摘要目的:评价血必净联合人免疫球蛋白在重型及危重型新型冠状病毒肺炎（新冠肺炎）中的临床疗效。方法:采用回顾性研究方法，分析重庆医科大学附属第二医院和重庆市中医院医疗团队2020年1月至3月在支援重庆市公共卫生医疗救治中心及重庆三峡中心医院抗击新冠肺炎期间收治的65例重型、危重型新冠肺炎患者的临床资料。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（炎性细胞因子升高者加用血必净注射液）和联合组（血必净联合人免疫球蛋白，淋巴细胞及其亚群监测结果提示免疫力低下者加用人免疫球蛋白）。观察3组患者治疗前后血常规、血气分析、心肌酶谱、肝肾功能、淋巴细胞及其亚群、细胞因子等相关指标和危重程度评分改善情况；采用Kaplan-Meier法绘制各组患者28 d生存曲线，比较各组累积生存率。结果:65例重型及危重型新冠肺炎患者中，仅接受常规治疗20例，加用血必净治疗22例，加用血必净联合人免疫球蛋白治疗23例。治疗前，联合组CD4 + T细胞计数明显低于其他两组，白细胞介素-6（IL-6）明显高于其他两组，而3组间其余指标差异均无统计学意义，提示3组患者治疗前基线较为均衡。常规治疗组治疗后患者病情有所减轻，表现为急性生理学与慢性健康状况评分Ⅱ（APACHEⅡ）和乳酸脱氢酶（LDH）较治疗前明显降低〔APACHEⅡ评分（分）：5.20±2.74比6.20±1.93，LDH（μmol·s -1·L -1）：4.1±1.0比4.7±0.9，均 P<0.01〕，但仍存在肝脏损伤，表现为天冬氨酸转氨酶（AST）较治疗前明显升高〔U/L：30.5（23.8，41.5）比21.0（17.0，34.0）， P<0.05〕。血必净组治疗后患者呼吸功能改善，免疫力有所增强，CD4 + T细胞比例改善程度较常规治疗组更加显著（4.86±6.31比-0.95±12.38， P<0.05），但仍存在"炎症风暴"且合并肝损伤，表现为IL-4较治疗前明显升高（ng/L：2.57±1.15比1.92±1.04， P<0.05），白蛋白（ALB）较治疗前明显下降〔g/L：33.0（30.5，35.6）比36.2（32.1，41.4）， P<0.01〕。血必净联合人免疫球蛋白治疗可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 2）、氧合指数（PaO 2/FiO 2）、T淋巴细胞计数、CD4 + T细胞比例、CD4 + T细胞计数、CD8 + T细胞计数和CD4 +/CD8 +比值均较治疗前明显升高，ALB、IL-6、APACHEⅡ和序贯器官衰竭评分（SOFA）均较治疗前明显降低；且联合组T淋巴细胞计数、CD4 + T细胞比例、IL-6改善程度较常规治疗组及血必净组更加显著〔T淋巴细胞计数（×10 9/L）：310.68±359.28比46.54±240.01、81.59±256.76，CD4 + T细胞比例：14.53±14.49比-0.95±12.38、4.86±6.31，IL-6（ng/L）：-25.53±39.05比-1.75±5.45、12.78±44.81〕，PaO 2/FiO 2改善程度较血必净组更加显著〔mmHg（1 mmHg＝0.133 kPa）：146.31±109.73比59.41±87.70〕，差异均有统计学意义（均 P<0.05）。 结论:血必净联合人免疫球蛋白可改善重型及危重型新冠肺炎患者呼吸功能，减轻"炎症风暴"，增强免疫力，同时减轻患者病情严重程度。

abstractsObjective: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).Methods: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.Results: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 (APACHEⅡ) score and lactate dehydrogenase (LDH) were significantly lower than those before treatment [APACHEⅡ score: 5.20±2.74 vs. 6.20±1.93, LDH (μmol·s -1·L -1): 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 2), oxygenation index (PaO 2/FiO 2), 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, APACHEⅡ 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 9/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 2/FiO 2 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). Conclusion: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.