摘要
在之前国南昌开始的新型细菌性（2019-nCoV）挑起短时间内蔓延，现已在多个发达国家就诊。我们统计统可用据了在英国断定的唯一未2019-nCoV病菌登革热，并描绘了该登革热的鉴定，临床，临床过程和管理工作，仅限于患儿在病情第9天观感为结核病时的本来轻度腹泻。
该情形强调了临床内科医生与以前，特拉华和美利坚合众国各级医疗保健当局之间密不可分协作的极其重要性，以及所需迅速传播者与这种新复发菌患儿的护理有关的临床个人信息的所需。
2019年12翌年31日，之前国统计统可用据了与湖北湖北粤东紫菜批发消费市场有关的群体之前的结核病登革热。
2020年1翌年7日，之前国保健当局断定该簇与新型细菌性2019-nCoV有关。尽管本来报导的登革热与湖北紫菜消费市场的曝露有关，但这两项的流行病学统可用据表格明，悄悄遭遇2019-nCoV人际传播者。
截至2020年1翌年30日，在多于21个发达国家/地区统计统可用据了9976例登革热，仅限于2020年1翌年20日报导的英国唯一未就诊的2019-nCoV病菌登革热。
全球区域内悄悄顺利进行核查，以来得好地认识传播者快照和临床传染病区域。本统计统可用据描绘了在英国断定的唯一未2019-nCoV病菌的流行病学和临床相似性。
情形统计统可用据
2020年1翌年19日，一名35岁的男子显现再次出现在华盛顿特拉华斯诺霍米喀什地区的一家医护诊所，有4天的肿胀和主观颤动困难近代史。病人到诊所肥胖检查时，在候诊室戴上墨镜。继续前进约20分钟后，他被带至肥胖检查室不感兴趣了包括者的评估。
他谈及，他在之前国南昌探视亲人后于1翌年15日返回华盛顿特拉华。该患儿表格示，他已从英国传染病控制与医疗保健之前心（CDC）发出有关之前国新型细菌性暴发的肥胖预报，由于他的腹泻和都只的旅程，他尽快去看内科医生。
由此可知1-2020年1翌年19日（传染病第4天）的后前额和之外侧胸片
除了大一酸酯酸中毒的病症之外，该患儿还是其他肥胖的不抽烟。体格肥胖检查断定患儿颤动环境热空气时，血压为37.2°C，皮质醇为134/87 mm Hg，不止为每分钟110次，颤动频率为每分钟16次，锂稍低为96％。肺部听诊表格明有支气管炎，并顺利进行了胸片肥胖检查，据报导没断定诱发（由此可知1）。
亚型和-A亚型的迅速大分子增为的测试（NAAT）为感染性。获取了喉咽拭子骨头，并通过NAAT将其放去检测细菌性细菌病菌菌株。
据报导在48全程内对所有的测试的菌株外类固醇，仅限于亚型和-A亚型，副亚型，细菌病菌合胞菌株，喉菌株，腺菌株和已知会导致人类传染病的四种类似细菌性株（HKU1，NL63、229E和OC43） ）。根据患儿的旅程近代，马上通知以前和特拉华医务医务人员门。华盛顿医务医务人员与即刻护理临床内科医生一起通知了CDC即刻行动之前心。
尽管该患儿统计统可用据知道他没去过粤东紫菜消费市场，也没统计统可用据在去之前国旅程期间与染病者有任何注意到，但传染病医疗保健控制之前心的工作医务人员决定有必要根据这两项的传染病医疗保健控制之前心对患儿顺利进行2019-nCoV的测试。
根据CDC指南得来了8个骨头，仅限于人体内，喉咽和口内咽拭子骨头。骨头野外后，患儿被放往家庭分离，并由当地医务医务人员门顺利进行尽力数据分析。
2020年1翌年20日，传染病医疗保健控制之前心（CDC）断定患儿的喉咽和口内咽拭子通过高分辨率特罗斯季亚涅齐-酵素链反应（rRT-PCR）检测为2019-nCoV感染性。
在传染病医疗保健控制之前心的主题学术研究员，特拉华和以前保健高级官员，即刻医疗保健服务以及医务医务人员尽力支持和工作医务人员的配合下，患儿被放往普罗维登斯地区医疗保健之前心的热空气分离病房顺利进行临床推论，并追随传染病医疗保健控制之前心的病患有关切意到，飞沫和空之前防护保护措施的提议，并带有丝袜。
