简要
在欧美郑州开始的新型冠状HIV（2019-nCoV）爆配很快散布，现已在多个发展中国家肺炎。我们学术研究报告了在英美两国认定的首开2019-nCoV病毒病症，并所述了该病症的鉴定，病患，诊断过程和管理制度，还包括高血压在病情恶化第9天请注意现为结核能病时的在此之前轻度癫痫状。
该近来强调了诊断内科医生与偏远沿海地区，特拉华和联邦各级预防港英政府相互间的关系协作的必要性，以及能够快速传递与这种新配病毒高血压的医护有关的诊断讯息的需求。
2019年12月初31日，欧美学术研究报告了与湖北省南昌市华南水果批配市场有关的人群中都的结核能病病症。
2020年1月初7日，欧美卫生港英政府认定该簇与新型冠状HIV2019-nCoV有关。尽管在此之前美联社的病症与南昌市水果市场的漏出有有关，但当前的医学研究图表请注意明，悄悄时有配生2019-nCoV彼此间传递。
截至2020年1月初30日，在至少21个发展中国家/沿海地区学术研究报告了9976例病症，还包括2020年1月初20日美联社的英美两国首开肺炎的2019-nCoV病毒病症。
正因如此球以内内悄悄同步进行核能查，以非常好地洞察传递高效率和诊断病因以内。本学术研究报告所述了在英美两国认定的首开2019-nCoV病毒的医学研究和诊断特征。
近来学术研究报告
2020年1月初19日，一名35岁的铁饼出有现在纽约特拉华鲍威尔霍米孟加拉国的主营急诊诊所，有4天的腹痛和有意识配烧近代史。病人到诊所检测时，在候诊室戴上头罩。才会达20分钟后，他被带到检测室拒绝接受了包括者的检验。
他问及，他在欧美郑州探望亲友都于1月初15日来到纽约特拉华。该高血压请注意示，他已从英美两国病因控制与预防中都心（CDC）收到有关欧美新型冠状HIV暴配的身体健康警报，由于他的癫痫状和都只的之旅，他要求去看内科医生。
由此可知1-2020年1月初19日（病因第4天）的后腰部和侧边胸片
除了初中酸酯血癫痫的病症则有，该高血压还是其他身体健康的不尼古丁。体格检测断定高血压气管环境液体时，心率为37.2°C，血压为134/87 mm Hg，脉搏为每分钟110次，气管频率为每分钟16次，氢稍低为96％。肺泡听诊标示出有有细菌性，并同步进行了胸片检测，据美联社从未断定反常（由此可知1）。
亚型和-B肺炎的快速遗传物质扩增次测试（NAAT）为同义。取得了喉咽拭子配现地，并通过NAAT将其送去试样HIV性肺泡病菌。
据美联社在48不间断内对所有次测试的病菌仅有圆形同义，还包括亚型和-B肺炎，副肺炎，肺泡合胞HIV，喉HIV，腺HIV和已知但会造成了人类病因的四种类似于冠状HIV株（HKU1，NL63、229E和OC43） ）。根据高血压的之旅近现代，立即通知偏远沿海地区和特拉华已对。华盛顿卫生部与救护车医护诊断内科医生一起通知了CDC救护车行动中都心。
尽管该高血压学术研究报告时说他无法去过华南水果市场，也无法学术研究报告在去欧美之旅之前与体弱者有任何注意到，但病因预防控制中都心的职员同意有必要根据当前的病因预防控制中都心对高血压同步进行2019-nCoV次测试。
根据CDC手册获取了8个配现地，还包括肝脏，喉咽和头咽拭子配现地。配现地野则有后，高血压被转送中产阶级可避免，并由当地已对同步进行更更进一步监测。
2020年1月初20日，病因预防控制中都心（CDC）认定高血压的喉咽和头咽拭子通过实时逆转录酶-蛋白酶不可逆（rRT-PCR）试样为2019-nCoV病毒性。
在病因预防控制中都心的主题学术研究员，特拉华和偏远沿海地区卫生官员，救护车卫生保健服务以及养老院拥护和职员的配合下，高血压被转送普罗维登斯沿海地区卫生保健中都心的液体可避免病房同步进行诊断掩蔽，并追随病因预防控制中都心的消防员有关注意到，飞沫和高空防护预防措施的劝告，并比如说护目镜。
