新型冠状病毒肺炎细胞因子的动态变化及与主要临床结局的关系

The Dynamic Characteristics of Cytokine Profiles in Patients with COVID-19 and Impacts on the Vital Clinical Outcomes

目的探讨新型冠状病毒肺炎(COVID-19)细胞因子水平的动态变化、在不同病情严重程度间的比较及与主要临床结局的相关性。方法纳入2020年1月25日—5月2日在福建省福州肺科医院确诊的COVID-19患者36例,分为轻症组和重症组。比较两组患者的临床资料及入院第4—6天、第7—10天、第11—15天及出院后1个月的白细胞介素-2(IL-2)、IL-4、IL-6、IL-10、肿瘤坏死因子(TNF)、γ-干扰素(IFN-γ)、IL-17A及α-干扰素(IFN-α)的水平。结果轻症组31例,重症组5例,无死亡病例,重症组年龄大于轻症组[(69.0±12.4)岁vs(42.6±14.4)岁,P<0.001];重症组合并心脑血管病比例高于轻症组(100.0%vs 25.8%,P=0.003);重症组白细胞(WBC)计数、中性粒细胞(NEU)计数、乳酸脱氢酶(LDH)、D-二聚体(D-D)、C反应蛋白(CRP)、IL-6、IL-10水平与轻症组比较,差别有统计学意义(P<0.05)。两两比较发现,两组患者的IL-6、IL-10在不同时间段、不同时间段的变化率不同,IL-6值在入院第7—10天达高峰,IL-10值在入院第4—6天达高峰。两组间IL-2、IFN-γ、IFN-α、TNF、IL-4、IL-17A比较,差别均无统计学意义(P>0.05)。直线回归分析提示,第4—6天IL-6水平与热退时间呈正相关(Y=2.394X+15.470,r=0.539,P=0.001),IL-10水平与核酸阴转时间呈正相关(Y=0.254X+2.636,r=0.466,P=0.004)。结论重症患者较轻症患者年龄大,常合并心脑血管病,低WBC计数、低NEU计数及升高的LDH、D-D、CRP、IL-6、IL-10水平有助于病情识别,IL-6、IL-10与主要临床结局相关。

Objective Compare the dynamic changes of cytokines in patients with Coronavirus disease 2019(COVID-19)and explore their correlation with the vital clinical outcomes.Method 36 patients admitted to Fuzhou pulmonary hospital of Fujian province from January 25,2020 to May 2,2020 were divided into mild group and severe group.Compare the differences of clinical data and the levels of cytokines including interleukin-2(IL-2),interleukin-4(IL-4),interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor(TNF),interferonγ(IFN-γ),interleukin-17A(IL-17A)and interferonα(IFN-α)on Day 4-6,Day 7-10,Day 11-15 after hospitalization and 1 month after discharged between two groups.Results The mild group has 31 patients and the severe group has 5 patients,no dead is found.The average age is higher in severe group than in mild group[(69.0±12.4)years vs(42.6±14.4)years,P<0.001];the rate with heart and brain vascular diseases in severe group is higher than in the mild group(100.0%vs 25.8%),P=0.003;there are lower white blood cell(WBC)counting and neutrophil(NEU)counting,higher lactate dehydrogenase(LDH),D dimer(D-D)and C reactive protein(CRP),higher IL-6 and IL-10 in sever group that has significant difference(P<0.05).Meanwhile,the values and change rates of IL-6 and IL-10 are not same in four periods after hospitalization and discharge where IL-6 reached peak on Day 7-10 after hospitalization while IL-10 on Day 4-6.There are no significance in the level of IL-2,IFN-γ,IFN-α,TNF,IL-4,IL-17A between two groups.Linear regression analysis shows the value of IL-6 on Day 4-6 has positive relation with the time of fever relieving(Y=2.394X+15.470,r=0.539),as well as IL-10 with the time of virus acid negative conversion(Y=0.254X+2.636,r=0.466).Conclusion Severe patients with COVID-19 are older than mild patients who have heart and brain vascular conditions more often than mild patients.Low WBC counting,low neutrophil counting and elevated LDH,D-D,CRP,IL-6 and IL-10 are favor to distinguish the severity of disease in early stage after disease onset.The value of IL-6 and IL-10 have close relations with some main clinical outcomes.