H7N9禽流感病毒與H5N1、pH1N1等流感病毒臨床特征的對(duì)比分析
發(fā)布時(shí)間：2019-06-28 20:53
【摘要】：2013年春季,一種新的禽源性甲型流感(H7N9)病毒在中國出現(xiàn)�；蚍治鲲@示病人中分離出來的H7N9禽流感病毒顯示出對(duì)哺乳動(dòng)物的部分適應(yīng)性,增加了與人類呼吸道上皮細(xì)胞唾液酸a-2,6型受體的親和力,對(duì)小鼠的毒力增加,對(duì)金剛烷胺耐藥,而對(duì)奧司他韋敏感。我們尚沒有這種病毒所致感染的臨床特點(diǎn)的資料。以及與其他流感病毒比如H5N1、pHlNl在發(fā)病危險(xiǎn)因素、臨床表現(xiàn)以及住院后疾病進(jìn)展方面的比較。 方法：我們?cè)O(shè)計(jì)病例報(bào)告表格,收集了截至2013年10月25日,中國大陸報(bào)道的137例經(jīng)實(shí)驗(yàn)室檢查確診的禽源性甲型流感病毒(H7N9)感染病人的數(shù)據(jù),以及119例H5N1和3486例pH1N1病人的臨床數(shù)據(jù)。評(píng)估校正了年齡和性別特異性的危險(xiǎn)因素流行率以后的因流感住院的危險(xiǎn)因素,比較了不同亞型之間的臨床、實(shí)驗(yàn)室以及臨床預(yù)后的差別。對(duì)其中的40例H7N9病人進(jìn)行了細(xì)胞因子和病毒載量的檢測,與疾病的嚴(yán)重性進(jìn)行了相關(guān)性分析；并分析了李氏人工肝治療疾病快速進(jìn)展,并檢測到細(xì)胞因子風(fēng)暴的重癥H7N9禽流感病毒病人的療效。 結(jié)果：在我們所研究的137例患者中,77.4%入住了重癥監(jiān)護(hù)病房(ICU)33.6%死亡�；颊吣挲g的中位數(shù)為61歲,42.3%的患者年齡≥65歲,其中31.4%為女性。共有61.9%的患者至少存在一種基礎(chǔ)疾病。發(fā)熱和咳嗽是最為常見的起病癥狀。入院時(shí),133例患者(98.5%)有肺炎的表現(xiàn)。雙肺毛玻璃樣陰影和實(shí)變是典型的x線表現(xiàn)。88.3%的患者中觀察到了淋巴細(xì)胞減少,73%的患者中觀察到了血小板減少。133例患者(97.1%)在發(fā)病后7天(中位時(shí)間)時(shí)開始了抗病毒藥物治療。發(fā)病及開始抗病毒治療至實(shí)時(shí)逆轉(zhuǎn)錄聚合酶鏈反應(yīng)檢測病毒結(jié)果為陰性的中位時(shí)間間隔分別為11天(四分位間距為9～16天)和6天(四分位間距為4～7天)。多變量分析結(jié)果顯示,存在基礎(chǔ)疾病是H7N9病人發(fā)生急性呼吸窘迫綜合征(ARDS)唯一的獨(dú)立危險(xiǎn)因素(比值比為3.44,95%可信區(qū)間為1.25-9.78,P=0.02)。 對(duì)其中40名H7N9病人進(jìn)行了細(xì)胞因子動(dòng)態(tài)檢測,發(fā)現(xiàn)與健康對(duì)照組比較,H7N9病人細(xì)胞因子水平高,通過Spearsman等級(jí)相關(guān)性分析發(fā)現(xiàn),患者外周血病毒載量與IP-10(p=-0.692)、HGF(p=-0.509)、MIG(p=-0.500)的水平密切相關(guān),患者APACHEII評(píng)分與IP-10(p=0.690), IL-18(p=0.658), HGF(p=0.642)水平密切相關(guān)。研究結(jié)果表明患者感染H7N9病毒細(xì)胞因子趨化因子水平顯著升高,起病第二周最為顯著,且與患者的疾病嚴(yán)重程度密切相關(guān)。 對(duì)16名疾病快速進(jìn)展,檢測到細(xì)胞因子風(fēng)暴的病人進(jìn)行了李氏人工肝治療,發(fā)現(xiàn)李氏人工肝可以快速下降血漿中細(xì)胞因子水平,對(duì)于IP-10水平的下降尤為顯著。 將其中的111例病人與其他流感病毒的比較發(fā)現(xiàn),H7N9組年齡的中位時(shí)間要大于其他組(61歲,P0.01),男性居多(68.6%,P0.02),校正年齡和性別以后,慢性心臟疾病與H7N9的住院風(fēng)險(xiǎn)增加有關(guān)(RR9.68;95%CI5.24-17.90). H7N9病人與H5N1比較,更易于出現(xiàn)咳痰和咳血,H7N9與H5N1相似,均有白細(xì)胞減少、血小板減少、轉(zhuǎn)氨酶、CK、CRP、LDH的升高,與pH1N1相比有顯著性差異P0.005,與H5N1、pH1N1比較,H7N9組有更長的住院時(shí)間。H5N1死亡風(fēng)險(xiǎn)最高,(55%,95%CI47-64%),發(fā)生更早,疾病出現(xiàn)到死亡的中位時(shí)間為11天,H7N9為18天(P=0.002), pHlN1與15天(P=0.154)。 結(jié)論：在研究期間,這種新的H7N9病毒引起了嚴(yán)重的疾病(包括肺炎和ARDS),患者的ICU入住率和死亡率均高。研究發(fā)現(xiàn)HGF, SCF,IL-18,IP-10,MIF以及SCGF-beta可以做為H7N9禽流感病毒感染嚴(yán)重性的生物標(biāo)志物,起病第二周是檢測這些生物標(biāo)志物的最佳時(shí)間,針對(duì)這些生物標(biāo)志物的治療可能成為潛在的治療靶點(diǎn)。李氏人工肝可以降低細(xì)胞因子,從而可能針對(duì)發(fā)病機(jī)制治療重癥H7N9病人。慢性心臟疾病是H7N9住院的危險(xiǎn)因素。H7N9住院病人的臨床特點(diǎn)與H5N1住院病人相似,但是與H5N1或pH1N1比較,H7N9的臨床過程更長。
[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,
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R511.7
本文編號(hào)：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,
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R511.7
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
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
，本文編號(hào)：2507609
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