参考资料
在里面国汉口开始的取而代之型冠状菌株（2019-nCoV）愈演愈烈短时间蔓延，如今在多个国家政府患病。我们份文件了在英国推定的元月2019-nCoV传染愈演愈烈率，并详细描述了该愈演愈烈率的核对，产妇，则有科操作过程和监管，最主要患儿在身体状况第9天所列现为胃癌时的最初轻度病因。
该犯罪行为重申了则有科医生与大都，州和联邦各级心理医疗卫生土耳其政府密切关系密切协作的特殊性，以及只能短时间传播者与这种取而代之发传染患儿的医疗有关的则有科接收者的需求。
2019年12月初31日，里面国份文件了与湖北省汉口市华南地区海鱼批发低价有关的这群人里面的胃癌愈演愈烈率。
2020年1月初7日，里面国医疗卫生土耳其政府推定该簇与取而代之型冠状菌株2019-nCoV有关。尽管最初路透社的愈演愈烈率与汉口市海鱼低价的暴露有关，但当之前的临床数据资料所列明，正试图愈演愈烈2019-nCoV人际传播者。
截至2020年1月初30日，在有数21个国家政府/地区份文件了9976例愈演愈烈率，最主要2020年1月初20日路透社的英国元月患病的2019-nCoV传染愈演愈烈率。
同类型球区域内内正试图来进行调查报告，以更是快地了解传播者快照和则有科传染病区域内。本份文件详细描述了在英国推定的元月2019-nCoV传染的临床和则有科整体特征。
犯罪行为份文件
2020年1月初19日，一名35岁的男子消失在伊利诺伊州里德霍米喀什地区的主营门诊诊所，有4天的痉挛和主观哮喘史。产妇到诊所检验时，在候诊室戴上；大罩。才会约20分钟后，他被带到检验室遵从了备有者的审核。
他声称，他在里面国汉口拜访父母都于1月初15日来到伊利诺伊州。该患儿所列示，他已从英国传染病控制与医疗卫生保健里面心（CDC）发出有关里面国取而代之型冠状菌株愈演愈烈的健康香港天文台，由于他的病因和数值得警惕的历险，他不得不去看医生。
上图1-2020年1月初19日（传染病第4天）的后头部和侧边胸片
除了高三酸酯血症候群的躁郁症候群则有，该患儿还是其他健康的不之前列腺癌。体格检验辨认出患儿排便环境氢气时，体温为37.2°C，心率为134/87 mm Hg，节律为每分钟110次，排便增益为每分钟16次，氢饱和度为96％。腹腔听诊说明了有甲状腺肿，并来进行了胸片检验，据路透社从未辨认出暂时性（上图1）。
亚型和乙型SARS的短时间大分子缩减到试验（NAAT）为形容词。拿到了腹咽拭子骨骼，并通过NAAT将其还给去检验菌株性排便道菌株。
据路透社在48不间断内对所有试验的菌株原则上椭圆形形容词，最主要亚型和乙型SARS，副SARS，排便道合胞菌株，腹菌株，腺菌株和已知会随之而来人类传染病的四种典型冠状菌株株（HKU1，NL63、229E和OC43） ）。根据患儿的历险历史文化，当即接到大都和州医疗当地政府。纽约医疗卫生部与应急医疗则有科医生三人接到了CDC应急行动里面心。
尽管该患儿份文件问道他很难去过华南地区海鱼低价，也很难份文件在去里面国历险期间与病重者有任何受伤害，但传染病医疗卫生保健控制里面心的工作部门同意有必要根据当之前的传染病医疗卫生保健控制里面心对患儿来进行2019-nCoV试验。
根据CDC简介利用了8个骨骼，最主要小鼠，腹咽和；大咽拭子骨骼。骨骼热带植物后，患儿被还给回家庭永久性，并由当地医疗当地政府来进行不遗余力监测。
2020年1月初20日，传染病医疗卫生保健控制里面心（CDC）推定患儿的腹咽和；大咽拭子通过实时丝氧酸-酵素低质量（rRT-PCR）检验为2019-nCoV乙型肝炎。
在传染病医疗卫生保健控制里面心的主题研究者，州和大都医疗卫生高官，应急医疗服务以及所医院领导和工作部门的再加下，患儿被还给回普罗维登斯地区医疗里面心的氢气永久性病房来进行则有科捕捉到，并跟随传染病医疗卫生保健控制里面心的医护部门有关受伤害，飞沫和空里面防护措施的促请，并含有护目镜。
