广州市135例新型冠状病毒肺炎患者的免疫学特征分析

Analysis of immunological features of 135 patients with corona virus disease 2019 in Guangzhou City

目的分析135例新型冠状病毒肺炎(COVID-19)患者的免疫学特征,为该病致病机制提供实验室依据。方法收集2020年1月23日至2月29日广州市第八人民医院确诊的135例COVID-19患者的临床和实验室资料。分析患者住院19(14,27)d时淋巴细胞亚群(CD4+T淋巴细胞、CD8+T淋巴细胞、B淋巴细胞、自然杀伤细胞和自然杀伤T细胞)和细胞因子[白细胞介素(interleukin,IL)-2、IL-4、IL-6、IL-10、肿瘤坏死因子(tumor necrosis factor,TNF)α和γ干扰素]的变化特征。统计学方法采用Kruskal-Wallis检验、Mann-Whitney U检验、χ^2检验、Spearman秩相关分析。结果根据疾病严重程度分为轻型组(14例)、普通型组(92例)和重症组(包括重型和危重型患者,29例)。44.4%(60/135)的患者CD4+T淋巴细胞计数下降,42.2%(57/135)的患者CD8+T淋巴细胞计数下降。与轻型组和普通型组相比,重症组患者CD4+T淋巴细胞计数(Z=4.379、3.799,均P<0.01)和CD8+T淋巴细胞计数(Z=2.684、3.306,P=0.022、0.003)均下降,差异均有统计学意义。25.3%(24/95)的患者B淋巴细胞计数下降;重症组B淋巴细胞计数最低[88(56,189)/μL],下降发生率最高[52.2%(12/23)];3组间B淋巴细胞计数和下降发生率差异均有统计学意义(Z=6.199,χ^2=11.723,P=0.045、0.003)。与轻型组和普通型组相比,重症组患者IL-6(Z=-4.022、-4.108,均P<0.01)和IL-10(Z=-3.261、-4.006,均P<0.01)水平升高,差异均有统计学意义。3组患者间IL-2、IL-4、TNF-α和γ干扰素水平差异均无统计学意义(均P>0.05)。IL-6水平与病毒持续时间呈正相关(r=0.301,P=0.007)。结论免疫介导的炎症损伤可能为病情恶化的重要原因,是治疗重症患者的关键。

Objective To investigate the immunological features of 135 patients with corona virus disease 2019(COVID-19),and to provide reference for the pathogenesis of the disease.Methods The clinical and laboratory data of 135 confirmed COVID-19 patients in Guangzhou Eighth People′s Hospital from January 23 to February 29,2020 were collected.The features of lymphocytes(CD4+and CD8+T lymphocytes,B lymphocytes,natural killer cells and natural killer T cells),and cytokines(interleukin(IL)-2,IL-4,IL-6,IL-10,tumor necrosis factor(TNF)-αand interferon(IFN)-γ)of patients at a median of 19(14,27)days of admission were analyzed.Kruskal-Wallis test,Mann-Whitney U test,chi-square test and Spearman rank correlation were used for statistical analysis.Results Patients were divided into three groups according to the relevant diagnostic criteria,including mild group(14 cases),ordinary group(92 cases)and severe group(29 cases).Decreased CD4+T lymphocytes were found in 44.4%(60/135)patients,while decreased CD8+T lymphocytes were found in 42.2%(57/135)patients.Compared to mild group and ordinary group,level of CD4+T lymphocytes in severe group was significant lower(Z=4.379 and 3.799,respectively,both P<0.01),and level of CD8+T lymphocytes was also significant lower(Z=2.684 and 3.306,respectively,P=0.022 and 0.003,respectively).Decreased B lymphocytes were found in 25.3%(24/95)patients and significant different among the three groups,with the lowest levels((88(56,189)/μL;Z=6.199,P=0.045)and most frequency of decreased levels((52.2%(12/23);χ^2=11.723,P=0.003)in the severe group.Compared to the mild group and the ordinary group,IL-6 level in severe group was significant higher(Z=-4.022 and-4.108,respectively,both P<0.01)and IL-10 level was also significant higher(Z=-3.261 and-4.006,respectively,both P<0.01).Similar levels of IL-2,IL-4,TNF-αand IFN-γwere found among three groups(all P>0.05).The IL-6 level was positively correlated with the persistence of viral shedding(r=0.301,P=0.007).Conclusion The immune-mediated inflammation may be the important cause of disease deterioration of COVID-19,which might be the key target of the treatment of severe cases.