Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial.
Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial.
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DOI：
10.1186/s13287-022-02796-1
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发表时间：
2022-03-21
影响因子：
7.5
通讯作者：
Correa A
中科院分区：
文献类型：
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作者：
Rebelatto CLK;Senegaglia AC;Franck CL;Daga DR;Shigunov P;Stimamiglio MA;Marsaro DB;Schaidt B;Micosky A;de Azambuja AP;Leitão CA;Petterle RR;Jamur VR;Vaz IM;Mallmann AP;Carraro Junior H;Ditzel E;Brofman PRS;Correa A
COVID-19 是一种多系统疾病，呈现急性和持续症状，即急性后遗症 (PASC)。长期症状可能是由于 SARS-CoV-2 引起的器官或组织损伤以及急性 COVID-19 期间相关的凝血或炎症过程造成的后果。临床医生正在选择各种策略来预防 COVID-19 重症病例；然而，单一疗法无法有效治疗如此复杂的疾病。间充质基质细胞（MSC）以其免疫调节特性和再生能力而闻名；因此，它们是治疗涉及免疫失调和广泛组织损伤的疾病的有前途的工具，就像 COVID-19 的情况一样。本研究旨在评估三种静脉注射剂量的 UC-MSC（脐带间充质干细胞）作为辅助治疗在恢复和减少 COVID-19 引起的急性后遗症方面的安全性并探讨其长期疗效。据我们所知，这是为数不多的对 COVID-19 患者进行 MSC 治疗后最长随访的报告之一。这是一项 I/II 期、前瞻性、单中心、随机、双盲、安慰剂对照临床试验。其中包括 17 名被诊断患有 COVID-19、需要重症监护和有创机械通气的危重患者。患者输注为 3 剂 5 × 105 个细胞/kg UC-MSC，给药间隔为 48 小时 (n = 11) 或安慰剂 (n = 6)。评估包括临床评估、病毒载量、实验室检测，包括血细胞计数、血清学、生化、细胞亚群、细胞因子和 CT 扫描。结果显示，UC-MSC组第14天铁蛋白、IL-6和MCP1-CCL2水平下降。第二个月，观察到反应性C蛋白、D-二聚体和中性粒细胞水平下降，TCD3、TCD4和NK淋巴细胞数量增加。第四个月时观察到肺损伤范围减少。所有这些参数的改善一直保持到患者随访结束。 UC-MSCs输注是安全的，并且可以作为辅助治疗发挥重要作用，无论是在早期阶段，预防严重并发症，还是在慢性阶段，减少重症COVID-19患者的急性后遗症。试验注册巴西临床试验注册处 (ReBEC)，UTN 代码-U1111-1254-9819。 2020 年 10 月 31 日注册 - 追溯注册，https://ensaiosclinicos.gov.br/rg/RBR-3fz9yr 在线版本包含可在 10.1186/s13287-022-02796-1 获取的补充材料。
COVID-19 is a multisystem disease that presents acute and persistent symptoms, the postacute sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARS-CoV-2, associated clotting or inflammatory processes during acute COVID-19. Various strategies are being chosen by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efficient in treating such a complex disease. Mesenchymal stromal cells (MSCs) are known for their immunomodulatory properties and regeneration ability; therefore, they are a promising tool for treating disorders involving immune dysregulation and extensive tissue damage, as is the case with COVID-19. This study aimed to assess the safety and explore the long-term efficacy of three intravenous doses of UC-MSCs (umbilical cord MSCs) as an adjunctive therapy in the recovery and postacute sequelae reduction caused by COVID-19. To our knowledge, this is one of the few reports that presents the longest follow-up after MSC treatment in COVID-19 patients. This was a phase I/II, prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Seventeen patients diagnosed with COVID-19 who require intensive care surveillance and invasive mechanical ventilation—critically ill patients—were included. The patient infusion was three doses of 5 × 105 cells/kg UC-MSCs, with a dosing interval of 48 h (n = 11) or placebo (n = 6). The evaluations consisted of a clinical assessment, viral load, laboratory testing, including blood count, serologic, biochemical, cell subpopulation, cytokines and CT scan. The results revealed that in the UC-MSC group, there was a reduction in the levels of ferritin, IL-6 and MCP1-CCL2 on the fourteen day. In the second month, a decrease in the levels of reactive C-protein, D-dimer and neutrophils and an increase in the numbers of TCD3, TCD4 and NK lymphocytes were observed. A decrease in extension of lung damage was observed at the fourth month. The improvement in all these parameters was maintained until the end of patient follow-up. UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients. Trial registration Brazilian Registry of Clinical Trials (ReBEC), UTN code-U1111-1254-9819. Registered 31 October 2020—Retrospectively registered, https://ensaiosclinicos.gov.br/rg/RBR-3fz9yr The online version contains supplementary material available at 10.1186/s13287-022-02796-1.