晕倒时高血压学术研究报告长时间腹痛，有2天的麻木和呕吐近代史。他学术研究报告时说他无法气管急促或心悸。生命恶性肿瘤在正常以内内。体格检测断定高血压上皮潮湿。其余的检测不一定不明显。
晕倒后，高血压拒绝接受了反对化疗，还包括2充生理盐水和恩丹以消除麻木。
由此可知2-根据病因日和出有院日（2020年1月初16日至2020年1月初30日）的癫痫状和最低心率
在出有院的第2至5天（体弱的第6至9天），高血压的生命恶性肿瘤基本持续保持稳定，除了出有现经年累月初配烧并伴有心动过速（由此可知2）。高血压之后学术研究报告非生产性腹痛，并出有现疲惫不堪。
在出有院第二天的下午，高血压吞咽保证了，腹部不适。凌晨有第二次屁股稀疏的美联社。获取该粪便的试样常用rRT-PCR次测试，以及其他肺泡配现地（喉咽和头咽）和肝脏。粪便和两个肺泡配现地后来仅有通过rRT-PCR试样为2019-nCoV病毒性，而肝脏仍为同义。
在此之前的化疗在太大程度上是反对性的。为了同步进行癫痫状执行，高血压能够根据能够拒绝接受解热疗法，该疗法还包括每4不间断650 mg咖啡因和每6不间断600 mg非甾体。在出有院的前六天，他还因长时间腹痛而服用了600毫克愈创醚和达6充生理盐水。
请注意1-诊断麻省理工学院结果
高血压可避免区块的形式在此之前仅允许即时卫生保健点麻省理工学院次测试；从养老院第3天开始可以同步进行正因如此血细胞可用和肝脏化学学术研究。
在养老院第3天和第5天（病因第7天和第9天）的麻省理工学院结果说明了出有白细胞减小癫痫，轻度血小板减小癫痫和肌酸激酶技术水平充高（请注意1）。此则有，酸中毒这两项也大大配生变化：碱性磷酸酶（每充68 U），丙一氧化氮酸一氧化氮基转移酶（每充105 U），胺基酸一氧化氮基转移酶（每充77 U）和三酸甘油酯脱氢酶（每充465 U）的技术水平大致相同：在出有院的第5天所有充高。鉴于高血压间歇配烧，在第4天取得肠道培养；在此之前，这些都无法上充。
由此可知3-2020年1月初22日（脸部第7天，养老院第3天）的后腰部和侧边胸片
由此可知4-2020年1月初24日（脸部第5天，养老院第9天）的后腰部X线片
据美联社，在养老院第3天（体弱第7天）拍的脸部X光片从未标示出有浸润或反常迹象（由此可知3）。
但是，从养老院第5天凌晨（体弱第9天）凌晨同步进行的第二次脸部X光片检测标示出有，左肺下叶有结核能病（由此可知4）。
这些检查和断定与从养老院第5天凌晨开始的气管状态配生变化在在，当时高血压在气管附近液体时通过脉搏高血压稍低测的高血压稍低数值下调90％。
在第6天，高血压开始拒绝接受说明氢气，该氢气由喉食道以每分钟2充的速度运载。直接影响诊断请注意现的配生变化和对养老院取得结核能病的瞩目，开始应用于万古霉素（1750 mg负荷浓度，然后每8不间断用药1 g）和嗪吡肟（每8不间断用药）化疗。
由此可知5-前后脸部X光片，2020年1月初26日（病因第十天，养老院第六天）
在养老院第6天（体弱第10天），第四次脸部X射线合照标示出有两个肺中都都有基底条状混浊，这一断定与非典型结核能病相符（由此可知5），并且在听诊时在两个肺中都都出有现了罗音。鉴于放射线检查和断定，要求拒绝接受氢气说明，高血压长时间配烧，多个部位长时间病毒性的2019-nCoV RNA病毒性，以及配请注意了与放射线结核能病工业配展原则上的致使结核能病在该高血压中都，诊断内科医生非常有同情心地应用于了学术研究课题抗HIV化疗。
用药瑞德昔韦（一种悄悄开配的新型蛋白质萘前药）在第7天凌晨开始，但从未掩蔽到与透析有关的所致事件。在对以次氢西林耐药的金黄色抗生素同步进行了连续的降钙素原技术水平和喉PCR试样后，在第7天凌晨撤除万古霉素，并在第二天撤除嗪吡肟。
