Combined Cell Therapy for High‑Mortality‑Risk COVID‑19 Patients (DECODE‑19)

Our group has previously demonstrated that SARS‑CoV‑2–specific memory T lymphocytes can be identified and isolated from the peripheral blood of COVID‑19 convalescent donors (Ferreras et al., 2021; Guerreiro et al., 2021). We have also shown that the intravenous infusion of escalating doses of these cells in patients with moderate to severe COVID‑19 is safe, feasible, and well tolerated up to a dose of 1 million cells/kg (Clinical Trial NCT04578210, Pérez‑Martínez et al., 2021, submitted). A phase 2 randomized controlled trial is currently underway in a larger population, evaluating allogeneic administration of SARS‑CoV‑2–specific memory T lymphocytes in patients with mild to severe COVID‑19 (n = 84 patients per arm: SoC vs. SoC + SARS‑CoV‑2 Tmem). In addition, we have shown that compassionate use of adipose‑derived mesenchymal stromal cells (MSC) in critically ill ICU patients requiring intubation and mechanical ventilation may reduce mortality from 85% to 15%, decrease inflammatory markers, and restore CD4+, CD8+, and B‑lymphocyte counts (Sánchez‑Guijo et al., 2020). In this project, we focus on COVID‑19 patients who meet early, well‑established criteria for High Mortality Risk (Fatal or Critical) at the time of hospital admission. We propose a Combinatorial Cell Therapy strategy for these high‑risk patients:
Antiviral therapy with SARS‑CoV‑2–specific memory T lymphocytes for stage I–II disease (WHO Grades 3–5), and Anti‑inflammatory, immunomodulatory, and regenerative therapy with mesenchymal stromal cells for critically ill patients in stages II–III (WHO Grades 4–6).