目的：探究喀什地区急性呼吸道感染(Acute respiratory infection, ARI)常见病毒性病原体病原谱构成,为临床治疗及药物的选择提供一定的循证学依据；了解本地区急性呼吸道感染病毒流性特征及与其地区的差异 ；并针对重症肺炎患者的个人一般信息及实验室检查资料进行统计分析，为重症肺炎患者的临床诊疗及预后提供参考。

方法：选取2019年11月至2020年10月于喀什地区第一人民医院因急性呼吸道感染就诊的患者以及来自包括泽普县、疏勒县、疏附县人民医院等来自喀什地区的共12个县医院的患者，采集咽拭子标本，采用实时荧光定量聚合酶链式反应法（Real Time Quantitative Polymerse Chain Reaction, RT-qPCR）检测六种常见呼吸道病毒：甲型流感病毒(Influenza A virus, Flu A)、乙型流感病毒(Influenza B virus, Flu B)、呼吸道合胞病毒(Respiratory Syncytial Virus, RSV)、 腺病毒(Adenovirus, ADV)、副流感病毒(Human parainfluenza virus, HPIVs)、肠道病毒(Human Enterovirus, HEV)核酸阳性率，分析不同年龄、季节和地区急性呼吸道感染相关病毒核酸检出情况，绘制本地区急性呼吸道感染常见病毒病原谱；同时收集所有病例的临床资料及入院首次实验室检查资料进行统计分析，建立重症肺炎预测模型。

结果：1.2019年11至2020年10月期间共检测喀什地区急性呼吸道感染病例1873例，病毒总体检出率为24.13%，六种病毒检出率由高到低依次是：Flu A(8.38%)、RSV(7.85％)、HEV(4.97％)、ADV(3.90％)、HPIVs(1.44％)、Flu B(0.48％)。2.纳入的1873例ARI病例中，成人(≥14岁)463例，病毒无性别分布差异(P>0.05)。3.六种病毒在儿童中的总体检出率(26.88%)高于成人(15.77%)。儿童中病毒检出率最高的是RSV(9.50%)，成人中病毒检出率最高的是Flu A(9.07%)，不同年龄层病原构成不尽相同。4.急性呼吸道感染病毒分布呈现一定的季节性，病毒感染高峰季多为冬季。5.在喀什地区大部分各县市中检出率最高的病毒均为Flu A，但岳普湖县、巴楚县、塔县检出率最高的病毒为RSV，泽普县检出率最高的病毒为HEV。6.维吾尔族和汉族中检出率最高的病毒均为Flu A(9.02%和6.05%)。7.单因素分析中，重症肺炎发生的影响因素为∶民族、年龄、存在先心病、WBC计数、NE%、LY%、PCT水平7个因素，与其他基础疾病（贫血、哮喘、营养不良）、CRP水平、 ESR水平、不同类型病毒感染无关；多因素回归分析中，WBC、NE%、年龄<3岁、患有先心病是重症肺炎发生的危险因素。8.最终以是否患有先心病、年龄是否＜3岁、WBC、NE%作为联合预测因子建立重症肺炎预测模型，AUC为0.741（95%CI∶0.685-0.797），约登指数为0.410，敏感性为0.53，特异性为0.88，此模型对于重症肺炎的诊断有一定的预测价值。

结论：1.喀什地区急性呼吸道感染常见病原体主要为Flu A和RSV。2.不同年龄、不同季节对应的呼吸道病原谱不同。呼吸道病毒总体检出率∶儿童高于成人，冬季高于其他季节。3.联合年龄、WBC、NE%和存在先心病建立的预测模型对于重症肺炎的诊断预测有一定的参考价值。

Objectives: By exploring the pathogen spectrum of acute respiratory infection virus in Kashgar area, we are aiming at providing evidence for clinical diagnosis and treatment, and describing the epidemiological characteristics of the virus in Kashgar area. Analyze the general information and laboratory datas of patients with severe pneumonia, to provide reference for clinical diagnosis, treatment and prognosis of patients with severe pneumonia.

Methods: Selected patients with acute respiratory infection who have admitted to the First People's Hospital of Kashgar and other surrounding county hospitals, including Zepu County, Shule County, Shufu County, and other counties of Kashgar from November 2019 to October 2020, collected patients' throat specimens. And real-time quantitative polymerse chain reaction (RT-qPCR) was used to detect six kind of viruses, including : Influenza A virus (Flu A), Influenza B virus (Flu B), respiratory syncytial virus (RSV), adenovirus (ADV), Human parainfluenza virus (HPIVs), Human Enterovirus, (HEV). We analyzed the positive rate of the virus among different regions and seasons, to draw the spectrum of the virus of acute respiratory infections in this region. We aslo collected and analyzed the related clinical and laboratory examination databases to establish a predictive model of severe pneumonia.