在养老院第8天（体弱第12天），高血压的诊断原因取得非常佳。停止说明氢气，他在气管附近液体时的氢稍低数值提高到94％至96％。原本的双侧下叶罗音不再存有。他的血清素取得非常佳，除了经年累月初干咳和喉漏则有，他无法癫痫状。
截至2020年1月初30日，高血压仍出有院。他有配热，除腹痛则有，所有癫痫状仅有已消除，腹痛的程度悄悄减轻。
原理
配现地野则有
根据CDC手册取得常用2019-nCoV病患次测试的诊断配现地。用尼龙拭子获取了12个喉咽和头咽拭子配现地。
将每个拭子放入包含2至3 mlHIV水路微粒的另行无菌将水都。将血集在肝脏分立将水都，然后根据CDC手册同步进行离心。肾脏和粪便配现地分别获取在无菌配现地托盘中都。试样在2°C至8°C相互间内含，直到作好运载至CDC。
在病因的第7、11和12天获取了重复同步进行的2019-nCoV次测试的配现地，还包括喉咽和头咽拭子，肝脏以及肾脏和粪便样本。
2019-NCOV的病患次测试
应用于从公开配布的HIV基因序列工业配展而来的rRT-PCR分析法次测试了诊断配现地。与原本针对重癫痫急性气管性疾病冠状HIV（SARS-CoV）和中都东气管性疾病冠状HIV（MERS-CoV）的病患原理类似于，它具有三个核能遗传物质基因核能酸和一个病毒性对照核能酸。该测的所述为RRT-PCR面板双链和电极和基因序列讯息中都必需的CDC麻省理工学院讯息com2019-nCoV上。
遗传脱氢核能糖遗传物质
2020年1月初7日，欧美学术研究人员通过英美两国国立卫生学术研究院GenBank图表库和正因如此球分享所有肺炎图表更更进一步反对（GISAID）图表库分享了2019-nCoV的数值得注意基因基因序列；随后配布了有关可避免2019-nCoV的学术研究报告。
从rRT-PCR病毒性配现地（头咽和喉咽）中都所含遗传物质，并在Sanger和新一代脱氢核能糖遗传物质的平台（Illumina和MinIon）上常用正因如此基因组脱氢核能糖遗传物质。应用于5.4.6版的Sequencher软体（Sanger）完成了基因序列拆解。minimap软体，原版2.17（MinIon）；和freebayes软体1.3.1版（MiSeq）。将数值得注意基因组与必需的2019-nCoV参看基因序列（GenBank登录号NC_045512.2）同步进行比较。
结果
2019-NCOV的配现地次测试
请注意2-2019年新型冠状HIV（2019-nCoV）的实时逆转录酶-蛋白酶-不可逆次测试结果
该高血压在体弱第4自是取得的初始肺泡样本（喉咽拭子和头咽拭子）在2019-nCoV类固醇（请注意2）。
尽管高血压在此之前请注意现为轻度癫痫状，但在病因第4天的高于循环阈数值（Ct）数值（喉咽配现地中都为18至20，头咽配现地中都为21至22）请注意明这些配现地中都HIV技术水平很高。
在病因第7天取得的两个上肺泡配现地在2019-nCoV仍持续保持病毒性，还包括喉咽拭子配现地中都长时间高技术水平（Ct数值23至24）。在病因第7天取得的粪便在2019-nCoV中都也类固醇（Ct数值为36至38）。两种野则有时间表的肝脏样本在2019-nCoV仅有为同义。
在病因第11天和第12天取得的喉咽和头咽配现地标示出有出有HIV技术水平下降的趋向于。
头咽配现地在体弱第12天的2019-nCoV次测试圆形同义。在这些时间表取得的肝脏的rRT-PCR结果仍从并不相同。
遗传脱氢核能糖遗传物质
头咽和喉咽配现地的数值得注意基因组基因序列彼此基本上原则上，并且与其他必需的2019-nCoV基因序列几乎基本上原则上。
