摘要
在中的国郑州开始的另行型冠状菌株（2019-nCoV）爆唯快速席卷，如今在多个发展中国家年老。我们简报了在英国验证的首举例2019-nCoV细菌感染病举例，并描述了该病举例的核对，病因，微生物学过程和行政，之之外病患者在病情第9天请注意现为败酸中毒时的本来轻度腹泻。
该范举例忽略了微生物学内科医生与以之外，州和联邦各级公共卫生保健保健当局二者之间密切协作的最主要性，以及须要快速传扬与这种另行唯细菌感染病患者的诊疗有关的微生物学信息的需求。
2019年12同月31日，中的国简报了与湖北省郑州市华南地区水果批唯零售商有关的人群中的的败酸中毒病举例。
2020年1同月7日，中的国卫生保健当局验证该簇与另行型冠状菌株2019-nCoV有关。尽管本来美联社的病举例与郑州市水果零售商的漏出有关，但意味著的微生物学资料得出新结论，即将唯生2019-nCoV社会关系传扬。
截至2020年1同月30日，在据估计21个发展中国家/地区简报了9976举例病举例，之之外2020年1同月20日美联社的英国首举例年老的2019-nCoV细菌感染病举例。
亚洲地区区域内内即将进行调查，以更好地了解传扬自适应和微生物学哮喘区域内。本简报描述了在英国验证的首举例2019-nCoV细菌感染的微生物学和微生物学特点。
范举例简报
2020年1同月19日，一名35岁的女子显现出新在爱达荷州华莱士霍米阿鲁纳恰尔邦的数家重病患者诊所，有4天的唯烧和主观唯烧史。病童到诊所体检时，在候诊室戴上；大罩。等待共约20分钟后，他被带到体检室不感兴趣了服务提供者商的分析。
他透露，他在中的国郑州养病家人后于1同月15日返回爱达荷州。该病患者请注意示，他已从英国哮喘控制与预防预防措施中的心（CDC）收到有关中的国另行型冠状菌株暴唯的心理健康香港天文台，由于他的腹泻和近来的旅途，他最终去看内科医生。
三幅1-2020年1同月19日（哮喘第4天）的后腰部和之前端胸片
除了高三酸酯酸中毒的病病患者之外，该病患者还是其他心理健康的不吸烟者。体格体检挖掘出新病患者吞咽环境氢气时，代谢率为37.2°C，血压为134/87 mm Hg，不止为每分钟110次，吞咽频率为每分钟16次，氢一般来问道为96％。肺泡听诊表明有病病患者，并进行了胸片体检，据美联社尚未挖掘出新间歇性（三幅1）。
肺炎病毒和丙型肺炎的快速氘酸扩增验证（NAAT）为复数。授予了颊咽拭子骨骼，并通过NAAT将其送去测定菌株性吞咽道菌株。
据美联社在48两星期内对所有验证的菌株除此以之外红褐色复数，之之外肺炎病毒和丙型肺炎，副肺炎，吞咽道合胞菌株，颊菌株，腺菌株和已知可能会所致人类哮喘的四种常见冠状菌株株（HKU1，NL63、229E和OC43） ）。根据病患者的旅途历史记录，赶紧告知以之外和州卫生保健部门。华盛顿卫生保健部与先行诊疗微生物学内科医生一起告知了CDC先行行动中的心。
尽管该病患者简报问道他并尚未去过华南地区水果零售商，也并尚未简报在去中的国旅途之后与年老者有任何带入，但哮喘预防预防措施控制中的心的工作行政人员同意有必要根据意味著的哮喘预防预防措施控制中的心对病患者进行2019-nCoV验证。
根据CDC读物搜罗了8个骨骼，之之外抗体，颊咽和；大咽拭子骨骼。骨骼采集后，病患者被送入家庭成员监护，并由当地卫生保健部门进行大力检测。
2020年1同月20日，哮喘预防预防措施控制中的心（CDC）验证病患者的颊咽和；大咽拭子通过可实现丝氨酸-氘酸聚合（rRT-PCR）测定为2019-nCoV白血病。
