diagnosed COVID-19, with the following characteristics: 1. A regulatory-approved test, collected no more than 3 days prior to study randomisation, with either a Ct value ≤30 or a positive antigen test. 2. Presence of any of the selected signs/symptom listed in the COVID-19 signs/symptoms checklist within the last 24 hours. * Participant already admitted or requiring hospital care for symptomatic COVID-19, for which at least one antiviral has failed or cannot be used (i.e., contraindication, absence of labelled indication, guidelines or drug unavailability), after a minimum washout period of 24 hours for small molecules (e.g., remdesivir, molnupiravir, nirmaltrevir, ritonavir) and 5 days for antiviral monoclonal antibodies (e.g., tixagevimab + cilgavimab) or convalescent plasma. * Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: 1. Absolute neutrophil count ≥500/mm\^3 (0.5 x 109/L). 2. Platelet count ≥ 50 000/mm3 (50 x 109/L). 3. Alanine transaminase (ALT) ≤3 x upper limit of normal (ULN) (≤5 x ULN if preexistent liver involvement by the underlying disease). 4. Serum bilirubin ≤1.5 x ULN (or direct bilirubin \<1.5 x ULN when total bilirubin is above ULN). 5. Estimated glomerular filtration rate ≥30 mL/min (CKD-EPI Creatinine Equation \[2021\]). * Females of child-bearing potential must have a negative serum or urine pregnancy test by local laboratory at screening and must be non-lactating. * Females of child-bearing potential and fertile males with partners of child-bearing potential must use contraceptive methods as specified in the protocol. Group-specific inclusion criteria: * Group 1 - Patients receiving, within the last 30 days, immune-suppressive therapy due to haematopoietic or organ transplantation. * Group 2 - Participants receiving B-cell depleting therapies within the last 6 months (with the exception of CAR-T cell therapy for which time restriction is not applicable). * Group 3 - Participants receiving, within the last 30 days, other immune-suppressive therapies. * Group 4 - Other situations with immunodeficiency. 1. Primary immune deficiencies. 2. Human immunodeficiency virus (HIV) infection, with CD4\^+ T lymphocyte \< 200 cells/μL in the last month. 3. Radiation therapy within the last 3 months- requires documentation of ALC \< 500 cells/μL. 4. Haematological neoplasia or myelodysplasia not currently receiving any therapy. 5. Other situations with a documentation of ALC \< 500 cells/μL. Exclusion Criteria: * Evidence of critical illness. * Any of the following cardiac conditions or risk factors: 1. Cardiac infarction or cardiac surgery episode within the last month. 2. History of known congenital QT prolongation. 3. Known structural cardiomyopathy with abnormal left ventricular ejection fraction (LVEF) (\<50%). 4. Current clinical evidence of heart failure or acute cardiac ischaemia (New York Heart Association (NYHA) class III-IV). * Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol) or contraindication to receive dexamethasone, antihistamine H1/H2, or anti-serotoninergic 5HT3 agents. * Females who are pregnant or breast-feeding. * Females and males with partners of child-bearing potential who are not using at least 1 protocol-specified method of contraception. * Any situation currently requiring increasing needs of immune-suppressive agents. * Any other clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, would jeopardise the safety of the participant or potentially impact on participant compliance or the safety/efficacy observations in the study. * Participation in another clinical study involving an investigational drug within 30 days prior to screening.