Results:1.From November 2019 to October 2020, 1873 cases of acute respiratory infections in Kashgar were detected, and the overall positive rate was 24.13%. The positive rates of the six viruses in descending order were: Flu A (8.38%), RSV (7.85%), HEV (4.97%), ADV (3.90%), HPIVs (1.44%), Flu B (0.48%). 2.Among the 1873 ARI cases, 463 were adults (≥14 years old) and 1410 were children (< 14 years old). There was no gender difference in virus distribution (P > 0.05). 3. The positive rate of six kind of virus in children (26.88%) was higher than that in adults (15.77%). RSV has the highest positive rate in children (9.50%) and Flu A has the highest positive rate in adults (9.07%). The composition of pathogens was different in different age groups. 4.The spread of acute respiratory virus presented certain seasonal characteristics. The peak season was winter. 5. In Kashgar, Flu A is the virus with the highest positive rate in most region in Kashgar area，but RSV was the most common virus in Yuepuhu county, Bachu county and Ta county, while HEV was the most common virus in Zepu county. 6. The highest positive rate was Flu A (9.02% and 6.05%) in Uygur and Han. 7. In univariate analysis, there were 7 factors which were ralated the severity of pneumonia，including nationality, age, presence of congenital heart disease, WBC count, NE% , LY% , PCT level, but it was not related to other basic diseases, such as anemia, asthma and malnutrition, and CRP level, ESR level and different types of virus infection. In multivariate regression analysis, there were four risk factors of severe pneumonia ,including WBC, NE%, whether were less than 3 years old, congenital heart disease. 8.Finally, the severe pneumonia prediction model was established based on whether the patients had congenital heart disease, whether they were less than 3 years old, WBC and NE%. AUC was 0.741 (95% CI: 0.685-0.797), Youden index was 0.410, sensitivity was 0.53, specificity was 0.88. This model has certain predictive value for the diagnosis of severe pneumonia.

Conclusion: 1.Flu A and RSV were the common pathogens of acute respiratory tract infection in Kashgar area. 2.The pathogen spectrum of respiratory tract was different among different ages and seasons. Total respiratory virus positive rate: higher in children than adults, higher in winter than other seasons. 3.The prediction model combined with age, WBC, NE% and the presence of congenital heart disease has a certain reference value for the diagnosis and prediction of severe pneumonia.

