【摘要】 目的分析新型冠状病毒肺炎(COVID-19)早期(起病14天内)外周血免疫学特征及其与疾病严重程度的关系。方法收集2020年1月至3月广州医科大学附属市八医院收治的98例确诊COVID-19患者住院资料,分析COVID-19早期外周血淋巴细胞亚群[CD4~+T、CD8~+T细胞、B细胞、自然杀伤(NK)细胞、NKT细胞与调节性T细胞]和细胞因子[白细胞介素(IL)-2、IL-4、IL-6、IL-10、肿瘤坏死因子-α和干扰素-γ]变化特征,以及上述指标与患者病情严重程度的关系。年龄、起病时间、白细胞、中性粒细胞、淋巴细胞、淋巴细胞亚群和细胞因子水平为非正态分布的计量资料,3组患者间比较采用Kruskal-Wallis检验;性别、基础疾病、吸烟、武汉流行病学史、家庭成员被感染、症状、实验室指标异常比例为计数资料,采用Pearson卡方检验或Fisher确切概率检验;以Logistic回归分析影响疾病严重性的高危因素。结果根据病情严重程度将入组患者分为轻型组(17例)、普通型组(73例)和重型组(8例)。早期55.1%(54/98)患者CD4~+T细胞、40.8%(40/98)患者CD8~+T细胞和11.8%(10/85)患者B细胞计数下降。3组患者间CD4~+T细胞(P=0.010)、CD8~+T细胞(P=0.003)和B细胞(P=0.022)计数存在显著差异,以重型组水平最低。3组患者IL-6表达差异有统计学意义(P=0.001),以重型组水平最高,而其他细胞亚群及细胞因子水平则无显著差异(P均> 0.05)。Logistic回归分析显示,IL-6升高(OR=12.277、P=0.024)和年龄> 50岁(OR=21.823、P=0.030)分别为发生肺炎和重型化的独立预测因素。结论 COVID-19早期即明显破坏患者机体细胞和体液免疫应答,与疾病进展密切相关。更多还原

【Abstract】 Objective To investigate the immunological features from peripheral blood of patients with coronavirus disease 2019(COVID-19) in early phase(within 14 days after symptom onset), and its association with the severity of disease. Methods Total of 98 patients with COVID-19 in Guangzhou Eighth People’s Hospital, Guangzhou Medical University from January to March 2020 were included. The features of patients of lymphocytes [CD4~+ T, CD8~+ T, B, natural killer(NK), NKT and Treg cells] and cytokines [interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α and interferon-γ] were analyzed in early phase, and also their associations with the severity of disease were evaluated. The nonparametric data such as age, days after symptom onset, levels of white blood cells, neutrophil, lymphocytes, lymphocytes subsets and cytokines were analyzed by Kruskal-Wallis test. The categorical variables such as sex, complications,smoke, exposure to Wuhan, family members infected, symptoms, abnormal frequency of laboratory test were analyzed by Pearson’s chi-squared test or Fisher’s exact test. The independent risk factors associated with the severity of disease were analyzed by Logistical regression analysis. Results Patients were divided into three groups according to the relevant diagnostic criteria: the mild group(17 cases), the normal group(73 cases) and the severe group(8 cases). Decreased CD4~+ T cells, CD8~+ T cells and B cells were found in 55.1%(54/98), 40.8%(40/98) and 11.8%(10/85) patients, respectively. The levels of CD4~+ T cells(P = 0.010), CD8~+ T cells(P = 0.003) and B cells(P = 0.022) were significantly different among the three groups, with the lowest levels in the severe group. The levels of IL-6(P = 0.001) were different among three groups, with the highest levels in the severe group. Levels of other lymphocytes and cytokines were similar, without significant differences(all P > 0.05). Increased level of IL-6(OR = 12.277, P = 0.024) was independently associated with pneumonia, and age over 50 years old(OR = 21.823, P = 0.030) was independently associated with the severe case by Logistic regression analysis. Conclusion The cellular and humoral immune response was significantly destroyed of patients with COVID-19 in early phase, which was significantly associated with the progression of disease.更多还原