摘要
在我国宜昌开始的新的型冠状免疫（2019-nCoV）挑起迅速散布，现已在多个国内就诊。我们通报了在澳大利亚认定的首度2019-nCoV细菌感染登革热，并刻画了该登革热的鉴定，就诊，临床数据分析操作过程和管理制度，都有病患在中风第9天所列现为胃癌时的刚开始轻度副作用。
该事例特别强调了临床数据分析医生与地方，一州和联邦各级预防措施当局之间密切协作的重要性，以及无需短时间传递与这种新的发细菌感染病患的护理有关的临床数据分析文档的需求。
2019年12翌年31日，我国通报了与湖北省宜昌市广东海鱼批发低价有关的人群里面的胃癌登革热。
2020年1翌年7日，我国卫生当局认定该簇与新的型冠状免疫2019-nCoV有关。尽管刚开始报道的登革热与宜昌市海鱼低价的暴露有关，但当从前的医学研究数据所列明，准备发生2019-nCoV人际关系传递。
截至2020年1翌年30日，在至少21个国内/周边地区通报了9976例登革热，都有2020年1翌年20日报道的澳大利亚首度就诊的2019-nCoV细菌感染登革热。
世界各地范围准备展开核查，以更好地知晓传递时序和临床数据分析病因范围。本通报刻画了在澳大利亚认定的首度2019-nCoV细菌感染的医学研究和临床数据分析特征。
事例通报
2020年1翌年19日，一名35岁的男子显现出在华盛顿一州斯诺霍米什县的一家医务人员托儿所，有4天的痉挛和主观高烧日本史。病人到托儿所体检时，在候诊室戴上便衣。等待约20分钟后，他被带到体检室接受了中介的检验。
他透露，他在我国宜昌探望家人元翌年1翌年15日返回华盛顿一州。该病患所列示，他已从澳大利亚病因控制与预防措施里面心（CDC）收到有关我国新的型冠状免疫暴发的有益警报，由于他的副作用和都只的历险，他同意去看医生。
左图1-2020年1翌年19日（病因第4天）的后背部和之外侧胸片
除了初中生酸酯血综合症的病因之外，该病患还是其他有益的不吸烟者。体格体检注意到病患痉挛环境气体时，体温为37.2°C，心率为134/87 mm Hg，----为每分钟110次，痉挛振幅为每分钟16次，氢一般而言为96％。胃部听诊结果显示有支气管炎，并展开了胸片体检，据报道仍未注意到异常（左图1）。
及第型和乙型SARS的短时间核酸扩增次测试（NAAT）为复数。赢取了楔咽拭子遗骸，并通过NAAT将其送去体检免疫性痉挛道免疫。
据报道在48天内内对所有次测试的免疫仅剩呈复数，都有及第型和乙型SARS，副SARS，痉挛道合胞免疫，楔免疫，腺免疫和已知会导致人类病因的四种常见冠状免疫株（HKU1，NL63、229E和OC43） ）。根据病患的历险持续发展日本史，立即通知地方和一州医务人员。华盛顿副部长与紧急护理临床数据分析医生一起通知了CDC紧急行动里面心。
尽管该病患通报时说他没有人去过广东海鱼低价，也没有人通报在去我国历险之前与体弱者有任何接触，但病因预防措施控制里面心的管理制度人员同意有必要根据当从前的病因预防措施控制里面心对病患展开2019-nCoV次测试。
根据CDCGuide抽取了8个遗骸，都有抗体，楔咽和；大咽拭子遗骸。遗骸搜集后，病患被转送家庭分离，并由当地医务人员展开积极监测。
2020年1翌年20日，病因预防措施控制里面心（CDC）认定病患的楔咽和；大咽拭子通过即时逆转录酶-酵素链反应（rRT-PCR）体检为2019-nCoVHIV。
在病因预防措施控制里面心的隐喻医学专家，一州和地方卫生官员，紧急卫生服务以及病房为首和管理制度人员的配合下，病患被转送普罗维登斯周边地区卫生里面心的气体分离病房展开临床数据分析通过观察，并跟随病因预防措施控制里面心的医护有关接触，飞沫和空里面破片措施的建议，并带有护目镜。