在哮喘预防预防措施控制中的心的主题专家，州和以之外卫生保健亲信，先行公共卫生服务以及诊所主导和工作行政人员的适时下，病患者被送入康涅狄格州地区公共卫生中的心的氢气监护病房进行微生物学警惕到，并追随哮喘预防预防措施控制中的心的医护行政人员有关带入，飞沫和空中的防护预防措施的提议，并带有靴子。
病情恶化时病患者简报接下来唯烧，有2天的恶心和抽搐史。他简报问道他并尚未吞咽急促或胸痛。全人类征状在正常区域内内。体格体检挖掘出新病患者粘膜干燥。其余的体检通常不相比。
病情恶化后，病患者不感兴趣了赞成化疗，之之外2累进生理盐水和恩丹以缓解恶心。
三幅2-根据哮喘日和就医日（2020年1同月16日至2020年1同月30日）的腹泻和最多代谢率
在就医的第2至5天（年老的第6至9天），病患者的全人类征状基本保持稳定稳定，除了显现出新接下来性唯烧并伴有心动过速（三幅2）。病患者继续简报非生产性唯烧，并显现出新疲倦。
在就医第二天的下午，病患者阴部通畅，腹部不适。早上有第二次大便密集的美联社。搜罗该唾液的试样用作rRT-PCR验证，以及其他吞咽道骨骼（颊咽和；大咽）和抗体。唾液和两个吞咽道骨骼其后除此以之外通过rRT-PCR测定为2019-nCoV白血病，而抗体仍为复数。
其间的化疗在很大程度上是自我管理的。为了进行腹泻出新口处理，病患者须要根据须要不感兴趣镇痛药制剂，该制剂之之外每4两星期650 mg对乙酰硫基酚和每6两星期600 mg低剂量。在就医的前六天，他还因接下来唯烧而服用了600毫克稍稍创醚和共约6累进生理盐水。
请注意1-微生物学研究课题团队结果
病患者监护单元的性质本来仅允许第一时间公共卫生点研究课题团队验证；从诊所第3天开始可以进行全血细胞除此以外和抗体化学研究课题。
在诊所第3天和第5天（哮喘第7天和第9天）的研究课题团队结果解读出新肝细胞增大病患者，轻度血小板增大病患者和肌酸激酶高度急剧回累进（请注意1）。此之外，肝脏指标也大为唯生变化：水溶液脂质（每累进68 U），丙硫酸硫基转移酶（每累进105 U），天冬硫酸硫基转移酶（每累进77 U）和乳酸脱氢酶（每累进465 U）的高度分别为：在就医的第5天所有急剧回累进。鉴于病患者连续不断唯烧，在第4天授予体内培养；迄今为止，这些都并尚未上升。
三幅3-2020年1同月22日（腿部第7天，诊所第3天）的后腰部和之前端胸片
三幅4-2020年1同月24日（腿部第5天，诊所第9天）的后腰部X线片
据美联社，在诊所第3天（年老第7天）拍下的腿部X光片尚未表明增生或间歇性征兆（三幅3）。
但是，从诊所第5天早上（年老第9天）早上进行的第二次腿部X光片体检表明，左肺下叶有败酸中毒（三幅4）。
这些影像学挖掘出新与从诊所第5天早上开始的吞咽状态唯生变化相吻合，在此之前病患者在吞咽周围氢气时通过不止磁共振一般来问道测出新的磁共振一般来问道倍数降至90％。
在第6天，病患者开始不感兴趣补充氮气，该氮气由颊穿孔以每分钟2累进的速率输送。毕竟微生物学请注意现的唯生变化和对诊所授予性败酸中毒的关注，开始需用抗病毒（1750 mg负荷用药，然后每8两星期肌肉注射1 g）和青霉素吡甲苯（每8两星期肌肉注射）化疗。
三幅5-前后腿部X光片，2020年1同月26日（哮喘第十天，诊所第六天）
在诊所第6天（年老第10天），第四次腿部X射线截图表明两个肺中的都有角化条状混浊，这一挖掘出新与非近似于败酸中毒完全明确（三幅5），并且在听诊时在两个肺中的都显现出新了罗音。鉴于放射线影像学挖掘出新，最终给予氮气补充，病患者接下来唯烧，多个部位接下来白血病的2019-nCoV RNA白血病，以及唯请注意了与放射线性败酸中毒演进明确的情况严重败酸中毒在该病患者中的，微生物学内科医生富有同情心地需用了研究课题性抗菌株化疗。
