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

Abstract

This prospective nonrandomized open-label cohort study addresses the safety and efficacy of exosomes (ExoFloÔ) 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 polymerase chain reaction-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. Patients received a single 15 mL intravenous dose of ExoFlo and were evaluated for both safety and efficacy from days 1 to 14 post-treatment. All safety endpoints were met with no adverse events observed within 72 h of ExoFlo administration. A survival rate of 83% was observed. In total, 17 of 24 (71%) patients recovered, 3 of 24 (13%) patients remained critically ill though stable, and 4 of 24 (16%) patients expired for reasons unrelated to the treatment. Overall, after one treatment, patients' clinical status and oxygenation improved with an average pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO 2 / FiO 2 ) 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, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. In conclusion, owing 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 randomized controlled trials (RCTs) are needed to determine ExoFlo therapeutic potential.

Safety and Feasibility of Umbilical Cord Mesenchymal Stem Cells in Patients with COVID-19 Pneumonia: A Pilot Study

“…Multiple clinical trials using stem cell therapy to treat the COVID-19 have been registered at www.clinicaltrials.gov. Two published studies showed that ACE2 − MSC and exosomes derived from bone marrow MSC could improve the clinical outcome of COVID-19 patients [4,8]. In accordance with our ndings, the use of exosomes derived from bone marrow MSC could increase the oxygenation index of severe COVID-19 patients which may reduce the need for invasive ventilator and shorten hospital stay [8].…”

Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

“…In the study by Sengupta et al, a significant mean reduction of 43% in ferritin level was observed in COVID‐19 patients after treatment with exosomes derived from allogeneic bone marrow mesenchymal stem cells 85 …”

Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans

“…This exosome-based vaccine is an excellent example demonstrating the possibilities of exosomes as nanotherapeutics. Vaccines are not the only possibility as already clinical trials using exosomes derived from allogeneic bone marrow mesenchymal stem cells (ExoFlo) have begun [ 131 ]. ExoFlo was used to treat 24 patients, testing positive for SARS-CoV-2 via polymerase chain reaction [ 131 ].…”