中风时病患通报长时间痉挛，有2天的羞耻和呕吐日本史。他通报时说他没有人痉挛急促或不止。生命体征在正常范围。体格体检注意到病患粘膜湿润。其余的体检通常不引人注意。
中风后，病患接受了支持用药，都有2充生理盐水和恩丹以缓解羞耻。
左图2-根据病因日和中风日（2020年1翌年16日至2020年1翌年30日）的副作用和最高体温
在中风的第2至5天（体弱的第6至9天），病患的生命体征大体上发挥作用，除了显现出间歇性高烧并伴有心动过速（左图2）。病患在此之前通报非生产性痉挛，并显现出疲倦。
在中风第二天的下午，病患排便通畅，腹部不适。中午有第二次饱稀少的报道。抽取该异味的样品用于rRT-PCR次测试，以及其他痉挛道遗骸（楔咽和；大咽）和抗体。异味和两个痉挛道遗骸其后仅剩通过rRT-PCR体检为2019-nCoVHIV，而抗体仍为复数。
在此之前的用药在更大程度上是支持性的。为了展开副作用处理，病患无需根据无需接受良药制剂，该制剂都有每4天内650 mg对乙酰尿素基酚和每6天内600 mg布洛芬。在中风的从前六天，他还因长时间痉挛而服食了600毫克愈创醚和约6充生理盐水。
所列1-临床数据分析的实验室结果
病患分离静态的性质刚开始仅强制即时卫生点的实验室次测试；从病房第3天开始可以展开仅剩红细胞计数和抗体矿物学数据分析。
在病房第3天和第5天（病因第7天和第9天）的的实验室结果解读出白细胞减少综合症，轻度血小板减少综合症和肌酸激酶程度充高（所列1）。此之外，肝功能高效率也难免改变：盐类脂质（每充68 U），丙尿素酸尿素基转移酶（每充105 U），天冬尿素酸尿素基转移酶（每充77 U）和乳酸脱氢酶（每充465 U）的程度分别为：在中风的第5天所有充高。鉴于病患有规律高烧，在第4天赢取血液培养；迄今为止，这些都没有人增长。
左图3-2020年1翌年22日（胸部第7天，病房第3天）的后背部和之外侧胸片
左图4-2020年1翌年24日（胸部第5天，病房第9天）的后背部X线片
据报道，在病房第3天（体弱第7天）拍摄的胸部X光片仍未结果显示经年累月或异常痕迹（左图3）。
但是，从病房第5天中午（体弱第9天）中午展开的第二次胸部X光片体检结果显示，左肺下叶有胃癌（左图4）。
这些影像学注意到与从病房第5天中午开始的痉挛状态改变相吻合，当时病患在痉挛周围气体时通过----血氢一般而言定量的血氢一般而言参数降至90％。
在第6天，病患开始接受多余氢气，该氢气由楔导管以每分钟2充的反应速度输送。考虑到临床数据分析所列现的改变和对病房赢取性胃癌的关注，开始用到抗病毒（1750 mg负荷剂量，然后每8天内肌肉注射1 g）和吲哚足总杯苯基（每8天内肌肉注射）用药。
左图5-从前后胸部X光片，2020年1翌年26日（病因第十天，病房第六天）
在病房第6天（体弱第10天），第四次胸部X射线照片结果显示两个肺里面都有基底长条混浊，这一注意到与非近似于胃癌完仅剩符合（左图5），并且在听诊时在两个肺里面都显现出了罗音。鉴于放射线影像学注意到，同意赋予氢气多余，病患长时间高烧，多个部位长时间HIV的2019-nCoV RNAHIV，以及发所列了与放射线性胃癌持续发展相符的不堪重负胃癌在该病患里面，临床数据分析医生富于同情心地用到了数据分析性抗免疫用药。
肌肉注射艾伦昔韦（一种准备共同开发的新的型核苷酸类似物从前药）在第7天中午开始，但仍未通过观察到与输注有关的不良事件。在对及第氢西林耐药的金黄色芽孢展开了连续的降钙素原程度和楔PCR体检后，在第7天中午停用抗病毒，并在第二天停用吲哚足总杯苯基。