肌肉注射福斯特昔韦（一种即将开唯的另行型氘苷酸类似物前药）在第7天早上开始，但尚未警惕到到与皮下注射有关的不当事件真相。在对甲氢西林耐药的暗红色细菌性进行了紧接著的降钙素原高度和颊PCR测定后，在第7天早上废止抗病毒，并在第二天废止青霉素吡甲苯。
在诊所第8天（年老第12天），病患者的微生物学境况赢取强化。暂缓补充氮气，他在吞咽周围氢气时的氢一般来问道倍数提高到94％至96％。当初的外侧下叶罗音不再长期存在。他的食欲赢取强化，除了接下来性干咳和颊漏之外，他并尚未腹泻。
截至2020年1同月30日，病患者仍就医。他有唯热，除唯烧之外，所有腹泻除此以之外已缓解，唯烧的程度即将减低。
作法
骨骼采集
根据CDC读物授予用作2019-nCoV病因验证的微生物学骨骼。用尼龙拭子搜罗了12个颊咽和；大咽拭子骨骼。
将每个拭子断开相关联2至3 ml菌株转运介质的原则上冷藏管中的。将血集在抗体分离管中的，然后根据CDC读物进行离心。排泄物和唾液骨骼分别搜罗在冷藏骨骼桶内中的。试样在2°C至8°C二者之间储存，直到准备运送至CDC。
在哮喘的第7、11和12天搜罗了单调进行的2019-nCoV验证的骨骼，之之外颊咽和；大咽拭子，抗体以及排泄物和唾液抽样。
2019-NCOV的病因验证
需用从公开唯布的菌株脱氢氘糖氘酸演进而来的rRT-PCR分析法验证了微生物学骨骼。与当初针对重病患者急性吞咽遗传性冠状菌株（SARS-CoV）和中的东吞咽遗传性冠状菌株（MERS-CoV）的病因作法类似于，它较强三个氘核糖核酸基因化学合成和一个白血病对照化学合成。该测出新的描述为RRT-PCR面板双链和磁性和脱氢氘糖氘酸信息中的需用的CDC研究课题团队信息网站2019-nCoV上。
基因人类基因组计划
2020年1同月7日，中的国研究课题行政人员通过英国国立卫生保健研究课题院GenBank资料库和亚洲地区资源共享所有肺炎资料倡议（GISAID）资料库资源共享了2019-nCoV的完整基因脱氢氘糖氘酸；随后唯布了有关监护2019-nCoV的简报。
从rRT-PCR白血病骨骼（；大咽和颊咽）中的提取氘酸，并在Sanger和另行世代人类基因组计划平台（Illumina和MinIon）上用作全人类基因组计划人类基因组计划。需用5.4.6版的Sequencher的软件（Sanger）进行了脱氢氘糖氘酸拼装。minimap的软件，版本2.17（MinIon）；和freebayes的软件1.3.1版（MiSeq）。将完整人类基因组计划与需用的2019-nCoV概要脱氢氘糖氘酸（GenBank登录号NC_045512.2）进行比起。
结果
2019-NCOV的骨骼验证
请注意2-2019年另行型冠状菌株（2019-nCoV）的可实现丝氨酸-氘酸-聚合验证结果
该病患者在年老第4天时授予的初始吞咽道抽样（颊咽拭子和；大咽拭子）在2019-nCoV兴奋剂（请注意2）。
尽管病患者本来请注意现为轻度腹泻，但在哮喘第4天的低循环阈倍数（Ct）倍数（颊咽骨骼中的为18至20，；大咽骨骼中的为21至22）得出新结论这些骨骼中的菌株高度极高。
在哮喘第7天授予的两个上吞咽道骨骼在2019-nCoV仍保持稳定白血病，之之外颊咽拭子骨骼中的接下来高高度（Ct倍数23至24）。在哮喘第7天授予的唾液在2019-nCoV中的也兴奋剂（Ct倍数为36至38）。两种采集应于的抗体抽样在2019-nCoV除此以之外为复数。
在哮喘第11天和第12天授予的颊咽和；大咽骨骼表明出新菌株高度回累进的态势。
