H7N9禽流感病毒与H5N1、pH1N1等流感病毒临床特征的对比分析
发布时间：2019-06-28 20:53
【摘要】：2013年春季,一种新的禽源性甲型流感(H7N9)病毒在中国出现。基因分析显示病人中分离出来的H7N9禽流感病毒显示出对哺乳动物的部分适应性,增加了与人类呼吸道上皮细胞唾液酸a-2,6型受体的亲和力,对小鼠的毒力增加,对金刚烷胺耐药,而对奥司他韦敏感。我们尚没有这种病毒所致感染的临床特点的资料。以及与其他流感病毒比如H5N1、pHlNl在发病危险因素、临床表现以及住院后疾病进展方面的比较。 方法：我们设计病例报告表格,收集了截至2013年10月25日,中国大陆报道的137例经实验室检查确诊的禽源性甲型流感病毒(H7N9)感染病人的数据,以及119例H5N1和3486例pH1N1病人的临床数据。评估校正了年龄和性别特异性的危险因素流行率以后的因流感住院的危险因素,比较了不同亚型之间的临床、实验室以及临床预后的差别。对其中的40例H7N9病人进行了细胞因子和病毒载量的检测,与疾病的严重性进行了相关性分析；并分析了李氏人工肝治疗疾病快速进展,并检测到细胞因子风暴的重症H7N9禽流感病毒病人的疗效。 结果：在我们所研究的137例患者中,77.4%入住了重症监护病房(ICU)33.6%死亡。患者年龄的中位数为61岁,42.3%的患者年龄≥65岁,其中31.4%为女性。共有61.9%的患者至少存在一种基础疾病。发热和咳嗽是最为常见的起病症状。入院时,133例患者(98.5%)有肺炎的表现。双肺毛玻璃样阴影和实变是典型的x线表现。88.3%的患者中观察到了淋巴细胞减少,73%的患者中观察到了血小板减少。133例患者(97.1%)在发病后7天(中位时间)时开始了抗病毒药物治疗。发病及开始抗病毒治疗至实时逆转录聚合酶链反应检测病毒结果为阴性的中位时间间隔分别为11天(四分位间距为9～16天)和6天(四分位间距为4～7天)。多变量分析结果显示,存在基础疾病是H7N9病人发生急性呼吸窘迫综合征(ARDS)唯一的独立危险因素(比值比为3.44,95%可信区间为1.25-9.78,P=0.02)。 对其中40名H7N9病人进行了细胞因子动态检测,发现与健康对照组比较,H7N9病人细胞因子水平高,通过Spearsman等级相关性分析发现,患者外周血病毒载量与IP-10(p=-0.692)、HGF(p=-0.509)、MIG(p=-0.500)的水平密切相关,患者APACHEII评分与IP-10(p=0.690), IL-18(p=0.658), HGF(p=0.642)水平密切相关。研究结果表明患者感染H7N9病毒细胞因子趋化因子水平显著升高,起病第二周最为显著,且与患者的疾病严重程度密切相关。 对16名疾病快速进展,检测到细胞因子风暴的病人进行了李氏人工肝治疗,发现李氏人工肝可以快速下降血浆中细胞因子水平,对于IP-10水平的下降尤为显著。 将其中的111例病人与其他流感病毒的比较发现,H7N9组年龄的中位时间要大于其他组(61岁,P0.01),男性居多(68.6%,P0.02),校正年龄和性别以后,慢性心脏疾病与H7N9的住院风险增加有关(RR9.68;95%CI5.24-17.90). H7N9病人与H5N1比较,更易于出现咳痰和咳血,H7N9与H5N1相似,均有白细胞减少、血小板减少、转氨酶、CK、CRP、LDH的升高,与pH1N1相比有显著性差异P0.005,与H5N1、pH1N1比较,H7N9组有更长的住院时间。H5N1死亡风险最高,(55%,95%CI47-64%),发生更早,疾病出现到死亡的中位时间为11天,H7N9为18天(P=0.002), pHlN1与15天(P=0.154)。 结论：在研究期间,这种新的H7N9病毒引起了严重的疾病(包括肺炎和ARDS),患者的ICU入住率和死亡率均高。研究发现HGF, SCF,IL-18,IP-10,MIF以及SCGF-beta可以做为H7N9禽流感病毒感染严重性的生物标志物,起病第二周是检测这些生物标志物的最佳时间,针对这些生物标志物的治疗可能成为潜在的治疗靶点。李氏人工肝可以降低细胞因子,从而可能针对发病机制治疗重症H7N9病人。慢性心脏疾病是H7N9住院的危险因素。H7N9住院病人的临床特点与H5N1住院病人相似,但是与H5N1或pH1N1比较,H7N9的临床过程更长。
[Abstract]:In the spring of 2013, a new avian influenza A (H7N9) virus appeared in China. The gene analysis showed that the H7N9 avian influenza virus isolated from the patient showed a partial adaptation to the mammal, increased the affinity of the sialic acid a-2,6-type receptor in the human respiratory tract epithelial cells, increased the virulence of the mouse, and was sensitive to the oseltamide. We have no information about the clinical features of this virus-induced infection. As well as the comparison with other influenza viruses such as H5N1, pHlNl at risk factors, clinical manifestations, and post-hospital disease progression. Methods: We designed a case report form to collect the data of 137 cases of avian influenza A virus (H7N9) infected with avian influenza A virus (H7N9) diagnosed by the Chinese mainland as of Oct.25,2013, and the clinical number of 119 cases of H5N1 and 3486 patients with pH1N1. The assessment of the risk factors that corrected age and gender-specific risk factors, followed by the risk factors for influenza, compared the difference between clinical, laboratory, and clinical outcomes between different subtypes In this paper,40 of the patients with H7N9 were tested for cytokines and viral load, and the relationship between the severity of the disease and the severity of the disease was analyzed. The rapid progress of the treatment of the disease was also analyzed, and the treatment of the severe H7N9 avian influenza virus (H7N9) with a cytokine storm was also detected. Results: Of the 137 patients we studied, 77.4% stayed in the intensive care unit (ICU) 33.6 % died. The median age of the patient was 61 years and 42.3% of the patients were 65 years of age, of whom 31.4% A total of 61.9% of patients had at least one group heat and cough are the most common Symptoms of the disease.133 patients (98.5%) had pneumonia at the time of admission The double-lung-glass-like shadow and real change were typical of the x-ray manifestations. In 88.3% of the patients, the number of lymphocytes was observed, and thrombocytopenia was observed in 73% of the patients.133 patients (97.1%) started antiviral drug at 7 days post-onset (median time) The median time interval between the onset and the initiation of antiviral therapy to the real-time reverse transcription polymerase chain reaction (RT-PCR) detection of the virus was 11 days (the interquartile spacing was 9-16 days) and the 6-day (quartile spacing was 4- The multivariate analysis showed that the underlying disease was the only independent risk factor (odds ratio 3.44,95% confidence interval 1.25-9.78, P = 0) for H7N9 patients with acute respiratory distress syndrome (ARDS). 