在病房第8天（体弱第12天），病患的临床数据分析长时间性给与优化。停止多余氢气，他在痉挛周围气体时的氢一般而言参数提升到94％至96％。先从前的从前部下叶罗音不再依赖于。他的食欲给与优化，除了间歇性干咳和楔漏之外，他没有人副作用。
截至2020年1翌年30日，病患仍中风。他有发烧，除痉挛之外，所有副作用仅剩已缓解，痉挛的程度准备减轻。
步骤
遗骸搜集
根据CDCGuide赢取用于2019-nCoV就诊次测试的临床数据分析遗骸。用合成纤维拭子抽取了12个楔咽和；大咽拭子遗骸。
将每个拭子插入相关联2至3 ml免疫运输颗粒的单独无害管里面。将血集在抗体分离管里面，然后根据CDCGuide展开离心。尿液和异味遗骸分别抽取在无害遗骸容器里面。样品在2°C至8°C之间储存，直到准备好运送至CDC。
在病因的第7、11和12天抽取了单调展开的2019-nCoV次测试的遗骸，都有楔咽和；大咽拭子，抗体以及尿液和异味抽样。
2019-NCOV的就诊次测试
用到从公开场合公布的免疫化学合成持续发展而来的rRT-PCR分析法次测试了临床数据分析遗骸。与先从前针对重综合症急性痉挛病症冠状免疫（SARS-CoV）和里面东痉挛病症冠状免疫（MERS-CoV）的就诊步骤相似，它兼具三个核衣壳基因索科利夫卡和一个HIV对照索科利夫卡。该定量的刻画为RRT-PCR显示器引物和探针和化学合成文档里面能用的CDC的实验室文档网站2019-nCoV上。
遗传化学合成
2020年1翌年7日，我国数据分析人员通过澳大利亚国立卫生数据分析院GenBank元数据和世界各地包涵所有SARS数据倡议（GISAID）元数据包涵了2019-nCoV的基本基因化学合成；随后公布了有关分离2019-nCoV的通报。
从rRT-PCRHIV遗骸（；大咽和楔咽）里面萃取核酸，并在Sanger和下一代化学合成平台（Illumina和MinIon）上用于仅剩化学合成化学合成。用到5.4.6版本的Sequencher应用软件（Sanger）完成了化学合成被装。minimap应用软件，版本本2.17（MinIon）；和freebayes应用软件1.3.1版本（MiSeq）。将基本化学合成与能用的2019-nCoV参见化学合成（GenBank登录号NC_045512.2）展开比较。
结果
2019-NCOV的遗骸次测试
所列2-2019年新的型冠状免疫（2019-nCoV）的即时逆转录酶-酵素-链反应次测试结果
该病患在体弱第4四海赢取的初始痉挛道抽样（楔咽拭子和；大咽拭子）在2019-nCoV呈HIV（所列2）。
尽管病患刚开始所列现为轻度副作用，但在病因第4天的低周而复始阻抗（Ct）参数（楔咽遗骸里面为18至20，；大咽遗骸里面为21至22）所列明这些遗骸里面免疫程度较高。
在病因第7天赢取的两个上痉挛道遗骸在2019-nCoV仍保持HIV，都有楔咽拭子遗骸里面长时间高程度（Ct参数23至24）。在病因第7天赢取的异味在2019-nCoV里面也呈HIV（Ct参数为36至38）。两种搜集日期的抗体抽样在2019-nCoV仅剩为复数。
在病因第11天和第12天赢取的楔咽和；大咽遗骸结果显示出免疫程度下降的21世纪。
；大咽遗骸在体弱第12天的2019-nCoV次测试呈复数。在这些日期赢取的抗体的rRT-PCR结果仍仍未定。
遗传化学合成
；大咽和楔咽遗骸的基本化学合成化学合成彼此并不相同，并且与其他能用的2019-nCoV化学合成大体上上并不相同。
该病患的免疫与2019-nCoV参见化学合成（NC_045512.2）在封闭阅读支架8处仅剩3个核苷酸和1个不同。该化学合成可通过GenBank赢取（登录号MN985325）。
讨论区
