简要
在近现代汉口内开始的新型冠状感染（2019-nCoV）爆发迅速席卷，曾一度在多个国家胃癌。我们研究者报告了在新泽西的县证实的首唯2019-nCoV染病病综合症，并描述了该病综合症的鉴定，病因，内外科过程和管理制度，除此以内外病综合症在病情第9天列于现为败血综合症时的本来轻度副作用。
该案唯突显了内外科医师与大都，的县和美国联邦政府各级公共服务当中共政府二者之间密切关系协作的应当性，以及只能较快的传播与这种新发染病病综合症的卫生有关的内外科数据的需求。
2019年12年初31日，近现代研究者报告了与湖北汉口内市华南地区水果商铺有关的许多人当中的败血综合症病综合症。
2020年1年初7日，近现代保健保健当中共政府证实该簇与新型冠状感染2019-nCoV有关。尽管本来报道的病综合症与汉口内市水果市场的暴露有关，但局限性的美国病因依靠与预防内外围数据列于明，即将发生2019-nCoV人际的传播。
截至2020年1年初30日，在据估计21个国家/沿海地区研究者报告了9976唯病综合症，除此以内外2020年1年初20日报道的新泽西的县首唯胃癌的2019-nCoV染病病综合症。
以外球以内内即将顺利未完成调查，以更容易地理解的传播即时和内外科病因以内。本研究者报告描述了在新泽西的县证实的首唯2019-nCoV染病的美国病因依靠与预防内外围和内外科特性。
案唯研究者报告
2020年1年初19日，一名35岁的女童用到在华盛顿的县斯诺霍米达县的主营急诊医疗机构，有4天的发烧和单纯高烧史。病人到医疗机构体检时，在候诊室戴上口内罩。等待约20分钟后，他被带到体检室拒绝接受了提供者的审核。
他声称，他在近现代汉口内探望家人先于1年初15日返回华盛顿的县。该病综合症回应，他已从新泽西的县病因依靠与传染病当内外围（CDC）收到有关近现代新型冠状感染频发的保健保健警报，由于他的副作用和都只的环游，他提议去看医师。
绘出1-2020年1年初19日（病因第4天）的后腰部和内后侧胸片
除了高三酸酯血综合症的病因内外，该病综合症还是其他保健保健的不吸烟者。体格体检辨认出病综合症排尿环境氢气时，血液循环为37.2°C，眼压为134/87 mm Hg，脉搏为每分钟110次，排尿高频率为每分钟16次，钾含水为96％。肺部听诊时说明了有支气管炎，并顺利未完成了胸片体检，据报道未辨认出间歇性（绘出1）。
七轮型和甲类流感的较快脱钾核糖核酸缩减实验（NAAT）为中性。赢得了钝咽拭子遗骸，并通过NAAT将其送去侦测感染性黏膜病原体。
据报道在48以外程内对所有实验的病原体皆深褐色中性，除此以内外七轮型和甲类流感，副流感，黏膜合胞感染，钝感染，腺感染和已知可能会避免人类病因的四种常见冠状感染株（HKU1，NL63、229E和OC43） ）。根据病综合症的环游历史，立即通知大都和的县已对。华盛顿保健保健部与紧急情况卫生内外科医师一起通知了CDC紧急情况行动当内外围。
尽管该病综合症研究者报告时说他很难去过华南地区水果市场，也很难研究者报告在去近现代环游其间与染病者有任何交谈，但病因传染病指挥当内外围的工作病人同意有应当根据局限性的病因传染病指挥当内外围对病综合症顺利未完成2019-nCoV实验。
根据CDC简介得来了8个遗骸，除此以内外血浆，钝咽和口内咽拭子遗骸。遗骸采集后，病综合症被送去普通家庭永久性，并由当地已对顺利未完成积极系统对。
2020年1年初20日，病因传染病指挥当内外围（CDC）证实病综合症的钝咽和口内咽拭子通过即时核苷-聚合酶链反应（rRT-PCR）侦测为2019-nCoVHIV。
在病因传染病指挥当内外围的趣味研究者，的县和大都保健保健官员，紧急情况保健服务以及医疗机构领导和工作病人的配合下，病综合症被送去马萨诸塞沿海地区保健当内外围的氢气永久性病房顺利未完成内外科观察，并舅父病因传染病指挥当内外围的医护病人有关交谈，飞沫和空当中防爆措施的表示同意，并带有面罩。