02) In 40 of the patients with H7N9, the cytokine level of H7N9 patients was found to be high, and the level of cytokines in H7N9 patients was high, and it was found that the viral load in the peripheral blood of the patient was closely related to the level of IP-10 (p =-0.692), HGF (p =-0.509), and MIG (p =-0.500), and the patient's APACHE II score was closely related to IP-10 (p = 0.690), IL-18 (p = 0 .658), HGF (p = 0.642) water The results showed that the level of the cytokines of H7N9 virus in the patients was significantly increased, the second week of the onset of disease was the most significant, and the severity of the disease was associated with the patient's disease. The results showed that Li's artificial liver can rapidly decrease the level of cytokines in plasma and to the level of IP-10, which is closely related to the rapid progress of 16 diseases and the detection of cytokine storm. The decrease was especially significant. The comparison of 111 patients with other influenza viruses found that the median time for the H7N9 group was greater than that of the other groups (61 years, P0.01), and that in the majority (68.6%, P0.01), the chronic heart disease was associated with an increase in the risk of hospitalization for H7N9 (R9.68;95% CI5). 24-17.90). H7N9 patients were more susceptible to expectoration and hemoptysis than in the case of H5N1. H7N9 was similar to that of H5N1. There were leukopenia, thrombocytopenia, transaminases, CK, CRP and LDH, and there was a significant difference between p0.05, H7N9 and H7N9. There was a longer hospital stay in the group. The highest risk of H5N1 death (55%,95% CI47-64%), earlier, the median time for disease to death was 11 days, H7N9 was 18 days (P = 0.002), pHlN1 and 15 days (P = 0.154). Conclusion: This new H7N9 virus causes serious disease (including pneumonia and ARDS) during the study, and the patient's I The study found that HGF, SCF, IL-18, IP-10, MIF and SCGF-beta could be used as biomarkers for the severity of H7N9 avian influenza virus infection. The second week of the disease was the best time to detect these biomarkers and the treatment of these biomarkers. It is possible to be a potential therapeutic target. Li's artificial liver can reduce the cytokine, which may be directed to the pathogenesis Treatment of severe H7N9 patients. Chronic heart disease is The risk factors for hospitalization of H7N9. The clinical characteristics of H7N9 inpatients were similar to those of the in-patient H5N1, but compared with the H5N1 or pH1N1,
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R511.7
本文编号：2507609
[Abstract]:In the spring of 2013, a new avian influenza A (H7N9) virus appeared in China. The gene analysis showed that the H7N9 avian influenza virus isolated from the patient showed a partial adaptation to the mammal, increased the affinity of the sialic acid a-2,6-type receptor in the human respiratory tract epithelial cells, increased the virulence of the mouse, and was sensitive to the oseltamide. We have no information about the clinical features of this virus-induced infection. As well as the comparison with other influenza viruses such as H5N1, pHlNl at risk factors, clinical manifestations, and post-hospital disease progression. Methods: We designed a case report form to collect the data of 137 cases of avian influenza A virus (H7N9) infected with avian influenza A virus (H7N9) diagnosed by the Chinese mainland as of Oct.25,2013, and the clinical number of 119 cases of H5N1 and 3486 patients with pH1N1. The assessment of the risk factors that corrected age and gender-specific risk factors, followed by the risk factors for influenza, compared the difference between clinical, laboratory, and clinical outcomes between different subtypes In this paper,40 of the patients with H7N9 were tested for cytokines and viral load, and the relationship between the severity of the disease and the severity of the disease was analyzed. The rapid progress of the treatment of the