摘要
在里面国武汉开始的新型病毒性（2019-nCoV）一触即发在促使蔓延，现已在多个国内肺癌。我们调查结果了在新泽西州断定的唯一未2019-nCoV细菌感染发在生率，并描述了该发在生率的比对，病患，医学每一次和管理机构，仅限于病症在病况第9天展现为心肌梗塞时的原先轻度病症。
该情形特别强调了医学医生与地方，和州和联邦议都会各级公共服务中国政府中间密切协作的层面，以及无需快速扩散与这种新发在细菌感染病症的看护有关的医学接收者的期望。
2019年12同月31日，里面国调查结果了与湖北省武汉市华南鱼肉批发在市场需求有关的人群里面的心肌梗塞发在生率。
2020年1同月7日，里面国公共卫生中国政府断定该簇与新型病毒性2019-nCoV有关。尽管原先另据的发在生率与武汉市鱼肉市场需求的暴露有关，但当年前的临床数据集确实，正在发在生2019-nCoV人际扩散。
截至2020年1同月30日，在至少21个国内/地区调查结果了9976例发在生率，仅限于2020年1同月20日另据的新泽西州唯一未肺癌的2019-nCoV细菌感染发在生率。
同类型世界区域内正在开展调查，以愈好来愈好多地认识到扩散高效率和医学营养不良区域。本调查结果描述了在新泽西州断定的唯一未2019-nCoV细菌感染的临床和医学特征。
情形调查结果
2020年1同月19日，一名35岁的男子注意到在克利夫兰和州克拉克霍米什县的一家急诊公立医院，有4天的痉挛和有意识发在烧巨著。病患到公立医院检验时，在候诊室戴上朝天罩。等待平均20分钟后，他被带入检验室放弃了提供者的风险评估。
他透露，他在里面国武汉陪伴亲友后于1同月15日回到克利夫兰和州。该病症注记示，他已从新泽西州营养不良控制与预防里面心（CDC）送造出有关里面国新型病毒性暴发在的心理健康警报，由于他的病症和最近的旅行者，他允诺去看医生。
平面图1-2020年1同月19日（营养不良第4天）的后头部和之内侧胸片
除了高三酸酯瓜硫酸的病巨著之外，该病症还是其他心理健康的不成年人。体格检验发在现病症腹腔环境氮气时，血液可逆为37.2°C，血压为134/87 mm Hg，不止为每分钟110次，腹腔频率为每分钟16次，氮含水为96％。腹腔听诊感叹明了有支气管炎，并开展了胸片检验，据另据未发在现异常（平面图1）。
病毒性和甲类心肌梗塞的快速核分裂酸增量试验（NAAT）为比如说。获了钝咽拭子骨骸，并通过NAAT将其送去去检验HIV性肠胃病原体。
据另据在48每隔内对所有试验的病原体均深褐色比如说，仅限于病毒性和甲类心肌梗塞，副心肌梗塞，肠胃合胞HIV，钝HIV，腺HIV和已知都会导致人类营养不良的四种常见病毒性株（HKU1，NL63、229E和OC43） ）。根据病症的旅行者历巨著，尽快告知地方和和州医务人员门。克利夫兰医务人员与紧急看护医学医生一同告知了CDC紧急行动里面心。
尽管该病症调查结果感叹他无法去过华南鱼肉市场需求，也无法调查结果在去里面国旅行者期间与年老者有任何保有联系，但营养不良预防控制里面心的工作人员允诺有必要根据当年前的营养不良预防控制里面心对病症开展2019-nCoV试验。
根据CDC简介抽取了8个骨骸，仅限于胰岛素，钝咽和朝天咽拭子骨骸。骨骸热带植物后，病症被送去往家庭主妇分开，并由当地医务人员门开展积极造出现异常。
2020年1同月20日，营养不良预防控制里面心（CDC）断定病症的钝咽和朝天咽拭子通过系统对丝硫酸-聚合酶链反应（rRT-PCR）检验为2019-nCoV阳性。
在营养不良预防控制里面心的主题专家，和州和地方公共卫生行政官员，紧急公共卫生保健服务以及疗养院领导和工作人员的立体化下，病症被送去往普罗维登斯地区公共卫生保健里面心的氮气分开病房开展医学注意到，并跟随营养不良预防控制里面心的医护人员有关保有联系，飞沫和空里面防护控制措施的劝告，并带有靴子。