该高血压的HIV与2019-nCoV参看基因序列（NC_045512.2）在封闭写出有框8处为数不多3个蛋白质和1个并不基本上原则上。该基因序列可通过GenBank取得（登录号MN985325）。
版主
我们关于英美两国首开2019-nCoV肺炎病症的学术研究报告时说明了这一新兴病因的几个方面尚从未基本上洞察，还包括传递高效率和诊断病因的正因如此部以内。
我们的病症高血压曾去过欧美郑州，但学术研究报告时说他在郑州之前无法去过水果批配市场或卫生保健机构，也无法生病的注意到。尽管他的2019-nCoV病毒的；也尚不明了，但已公开了人对人传递的证据。
到2020年1月初30日，尚从未断定与此病症特别的2019-nCoV继肺癌症，但仍在的关系看管下。
在病因的第4天和第7天从上肺泡配现地中都试样到具有高于Ct数值的2019-nCoV RNA，请注意明HIV载量高且具有传递潜力。
数值得注意的是，我们还在高血压体弱第7天获取的粪便样本中都试样到了2019-nCoV RNA。尽管我们病症高血压的肝脏配现地间歇出有现2019-nCoV同义，但在欧美重癫痫高血压的肠道中都仍试样到HIVRNA。然而，肺则有试样HIVRNA并不一定这样一来存有传染性HIV，迄今尚不明了在肺泡直接试样HIVRNA的诊断意义。
迄今，我们对2019-nCoV病毒的诊断以内的洞察非常有限。在欧美，仍未美联社了诸如致使的结核能病，气管衰竭，急性气管窘迫性疾病（ARDS）和胸腔损伤等并配癫痫，还包括致命的不可避免。然而，不可忽视的是要注意，这些病症是根据其结核能病病患确切的，因此显然但会使学术研究报告偏向非常致使的结果。
我们的病症高血压在此之前请注意现为轻度腹痛和高于度经年累月初配烧，在体弱的第4天无法脸部X光检测的结核能病迹象，而在体弱第9天工业配展为结核能病之前，这些非甲基化恶性肿瘤和癫痫状在早期在诊断上，2019-nCoV病毒的诊断过程显然与许多其他类似于结核能病无法明显区别，尤其是在夏季肺泡HIV干季。
另则有，本病症高血压在病因的第9天工业配展为结核能病的时机与近期气管困难的配作（肺癌后中都位数为8天）原则上。尽管根据高血压的诊断原因变差要求前提拒绝接受remdesivir慈悲的应用于，但仍能够同步进行随机对照次测试以确切remdesivir和任何其他学术研究抗生素化疗2019-nCoV病毒的安正因如此性和有效性。
我们学术研究报告了英美两国首开学术研究报告的2019-nCoV病毒高血压的诊断特征。
该病症的关键方面还包括高血压在写出有有关暴配的预防警告后要求寻求卫生保健；由当地卫生保健服务包括者认定高血压都只到郑州的之旅近现代，随后在当地，特拉华和联邦预防官员相互间同步进行协调；并确切显然的2019-nCoV病毒，从而可以很快可避免高血压并随后对2019-nCoV同步进行麻省理工学院认定，并允许高血压晕倒更进一步检验和管理制度。
该病症学术研究报告强调了诊断内科医生对于任何出有现急性病因癫痫状的就诊高血压，要总结出有都只的之旅经历或注意到病症的必要性，为了尽可能合理比对和立刻可避免显然面临2019-nCoV病毒风险的高血压，并帮助减小更进一步的传递。
最后，本学术研究报告强调能够确切与2019-nCoV病毒特别的诊断病因，肺癌内源性和HIV折断长时间时间的
正因如此部以内和连续性近现代，以为诊断管理制度和预防决断包括依据。
下述为译者
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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.
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