[1]Influenza and other emerging respiratory viruses[J]. Medicine, 2014, 42(1):45-51. [2] Haagsma J AGraetz N, Bolliger I, et al. The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013[J]. Inj Prev, 2016, 22:3-18. [3]Al-Tawfiq J A, Zumla A, Gautret P, et al. Surveillance for emerging respiratory viruses[J]. Lancet Infect Dis,2014,14(10):992-1000. [4]Ncov N C . Infection prevention and control measures for acute respiratory infections in healthcare settings: an update (WHO/EMRO, abstract)[J]. Al Majallah Al ?i??īyah LI Sharq Al Mutawassi?, 2013, 19 Suppl 1(2):S39. [5] Uyeki T M , Bernstein H H , Bradley J S , et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa[J]. Clinical Infectious Diseases(6):6. [6] Widmer K, Zhu Y, Williams JV, Griffin MR, Edwards KM, Talbot HK:Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults,The Journal of infectious diseases,2012, 206(1):56-62. [7]Al-Tawfiq J A, Zumla A, Gautret P,et al. Surveillance for emerging respiratory viruses[J]. Lancet Infect Dis,2014,14(10):992-1000. [8]Edwards KM, Zhu Y, Griffin MR, Weinberg GA, Hall CB, Szilagyi PG, Staat MA, Iwane M, Prill MM, Williams JV et al:Burden of human metapneumovirus infection in young children,The New England journal of medicine 2013, 368(7):633-643. [9]Ahmed JA, Katz MA, Auko E, Njenga MK, Weinberg M, Kapella BK, Burke H, Nyoka R, Gichangi A, Waiboci LW et al:Epidemiology of respiratory viral infections in two long-term refugee camps in Kenya, 2007-2010,BMC infectious diseases,2012, 12:7. [10]Esposito S, Daleno C, Prunotto G, Scala A, Tagliabue C, Borzani I, Fossali E, Pelucchi C, Principi N:Impact of viral infections in children with community-acquired pneumonia:results of a study of 17 respiratory viruses,Influenza and other respiratory viruses 2013, 7(1):18-26. [11]Bavagnoli L, Maga G:The 2009 influenza pandemic:promising lessons for antiviral therapy for future outbreaks,Current medicinal chemistry 2011, 18(35):5466-5475. [12]Prevention and Control of Childhood Pneumonia and Diarrhea[J]. Pediatric Clinics of North America, 2016, 63(1):67-79. [13]Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K，Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus,New England Journal of Medicine,2013,368(20):1888-97. [14]Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, Ahuja A, Yung MY, Leung C, To K:A major outbreak of severe acute respiratory syndrome in Hong Kong,New England Journal of Medicine,2003, 348(20):1986-1994. [15]World Healthy Organization Influenza(seasonal),Fact sheet No. 211, 2009,Http://www. who. int/bulletin/volumes/90/4/11-097808 / en/. [16]陈霞,刘文恩,蒋红梅,傅锦芳.1691例呼吸道感染患者病原学流行病学调查[J].实用预防医学,2018,25(08):975-977. [17]余云芳,张谨,韩福郎,马静,余枫华,吴谨呈.宜昌市发热呼吸道症候群病原学调查[J].公共卫生与预防医学,2011,22(02):77-78. [18]杨婉琪.我国部分地区住院儿童急性呼吸道感染病毒性病原谱及流行特征研究[D]. 2017. [19]张静.儿童呼吸道感染病毒病原学及分子流行病学研究[D].兰州大学, 2011. [20]雷小英,彭东红. 2009-2011年重庆地区儿童呼吸道病毒感染流行特征分析[J].重庆医科大学学报, 2013(9):1052-1057. [21]李学朝,杨筱婷,申希平,等. 甘肃省2009-2015年发热呼吸道症候群主要病原的Bayes判别分析法分类研究[J]. 中华流行病学杂志, 2017, 38(008):1094-1097. [22]Jiang W,Wu M ,Zhou J,et al. Etiologic spectrum and occurrence of coinfections in children hospitalized with community-acquired pneumonia[J]. Bmc Infectious Diseases, 2017, 17(1):787. [23]Drishti Kaul,Raveen Rathnasinghe,Marcela Ferres,Gene S. Tan,Aldo Barrera,Brett E. Pickett,Barbara A. Methe,Suman Das,Isolda Budnik,Rebecca A. Halpin,David Wentworth,Mirco Schmolke,Ignacio Mena,Randy A. Albrecht,Indresh Singh,Karen E. Nelson,Adolfo García-Sastre,Chris L. Dupont,Rafael A. Medina. Microbiome disturbance and resilience dynamics of the upper respir