我们关于澳大利亚首度2019-nCoV就诊登革热的通报时说明了这一新的兴病因的几个特别由此可知仍未完仅剩知晓，都有传递时序和临床数据分析病因的仅剩部范围。
我们的登革热病患曾去过我国宜昌，但通报时说他在宜昌之前没有人去过海鱼批发低价或卫生机构，也没有人生病的接触。尽管他的2019-nCoV细菌感染的相关联由此可知不确实，但已公开场合了人对人传递的证据。
到2020年1翌年30日，由此可知仍未注意到与此登革热具体的2019-nCoV诱发登革热，但仍在密切监视下。
在病因的第4天和第7天从上痉挛道遗骸里面体检到兼具低Ct参数的2019-nCoV RNA，所列明免疫储存量高且兼具传递创造力。
参数得注意的是，我们还在病患体弱第7天抽取的异味抽样里面体检到了2019-nCoV RNA。尽管我们登革热病患的抗体遗骸有规律显现出2019-nCoV复数，但在我国重综合症病患的血液里面仍体检到免疫RNA。然而，肺之外体检免疫RNA并不一定仅仅依赖于传染性免疫，目从前由此可知不确实在痉挛道之本体体检免疫RNA的临床数据分析意义。
目从前，我们对2019-nCoV细菌感染的临床数据分析范围的知晓非常有限。在我国，之前报道了诸如不堪重负的胃癌，痉挛衰竭，急性痉挛拮据病症（ARDS）和胸腔损伤等并发综合症，都有灾难性的必然。然而，重要的是要注意，这些登革热是根据其胃癌就诊确定的，因此也许会使通报偏向更不堪重负的结果。
我们的登革热病患刚开始所列现为轻度痉挛和低度间歇性高烧，在体弱的第4天没有人胸部X光体检的胃癌痕迹，而在体弱第9天持续发展为胃癌之从前，这些非抗原体征和副作用在以前在临床数据分析上，2019-nCoV细菌感染的临床数据分析操作过程也许与许多其他常见流行病没有人引人注意区别，相比之下是在夏季则痉挛道免疫季节。
另之外，本登革热病患在病因的第9天持续发展为胃癌的时机与近期痉挛困难的复发（得病后里面位数为8天）相符。尽管根据病患的临床数据分析长时间性恶化同意是否赋予remdesivir慈悲的用到，但仍无需展开随机对照试验以确定remdesivir和任何其他数据分析药物用药2019-nCoV细菌感染的有效性和有效性。
我们通报了澳大利亚首度通报的2019-nCoV细菌感染病患的临床数据分析特征。
该登革热的关键特别都有病患在阅读有关暴发的预防措施警告后同意寻求卫生；由当地卫生服务中介认定病患都只到宜昌的历险持续发展日本史，随后在当地，一州和联邦预防措施官员之间展开解决问题；并确定也许的2019-nCoV细菌感染，从而可以迅速分离病患并随后对2019-nCoV展开的实验室认定，并强制病患中风大幅度检验和管理制度。
该登革热通报特别强调了临床数据分析医生对于任何显现出急性病因副作用的就诊病患，要总结出都只的历险境况或接触病因的重要性，为了确保正确辨识和适时分离也许陷于2019-nCoV细菌感染风险的病患，并帮助减少大幅度的传递。
再次，本通报特别强调无需确定与2019-nCoV细菌感染具体的临床数据分析病因，得病机理和免疫脱落长时间时间的
仅剩部范围和自然持续发展日本史，以为临床数据分析管理制度和预防措施对政府提供依据。
以下为译者
——————
Summary
An outbreak of novel coronirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
On December 31, 2019, China reported a cluster of cases of pneumonia in people associated with the Huanan Seafood Wholesale Market in Wuhan, Hubei Province.