入院时病症调查结果接下来痉挛，有2天的头痛和腹泻巨著。他调查结果感叹他无法腹腔急促或征状。肉体哮喘在较长时间区域内。体格检验发在现病症粘膜干燥。其余的检验通常不引人注意。
入院后，病症放弃了支持病患，仅限于2升生理盐水和恩丹以减轻头痛。
平面图2-根据营养不良日和开刀日（2020年1同月16日至2020年1同月30日）的病症和最高血液可逆
在开刀的第2至5天（年老的第6至9天），病症的肉体哮喘大体上始终保有，除了注意到经年累月发在烧并伴有心动过速（平面图2）。病症继续调查结果非生产性痉挛，并注意到疲倦。
在开刀第二天的下午，病症排便通畅，腹部不适。晚间有第二次喝水稀疏的另据。抽取该异味的样品主要用途rRT-PCR试验，以及其他肠胃骨骸（钝咽和朝天咽）和胰岛素。异味和两个肠胃骨骸便均通过rRT-PCR检验为2019-nCoV阳性，而胰岛素仍为比如说。
先后的病患在很大持续性上是经常性的。为了开展病症管控，病症无需根据无需放弃利尿疗法，该疗法仅限于每4每隔650 mg阿司匹林和每6每隔600 mg布洛芬。在开刀的年前六天，他还因接下来痉挛而服用了600毫克愈好创醚和平均6升生理盐水。
注记1-医学科学实验结果
病症分开单元的形式原先仅必需即时公共卫生保健点科学实验试验；从疗养院第3天开始可以开展同类型血细胞计数和胰岛素矿物学科学研究。
在疗养院第3天和第5天（营养不良第7天和第9天）的科学实验结果反映造出白细胞减缓症，轻度血栓减缓症和肌酸激酶低水平上升时（注记1）。此之外，肾功能指标也有所变化：碱性磷酸酶（每升68 U），丙硫酸硫基转移酶（每升105 U），天冬硫酸硫基转移酶（每升77 U）和乳酸谷硫酸（每升465 U）的低水平分别为：在开刀的第5天所有上升时。鉴于病症反复发在烧，在第4天获尿液培养；迄今为止，这些都无法持续增长。
平面图3-2020年1同月22日（腹部第7天，疗养院第3天）的后头部和之内侧胸片
平面图4-2020年1同月24日（腹部第5天，疗养院第9天）的后头部X线片
据另据，在疗养院第3天（年老第7天）拍摄的腹部X光片未感叹明了伴生或异常可能（平面图3）。
但是，从疗养院第5天晚间（年老第9天）晚间开展的第二次腹部X光片检验感叹明了，左肺下叶有心肌梗塞（平面图4）。
这些放大镜发在现与从疗养院第5天晚间开始的腹腔状态变化相吻合合，当时病症在腹腔周围氮气时通过不止泌尿系统含水测量的泌尿系统含水最大值降至90％。
在第6天，病症开始放弃多余压缩氮气，该压缩氮气由钝食道以每分钟2升的速度快输送去。考虑到医学展现的变化和对疗养院获性心肌梗塞的关注，开始采用布洛芬（1750 mg负荷副作用，然后每8每隔用药1 g）和唑两场醛（每8每隔用药）病患。
平面图5-年前后腹部X光片，2020年1同月26日（营养不良第十天，疗养院第六天）
在疗养院第6天（年老第10天），第四次腹部X射线特写感叹明了两个肺里面都有基底条状混浊，这一发在现与非近似于心肌梗塞相吻合（平面图5），并且在听诊时在两个肺里面都注意到了罗音。鉴于放射线放大镜发在现，允诺给予压缩氮气多余，病症接下来发在烧，多个部位接下来阳性的2019-nCoV RNA阳性，以及发在注记了与放射线性心肌梗塞发在展原则上的严重心肌梗塞在该病症里面，医学医生富有同情心地采用了科学研究性抗HIV病患。
用药瑞德昔韦（一种正在开发在的新型硫基酸类似物年前药）在第7天晚间开始，但未注意到到与透析有关的不良事件。在对甲氮馨耐药的金黄色葡萄球菌开展了整年的降钙素原低水平和钝PCR检验后，在第7天晚间改用布洛芬，并在第二天改用唑两场醛。
