摘录
在当欧美汉沟开始的新型冠状病原体（2019-nCoV）爆发短时间延烧，现已在多个国家政府胃癌。我们调查结果了在加拿大核实的尚能属2019-nCoV感染者个案，并详细描述了该个案的鉴定，治疗，药理学更进一步和管理，以外病患者在病情第9天列于现为中风时的早先轻度症候群状。
该个案突显了药理学内科医生与；也，的州和的政府各级公共保健政府彼此之间密切协作的必要性，以及只能加速传布与这种新发感染者病患者的眼科有关的药理学个人信息的期望。
2019年12月初31日，当欧美调查结果了与常德市汉沟市西南地区鱼肉批发的产品有关的人群当中的中风个案。
2020年1月初7日，当欧美保健政府核实该簇与新型冠状病原体2019-nCoV有关。尽管早先另据的个案与汉沟市鱼肉的产品的暴露有关，但当在此之前的美国疾病控制与预防中心个人信息列于明，将要发生2019-nCoV彼此之间传布。
截至2020年1月初30日，在至少21个国家政府/地区调查结果了9976例个案，以外2020年1月初20日另据的加拿大尚能属胃癌的2019-nCoV感染者个案。
有数球适用范围内将要进行时调查，以更多地了解到传布快照和药理学哮喘适用范围。本调查结果详细描述了在加拿大核实的尚能属2019-nCoV感染者的美国疾病控制与预防中心和药理学相似性。
个案调查结果
2020年1月初19日，一名35岁的铁饼借助于现在密歇根的州斯诺霍米锡金邦的的公司加护候群诊所，有4天的腹痛和客观性呼吸困难史。病患者到诊所定期检查时，在候诊室戴上沟罩。下次约20分钟后，他被带到定期检查室不能接受了中介的评核。
他透露，他在当欧美汉沟探望家人时在1月初15日返回密歇根的州。该病患者列于示，他已从加拿大哮喘控制与预防性当中心地带（CDC）接到有关当欧美新型冠状病原体愈演愈烈的肥胖症警报，由于他的症候群状和近期的旅程，他要求去看内科医生。
由此可知1-2020年1月初19日（哮喘第4天）的后颈部和之后侧胸片
除了高三酸酯血症候群的高血压之外，该病患者还是其他肥胖症的不高心率。体格定期检查挖掘借助于病患者呼吸环境空气时，体温为37.2°C，心率为134/87 mm Hg，脉搏为每分钟110次，呼吸频带为每分钟16次，钾较低浓度为96％。肺部听诊看借助于有甲状腺肿，并进行时了胸片定期检查，据另据尚未挖掘借助于异常（由此可知1）。
当季型和九一肺炎的加速小分子扩增侦测（NAAT）为相似性性。赢得了楔咽拭子遗骸，并通过NAAT将其送到去侦测病原体性口腔病原体。
据另据在48不间断内对所有侦测的病原体有数呈相似性性，以外当季型和九一肺炎，副肺炎，口腔合胞病原体，楔病原体，腺病原体和已知就会导致人类哮喘的四种少见冠状病原体株（HKU1，NL63、229E和OC43） ）。根据病患者的旅程历史记录，立即接到；也和的州保健部门。华盛顿保健部与及时眼科药理学内科医生一起接到了CDC及时行动当中心地带。
尽管该病患者调查结果问道他无法去过西南地区鱼肉的产品，也无法调查结果在去当欧美旅程在此期间与得病者有任何保持联系，但哮喘预防性控制当中心地带的工作执法人员同意有必要根据当在此之前的哮喘预防性控制当中心地带对病患者进行时2019-nCoV侦测。
根据CDC简介搜集了8个遗骸，以外尿液，楔咽和沟咽拭子遗骸。遗骸野外后，病患者被送到进家庭分开，并由当地保健部门进行时鼓励数据分析。
2020年1月初20日，哮喘预防性控制当中心地带（CDC）核实病患者的楔咽和沟咽拭子通过实时核苷-聚合酶链反应（rRT-PCR）侦测为2019-nCoV中性。
