Chen Li, Zhang An, Li Quntang, Cui Yong, Yuan Guodan
Department of Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Preventive Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Apr;33(4):399-404. doi: 10.3760/cma.j.cn121430-20200628-00490.
To evaluate the clinical efficacy of Xuebijing combined with human immunoglobulin for the treatment of severe and critically ill patients with coronavirus disease 2019 (COVID-19).
A retrospective study was conducted. The clinical data of 65 patients with severe and critical COVID-19 admitted to Chongqing Public Health Medical Center and Chongqing Three Gorges Central Hospital from January 2020 to March 2020 during the period of supporting to combat COVID-19 by the medical team of the Second Affiliated Hospital of Chongqing Medical University and Chongqing Hospital of Traditional Chinese Medicine were analyzed. According to different treatment regimens, patients were divided into conventional treatment group (conventional antivirus, anti-infection and symptomatic support treatments), Xuebijing group (Xuebijing was applied to patients with elevated inflammatory cytokines) and combination group (Xuebijing combined with human immunoglobulin, human immunoglobulin was applied to patients with low immunity indicated by monitoring results of lymphocytes and their subsets). The improvement of blood routine examination, blood gas analysis, myocardial enzyme spectrum, liver and kidney function, lymphocytes and their subsets and cytokines as well as severity score in three groups before and after treatment were observed. Kaplan-Meier method was used to draw the 28-day survival curve of each group, and the cumulative survival rate among the groups was compared.
Among the 65 severe and critically ill COVID-19 patients, only 20 patients received conventional treatment, 22 patients were treated with Xuebijing based on conventional treatment, and 23 patients were treated with Xuebijing combined with human immunoglobulin based on conventional treatment. Before treatment, CD4 T cell count in combination group was higher than other two groups, and interleukin-6 (IL-6) was lower than other two groups, while other indicators showed no statistically significant differences among the three groups, suggesting that the baseline of the three groups was relatively balanced before treatment. The patients in the conventional treatment group were relieved after treatment, and it was characterized by that the acute physiology and chronic health evaluation II (APACHE II) score and lactate dehydrogenase (LDH) were significantly lower than those before treatment [APACHE II score: 5.20±2.74 vs. 6.20±1.93, LDH (μmol×s×L): 4.1±1.0 vs. 4.7±0.9, both P < 0.01], but there was still liver damage, which was manifested as higher aspartate aminotransferase (AST) than that before treatment [U/L: 30.5 (23.8, 41.5) vs. 21.0 (17.0, 34.0), P < 0.05]. In Xuebijing group, the respiratory function and immunity of patients were improved after treatment, and the improvement degree of the ratio of CD4 T cell was more significant than that in the conventional treatment group (4.86±6.31 vs. -0.95±12.38, P < 0.05). However, the patients still lived with an "inflammatory storm" and liver damage after treatment. It was shown that IL-4 was significantly higher than that before treatment (ng/L: 2.57±1.15 vs. 1.92±1.04, P < 0.05), while albumin (ALB) decreased significantly compared with before treatment [g/L: 33.0 (30.5, 35.6) vs. 36.2 (32.1, 41.4), P < 0.01]. While the treatment of Xuebijing combined with human immunoglobulin could improve patients' respiratory function and enhance their immunity more effectively, it was shown that arterial partial pressure of oxygen (PaO), oxygenation index (PaO/FiO), T lymphocyte count, ratio of CD4 T cell, CD4 T cell count, CD8 T cell count and CD4/CD8 ratio were significantly higher than those before treatment, while ALB, IL-6, APACHE II score and sequential organ failure assessment (SOFA) score were significantly lower than those before treatment. T lymphocyte count, the ratio of CD4 T cell and IL-6 in combination group were improved more significantly than those in conventional treatment group and Xuebijing group [T lymphocyte count (×10/L): 310.68±359.28 vs. 46.54±240.01, 81.59±256.76; ratio of CD4 T cell: 14.53±14.49 vs. -0.95±12.38, 4.86±6.31; IL-6 (ng/L): -25.53±39.05 vs. -1.75±5.45, 12.78±44.81], PaO/FiO was improved more significantly as compared with the Xuebijing group [mmHg (1 mmHg = 0.133 kPa): 146.31±109.73 vs. 59.41±87.70], and the differences were statistically different (all P < 0.05).