On January 7, 2020, Chinese health authorities confirmed that this cluster was associated with a novel coronirus, 2019-nCoV.
Although cases were originally reported to be associated with exposure to the seafood market in Wuhan, current epidemiologic data indicate that person-to-person transmission of 2019-nCoV is occurring.
As of January 30, 2020, a total of 9976 cases had been reported in at least 21 countries,including the first confirmed case of 2019-nCoV infection in the United States, reported on January 20, 2020.
Investigations are under way worldwide to better understand transmission dynamics and the spectrum of clinical illness.
This report describes the epidemiologic and clinical features of the first case of 2019-nCoV infection confirmed in the United States.
Case Report
On January 19, 2020, a 35-year-old man presented to an urgent care clinic in Snohomish County, Washington, with a 4-day history of cough and subjective fever.
On checking into the clinic, the patient put on a mask in the waiting room. After waiting approximately 20 minutes, he was taken into an examination room and underwent evaluation by a provider. He disclosed that he had returned to Washington State on January 15 after treling to visit family in Wuhan, China.
The patient stated that he had seen a health alert from the U.S. Centers for Disease Control and Prevention (CDC) about the novel coronirus outbreak in China and, because of his symptoms and recent trel, decided to see a health care provider.
Figure 1.Posteroanterior and Lateral Chest Radiographs, January 19, 2020 (Illness Day 4).
Apart from a history of hypertriglyceridemia, the patient was an otherwise healthy nonsmoker. The physical examination revealed a body temperature of 37.2°C, blood pressure of 134/87 mm Hg, pulse of 110 beats per minute, respiratory rate of 16 breaths per minute, and oxygen saturation of 96% while the patient was breathing ambient air. Lung auscultation revealed rhonchi, and chest radiography was performed, which was reported as showing no abnormalities (Figure 1).
A rapid nucleic acid amplification test (NAAT) for influenza A and B was negative. A nasopharyngeal swab specimen was obtained and sent for detection of viral respiratory pathogens by NAAT; this was reported back within 48 hours as negative for all pathogens tested, including influenza A and B, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, and four common coronirus strains known to cause illness in humans (HKU1, NL63, 229E, and OC43).
Given the patient’s trel history, the local and state health departments were immediately notified. Together with the urgent care clinician, the Washington Department of Health notified the CDC Emergency Operations Center.
Although the patient reported that he had not spent time at the Huanan seafood market and reported no known contact with ill persons during his trel to China, CDC staff concurred with the need to test the patient for 2019-nCoV on the basis of current CDC “persons under investigation” case definitions.
Specimens were collected in accordance with CDC guidance and included serum and nasopharyngeal and oropharyngeal swab specimens. After specimen collection, the patient was discharged to home isolation with active monitoring by the local health department.
On January 20, 2020, the CDC confirmed that the patient’s nasopharyngeal and oropharyngeal swabs tested positive for 2019-nCoV by real-time reverse-transcriptase–polymerase-chain-reaction (rRT-PCR) assay.
In coordination with CDC subject-matter experts, state and local health officials, emergency medical services, and hospital leadership and staff, the patient was admitted to an airborne-isolation unit at Providence Regional Medical Center for clinical observation, with health care workers following CDC recommendations for contact, droplet, and airborne precautions with eye protection.
On admission, the patient reported persistent dry cough and a 2-day history of nausea and vomiting; he reported that he had no shortness of breath or chest pain. Vital signs were within normal ranges. On physical examination, the patient was found to he dry mucous membranes. The remainder of the examination was generally unremarkable. After admission, the patient received supportive care, including 2 liters of normal saline and ondansetron for nausea.