在疗养院第8天（年老第12天），病症的医学境况获得提升。暂停多余压缩氮气，他在腹腔周围氮气时的氮含水最大值更高到94％至96％。在此之后的双侧下叶罗音不再依赖于。他的食欲获得提升，除了经年累月干咳和钝漏之外，他无法病症。
截至2020年1同月30日，病症仍开刀。他有发在热，除痉挛之外，所有病症均已减轻，痉挛的持续性正在过重。
方法
骨骸热带植物
根据CDC简介获主要用途2019-nCoV病患试验的医学骨骸。用矿物学纤维拭子抽取了12个钝咽和朝天咽拭子骨骸。
将每个拭子插入包括2至3 mlHIV转运电磁辐射的单独施用管里面。将血集在胰岛素分离管里面，然后根据CDC简介开展离心。血浆和异味骨骸分别抽取在施用骨骸容器里面。样品在2°C至8°C中间储存，直到准备就绪输送去至CDC。
在营养不良的第7、11和12天抽取了重复开展的2019-nCoV试验的骨骸，仅限于钝咽和朝天咽拭子，胰岛素以及血浆和异味抽取。
2019-NCOV的病患试验
采用从未公开发在布的HIV遗传序列发在展而来的rRT-PCR分析法试验了医学骨骸。与在此之后针对心绞痛急性腹腔性营养不良病毒性（SARS-CoV）和里面东腹腔性营养不良病毒性（MERS-CoV）的病患方法相似，它较强三个核分裂亚基遗传靶标和一个阳性折衷靶标。该测量的描述为RRT-PCR平板引物和样品和遗传序列接收者里面需用的CDC科学实验接收者com2019-nCoV上。
遗传型DNA
2020年1同月7日，里面国科学研究人员通过新泽西州国立公共卫生科学研究院GenBank数据集库和同类型世界共享所有心肌梗塞数据集倡议（GISAID）数据集库共享了2019-nCoV的清晰脱氧核分裂糖核分裂酸；随后发在布了有关分开2019-nCoV的调查结果。
从rRT-PCR阳性骨骸（朝天咽和钝咽）里面提取核分裂酸，并在Sanger和下一代DNA跨平台（Illumina和MinIon）上主要用途同类型遗传物质DNA。采用5.4.6版的Sequencher该软件（Sanger）已完成了遗传序列拆解。minimap该软件，版本2.17（MinIon）；和freebayes该软件1.3.1版（MiSeq）。将清晰遗传物质与需用的2019-nCoV参考资料遗传序列（GenBank登录号NC_045512.2）开展比较。
结果
2019-NCOV的骨骸试验
注记2-2019年新型病毒性（2019-nCoV）的系统对丝硫酸-聚合酶-链反应试验结果
该病症在年老第4天时获的初始肠胃抽取（钝咽拭子和朝天咽拭子）在2019-nCoV药检（注记2）。
尽管病症原先展现为轻度病症，但在营养不良第4天的很低可逆阈最大值（Ct）最大值（钝咽骨骸里面为18至20，朝天咽骨骸里面为21至22）确实这些骨骸里面HIV低水平较低。
在营养不良第7天获的两个上肠胃骨骸在2019-nCoV仍保有阳性，仅限于钝咽拭子骨骸里面接下来高低水平（Ct最大值23至24）。在营养不良第7天获的异味在2019-nCoV里面也药检（Ct最大值为36至38）。两种热带植物应于的胰岛素抽取在2019-nCoV均为比如说。
在营养不良第11天和第12天获的钝咽和朝天咽骨骸感叹明了造出HIV低水平下降的近来。
朝天咽骨骸在年老第12天的2019-nCoV试验深褐色比如说。在这些应于获的胰岛素的rRT-PCR结果仍未定。
遗传型DNA
朝天咽和钝咽骨骸的清晰遗传物质遗传序列彼此大致相同，并且与其他需用的2019-nCoV遗传序列仍然大致相同。
该病症的HIV与2019-nCoV参考资料遗传序列（NC_045512.2）在开放写造出框8处为数不多3个硫基酸和1个有所不同。该遗传序列可通过GenBank获（登录号MN985325）。
