This prospective nonrandomized open-label cohort study addresses the safety and efficacy of exosomes (ExoFlo™) 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 (PaO₂/FiO₂) 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.

中文翻译：

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源自骨髓间充质干细胞的外泌体用于治疗严重的 COVID-19。

这项前瞻性非随机开放标签队列研究探讨了源自同种异体骨髓间充质干细胞的外泌体 (ExoFlo™) 作为治疗严重 COVID-19 的安全性和有效性。2020 年 4 月，ExoFlo 被提供给一家医院中心的 24 名 SARS-CoV-2 聚合酶链反应阳性患者，所有患者均符合严重 COVID-19 和中度至重度急性呼吸窘迫综合征的标准。患者接受了单次 15 mL 静脉内剂量的 ExoFlo，并在治疗后第 1 天至第 14 天评估其安全性和有效性。在 ExoFlo 给药的 72 小时内，所有安全终点均未观察到不良事件。观察到83%的存活率。总共 24 名 (71%) 患者中有 17 名康复，24 名患者中有 3 名 (13%) 病情稳定但仍处于危急状态，24 名患者中有 4 名 (16%) 因与治疗无关的原因死亡。总体而言，经过一次治疗后，患者的临床状态和氧合情况有所改善，动脉氧平均压力与吸入氧分数 (PaO₂ /FiO ₂ ) 增加了 192% ( P  < 0.001)。实验室值显示绝对中性粒细胞计数显着改善 [平均减少 32% ( P值 <0.001)] 和淋巴细胞减少，平均 CD3 ⁺、CD4 ⁺和 CD8 ⁺淋巴细胞计数增加 46% ( P  < 0.05)、 45% ( P  < 0.05) 和 46% ( P  < 0.001)，分别。同样，急性期反应物下降，平均 C 反应蛋白、铁蛋白和 D-二聚体减少 77% ( P  < 0.001)、43% ( P  < 0.001) 和 42% ( P < 0.05)，分别。总之，由于其安全性、恢复氧合、下调细胞因子风暴和重建免疫的能力，ExoFlo 是严重 COVID-19 的有希望的治疗候选者。需要未来的随机对照试验 (RCT) 来确定 ExoFlo 的治疗潜力。