disease was also analyzed, and the treatment of the severe H7N9 avian influenza virus (H7N9) with a cytokine storm was also detected. Results: Of the 137 patients we studied, 77.4% stayed in the intensive care unit (ICU) 33.6 % died. The median age of the patient was 61 years and 42.3% of the patients were 65 years of age, of whom 31.4% A total of 61.9% of patients had at least one group heat and cough are the most common Symptoms of the disease.133 patients (98.5%) had pneumonia at the time of admission The double-lung-glass-like shadow and real change were typical of the x-ray manifestations. In 88.3% of the patients, the number of lymphocytes was observed, and thrombocytopenia was observed in 73% of the patients.133 patients (97.1%) started antiviral drug at 7 days post-onset (median time) The median time interval between the onset and the initiation of antiviral therapy to the real-time reverse transcription polymerase chain reaction (RT-PCR) detection of the virus was 11 days (the interquartile spacing was 9-16 days) and the 6-day (quartile spacing was 4- The multivariate analysis showed that the underlying disease was the only independent risk factor (odds ratio 3.44,95% confidence interval 1.25-9.78, P = 0) for H7N9 patients with acute respiratory distress syndrome (ARDS). 02) In 40 of the patients with H7N9, the cytokine level of H7N9 patients was found to be high, and the level of cytokines in H7N9 patients was high, and it was found that the viral load in the peripheral blood of the patient was closely related to the level of IP-10 (p =-0.692), HGF (p =-0.509), and MIG (p =-0.500), and the patient's APACHE II score was closely related to IP-10 (p = 0.690), IL-18 (p = 0 .658), HGF (p = 0.642) water The results showed that the level of the cytokines of H7N9 virus in the patients was significantly increased, the second week of the onset of disease was the most significant, and the severity of the disease was associated with the patient's disease. The results showed that Li's artificial liver can rapidly decrease the level of cytokines in plasma and to the level of IP-10, which is closely related to the rapid progress of 16 diseases and the detection of cytokine storm. The decrease was especially significant. The comparison of 111 patients with other influenza viruses found that the median time for the H7N9 group was greater than that of the other groups (61 years, P0.01), and that in the majority (68.6%, P0.01), the chronic heart disease was associated with an increase in the risk of hospitalization for H7N9 (R9.68;95% CI5). 24-17.90). H7N9 patients were more susceptible to expectoration and hemoptysis than in the case of H5N1. H7N9 was similar to that of H5N1. There were leukopenia, thrombocytopenia, transaminases, CK, CRP and LDH, and there was a significant difference between p0.05, H7N9 and H7N9. There was a longer hospital stay in the group. The highest risk of H5N1 death (55%,95% CI47-64%), earlier, the median time for disease to death was 11 days, H7N9 was 18 days (P = 0.002), pHlN1 and 15 days (P = 0.154). Conclusion: This new H7N9 virus causes serious disease (including pneumonia and ARDS) during the study, and the patient's I The study found that HGF, SCF, IL-18, IP-10, MIF and SCGF-beta could be used as biomarkers for the severity of H7N9 avian influenza virus infection. The second week of the disease was the best time to detect these biomarkers and the treatment of these biomarkers. It is possible to be a potential therapeutic target. Li's artificial liver can reduce the cytokine, which may be directed to the pathogenesis Treatment of severe H7N9 patients. Chronic heart disease is The risk factors for hospitalization of H7N9. The clinical characteristics of H7N9 inpatients were similar to those of the in-patient H5N1, but compared with the H5N1 or pH1N1,
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R511.7
【参考文献】
相关期刊论文 前1条
1 LI Jun;YU XinFen;PU XiaoYing;XIE Li;SUN YongXiang;XIAO HaiXia;WANG FenJuan;DIN Hua;WU Ying;LIU Di;ZHAO GuoQiu;LIU Jun;PAN JingCao;;Environmental connections of novel avian-origin H7N9 influenza virus infection and virus adaptation to the human[J];Science China(Life Sciences);2013年06期
，本文编号：2507609
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