Exosomes Derived From Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19.

Sengupta, Vikram; Sengupta, Sascha; Lazo, Angel; Woods, Peter; Nolan, Anna; Bremer, Nicholas

This prospective, non-randomized, open-label, cohort study addresses the safety and efficacy of exosomes (ExoFloâ„¢) derived from allogeneic bone marrow mesenchymal stem cells as treatment for severe COVID-19. During April 2020, ExoFlo was provided to 24 SARS-CoV-2 PCR positive patients at a single hospital center, all of whom met criteria for severe COVID-19 as well as moderate to severe Acute Respiratory Distress Syndrome (ARDS). Patients received a single 15 mL intravenous dose of ExoFlo and were evaluated for both safety and efficacy day 1-14 post-treatment. All safety endpoints were met with no adverse events observed within 72 hours of ExoFlo administration. A survival rate of 83% was observed. 17/24 (71%) of the patients recovered; 3/24 (13%) remained critically ill though stable; 4/24 (16%) expired for reasons unrelated to the treatment. Overall, after one treatment, patients' clinical status and oxygenation improved with an average PaO2/FiO2 ratio increase of 192% (p < 0.001). Laboratory values revealed significant improvements in absolute neutrophil count [mean reduction 32% [(p-value < 0.001)] and lymphopenia with average CD3+, CD4+ and CD8+ lymphocyte counts increasing by 46% (p < 0.05), 45% (p < 0.05), and 46% (p < 0.001), respectively. Likewise, acute phase reactants declined, with mean C-reactive protein (CRP), Ferritin, and D-dimer reduction of 77% (p < .001), 43% (p < .001), 42% (p <0.05), respectively. In conclusion, due to its safety profile, capacity to restore oxygenation, downregulate cytokine storm, and reconstitute immunity, ExoFlo is a promising therapeutic candidate for severe COVID-19. Future RCTs are needed to determine ExoFlo therapeutic potential.