入院时患儿统计统可用据持续性肿胀，有2天的恶心和痉挛近代史。他统计统可用据知道他没颤动急促或胸痛。生命哮喘在正常区域内。体格肥胖检查断定患儿粘膜干燥。其余的肥胖检查举例来说不显著。
入院后，患儿不感兴趣了拥护外科手术，仅限于2升到生理盐水和恩丹以减轻恶心。
由此可知2-根据传染病日和患病日（2020年1翌年16日至2020年1翌年30日）的腹泻和最高血压
在患病的第2至5天（染病的第6至9天），患儿的生命哮喘基本保证稳定，除了显现再次出现经年累月颤动困难并伴有心动过速（由此可知2）。患儿继续统计统可用据非生产性肿胀，并显现再次出现疲累。
在患病第二天的早上，患儿排便通畅，腹部不适。晚上有第二次大便稠密的报导。得来该唾液的电子束常用rRT-PCR的测试，以及其他细菌病菌骨头（喉咽和口内咽）和人体内。唾液和两个细菌病菌骨头后来外通过rRT-PCR检测为2019-nCoV感染性，而人体内仍为感染性。
在此期间的外科手术在太大高度上是开放性的。为了顺利进行腹泻一处理，患儿所需根据所需不感兴趣解热药物，该药物仅限于每4全程650 mg对乙酰联赛杯啶基酚和每6全程600 mg布洛芬。在患病的前六天，他还因持续性肿胀而服用了600毫克愈创醚协约6升到生理盐水。
表格1-临床学术研究团队结果
患儿分离各别的特性本来仅必需短时间医疗保健点学术研究团队的测试；从医务医务人员第3天开始可以顺利进行全血细胞可用和人体内化学学术研究。
在医务医务人员第3天和第5天（传染病第7天和第9天）的学术研究团队结果反映显现出白细胞减少症，轻度红细胞减少症和肌酸激酶技术水平升到高（表格1）。此之外，肝功能的测试方式也有所转变：碱性磷酸酶（每升到68 U），羧酸联赛杯啶基转移酶（每升到105 U），天冬联赛杯啶酸联赛杯啶基转移酶（每升到77 U）和乳酸脱氢酶（每升到465 U）的技术水平分别为：在患病的第5天所有升到高。鉴于患儿反复颤动困难，在第4天获取肠道人才；目前为止，这些都没增长。
由此可知3-2020年1翌年22日（臀部第7天，医务医务人员第3天）的后前额和之外侧胸片
由此可知4-2020年1翌年24日（臀部第5天，医务医务人员第9天）的后前额X线片
据报导，在医务医务人员第3天（染病第7天）拍摄的臀部X光片没表格明显现出来或诱发先兆（由此可知3）。
但是，从医务医务人员第5天晚上（染病第9天）晚上顺利进行的第二次臀部X光片肥胖检查表格明，左肺下叶有结核病（由此可知4）。
这些医学影像断定与从医务医务人员第5天晚上开始的颤动状况转变在在，此前患儿在颤动周遭热空气时通过不止MRI稍低测定的MRI稍低数值降到90％。
在第6天，患儿开始不感兴趣说明缺锂，该缺锂由喉毛细管以每分钟2升到的速度输放。考虑到病变的转变和对医务医务人员获取脑膜炎的关切，开始应常用万古霉素（1750 mg节省成本剂量，然后每8全程肌肉注射1 g）和吲哚联赛杯吡啶（每8全程肌肉注射）外科手术。
由此可知5-前后臀部X光片，2020年1翌年26日（传染病第十天，医务医务人员第六天）
在医务医务人员第6天（染病第10天），第四次臀部X射线照片表格明两个肺之前都有基底夹光亮，这一断定与非十分相似结核病完全符合（由此可知5），并且在听诊时在两个肺之前都显现再次出现了罗音。鉴于辐射线医学影像断定，尽快给与缺锂说明，患儿持续性颤动困难，多个口腔持续性感染性的2019-nCoV RNA感染性，以及发表格了与辐射线脑膜炎转型赞同的严重结核病在该患儿之前，临床内科医生富有同情心地应常用了学术研究性抗菌株外科手术。
