Safety and efficacy of placental mesenchymal stem cell-derived extracellular vesicle in severe COVID-19 patients: Phase I & II Clinical Trials

Introduction: Most mortality in COVID-19 cases was due to the increased inflammatory cytokines and cytokine storm. As mesenchymal stem cells (MSCs) possess immunomodulatory properties, this study assessed the therapeutic effects of placental MSC-derived extracellular vesicles on the inflammation and pulmonary injury caused by COVID-19. Methods: The study was carried out in phases I (safety study, 101 patients) and II (efficacy study, 80 patients) in a randomized, double-blind study at four hospital centers from April 2021 to August 2021. In addition to standard treatments, 15 mL of normal saline solution containing 15×109 vesicles was injected intravenously for five consecutive days. Results: No reaction or adverse events were observed in any patients. In the intervention group, after 5 days of treatment, patients’ clinical status and oxygenation improved, and 75% of patients presented an increased SpO2 after 5 days. Besides, inflammatory parameters assessment indicated a 21% decrease in neutrophil-lymphocyte ratio and a 54% reduction in C-reactive protein after day five of the intervention. Conclusion: PMSC-derived extracellular vesicles were safe and well-tolerated, down-regulated cytokine storms, and restored oxygenation. Thus, they can be considered a promising therapeutic candidate for severe COVID-19.