Figure 2.Symptoms and Maximum Body Temperatures According to Day of Illness and Day of Hospitalization, January 16 to January 30, 2020.
On days 2 through 5 of hospitalization (days 6 through 9 of illness), the patient’s vital signs remained largely stable, apart from the development of intermittent fevers accompanied by periods of tachycardia (Figure 2).
The patient continued to report a nonproductive cough and appeared fatigued. On the afternoon of hospital day 2, the patient passed a loose bowel movement and reported abdominal discomfort. A second episode of loose stool was reported overnight; a sample of this stool was collected for rRT-PCR testing, along with additional respiratory specimens (nasopharyngeal and oropharyngeal) and serum.
The stool and both respiratory specimens later tested positive by rRT-PCR for 2019-nCoV, whereas the serum remained negative.
Treatment during this time was largely supportive. For symptom management, the patient received, as needed, antipyretic therapy consisting of 650 mg of acetaminophen every 4 hours and 600 mg of ibuprofen every 6 hours. He also received 600 mg of guaifenesin for his continued cough and approximately 6 liters of normal saline over the first 6 days of hospitalization.
Table 1.Clinical Laboratory Results.
The nature of the patient isolation unit permitted only point-of-care laboratory testing initially; complete blood counts and serum chemical studies were ailable starting on hospital day 3.
Laboratory results on hospital days 3 and 5 (illness days 7 and 9) reflected leukopenia, mild thrombocytopenia, and elevated levels of creatine kinase (Table 1).
In addition, there were alterations in hepatic function measures: levels of alkaline phosphatase (68 U per liter), alanine aminotransferase (105 U per liter), aspartate aminotransferase (77 U per liter), and lactate dehydrogenase (465 U per liter) were all elevated on day 5 of hospitalization.
Given the patient’s recurrent fevers, blood cultures were obtained on day 4; these he shown no growth to date.
Figure 3.Posteroanterior and Lateral Chest Radiographs, January 22, 2020 (Illness Day 7, Hospital Day 3).
Figure 4.Posteroanterior Chest Radiograph, January 24, 2020 (Illness Day 9, Hospital Day 5).
A chest radiograph taken on hospital day 3 (illness day 7) was reported as showing no evidence of infiltrates or abnormalities (Figure 3).
However, a second chest radiograph from the night of hospital day 5 (illness day 9) showed evidence of pneumonia in the lower lobe of the left lung (Figure 4).
These radiographic findings coincided with a change in respiratory status starting on the evening of hospital day 5, when the patient’s oxygen saturation values as measured by pulse oximetry dropped to as low as 90% while he was breathing ambient air.
On day 6, the patient was started on supplemental oxygen, delivered by nasal cannula at 2 liters per minute.
Given the changing clinical presentation and concern about hospital-acquired pneumonia, treatment with vancomycin (a 1750-mg loading dose followed by 1 g administered intrenously every 8 hours) and cefepime (administered intrenously every 8 hours) was initiated.
Figure 5.Anteroposterior and Lateral Chest Radiographs, January 26, 2020 (Illness Day 10, Hospital Day 6).
On hospital day 6 (illness day 10), a fourth chest radiograph showed basilar streaky opacities in both lungs, a finding consistent with atypical pneumonia (Figure 5), and rales were noted in both lungs on auscultation.
Given the radiographic findings, the decision to administer oxygen supplementation, the patient’s ongoing fevers, the persistent positive 2019-nCoV RNA at multiple sites, and published reports of the development of severe pneumonia at a period consistent with the development of radiographic pneumonia in this patient, clinicians pursued compassionate use of an investigational antiviral therapy.
Treatment with intrenous remdesivir (a novel nucleotide ogue prodrug in development) was initiated on the evening of day 7, and no adverse events were observed in association with the infusion.
