Abstract：
The novel coronavirus is still mutating, and the pandemic continues. Meanwhile, many COVID-19 survivors have residual postinfection clinical manifestations. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been shown to be effective in the early stages of COVID-19.
The aim of this study was to investigate long-term safety and efficacy of treatment in patients with severe COVID-19 patients who had received hUC-MSCs therapy.
Twenty-five discharged patients who had severe COVID-19 (including the standard treatment group and the standard treatment plus hUC-MSCs group) were enrolled in a 1-year follow-up. The assessment considered adverse effects (including effects on liver and kidney function, coagulation, ECG, tumor marker, and so on), pulmonary function, St George\'s Respiratory Questionnaire (SGRQ), postinfection sequelae and serum concentration of Krebs von den Lungen-6 (KL-6), malondialdehyde (MDA), H2S, carnitine, and N-6 long-chain polyunsaturated fatty acids (N-6 LC-PUFAs).
Pulmonary ventilation function had significantly improved at the 1-year follow-up in both the hUC-MSCs group and the control group compared with the 3-month follow-up (P < 0.01). Fatigue (60% [15/25]) remained the most common symptom at the 1-year follow-up. The rate of fatigue relief was significantly reduced in the hUC-MSCs group (25% [2/8]) compared to the control group (76.5% [13/17]) (P = 0.028). The level of KL-6 was significantly lower in the hUC-MSCs group (2585.5 ± 186.5 U/ml) than in the control group (3120.7 ± 158.3 U/ml) (P < 0.001). Compared with the control group, the hUC-MSCs group had a lower level of MDA (9.27 ± 0.54 vs. 9.91 ± 0.72 nmol/ml, P = 0.036). No obvious adverse effects were observed in the hUC-MSCs treatment group at 1 year after discharge.
Intravenous transplantation of hUC-MSCs was a safe approach in the long term in the treatment of patients with severe COVID-19. In addition, hUC-MSCs had a positive effect on postinfection sequelae in COVID-19 survivors.
Chinese Clinical Trial Registration; ChiCTR2000031494; Registered 02 April 2020-Retrospectively registered, http://www.medresman.org.
The aim of this study was to investigate long-term safety and efficacy of treatment in patients with severe COVID-19 patients who had received hUC-MSCs therapy.
Twenty-five discharged patients who had severe COVID-19 (including the standard treatment group and the standard treatment plus hUC-MSCs group) were enrolled in a 1-year follow-up. The assessment considered adverse effects (including effects on liver and kidney function, coagulation, ECG, tumor marker, and so on), pulmonary function, St George\'s Respiratory Questionnaire (SGRQ), postinfection sequelae and serum concentration of Krebs von den Lungen-6 (KL-6), malondialdehyde (MDA), H2S, carnitine, and N-6 long-chain polyunsaturated fatty acids (N-6 LC-PUFAs).
Pulmonary ventilation function had significantly improved at the 1-year follow-up in both the hUC-MSCs group and the control group compared with the 3-month follow-up (P < 0.01). Fatigue (60% [15/25]) remained the most common symptom at the 1-year follow-up. The rate of fatigue relief was significantly reduced in the hUC-MSCs group (25% [2/8]) compared to the control group (76.5% [13/17]) (P = 0.028). The level of KL-6 was significantly lower in the hUC-MSCs group (2585.5 ± 186.5 U/ml) than in the control group (3120.7 ± 158.3 U/ml) (P < 0.001). Compared with the control group, the hUC-MSCs group had a lower level of MDA (9.27 ± 0.54 vs. 9.91 ± 0.72 nmol/ml, P = 0.036). No obvious adverse effects were observed in the hUC-MSCs treatment group at 1 year after discharge.
Intravenous transplantation of hUC-MSCs was a safe approach in the long term in the treatment of patients with severe COVID-19. In addition, hUC-MSCs had a positive effect on postinfection sequelae in COVID-19 survivors.
Chinese Clinical Trial Registration; ChiCTR2000031494; Registered 02 April 2020-Retrospectively registered, http://www.medresman.org.
摘要：
新型冠状病毒仍在变异，大流行仍在继续。同时,许多COVID-19幸存者有残留的感染后临床表现。人脐带间充质干细胞（hUC-MSCs）已被证明在COVID-19的早期阶段是有效的。
这项研究的目的是研究接受hUC-MSCs治疗的重症COVID-19患者的长期安全性和有效性。
对25例重度COVID-19出院患者（包括标准治疗组和标准治疗加hUC-MSCs组）进行1年随访。评估认为不良反应（包括对肝肾功能的影响，凝血,心电图,肿瘤标志物，等等)，肺功能,圣乔治呼吸问卷(SGRQ)，感染后后遗症和KrebsvondenLungen-6（KL-6）的血清浓度，丙二醛（MDA），H2S,肉碱,和N-6长链多不饱和脂肪酸(N-6LC-PUFA)。
hUC-MSCs组及对照组随访1年肺通气功能均较随访3个月明显改善(P<0.01)。在1年的随访中，疲劳（60％[15/25]）仍然是最常见的症状。与对照组(76.5%[13/17])相比,hUC-MSCs组(25%[2/8])的疲劳缓解率显著降低(P=0.028)。hUC-MSCs组KL-6水平(2585.5±186.5U/ml)显著低于对照组(3120.7±158.3U/ml)(P<0.001)。与对照组相比,hUC-MSCs组MDA水平较低(9.27±0.54vs.9.91±0.72nmol/ml，P=0.036)。hUC-MSCs治疗组出院后1年未见明显不良反应。
静脉移植hUC-MSCs是治疗重症COVID-19患者的长期安全方法。此外,hUC-MSCs对COVID-19幸存者感染后后遗症有积极作用。
中国临床试验注册；ChiCTR2000031494；注册2020年4月2日-回顾性注册，http://www。medresman.org.
这项研究的目的是研究接受hUC-MSCs治疗的重症COVID-19患者的长期安全性和有效性。
对25例重度COVID-19出院患者（包括标准治疗组和标准治疗加hUC-MSCs组）进行1年随访。评估认为不良反应（包括对肝肾功能的影响，凝血,心电图,肿瘤标志物，等等)，肺功能,圣乔治呼吸问卷(SGRQ)，感染后后遗症和KrebsvondenLungen-6（KL-6）的血清浓度，丙二醛（MDA），H2S,肉碱,和N-6长链多不饱和脂肪酸(N-6LC-PUFA)。
hUC-MSCs组及对照组随访1年肺通气功能均较随访3个月明显改善(P<0.01)。在1年的随访中，疲劳（60％[15/25]）仍然是最常见的症状。与对照组(76.5%[13/17])相比,hUC-MSCs组(25%[2/8])的疲劳缓解率显著降低(P=0.028)。hUC-MSCs组KL-6水平(2585.5±186.5U/ml)显著低于对照组(3120.7±158.3U/ml)(P<0.001)。与对照组相比,hUC-MSCs组MDA水平较低(9.27±0.54vs.9.91±0.72nmol/ml，P=0.036)。hUC-MSCs治疗组出院后1年未见明显不良反应。
静脉移植hUC-MSCs是治疗重症COVID-19患者的长期安全方法。此外,hUC-MSCs对COVID-19幸存者感染后后遗症有积极作用。
中国临床试验注册；ChiCTR2000031494；注册2020年4月2日-回顾性注册，http://www。medresman.org.