[1]Influenza and other emerging respiratory viruses[J]. Medicine, 2014, 42(1):45-51. [2] Haagsma J AGraetz N, Bolliger I, et al. The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013[J]. Inj Prev, 2016, 22:3-18. [3]Al-Tawfiq J A, Zumla A, Gautret P, et al. Surveillance for emerging respiratory viruses[J]. Lancet Infect Dis,2014,14(10):992-1000. [4]Ncov N C . Infection prevention and control measures for acute respiratory infections in healthcare settings: an update (WHO/EMRO, abstract)[J]. Al Majallah Al ?i??īyah LI Sharq Al Mutawassi?, 2013, 19 Suppl 1(2):S39. [5] Uyeki T M , Bernstein H H , Bradley J S , et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa[J]. Clinical Infectious Diseases(6):6. [6] Widmer K, Zhu Y, Williams JV, Griffin MR, Edwards KM, Talbot HK:Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults,The Journal of infectious diseases,2012, 206(1):56-62. [7]Al-Tawfiq J A, Zumla A, Gautret P,et al. Surveillance for emerging respiratory viruses[J]. Lancet Infect Dis,2014,14(10):992-1000. [8]Edwards KM, Zhu Y, Griffin MR, Weinberg GA, Hall CB, Szilagyi PG, Staat MA, Iwane M, Prill MM, Williams JV et al:Burden of human metapneumovirus infection in young children,The New England journal of medicine 2013, 368(7):633-643. [9]Ahmed JA, Katz MA, Auko E, Njenga MK, Weinberg M, Kapella BK, Burke H, Nyoka R, Gichangi A, Waiboci LW et al:Epidemiology of respiratory viral infections in two long-term refugee camps in Kenya, 2007-2010,BMC infectious diseases,2012, 12:7. [10]Esposito S, Daleno C, Prunotto G, Scala A, Tagliabue C, Borzani I, Fossali E, Pelucchi C, Principi N:Impact of viral infections in children with community-acquired pneumonia:results of a study of 17 respiratory viruses,Influenza and other respiratory viruses 2013, 7(1):18-26. [11]Bavagnoli L, Maga G:The 2009 influenza pandemic:promising lessons for antiviral therapy for future outbreaks,Current medicinal chemistry 2011, 18(35):5466-5475. [12]Prevention and Control of Childhood Pneumonia and Diarrhea[J]. Pediatric Clinics of North America, 2016, 63(1):67-79. [13]Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K，Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus,New England Journal of Medicine,2013,368(20):1888-97. [14]Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, Ahuja A, Yung MY, Leung C, To K:A major outbreak of severe acute respiratory syndrome in Hong Kong,New England Journal of Medicine,2003, 348(20):1986-1994. [15]World Healthy Organization Influenza(seasonal),Fact sheet No. 211, 2009,Http://www. who. int/bulletin/volumes/90/4/11-097808 / en/. [16]陈霞,刘文恩,蒋红梅,傅锦芳.1691例呼吸道感染患者病原学流行病学调查[J].实用预防医学,2018,25(08):975-977. [17]余云芳,张谨,韩福郎,马静,余枫华,吴谨呈.宜昌市发热呼吸道症候群病原学调查[J].公共卫生与预防医学,2011,22(02):77-78. [18]杨婉琪.我国部分地区住院儿童急性呼吸道感染病毒性病原谱及流行特征研究[D]. 2017. [19]张静.儿童呼吸道感染病毒病原学及分子流行病学研究[D].兰州大学, 2011. [20]雷小英,彭东红. 2009-2011年重庆地区儿童呼吸道病毒感染流行特征分析[J].重庆医科大学学报, 2013(9):1052-1057. [21]李学朝,杨筱婷,申希平,等. 甘肃省2009-2015年发热呼吸道症候群主要病原的Bayes判别分析法分类研究[J]. 中华流行病学杂志, 2017, 38(008):1094-1097. [22]Jiang W,Wu M ,Zhou J,et al. Etiologic spectrum and occurrence of coinfections in children hospitalized with community-acquired pneumonia[J]. Bmc Infectious Diseases, 2017, 17(1):787. [23]Drishti Kaul,Raveen Rathnasinghe,Marcela Ferres,Gene S. Tan,Aldo Barrera,Brett E. Pickett,Barbara A. Methe,Suman Das,Isolda Budnik,Rebecca A. Halpin,David Wentworth,Mirco Schmolke,Ignacio Mena,Randy A. Albrecht,Indresh Singh,Karen E. Nelson,Adolfo García-Sastre,Chris L. Dupont,Rafael A. Medina. Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza A virus infection[J]. Nature Communications,2020,11(1). [24]Nikolai Siemens,Nikolai Siemens,Sonja Oehmcke-Hecht,Thomas C. Mettenleiter,Bernd Kreikemeyer,Peter Valentin-Weigand,Sven Hammerschmidt. Port d’Entrée for Respiratory Infections-Does the Influenza A Virus Pave the Way for Bacteria?[J]. Frontiers in Microbiology,2017,8. [25]Niveen M Gad,Doaa Refaay,Naglaa M Gad,Zakia A Z Mohamed. Viral Infections in Egyptian Hospitalized Children With Acute Respiratory Tract Infections[J]. Journal of Clinical & Cellular Immunology,2017,8(5). [26]王丽,黄娟,莫庆仪,周涛.中山地区住院患儿呼吸道博卡病毒感染的临床研究[J].检验医学与临床,2019,16(08):1009-1011+1014. [27]Arruda Eurico,Jones Marcus H,Escremim de Paula Flavia,Chong Debora,Bugarin Gabriela,Notario Gerard,Matsuno Alessandra K,Pitrez Paulo M,Vo Pamela,Suzuki Claudia,Rosario Filho Nelson,Stein Renato T. The burden of single virus and viral coinfections on severe lower respiratory tract infections among preterm infants: a prospective birth cohort study in Brazil.[J]. The Pediatric infectious disease journal,2014,33(10). [28]李慧敏.小儿呼吸道混合感染流行病学及临床特征的研究[D].南京医科大学,2018. [29]Moriyama Miyu,Hugentobler Walter J.,Iwasaki Akiko. Seasonality of Respiratory Viral Infections[J]. Annual Review of Virology,2020,7. [30]葛小丽. 无锡部分地区儿童七种呼吸道病毒的流行病学及混合感染炎症因子的研究[D]. 苏州大学. [31]Thongpan Ilada,Suntronwong Nungruthai,Vichaiwattana Preeyaporn,Wanlapakorn Nasamon,Vongpunsawad Sompong,Poovorawan Yong. Respiratory syncytial virus, human metapneumovirus, and influenza virus infection in Bangkok, 2016-2017.[J]. PeerJ,2019,7. [32]儿童社区获得性肺炎管理指南(2013修订)(上)[J]. 中华儿科杂志, 2013, 51(010):745-752. [33]黄华, 陈茜, 梁红梅,等. 流感病毒快速诊断的临床应用价值[J]. 国际检验医学杂志, 2012(16):1932-1933. [34]杨厚宇,王旻晋,梁宗安.呼吸道病毒核酸检测结果分析[J].四川大学,2017,38(04)):415-420. [35]田国保，王笑灵, 孙静怡,等. 北京市儿童和成年人社区获得性肺炎病例呼吸道病毒分布的差异性研究[J]. 国际病毒学杂志, 2018(4):261-264. [36]马颖,张峰波,季萍,夏宇,贾斌,胡金伟,丁剑冰.新疆非典型呼吸道感染病原体检测结果分析[J].新疆医科大学学报,2016,39(01):87-89. [37]李晓晨,赵志鹏,赵秀英.北京地区1459例成人呼吸道病原体IgM检测结果临床分析[J].中国实验诊断学,2019,23(06):999-1002. [38]车荣飞,白茹,孙聪,杨家盛,王燕,陈苏君,孙瑞琳.广州市2018—2019年呼吸道感染病毒性病原谱研究[J].中华实验和临床病毒学杂志,2020,34(06):630-635. [39] Iek C,Arslan A,Karaku H S , et al. [Prevalence and seasonal distribution of respiratory viruses in patients with acute respiratory tract infections, 2002-2014].[J]. Mikrobiyoloji Bulteni, 2015, 49(2):188. [40]孙兵，唐晓，李绪言,等. 2017-2018年冬春季重症流感病毒性肺炎所致急性呼吸窘迫综合征的临床特点及预后危险因素分析[J]. 中华结核和呼吸杂志, 2019, 42(1):9-14. [41]Milucky J , Pondo T , Gregory C J , et al. The epidemiology and estimated etiology of pathogens detected from the upper respiratory tract of adults with severe acute respiratory infections in multiple countries, 2014–2015[J]. PLoS ONE, 2020, 15(10):e0240309. [42]崔朝杰，刘义庆，田文君,等. 山东地区2016-2018年呼吸道相关病原体感染情况调查[J]. 国际检验医学杂志, 2019, 040(019):2336-2339. [43]蒋小娟. 兰州市2010-2013年发热呼吸道症候群及常见病毒病原流行规律研究[D]. 兰州大学, 2014. [44]赵俊,刘万里,郜振国,张璇,刘红斌,马合木提,邓红,岳锡宏.347例SARI病例15种常见呼吸道病原特征分析[J].病毒学报,2017,33(05):761-766. [45]冯录召. 急性呼吸道感染住院病例病毒性病原谱及流感季节性研究[D].中国疾病预防控制中心,2014. [46]Moriyama Miyu,Hugentobler Walter J.,Iwasaki Akiko. Seasonality of Respiratory Viral Infections[J]. Annual Review of Virology,2020,7. [47]胡彩红.西宁地区儿童急性呼吸道感染鼻咽分泌物病毒抗原分析[J].高原医学杂志,2012,22(03):59-60. [48]张业成. 2010-2015年武汉及周边地区发热呼吸道感染病毒病原学研究[D].武汉大学,2017. [49]2017-2018年度广州地区流感的流行病学及临床特征分析[D].南方医科大学,2019. [50]Landires I , NÚÑEz-Samudio V . Epidemiology of Viral Respiratory Infections in a Pediatric Reference Hospital in Central Panama[J]. Social Science Electronic Publishing.