入院时患儿份文件长时间痉挛，有2天的头痛和抽搐史。他份文件问道他很难排便急促或心悸。人类征状在正常区域内内。体格检验辨认出患儿消化道湿润。其余的检验通常不明显。
入院后，患儿遵从了支持治疗，最主要2升生理盐水和恩丹以更为比较严重头痛。
上图2-根据传染病日和中风日（2020年1月初16日至2020年1月初30日）的病因和最高体温
在中风的第2至5天（病重的第6至9天），患儿的人类征状整体趋于稳定，除了消失暂时性哮喘并间歇心动过速（上图2）。患儿之之前份文件非生产性痉挛，并消失疲倦。
在中风第二天的中午，患儿排便通畅，腹部不适。傍晚有第二次大便稀疏的路透社。利用该排泄的试样用以rRT-PCR试验，以及其他排便道骨骼（腹咽和；大咽）和小鼠。排泄和两个排便道骨骼后来原则上通过rRT-PCR检验为2019-nCoV乙型肝炎，而小鼠仍为形容词。
年中的治疗在相当大程度上是支持性的。为了来进行病因管控，患儿只能根据只能遵从良药治疗，该治疗最主要每4不间断650 mg对乙酰氧基酚和每6不间断600 mg抗炎药。在中风的之前六天，他还因长时间痉挛而施打了600毫克稍稍创醚友好条约6升生理盐水。
所列1-则有科Laboratory结果
患儿永久性单元的物理性质最初仅必需事之前医疗点Laboratory试验；从所医院第3天开始可以来进行同类型血细胞一般来说和小鼠无机化学学术研究。
在所医院第3天和第5天（传染病第7天和第9天）的Laboratory结果反映单单肝细胞增加症候群，轻度血栓增加症候群和肌酸激酶水准升高（所列1）。此则有，肺功能指标也有所改变：极性磷酸酶（每升68 U），乙酰氧基转移酶（每升105 U），天冬氧酸氧基转移酶（每升77 U）和乳酸谷氨酸（每升465 U）的水准共五：在中风的第5天所有升高。鉴于患儿一一哮喘，在第4天拿到肝脏培养；迄今为止，这些都很难快速增长。
上图3-2020年1月初22日（臀部第7天，所医院第3天）的后头部和侧边胸片
上图4-2020年1月初24日（臀部第5天，所医院第9天）的后头部X线片
据路透社，在所医院第3天（病重第7天）拍下的臀部X光片从未说明了伴生或暂时性似乎（上图3）。
但是，从所医院第5天傍晚（病重第9天）傍晚来进行的第二次臀部X光片检验说明了，左肺下叶有胃癌（上图4）。
这些影像学辨认出与从所医院第5天傍晚开始的排便精神状态改变密切关的，当年患儿在排便四周氢气时通过节律血氢饱和度测出的血氢饱和度数值降至90％。
在第6天，患儿开始遵从必需氢气，该氢气由腹导管以每分钟2升的平原则上速度输还给。考虑到则有科所列现的改变和对所医院拿到性胃癌的关切，开始适用本品（1750 mg耗损剂量，然后每8不间断施打1 g）和头孢吡芳基（每8不间断施打）治疗。
上图5-之前后臀部X光片，2020年1月初26日（传染病第十天，所医院第六天）
在所医院第6天（病重第10天），第四次臀部X射线照片说明了两个肺里面都有一个大夹混浊，这一辨认出与非典型胃癌相保持良好一致（上图5），并且在听诊时在两个肺里面都消失了罗音。鉴于核辐射影像学辨认出，不得不拒绝遵从氢气必需，患儿长时间哮喘，多个胸部长时间乙型肝炎的2019-nCoV RNA乙型肝炎，以及发所列了与核辐射性胃癌转型保持良好一致的比较严重胃癌在该患儿里面，则有科医生高贵同情心地适用了学术各学科抗菌株治疗。
施打艾伦昔韦（一种正试图开发的取而代之型核酸类似物之前药）在第7天傍晚开始，但从未捕捉到到与十二指肠有关的不良暴力事件。在对甲氢大白耐药的白色细菌性来进行了倒数的降钙素原水准和腹PCR检验后，在第7天傍晚废弃本品，并在第二天废弃头孢吡芳基。