网志
我们关于新泽西州唯一未2019-nCoV肺癌发在生率的调查结果感叹明了这一新兴营养不良的几个方面唯未完同类型认识到，仅限于扩散高效率和医学营养不良的同类型部区域。
我们的发在生率病症曾去过里面国武汉，但调查结果感叹他在武汉期间无法去过鱼肉批发在市场需求或公共卫生保健机构，也无法身体虚弱的保有联系。尽管他的2019-nCoV细菌感染的比如说唯不清楚，但已未公开了人对人扩散的证据。
到2020年1同月30日，唯未发在现与此发在生率特别的2019-nCoV继发在发在生率，但仍在密切监视下。
在营养不良的第4天和第7天从上肠胃骨骸里面检验到较强很低Ct最大值的2019-nCoV RNA，确实HIV载量高且较强扩散潜力。
最大相比较的是，我们还在病症年老第7天抽取的异味抽取里面检验到了2019-nCoV RNA。尽管我们发在生率病症的胰岛素骨骸反复注意到2019-nCoV比如说，但在里面国心绞痛病症的尿液里面仍检验到HIVRNA。然而，肺之外检验HIVRNA未必意味着依赖于传染性HIV，迄今为止唯不清楚在肠胃之外部检验HIVRNA的医学意义。
迄今为止，我们对2019-nCoV细菌感染的医学区域的认识到非常有限。在里面国，早就另据了诸如严重的心肌梗塞，腹腔衰竭，急性腹腔窘迫性营养不良（ARDS）和心脏损伤等造出血，仅限于致命的后果。然而，重要的是要注意，这些发在生率是根据其心肌梗塞病患确认的，因此或许都会使调查结果相反愈好来愈好严重的结果。
我们的发在生率病症原先展现为轻度痉挛和很低度经年累月发在烧，在年老的第4天无法腹部X光检验的心肌梗塞可能，而在年老第9天发在展为心肌梗塞以年前，这些非特异性哮喘和病症在一时期在医学上，2019-nCoV细菌感染的医学每一次或许与许多其他常见登革热无法引人注意有所不同点，尤其是在冬季肠胃HIV干季。
另之外，本发在生率病症在营养不良的第9天发在展为心肌梗塞的意图与近期腹腔困难的心脏病（发在病后里面位数为8天）原则上。尽管根据病症的医学境况恶化允诺应该给予remdesivir慈悲的采用，但仍无需开展随机折衷试验以确认remdesivir和任何其他科学研究药物病患2019-nCoV细菌感染的安同类型性和有效性。
我们调查结果了新泽西州唯一未调查结果的2019-nCoV细菌感染病症的医学特征。
该发在生率的极为重要方面仅限于病症在写造出有关暴发在的公共服务提醒后允诺促成公共卫生保健；由当地公共卫生保健服务提供商断定病症最近到武汉的旅行者历巨著，随后在当地，和州和联邦议都会公共服务行政官员中间开展相互立体化；并确认或许的2019-nCoV细菌感染，从而可以促使分开病症并随后对2019-nCoV开展科学实验断定，并必需病症入院进一步风险评估和管理机构。
该发在生率调查结果特别强调了医学医生对于任何注意到急性营养不良病症的诊治病症，要揭示造出最近的旅行者经历或保有联系病巨著的层面，为了确保正确识别系统和及时分开或许面临2019-nCoV细菌感染风险的病症，并帮助减缓进一步的扩散。
最后，本调查结果特别强调无需确认与2019-nCoV细菌感染特别的医学营养不良，发在病衍生物和HIV松脱接下来时间的
同类型部区域和自然地历巨著，以为医学管理机构和公共服务决策提供依据。
以下为英文版
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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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