Vancomycin was discontinued on the evening of day 7, and cefepime was discontinued on the following day, after serial negative procalcitonin levels and negative nasal PCR testing for methicillin-resistant Staphylococcus aureus.
On hospital day 8 (illness day 12), the patient’s clinical condition improved. Supplemental oxygen was discontinued, and his oxygen saturation values improved to 94 to 96% while he was breathing ambient air.
The previous bilateral lower-lobe rales were no longer present. His appetite improved, and he was asymptomatic aside from intermittent dry cough and rhinorrhea.
As of January 30, 2020, the patient remains hospitalized. He is afebrile, and all symptoms he resolved with the exception of his cough, which is decreasing in severity.
Methods
SPECIMEN COLLECTIONClinical specimens for 2019-nCoV diagnostic testing were obtained in accordance with CDC guidelines. Nasopharyngeal and oropharyngeal swab specimens were collected with synthetic fiber swabs; each swab was inserted into a separate sterile tube containing 2 to 3 ml of viral transport medium. Serum was collected in a serum separator tube and then centrifuged in accordance with CDC guidelines. The urine and stool specimens were each collected in sterile specimen containers. Specimens were stored between 2°C and 8°C until ready for shipment to the CDC. Specimens for repeat 2019-nCoV testing were collected on illness days 7, 11, and 12 and included nasopharyngeal and oropharyngeal swabs, serum, and urine and stool samples.
DIAGNOSTIC TESTING FOR 2019-NCOV
Clinical specimens were tested with an rRT-PCR assay that was developed from the publicly released virus sequence. Similar to previous diagnostic assays for severe acute respiratory syndrome coronirus (SARS-CoV) and Middle East respiratory syndrome coronirus (MERS-CoV), it has three nucleocapsid gene targets and a positive control target.
A description of this assay and sequence information for the rRT-PCR panel primers and probes are ailable on the CDC Laboratory Information website for 2019-nCoV.
GENETIC SEQUENCING
On January 7, 2020, Chinese researchers shared the full genetic sequence of 2019-nCoV through the National Institutes of Health GenBank database and the Global Initiative on Sharing All Influenza Data (GISAID) database; a report about the isolation of 2019-nCoV was later published.
Nucleic acid was extracted from rRT-PCR–positive specimens (oropharyngeal and nasopharyngeal) and used for whole-genome sequencing on both Sanger and next-generation sequencing platforms (Illumina and MinIon).
Sequence assembly was completed with the use of Sequencher software, version 5.4.6 (Sanger); minimap software, version 2.17 (MinIon); and freebayes software, version 1.3.1 (MiSeq). Complete genomes were compared with the ailable 2019-nCoV reference sequence (GenBank accession number NC_045512.2).
Results
SPECIMEN TESTING FOR 2019-NCOV
Table 2.Results of Real-Time Reverse-Transcriptase–Polymerase-Chain-Reaction Testing for the 2019 Novel Coronirus (2019-nCoV).
The initial respiratory specimens (nasopharyngeal and oropharyngeal swabs) obtained from this patient on day 4 of his illness were positive for 2019-nCoV (Table 2).
The low cycle threshold (Ct) values (18 to 20 in nasopharyngeal specimens and 21 to 22 in oropharyngeal specimens) on illness day 4 suggest high levels of virus in these specimens, despite the patient’s initial mild symptom presentation.
Both upper respiratory specimens obtained on illness day 7 remained positive for 2019-nCoV, including persistent high levels in a nasopharyngeal swab specimen (Ct values, 23 to 24). Stool obtained on illness day 7 was also positive for 2019-nCoV (Ct values, 36 to 38).
Serum specimens for both collection dates were negative for 2019-nCoV. Nasopharyngeal and oropharyngeal specimens obtained on illness days 11 and 12 showed a trend toward decreasing levels of virus. The oropharyngeal specimen tested negative for 2019-nCoV on illness day 12. The rRT-PCR results for serum obtained on these dates are still pending.