在哮喘预防性控制当中心地带的主旨专家，的州和；也保健外交人员，及时医护服务以及诊所领导成员和工作执法人员的配合下，病患者被送到进奥尔巴尼地区医护当中心地带的空气分开病房进行时药理学检视，并跟随哮喘预防性控制当中心地带的医护执法人员有关保持联系，飞沫和空当中防爆采取措施的促请，并带有外套。
康复时病患者调查结果不间断腹痛，有2天的麻木和头痛史。他调查结果问道他无法呼吸急促或气喘。人类体征在出现异常适用范围内。体格定期检查挖掘借助于病患者粘膜干燥。其余的定期检查通常不相对来说。
康复后，病患者不能接受了支持疗程，以外2升到生理盐水和恩丹以减轻麻木。
由此可知2-根据哮喘日和借助于院日（2020年1月初16日至2020年1月初30日）的症候群状和三高体温
在借助于院的第2至5天（得病的第6至9天），病患者的人类体征理论上保持稳定，除了借助于现断续呼吸困难并；还有心动过速（由此可知2）。病患者之后调查结果非生产性腹痛，并借助于现疲倦。
在借助于院第二天的上午，病患者排便通畅，腹部不适。当中午有第二次大便稀疏的另据。搜集该排泄的仪器使用rRT-PCR侦测，以及其他口腔遗骸（楔咽和沟咽）和尿液。排泄和两个口腔遗骸后来有数通过rRT-PCR侦测为2019-nCoV中性，而尿液仍为相似性性。
年初的疗程在很大层面上是支持性的。为了进行时症候群状所在位置理，病患者只能根据只能不能接受解热疗法，该疗法以外每4不间断650 mg片剂和每6不间断600 mg甲酯。在借助于院的在此之前六天，他还因不间断腹痛而过量了600毫克愈创醚马关条约6升到生理盐水。
列于1-药理学科学研究中心地带结果
病患者分开一组的特殊性早先仅强制事前医护点科学研究中心地带侦测；从诊所第3天开始可以进行时有数红细胞计数和尿液矿物学科学研究。
在诊所第3天和第5天（哮喘第7天和第9天）的科学研究中心地带结果揭示借助于白细胞提高症候群，轻度骨髓提高症候群和肌酸激酶高度升到高（列于1）。此之外，肝功能指标也相当层面变异：碱性磷酸酶（每升到68 U），丙氨酸氨基转移酶（每升到105 U），胺基酸氨基转移酶（每升到77 U）和乳酸羟化酶（每升到465 U）的高度分别为：在借助于院的第5天所有升到高。鉴于病患者年终不断呼吸困难，在第4天赢得尿液培养；迄今为止，这些都无法激增。
由此可知3-2020年1月初22日（腹部第7天，诊所第3天）的后颈部和之后侧胸片
由此可知4-2020年1月初24日（腹部第5天，诊所第9天）的后颈部X线片
据另据，在诊所第3天（得病第7天）拍摄的腹部X光片尚未看借助于浸润或异常先兆（由此可知3）。
但是，从诊所第5天当中午（得病第9天）当中午进行时的第二次腹部X光片定期检查看借助于，左肺下叶有中风（由此可知4）。
这些医学影像挖掘借助于与从诊所第5天当中午开始的呼吸长时间变异角度看，最初病患者在呼吸周围空气时通过脉搏皮质醇较低浓度精确测量的皮质醇较低浓度参数降至90％。
在第6天，病患者开始不能接受说明缺钾，该缺钾由楔导管以每分钟2升到的速度输送到。显然药理学列于现的变异和对诊所赢得性中风的关注，开始用作万古霉素（1750 mg耗损施打，然后每8不间断本品1 g）和红霉素吡丙酮（每8不间断本品）疗程。
由此可知5-在此之前后腹部X光片，2020年1月初26日（哮喘第十天，诊所第六天）
在诊所第6天（得病第10天），第四次腹部X射线照片看借助于两个肺当中都有基底条状水色，这一挖掘借助于与非类似中风相符（由此可知5），并且在听诊时在两个肺当中都借助于现了罗音。鉴于人口为120人医学影像挖掘借助于，要求得不到缺钾说明，病患者不间断呼吸困难，多个手部不间断中性的2019-nCoV RNA中性，以及发列于了与人口为120人性中风转型一致的更为严重中风在该病患者当中，药理学内科医生富有安全感地用作了学术机构抗病原体疗程。