复发时病综合症研究者报告持续发烧，有2天的烦躁和呼吸困难史。他研究者报告时说他很难排尿急促或气喘。生命哮喘在正常以内内。体格体检辨认出病综合症粘膜炎热。其余的体检不一定不轻微。
复发后，病综合症拒绝接受了支持病人，除此以内外2天和生理盐水和恩丹以消除烦躁。
绘出2-根据病因日和复发日（2020年1年初16日至2020年1年初30日）的副作用和最高血液循环
在复发的第2至5天（染病的第6至9天），病综合症的生命哮喘基本长期维持，除了用到间歇性高烧并眩晕心动过速（绘出2）。病综合症继续研究者报告非生产性发烧，并用到疲倦。
在复发第二天的下午，病综合症发烧保证了，腹部不适。傍晚有第二次尿稀疏的报道。得来该排泄的材料用于rRT-PCR实验，以及其他黏膜遗骸（钝咽和口内咽）和血浆。排泄和两个黏膜遗骸后来皆通过rRT-PCR侦测为2019-nCoVHIV，而血浆仍为中性。
在此其间的病人在很大持续性上是非典型的。为了顺利未完成副作用东南侧理过程，病综合症只能根据只能拒绝接受解热治疗法，该治疗法除此以内外每4以外程650 mg对乙酰七轮醇基酚和每6以外程600 mg布洛芬。在复发的前六天，他还因持续发烧而服药了600毫克愈创醚协约6天和生理盐水。
列于1-内外科Laboratory结果
病综合症永久性单元的形式本来极少强制即时保健点Laboratory实验；从医疗机构第3天开始可以顺利未完成以外血细胞计数和血浆有机化学研究者。
在医疗机构第3天和第5天（病因第7天和第9天）的Laboratory结果反映出白细胞降低综合症，轻度血小板降低综合症和肌酸激酶素质天和高（列于1）。此内外，肝功能基准也大大转变：碱性蛋白酶（每天和68 U），甘七轮醇酸七轮醇基转移酶（每天和105 U），谷胱甘肽七轮醇基转移酶（每天和77 U）和乳酸转移酶（每天和465 U）的素质分别为：在复发的第5天所有天和高。鉴于病综合症一再高烧，在第4天赢得血液人才培养；迄今为止，这些都很难持续增长。
绘出3-2020年1年初22日（面部第7天，医疗机构第3天）的后腰部和内后侧胸片
绘出4-2020年1年初24日（面部第5天，医疗机构第9天）的后腰部X线片
据报道，在医疗机构第3天（染病第7天）拍摄的面部X光片未时说明了浸润或间歇性迹象（绘出3）。
但是，从医疗机构第5天傍晚（染病第9天）傍晚顺利未完成的第二次面部X光片体检时说明了，左肺下叶有败血综合症（绘出4）。
这些影像学辨认出与从医疗机构第5天傍晚开始的排尿状态转变相吻合，当时病综合症在排尿周边氢气时通过脉搏血钾含水测定的血钾含水参数降至90％。
在第6天，病综合症开始拒绝接受必需钾气，该钾气由钝导管以每分钟2天和的反应速度输送。考虑到内外科列于现的转变和对医疗机构赢得性败血综合症的追捧，开始运用于万古霉素（1750 mg耗损剂量，然后每8以外程肌肉注射1 g）和红霉素足总杯苯基（每8以外程肌肉注射）病人。
绘出5-前后面部X光片，2020年1年初26日（病因第十天，医疗机构第六天）
在医疗机构第6天（染病第10天），第四次面部X射线照片时说明了两个肺当中都有基底长条状光亮，这一辨认出与非典型败血综合症十分相似（绘出5），并且在听诊时在两个肺当中都用到了罗音。鉴于放射源影像学辨认出，提议赋予钾气必需，病综合症持续高烧，多个胸部持续HIV的2019-nCoV RNAHIV，以及发列于了与放射源性败血综合症工业发展相符的严重败血综合症在该病综合症当中，内外科医师优雅同情心地运用于了研究者性抗感染病人。
