Epidemiology and Clinical Features of Human Coronavirus

描述（由申请人提供）：人类冠状病毒（HCoV）最初在20世纪60年代被确定为急性呼吸道疾病的主要原因。由于培养困难，两种HCoV OC43和229E仅用血清学方法建立了流行病学。在过去三年中，已经报道了三种新的HCoV[1-4]：严重急性呼吸综合征冠状病毒（SARS-CoV）[4]，人类冠状病毒荷兰（HCoV- nl）[1,2]和人类冠状病毒香港（CoV-HKU1）[3]。这些新病毒都与下呼吸道疾病（LRI）有关。这些病毒的发现重新引起了人们对以前已知的HCoV OC43和229E的兴趣，这两种病毒已知会引起上呼吸道疾病。与新发现的冠状病毒一样，HCoV OC43和229E也与LRI有关。然而，目前还没有发表过使用高灵敏度分子诊断方法对OC43和229E进行大规模流行病学研究的文章。本研究的目的是在20年期间对2000多名健康门诊儿童进行队列研究，确定与新型人类冠状病毒HCoV- nl和原型HCoV OC43和229E相关的患病率和临床疾病。我们还将通过扩增和测序HCoV刺突蛋白基因来确定这些病毒的遗传变异性。范德比尔特疫苗诊所（WC）的临床数据库和样本档案为我们提供了实现这些目标的工具。WC为大量门诊儿童提供了全面的医疗护理，这些儿童常规接受呼吸道分泌物和血清样本的监测培养，从而获得了数千份鼻洗和血清样本，以及可靠的、前瞻性收集的临床数据。这为调查新出现的人类病原体的重要性提供了一个独特的机会。我们使用来自世界卫生组织样本的初步数据表明，冠状病毒是具有一系列疾病和发病率的儿童呼吸道感染的重要原因。

DESCRIPTION (provided by applicant): Human coronaviruses (HCoV) were initially identified as major causes of acute respiratory tract disease in the 1960's. The epidemiology of two HCoV, OC43 and 229E, was established using only serological methods, due to difficulty culturing the viruses. Three new HCoV have been described in the last three years [1-4]: severe acute respiratory syndrome coronavirus (SARS-CoV) [4], human coronavirus Netherlands (HCoV-NL) [1, 2], and human coronavirus Hong Kong (CoV-HKU1) [3]. Each of these new viruses has been described in association with lower respiratory tract illness (LRI). The discovery of these viruses has renewed interest into the previously known HCoV OC43 and 229E which were known to cause upper respiratory tract illness (URI). HCoV OC43 and 229E have also been associated with LRI like the newly discovered coronaviruses. However, there are no published large-scale epidemiologic studies of OC43 and 229E using highly sensitive molecular diagnostic methods. The objectives of this study are to define the prevalence and clinical illnesses associated with the new human coronavirus HCoV-NL and the prototypic HCoV, OC43 and 229E, over a 20-year period in a cohort of over 2,000 previously healthy outpatient children. We also will determine the genetic variability of these viruses by amplifying and sequencing the HCoV spike protein gene. The Vanderbilt Vaccine Clinic (WC) clinical database and sample archive provide us with the tools to accomplish these goals. The WC provided comprehensive medical care to a large cohort of outpatient children who routinely had surveillance cultures of respiratory secretions and serum samples obtained, thus thousands of nasal wash and serum specimens are available for study, along with robust, prospectively collected clinical data. This provides a unique opportunity to investigate the importance of emerging human pathogens. Our preliminary data using samples from the WC indicate that coronaviruses are a significant cause of respiratory tract infection in children with a spectrum of illness and morbidity.