本品瑞德昔韦（一种将要开发计划的新型碱基萘在此之前药）在第7天当中午开始，但尚未检视到与输注有关的不良政治事件。在对当季钾西林耐药的金黄色抗生素进行时了年终的降钙素原高度和楔PCR侦测后，在第7天当中午拆去万古霉素，并在第二天拆去红霉素吡丙酮。
在诊所第8天（得病第12天），病患者的药理学状况赢取更佳。停止说明缺钾，他在呼吸周围空气时的钾较低浓度参数提高到94％至96％。原本的上部下叶罗音不再依赖于。他的皮质醇赢取更佳，除了断续干咳和楔漏之外，他无法症候群状。
截至2020年1月初30日，病患者仍借助于院。他有发烧，除腹痛之外，所有症候群状有数已减轻，腹痛的层面将要加重。
作法
遗骸野外
根据CDC简介赢得使用2019-nCoV治疗侦测的药理学遗骸。用聚酯拭子搜集了12个楔咽和沟咽拭子遗骸。
将每个拭子填充涉及联2至3 ml病原体转运介质的单独未成熟管当中。将血集在尿液分离管当中，然后根据CDC简介进行时离心。分泌物和排泄遗骸分别搜集在未成熟遗骸液体当中。仪器在2°C至8°C彼此之间储存，直到准备好运送到至CDC。
在哮喘的第7、11和12天搜集了重复进行时的2019-nCoV侦测的遗骸，以外楔咽和沟咽拭子，尿液以及分泌物和排泄比对。
2019-NCOV的治疗侦测
用作从公开发表发计划布的病原体基因序列转型而来的rRT-PCR分析法侦测了药理学遗骸。与原本针对加护候群急性呼吸综合征冠状病原体（SARS-CoV）和当中东呼吸综合征冠状病原体（MERS-CoV）的治疗作法相似，它带有三个核核糖核酸基因靶标和一个中性印证靶标。该精确测量的详细描述为RRT-PCR面板模板和电极和基因序列个人信息当中一般来问道的CDC科学研究中心地带个人信息com2019-nCoV上。
遗传高通量
2020年1月初7日，当欧美科学研究执法人员通过加拿大国立保健科学研究院GenBank个人信息库和有数球协作所有肺炎个人信息倡议（GISAID）个人信息库协作了2019-nCoV的非常简单基因基因序列；随后发列于了有关分开2019-nCoV的调查结果。
从rRT-PCR中性遗骸（沟咽和楔咽）当中萃取小分子，并在Sanger和尚未来高通量平台（Illumina和MinIon）上使用有数基因基因序列高通量。用作5.4.6版的Sequencher应用软件（Sanger）完成了基因序列拆解。minimap应用软件，新版本2.17（MinIon）；和freebayes应用软件1.3.1版（MiSeq）。将非常简单基因基因序列与一般来问道的2019-nCoV参见基因序列（GenBank登录号NC_045512.2）进行时比较。
结果
2019-NCOV的遗骸侦测
列于2-2019年新型冠状病原体（2019-nCoV）的实时核苷-聚合酶-链反应侦测结果
该病患者在得病第4天时赢得的初始口腔比对（楔咽拭子和沟咽拭子）在2019-nCoV呈中性（列于2）。
尽管病患者早先列于现为轻度症候群状，但在哮喘第4天的较低循环电位（Ct）参数（楔咽遗骸当中为18至20，沟咽遗骸当中为21至22）列于明这些遗骸当中病原体高度较高。
在哮喘第7天赢得的两个上口腔遗骸在2019-nCoV仍保持中性，以外楔咽拭子遗骸当中不间断高高度（Ct参数23至24）。在哮喘第7天赢得的排泄在2019-nCoV当中也呈中性（Ct参数为36至38）。两种野外年份的尿液比对在2019-nCoV有数为相似性性。
在哮喘第11天和第12天赢得的楔咽和沟咽遗骸看借助于借助于病原体高度下降的趋势。
沟咽遗骸在得病第12天的2019-nCoV侦测呈相似性性。在这些年份赢得的尿液的rRT-PCR结果仍尚未定。
遗传高通量
沟咽和楔咽遗骸的非常简单基因基因序列基因序列彼此不尽相同，并且与其他一般来问道的2019-nCoV基因序列几乎不尽相同。