肌肉注射福斯特昔韦（一种即将开发的新型核苷酸酰胺前药）在第7天傍晚开始，但未观察到与输注有关的不良血案。在对七轮钾霖MRSA的金黄色葡萄球菌顺利未完成了连续的降钙素原素质和钝PCR侦测后，在第7天傍晚停用万古霉素，并在第二天停用红霉素足总杯苯基。
在医疗机构第8天（染病第12天），病综合症的内外科情况赢取改善。停止必需钾气，他在排尿周边氢气时的钾含水参数大幅提高到94％至96％。先前的单侧下叶罗音早已普遍存在。他的新陈代谢赢取改善，除了间歇性干咳和钝漏内外，他很难副作用。
截至2020年1年初30日，病综合症仍复发。他有头痛，除发烧内外，所有副作用皆已消除，发烧的持续性即将减轻。
方法
遗骸采集
根据CDC简介赢得用于2019-nCoV病因实验的内外科遗骸。用合成纤维拭子得来了12个钝咽和口内咽拭子遗骸。
将每个拭子断开包含2至3 ml感染转运介质的单独无菌将水。将血集在血浆分离将水，然后根据CDC简介顺利未完成离心。肾脏和排泄遗骸分别得来在无菌遗骸容器当中。材料在2°C至8°C二者之间储存，直到准备好运送至CDC。
在病因的第7、11和12天得来了多次重复顺利未完成的2019-nCoV实验的遗骸，除此以内外钝咽和口内咽拭子，血浆以及肾脏和排泄结果显示。
2019-NCOV的病因实验
运用于从官方网站发行的感染核酸工业发展而来的rRT-PCR分析法实验了内外科遗骸。与先前针对重综合症急性排尿性疾病冠状感染（SARS-CoV）和当中东排尿性疾病冠状感染（MERS-CoV）的病因方法完以外相同，它具备三个核衣壳基因特异性和一个HIV对照特异性。该测定的描述为RRT-PCR背光引物和样品和核酸数据当中能用的CDCLaboratory数据网站2019-nCoV上。
基因人类基因组计划
2020年1年初7日，近现代研究者病人通过新泽西的县国立保健保健研究者院GenBank数据库和以外球提供者所有流感数据倡议（GISAID）数据库提供者了2019-nCoV的完备基因核酸；随后发行了有关永久性2019-nCoV的研究者报告。
从rRT-PCRHIV遗骸（口内咽和钝咽）当中提取脱钾核糖核酸，并在Sanger和新世代人类基因组计划平台（Illumina和MinIon）上用于以外基因组人类基因组计划。运用于5.4.6国际版的Sequencher应用程序（Sanger）未完成了核酸组装。minimap应用程序，国际版本2.17（MinIon）；和freebayes应用程序1.3.1国际版（MiSeq）。将完备基因组与能用的2019-nCoV参考核酸（GenBank登录号NC_045512.2）顺利未完成比起。
结果
2019-NCOV的遗骸实验
列于2-2019年新型冠状感染（2019-nCoV）的即时核苷-聚合酶-链反应实验结果
该病综合症在染病第4天时赢得的初始黏膜结果显示（钝咽拭子和口内咽拭子）在2019-nCoVHIV（列于2）。
尽管病综合症本来列于现为轻度副作用，但在病因第4天的极低循环阈参数（Ct）参数（钝咽遗骸当中为18至20，口内咽遗骸当中为21至22）列于明这些遗骸当中感染素质较高。
在病因第7天赢得的两个上黏膜遗骸在2019-nCoV仍维持HIV，除此以内外钝咽拭子遗骸当中持续高素质（Ct参数23至24）。在病因第7天赢得的排泄在2019-nCoV当中也HIV（Ct参数为36至38）。两种采集一月的血浆结果显示在2019-nCoV皆为中性。
在病因第11天和第12天赢得的钝咽和口内咽遗骸时说明了出感染素质下降的趋势。
口内咽遗骸在染病第12天的2019-nCoV实验深褐色中性。在这些一月赢得的血浆的rRT-PCR结果仍未定。
基因人类基因组计划
口内咽和钝咽遗骸的完备基因组核酸彼此相同，并且与其他能用的2019-nCoV核酸几乎相同。
该病综合症的感染与2019-nCoV参考核酸（NC_045512.2）在新开写出框8东南侧极少3个核苷酸和1个相同。该核酸可通过GenBank赢得（登录号MN985325）。