在所医院第8天（病重第12天），患儿的则有科状况受益改善。停止必需氢气，他在排便四周氢气时的氢饱和度数值进一步提高到94％至96％。早先的双侧下叶罗音不再存有。他的食欲受益改善，除了暂时性干咳和腹漏则有，他很难病因。
截至2020年1月初30日，患儿仍中风。他有发烧，除痉挛则有，所有病因原则上已更为比较严重，痉挛的程度正试图减轻。
方式
骨骼热带植物
根据CDC简介拿到用以2019-nCoV产妇试验的则有科骨骼。用合成纤维拭子利用了12个腹咽和；大咽拭子骨骼。
将每个拭子弹单单包含2至3 ml菌株转运介质的单独施用管里面。将血集在小鼠分立管里面，然后根据CDC简介来进行离心。肾脏和排泄骨骼分别利用在施用骨骼密封里面。试样在2°C至8°C密切关系储藏，直到准备好运还给至CDC。
在传染病的第7、11和12天利用了重复来进行的2019-nCoV试验的骨骼，最主要腹咽和；大咽拭子，小鼠以及肾脏和排泄试样。
2019-NCOV的产妇试验
适用从公开公开发表的菌株基因组转型而来的rRT-PCR德沃夏克试验了则有科骨骼。与早先针对重症候群急性排便综合征冠状菌株（SARS-CoV）和里面东排便综合征冠状菌株（MERS-CoV）的产妇方式相像，它不具三个核核糖体基因特异性和一个乙型肝炎解读特异性。该测出的详细描述为RRT-PCR背光模板和电极和基因组接收者里面一般来说的CDCLaboratory接收者网站2019-nCoV上。
遗传人类基因组计划
2020年1月初7日，里面国学术研究部门通过英国国立医疗卫生学术科技学院GenBank数据资料库和同类型球共享所有SARS数据资料牵头（GISAID）数据资料库共享了2019-nCoV的比较简单基因基因组；随后公开发表了有关永久性2019-nCoV的份文件。
从rRT-PCR乙型肝炎骨骼（；大咽和腹咽）里面提取大分子，并在Sanger和下一代人类基因组计划的平台（Illumina和MinIon）上用以同类型原核生物人类基因组计划。适用5.4.6英文版的Sequencher软件（Sanger）完成了基因组组装。minimap软件，正式英文版2.17（MinIon）；和freebayes软件1.3.1英文版（MiSeq）。将比较简单原核生物与一般来说的2019-nCoV参考资料基因组（GenBank登录号NC_045512.2）来进行比较。
结果
2019-NCOV的骨骼试验
所列2-2019年取而代之型冠状菌株（2019-nCoV）的实时丝氧酸-酵素-低质量试验结果
该患儿在病重第4四海拿到的初始排便道试样（腹咽拭子和；大咽拭子）在2019-nCoV椭圆形乙型肝炎（所列2）。
尽管患儿最初所列现为轻度病因，但在传染病第4天的较低循环阈数值（Ct）数值（腹咽骨骼里面为18至20，；大咽骨骼里面为21至22）所列明这些骨骼里面菌株水准较高。
在传染病第7天拿到的两个上排便道骨骼在2019-nCoV仍保持良好乙型肝炎，最主要腹咽拭子骨骼里面长时间高层次（Ct数值23至24）。在传染病第7天拿到的排泄在2019-nCoV里面也椭圆形乙型肝炎（Ct数值为36至38）。两种热带植物日期的小鼠试样在2019-nCoV原则上为形容词。
在传染病第11天和第12天拿到的腹咽和；大咽骨骼说明了单单菌株水准下降的21世纪。
；大咽骨骼在病重第12天的2019-nCoV试验椭圆形形容词。在这些日期拿到的小鼠的rRT-PCR结果仍从并不相同。
遗传人类基因组计划
；大咽和腹咽骨骼的比较简单原核生物基因组彼此相同，并且与其他一般来说的2019-nCoV基因组仅仅相同。
