Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

[Symptomatic hypercalcemia presenting as a case of isolated splenic tuberculosis]. / Hipercalcemia sintomática como forma de presentación de un caso de tuberculosis esplénica aislada.

BACKGROUND AND OBJECTIVE: To describe an unusual clinical presentation as isolated splenic tuberculosis. PATIENT AND METHODS: We report a case of isolated splenic tuberculosis, a rare form of extrapulmonary tuberculosis in an immunocompetent patient, and, as a peculiarity, debuts in the form of symptomatic hypercalcemia. RESULTS: We deeply report the clinical case and the procedures performed to exclude other diseases. We emphasize the usefulness of fine needle aspiration of the spleen to obtain microbiological samples, and the use of specific polymerase chain reaction for mycobacterias to establish the definitive diagnosis of this entity. In agreement with other authors, we chose initial medical treatment with antituberculous drugs, reserving surgery for refractory cases or in case of spontaneous splenic rupture. CONCLUSION: Hypercalcemia can be a presentation of granulomatous diseases. The isolated involvement of the spleen by mycobacterias is a rare form of extrapulmonary tuberculosis and more so in immunocompetent patients.