The combination of Xuebijing and human immunoglobulin for the treatment of patients with COVID-19 can improve patients' respiratory function, reduce "inflammatory storm", enhance immunity, and alleviate severity of patients' condition.
评价血必净联合人免疫球蛋白治疗新型冠状病毒肺炎(COVID-19)重症及危重症患者的临床疗效。
进行一项回顾性研究。分析了2020年1月至2020年3月期间,重庆医科大学附属第二医院和重庆市中医院医疗队在支援抗击COVID-19期间,重庆公共卫生医疗中心和重庆三峡中心医院收治的65例COVID-19重症及危重症患者的临床资料。根据不同治疗方案,将患者分为常规治疗组(常规抗病毒、抗感染及对症支持治疗)、血必净组(炎症因子升高患者应用血必净)和联合组(血必净联合人免疫球蛋白,根据淋巴细胞及其亚群监测结果,将人免疫球蛋白应用于免疫力低下患者)。观察三组治疗前后血常规、血气分析、心肌酶谱、肝肾功能、淋巴细胞及其亚群、细胞因子的改善情况以及病情严重程度评分。采用Kaplan-Meier法绘制各组28天生存曲线,并比较各组间的累积生存率。
65例COVID-19重症及危重症患者中,仅20例接受常规治疗,22例在常规治疗基础上加用血必净治疗,23例在常规治疗基础上加用血必净联合人免疫球蛋白治疗。治疗前,联合组CD4 T细胞计数高于其他两组,白细胞介素-6(IL-6)低于其他两组,而三组间其他指标差异无统计学意义,提示三组治疗前基线相对均衡。常规治疗组患者治疗后病情缓解,表现为急性生理与慢性健康状况评分系统II(APACHE II)评分和乳酸脱氢酶(LDH)显著低于治疗前[APACHE II评分:5.20±2.74 vs. 6.20±1.93,LDH(μmol×s×L):4.1±1.0 vs. 4.7±0.9,均P < 0.01],但仍存在肝损伤,表现为天门冬氨酸氨基转移酶(AST)高于治疗前[U/L:30.5(23.8,41.5)vs. 21.0(17.0,34.0),P < 0.05]。血必净组患者治疗后呼吸功能和免疫力改善,CD4 T细胞比例改善程度较常规治疗组更显著(4.86±6.31 vs. -0.95±12.38,P < 0.05)。然而,患者治疗后仍存在“炎症风暴”和肝损伤。结果显示IL-4显著高于治疗前(ng/L:2.57±1.15 vs. 1.92±1.04,P < 0.05),而白蛋白(ALB)较治疗前显著降低[g/L:33.0(30.5,35.6)vs. 36.2(32.1,41.4),P < 0.01]。而血必净联合人免疫球蛋白治疗能更有效地改善患者呼吸功能,增强免疫力,表现为动脉血氧分压(PaO)、氧合指数(PaO/FiO)、T淋巴细胞计数、CD4 T细胞比例、CD4 T细胞计数、CD8 T细胞计数及CD4/CD8比值均显著高于治疗前,而ALB、IL-6、APACHE II评分及序贯器官衰竭评估(SOFA)评分均显著低于治疗前。联合组T淋巴细胞计数、CD4 T细胞比例及IL-6较常规治疗组和血必净组改善更显著[T淋巴细胞计数(×10/L):310.68±359.28 vs. 46.54±240.01,81.59±256.76;CD4 T细胞比例:14.53±14.49 vs. -0.95±12.38,4.86±6.31;IL-6(ng/L):-25.53±39.05 vs. -1.75±5.45,12.78±44.81],PaO/FiO较血必净组改善更显著[mmHg(1 mmHg = 0.133 kPa):146.31±109.73 vs. 59.41±87.70],差异均有统计学意义(均P < 0.05)。
血必净与人免疫球蛋白联合治疗COVID-19患者可改善患者呼吸功能,减轻“炎症风暴”,增强免疫力,缓解患者病情严重程度。