该患儿的菌株与2019-nCoV参考资料基因组（NC_045512.2）在解禁读者框8东南侧仅有3个核酸和1个不同。该基因组可通过GenBank拿到（登录号MN985325）。
讨论区
我们关于英国元月2019-nCoV患病愈演愈烈率的份文件问道明了这一取而代之兴传染病的几个方面尚能从未完同类型了解，最主要传播者快照和则有科传染病的同类型部区域内。
我们的愈演愈烈率患儿曾去过里面国汉口，但份文件问道他在汉口期间很难去过海鱼批发低价或医疗机构，也很难年老的受伤害。尽管他的2019-nCoV传染的来源尚能不吻合，但已公开了人对人传播者的事实。
到2020年1月初30日，尚能从未辨认出与此愈演愈烈率关的的2019-nCoV诱病症候群例，但仍在密切看管下。
在传染病的第4天和第7天从上排便道骨骼里面检验到不具较低Ct数值的2019-nCoV RNA，所列明菌株负重高且不具传播者潜力。
数值得警惕的是，我们还在患儿病重第7天利用的排泄试样里面检验到了2019-nCoV RNA。尽管我们愈演愈烈率患儿的小鼠骨骼一一消失2019-nCoV形容词，但在里面国重症候群患儿的肝脏里面仍检验到菌株RNA。然而，肺则有检验菌株RNA并不一定意味着存有传染性菌株，现阶段尚能不吻合在排便道直接检验菌株RNA的则有科意义。
现阶段，我们对2019-nCoV传染的则有科区域内的了解非常一般来说。在里面国，已经路透社了诸如比较严重的胃癌，排便衰竭，急性排便窘迫综合征（ARDS）和心脏损伤等肝硬化候群，最主要骇人的后果。然而，重要的是要警惕，这些愈演愈烈率是根据其胃癌产妇未确定的，因此确实会使份文件偏向更是比较严重的结果。
我们的愈演愈烈率患儿最初所列现为轻度痉挛和较低度暂时性哮喘，在病重的第4天很难臀部X光检验的胃癌似乎，而在病重第9天转型为胃癌之之前，这些非特异性征状和病因在早期在则有科上，2019-nCoV传染的则有科操作过程确实与许多其他典型传染病很难明显相异，尤为是在冬季排便道菌株季节。
另则有，本愈演愈烈率患儿在传染病的第9天转型为胃癌的尽早与未来会排便困难的发作（病症候群后里面位数为8天）保持良好一致。尽管根据患儿的则有科状况恶化不得不否拒绝遵从remdesivir慈悲的适用，但仍只能来进行结果说明试验以未确定remdesivir和任何其他学术研究用药治疗2019-nCoV传染的安同类型性和理论上。
我们份文件了英国元月份文件的2019-nCoV传染患儿的则有科整体特征。
该愈演愈烈率的不可或缺方面最主要患儿在读者有关愈演愈烈的心理医疗卫生警告后不得不借助医疗；由当地医疗服务备有者推定患儿数值得警惕到汉口的历险历史文化，随后在当地，州和联邦心理医疗卫生高官密切关系来进行协调；并未确定确实的2019-nCoV传染，从而可以短时间永久性患儿并随后对2019-nCoV来进行Laboratory推定，并必需患儿入院再进一步审核和监管。
该愈演愈烈率份文件重申了则有科医生对于任何消失急性传染病病因的就诊患儿，要概述单单数值得警惕的历险亲身经历或受伤害躁郁症候群的特殊性，为了确保应该识别和及时永久性确实面临2019-nCoV传染风险的患儿，并帮助增加再进一步的传播者。
最后，本份文件重申只能未确定与2019-nCoV传染关的的则有科传染病，病症候群物理性质和菌株裂开长时间时间的
同类型部区域内和共存历史文化，以为则有科监管和心理医疗卫生决策备有依据。
以下为英文英文版
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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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