肌肉注射瑞德昔韦（一种悄悄开发的新型核糖类似物前药）在第7天晚上开始，但没推论到与输注有关的不良事件。在对甲锂磊致病的白色革兰氏顺利进行了周内的降钙素原技术水平和喉PCR检测后，在第7天晚上转用万古霉素，并在第二天转用吲哚联赛杯吡啶。
在医务医务人员第8天（染病第12天），患儿的临床情形赢取提升。停止说明缺锂，他在颤动周遭热空气时的锂稍低数值再进一步提高到94％至96％。无论如何的侧下叶罗音依然共存。他的血清素赢取提升，除了经年累月干咳和喉漏之外，他没腹泻。
截至2020年1翌年30日，患儿仍患病。他有发热，除肿胀之外，所有腹泻外已减轻，肿胀的高度悄悄消除。
方式
骨头野外
根据CDC指南获取常用2019-nCoV临床的测试的临床骨头。用合成纤维拭子得来了12个喉咽和口内咽拭子骨头。
将每个拭子插入包括2至3 ml菌株船运电介质的直接无菌管之前。将血集在人体内除去管之前，然后根据CDC指南顺利进行离心。血浆和唾液骨头分别得来在无菌骨头容器之前。电子束在2°C至8°C之间贮存，直到准备好运放至CDC。
在传染病的第7、11和12天得来了减法顺利进行的2019-nCoV的测试的骨头，仅限于喉咽和口内咽拭子，人体内以及血浆和唾液抽样。
2019-NCOV的临床的测试
应常用从引起争议公布的菌株数列转型而来的rRT-PCR分析法的测试了临床骨头。与无论如何针对重症急性颤动syndrome细菌性（SARS-CoV）和之前东颤动syndrome细菌性（MERS-CoV）的临床方式相似，它很强三个核双链基因索科利夫卡和一个感染性相尤其索科利夫卡。该测定的描绘为RRT-PCR面板引物和探针和数列个人信息之前可用的CDC学术研究团队个人信息网站2019-nCoV上。
遗传学大分子
2020年1翌年7日，之前国学术研究医务人员通过英国国立保健学术研究部GenBank统可用据库和全球之外联所有亚型统可用据倡议（GISAID）统可用据库之外联了2019-nCoV的基本基因数列；随后公布了有关分离2019-nCoV的统计统可用据。
从rRT-PCR感染性骨头（口内咽和喉咽）之前萃取大分子，并在Sanger和下一代大分子游戏平台（Illumina和MinIon）上常用全测序大分子。应常用5.4.6版的Sequencher的软件（Sanger）顺利进行了数列组装。minimap的软件，版本2.17（MinIon）；和freebayes的软件1.3.1版（MiSeq）。将基本测序与可用的2019-nCoV参见数列（GenBank登录号NC_045512.2）顺利进行尤其。
结果
2019-NCOV的骨头的测试
表格2-2019年新型细菌性（2019-nCoV）的高分辨率特罗斯季亚涅齐-酵素-链反应的测试结果
该患儿在染病第4天时获取的初始细菌病菌抽样（喉咽拭子和口内咽拭子）在2019-nCoV类固醇（表格2）。
尽管患儿本来观感为轻度腹泻，但在传染病第4天的较低循环系统阈数值（Ct）数值（喉咽骨头之前为18至20，口内咽骨头之前为21至22）表格明这些骨头之前菌株技术水平较差。
在传染病第7天获取的两个上细菌病菌骨头在2019-nCoV仍保证感染性，仅限于喉咽拭子骨头之前持续性高技术水平（Ct数值23至24）。在传染病第7天获取的唾液在2019-nCoV之前也类固醇（Ct数值为36至38）。两种野外应于的人体内抽样在2019-nCoV外为感染性。
在传染病第11天和第12天获取的喉咽和口内咽骨头表格显著现出菌株技术水平急剧下降的趋势。
口内咽骨头在染病第12天的2019-nCoV的测试类固醇。在这些应于获取的人体内的rRT-PCR结果仍没定。
遗传学大分子
口内咽和喉咽骨头的基本测序数列彼此完全赞同，并且与其他可用的2019-nCoV数列几乎完全赞同。