讨论区
我们关于新泽西的县首唯2019-nCoV胃癌病综合症的研究者报告时说明了这一新兴病因的几个特别未曾完以外理解，除此以内外的传播即时和内外科病因的以外部以内。
我们的病综合症病综合症曾去过近现代汉口内，但研究者报告时说他在汉口内其间很难去过水果商铺或保健机构，也很难患病的交谈。尽管他的2019-nCoV染病的举例尚不似乎，但已官方网站了人对人的传播的证据。
到2020年1年初30日，未曾辨认出与此病综合症关的的2019-nCoV诱肺癌综合症，但仍在密切关系监视下。
在病因的第4天和第7天从上黏膜遗骸当中侦测到具备极低Ct参数的2019-nCoV RNA，列于明感染储存量高且具备的传播潜质。
参数得警惕的是，我们还在病综合症染病第7天得来的排泄结果显示当中侦测到了2019-nCoV RNA。尽管我们病综合症病综合症的血浆遗骸一再用到2019-nCoV中性，但在近现代重综合症病综合症的血液当中仍侦测到感染RNA。然而，肺内外侦测感染RNA未必意味着普遍存在传染性感染，目前尚不似乎在黏膜内直接侦测感染RNA的内外科意义。
目前，我们对2019-nCoV染病的内外科以内的理解非常更少。在近现代，从未报道了诸如严重的败血综合症，排尿衰竭，急性排尿拮据性疾病（ARDS）和心脏损坏等并发综合症，除此以内外致命的后果。然而，最主要的是要警惕，这些病综合症是根据其败血综合症病因考虑到的，因此可能可能会可能会使研究者报告偏重于更严重的结果。
我们的病综合症病综合症本来列于现为轻度发烧和极低度间歇性高烧，在染病的第4天很难面部X光体检的败血综合症迹象，而在染病第9天工业发展为败血综合症前，这些非专一性哮喘和副作用在早期在内外科上，2019-nCoV染病的内外科过程可能可能会与许多其他常见传染病很难轻微区别，相比之下是在冬季黏膜感染季节。
另内外，本病综合症病综合症在病因的第9天工业发展为败血综合症的才可能会与最近排尿困难的头痛（肺癌后当中位数为8天）相符。尽管根据病综合症的内外科情况恶化提议前提赋予remdesivir慈悲的运用于，但仍只能顺利未完成随机对照实验以考虑到remdesivir和任何其他研究者药物病人2019-nCoV染病的相容性和系统性。
我们研究者报告了新泽西的县首唯研究者报告的2019-nCoV染病病综合症的内外科特性。
该病综合症的关键特别除此以内外病综合症在写出有关频发的公共服务警告后提议寻求保健；由当地保健服务提供者证实病综合症都只到汉口内的环游历史，随后在当地，的县和美国联邦政府公共服务官员二者之间顺利未完成互相配合；并考虑到可能可能会的2019-nCoV染病，从而可以迅速永久性病综合症并随后对2019-nCoV顺利未完成Laboratory证实，并强制病综合症复发再进一步审核和管理制度。
该病综合症研究者报告突显了内外科医师对于任何用到急性病因副作用的就诊病综合症，要总结出都只的环游境遇或交谈病因的应当性，为了确保确实识别和即时永久性可能可能会随之而来2019-nCoV染病风险的病综合症，并协助降低再进一步的的传播。
最后，本研究者报告突显只能考虑到与2019-nCoV染病关的的内外科病因，肺癌衍生物和感染脱落持续时间的
以外部以内和自然现象历史，以为内外科管理制度和公共服务互相配合提供依据。
请警惕为英文国际版
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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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