Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle Treatment of Respiratory Failure from COVID-19: Endpoint Analysis of Expanded Access Safety Trial.

The safety of an extracellular vesicle (EV) enriched secretome from bone marrow mesenchymal stem cells (BM-MSCs) was evaluated in a multi-site, prospective, expanded access trial as potential treatment for respiratory failure due to COVID-19. Subjects (103) received up to three doses of 15 mL IP every 72 h. The primary outcome was all cause 60-day mortality. Secondary outcomes included serious adverse events. One TEAE (grade 1 hyperpigmentation at the infusion site) related to IP occurred. 60-day mortality was 29% for all patients, 22.4% in patients < 65 years and 41.7% in patients ≥ 65 years. Mean ventilation free days was 40.8 for all patients, 44.7 days in patients < 65 years and 33.4 days in patients ≥ 65 years. Median time to hospital (IQR) discharge by Kaplan-Meier was 11 (5.0-NR) days in all patients, 9 (5.0-NR) days in patients < 65 years and 19 (5.5-NR) days in patients ≥ 65 years. The IP (15 mL dose) is safe in patients with severe or critical COVID-19 respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04657458 (2020-12-08).