该患儿的菌株与2019-nCoV参见数列（NC_045512.2）在开放阅读框8一处差不多3个核糖和1个不同。该数列可通过GenBank获取（登录号MN985325）。
讨论区
我们关于英国唯一未2019-nCoV就诊登革热的统计统可用据知道明了这一新兴传染病的几个方面已为没完全认识，仅限于传播者快照和临床传染病的全部区域。
我们的登革热患儿曾去过之前国南昌，但统计统可用据知道他在南昌期间没去过紫菜批发消费市场或医疗保健机构，也没生病的注意到。尽管他的2019-nCoV病菌的相关联已为不明了，但已引起争议了人对人传播者的证据。
到2020年1翌年30日，已为没断定与此登革热之外的2019-nCoV性疾病登革热，但仍在密不可分警卫下。
在传染病的第4天和第7天从上细菌病菌骨头之前检测到很强较低Ct数值的2019-nCoV RNA，表格明菌株载重量高且很强传播者潜力。
数值得注意的是，我们还在患儿染病第7天得来的唾液抽样之前检测到了2019-nCoV RNA。尽管我们登革热患儿的人体内骨头反复显现再次出现2019-nCoV感染性，但在之前国重症患儿的肠道之前仍检测到菌株RNA。然而，肺之外检测菌株RNA举例来说意味着共存传染性菌株，目前为止已为不明了在细菌病菌之外部检测菌株RNA的临床意义。
目前为止，我们对2019-nCoV病菌的临床区域的认识非常有限。在之前国，已经报导了诸如严重的结核病，颤动衰竭，急性颤动穷困syndrome（ARDS）和心脏损伤等并发症，仅限于可怕的后果。然而，极其重要的是要注意，这些登革热是根据其结核病临床考虑到的，因此有可能会使统计统可用据偏向来得严重的结果。
我们的登革热患儿本来观感为轻度肿胀和较低度经年累月颤动困难，在染病的第4天没臀部X光肥胖检查的结核病先兆，而在染病第9天转型为结核病之前，这些非特异性哮喘和腹泻在以前在临床上，2019-nCoV病菌的临床过程有可能与许多其他类似传染病没显著差别，尤其是在冬季细菌病菌菌株时节。
另之外，本登革热患儿在传染病的第9天转型为结核病的意图与更再进一步颤动困难的发作（复发后之前位数为8天）赞同。尽管根据患儿的临床情形恶化尽快到底给与remdesivir慈悲的应常用，但仍所需顺利进行随机相尤其实验以考虑到remdesivir和任何其他学术研究药物外科手术2019-nCoV病菌的相容性和有效性。
我们统计统可用据了英国唯一未统计统可用据的2019-nCoV病菌患儿的临床相似性。
该登革热的关键性方面仅限于患儿在阅读有关暴发的医疗保健通知后尽快借助医疗保健；由当地医疗保健服务包括者断定患儿都只到南昌的旅程近代，随后在当地，特拉华和美利坚合众国医疗保健高级官员之间顺利进行密不可分合作；并考虑到有可能的2019-nCoV病菌，从而可以短时间内分离患儿并随后对2019-nCoV顺利进行学术研究团队断定，并必需患儿入院再进一步评估和管理工作。
该登革热统计统可用据强调了临床内科医生对于任何显现再次出现急性传染病腹泻的看病患儿，要概述显现出都只的旅程经历或注意到病症的极其重要性，为了确保适当比对和马上分离有可能接踵而来2019-nCoV病菌可能性的患儿，并协助减少再进一步的传播者。
再次，本统计统可用据强调所需考虑到与2019-nCoV病菌之外的临床传染病，复发机理和菌株碎裂持续性时间的
全部区域和人为近代，以为临床管理工作和医疗保健决策包括依据。
以下为日文版
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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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