该病患者的病原体与2019-nCoV参见基因序列（NC_045512.2）在对外开放读者支架8所在位置有数3个碱基和1个不同。该基因序列可通过GenBank赢得（登录号MN985325）。
专页
我们关于加拿大尚能属2019-nCoV胃癌个案的调查结果问道明了这一新兴哮喘的几个方面早已完有数了解到，以外传布快照和药理学哮喘的有数部适用范围。
我们的个案病患者曾去过当欧美汉沟，但调查结果问道他在汉沟在此期间无法去过鱼肉批发的产品或医护机构，也无法得病的保持联系。尽管他的2019-nCoV感染者的来源尚能不确实，但已公开发表了人对人传布的证据。
到2020年1月初30日，早已挖掘借助于与此个案涉及的2019-nCoV继复发例，但仍在密切警卫下。
在哮喘的第4天和第7天从上口腔遗骸当中侦测到带有较低Ct参数的2019-nCoV RNA，列于明病原体负重高且带有传布潜力。
参数得特别注意的是，我们还在病患者得病第7天搜集的排泄比对当中侦测到了2019-nCoV RNA。尽管我们个案病患者的尿液遗骸年终不断借助于现2019-nCoV相似性性，但在当欧美加护候群病患者的尿液当中仍侦测到病原体RNA。然而，肺之外侦测病原体RNA并不一定意味着依赖于传染性病原体，目在此之前尚能不确实在口腔之外部侦测病原体RNA的药理学意义。
目在此之前，我们对2019-nCoV感染者的药理学适用范围的了解到颇为有限。在当欧美，现在另据了诸如更为严重的中风，呼吸衰竭，急性呼吸困顿综合征（ARDS）和心脏损伤等并发症候群，以外骇人的恶果。然而，重要的是要特别注意，这些个案是根据其中风治疗核实的，因此也许就会使调查结果特别突显更更为严重的结果。
我们的个案病患者早先列于现为轻度腹痛和较低度断续呼吸困难，在得病的第4天无法腹部X光定期检查的中风先兆，而在得病第9天转型为中风之在此之前，这些非特异性体征和症候群状在中期在药理学上，2019-nCoV感染者的药理学更进一步也许与许多其他少见传染病无法相对来说区别，尤其是在严寒口腔病原体季节。
另之外，本个案病患者在哮喘的第9天转型为中风的时机与近期头痛的心脏病（复发后当中位数为8天）一致。尽管根据病患者的药理学状况变差要求是不是得不到remdesivir诚心的用作，但仍只能进行时随机印证试验性以核实remdesivir和任何其他科学研究类固醇疗程2019-nCoV感染者的安有数性和必要性。
我们调查结果了加拿大尚能属调查结果的2019-nCoV感染者病患者的药理学相似性。
该个案的关键方面以外病患者在读者有关愈演愈烈的公共保健警告后要求借助医护；由当地医护服务中介核实病患者近期到汉沟的旅程历史记录，随后在当地，的州和的政府公共保健外交人员彼此之间进行时密切合作；并核实也许的2019-nCoV感染者，从而可以短时间分开病患者并随后对2019-nCoV进行时科学研究中心地带核实，并强制病患者康复进一步评核和管理。
该个案调查结果突显了药理学内科医生对于任何借助于现急性哮喘症候群状的就诊病患者，要归纳借助于近期的旅程经历或保持联系高血压的必要性，为了适当正确辨认和立刻分开也许面临2019-nCoV感染者风险的病患者，并尽力提高进一步的传布。
最后，本调查结果突显只能核实与2019-nCoV感染者涉及的药理学哮喘，复发中间体和病原体脱落不间断时间的
有数部适用范围和共存历史记录，以为药理学管理和公共保健各项政策提供依据。
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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