GENETIC SEQUENCING
The full genome sequences from oropharyngeal and nasopharyngeal specimens were identical to one another and were nearly identical to other ailable 2019-nCoV sequences.
There were only 3 nucleotides and 1 amino acid that differed at open reading frame 8 between this patient’s virus and the 2019-nCoV reference sequence (NC_045512.2). The sequence is ailable through GenBank (accession number MN985325).
DISCUSSION
Our report of the first confirmed case of 2019-nCoV in the United States illustrates several aspects of this emerging outbreak that are not yet fully understood, including transmission dynamics and the full spectrum of clinical illness.
Our case patient had treled to Wuhan, China, but reported that he had not visited the wholesale seafood market or health care facilities or had any sick contacts during his stay in Wuhan. Although the source of his 2019-nCoV infection is unknown, evidence of person-to-person transmission has been published.
Through January 30, 2020, no secondary cases of 2019-nCoV related to this case he been identified, but monitoring of close contacts continues.
Detection of 2019-nCoV RNA in specimens from the upper respiratory tract with low Ct values on day 4 and day 7 of illness is suggestive of high viral loads and potential for transmissibility.
It is notable that we also detected 2019-nCoV RNA in a stool specimen collected on day 7 of the patient’s illness. Although serum specimens from our case patient were repeatedly negative for 2019-nCoV, viral RNA has been detected in blood in severely ill patients in China.
However, extrapulmonary detection of viral RNA does not necessarily mean that infectious virus is present, and the clinical significance of the detection of viral RNA outside the respiratory tract is unknown at this time.
Currently, our understanding of the clinical spectrum of 2019-nCoV infection is very limited. Complications such as severe pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), and cardiac injury, including fatal outcomes, he been reported in China.
However, it is important to note that these cases were identified on the basis of their pneumonia diagnosis and thus may bias reporting toward more severe outcomes.
Our case patient initially presented with mild cough and low-grade intermittent fevers, without evidence of pneumonia on chest radiography on day 4 of his illness, before hing progression to pneumonia by illness day 9.
These nonspecific signs and symptoms of mild illness early in the clinical course of 2019-nCoV infection may be indistinguishable clinically from many other common infectious diseases, particularly during the winter respiratory virus season. In addition, the timing of our case patient’s progression to pneumonia on day 9 of illness is consistent with later onset of dyspnea (at a median of 8 days from onset) reported in a recent publication.
Although a decision to administer remdesivir for compassionate use was based on the case patient’s worsening clinical status, randomized controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection.
We report the clinical features of the first reported patient with 2019-nCoV infection in the United States.
Key aspects of this case included the decision made by the patient to seek medical attention after reading public health warnings about the outbreak; recognition of the patient’s recent trel history to Wuhan by local providers, with subsequent coordination among local, state, and federal public health officials; and identification of possible 2019-nCoV infection, which allowed for prompt isolation of the patient and subsequent laboratory confirmation of 2019-nCoV, as well as for admission of the patient for further evaluation and management.
This case report highlights the importance of clinicians eliciting a recent history of trel or exposure to sick contacts in any patient presenting for medical care with acute illness symptoms, in order to ensure appropriate identification and prompt isolation of patients who may be at risk for 2019-nCoV infection and to help reduce further transmission.
Finally, this report highlights the need to determine the full spectrum and natural history of clinical disease, pathogenesis, and duration of viral shedding associated with 2019-nCoV infection to inform clinical management and public health decision making.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
This article was published on January 31, 2020, at NEJM.org.
We thank the patient; the nurses and clinical staff who are providing care for the patient; staff at the local and state health departments; staff at the Washington State Department of Health Public Health Laboratories and at the Centers for Disease Control and Prevention (CDC) Division of Viral Disease Laboratory; CDC staff at the Emergency Operations Center; and members of the 2019-nCoV response teams at the local, state, and national levels.
相关新闻
下一页：心肌梗塞如何诊断
相关问答