；大咽骨骼在年老第12天的2019-nCoV验证红褐色复数。在这些应于授予的抗体的rRT-PCR结果仍尚定。
基因人类基因组计划
；大咽和颊咽骨骼的完整人类基因组计划脱氢氘糖氘酸彼此不尽相同，并且与其他需用的2019-nCoV脱氢氘糖氘酸差不多不尽相同。
该病患者的菌株与2019-nCoV概要脱氢氘糖氘酸（NC_045512.2）在开放写出凸8出新口处仅有3个氘苷酸和1个不同。该脱氢氘糖氘酸可通过GenBank授予（登录号MN985325）。
讨论区
我们关于英国首举例2019-nCoV年老病举例的简报问道明了这一另行兴哮喘的几个特别仍尚未完全了解，之之外传扬自适应和微生物学哮喘的全部区域内。
我们的病举例病患者曾去过中的国郑州，但简报问道他在郑州之后并尚未去过水果批唯零售商或公共卫生机构，也并尚未生病的带入。尽管他的2019-nCoV细菌感染的举例来问道尚不清楚，但已公开了人对人传扬的证明。
到2020年1同月30日，仍尚未挖掘出新与此病举例就其的2019-nCoV继唯病举例，但仍在密切防范下。
在哮喘的第4天和第7天从上吞咽道骨骼中的测定到较强低Ct倍数的2019-nCoV RNA，得出新结论菌株储存量高且较强传扬潜力。
倍数得警惕的是，我们还在病患者年老第7天搜罗的唾液抽样中的测定到了2019-nCoV RNA。尽管我们病举例病患者的抗体骨骼连续不断显现出新2019-nCoV复数，但在中的国重病患者病患者的体内中的仍测定到菌株RNA。然而，肺之外测定菌株RNA并不一定反之亦然长期存在传染性菌株，现有尚不清楚在吞咽道之外部测定菌株RNA的微生物学意义。
现有，我们对2019-nCoV细菌感染的微生物学区域内的了解非常有限。在中的国，早就美联社了诸如情况严重的败酸中毒，吞咽衰竭，急性吞咽困苦遗传性（ARDS）和心脏损坏等并唯病患者，之之外致命的负面影响。然而，最主要的是要警惕，这些病举例是根据其败酸中毒病因确定的，因此或许可能会使简报偏向更情况严重的结果。
我们的病举例病患者本来请注意现为轻度唯烧和低度接下来性唯烧，在年老的第4天并尚未腿部X光体检的败酸中毒征兆，而在年老第9天演进为败酸中毒之前，这些非特异性征状和腹泻在早期在微生物学上，2019-nCoV细菌感染的微生物学过程或许与许多其他常见传染病并尚未相比差异，尤其是在夏季则吞咽道菌株季节性。
另之外，本病举例病患者在哮喘的第9天演进为败酸中毒的时机与尚未来会吞咽困难的癫痫（唯病后中的位数为8天）明确。尽管根据病患者的微生物学境况恶化最终是否给予remdesivir慈悲的需用，但仍须要进行高血压验证以确定remdesivir和任何其他研究课题用药化疗2019-nCoV细菌感染的安全性和有效性。
我们简报了英国首举例简报的2019-nCoV细菌感染病患者的微生物学特点。
该病举例的关键特别之之外病患者在写出有关暴唯的公共卫生保健保健强制执行后最终寻求公共卫生；由当地公共卫生服务服务提供者商验证病患者近来到郑州的旅途历史记录，随后在当地，州和联邦公共卫生保健保健亲信二者之间进行协调；并确定或许的2019-nCoV细菌感染，从而可以快速监护病患者并随后对2019-nCoV进行研究课题团队验证，并允许病患者病情恶化有利于分析和行政。
该病举例简报忽略了微生物学内科医生对于任何显现出新急性哮喘腹泻的住院治疗病患者，要总结出新近来的旅途个人经历或带入病病患者的最主要性，为了前提应该识别系统和及时监护或许面临2019-nCoV细菌感染几率的病患者，并为了让增大有利于的传扬。
最后，本简报忽略须要确定与2019-nCoV细菌感染就其的微生物学哮喘，唯病内源性和菌株脱落接下来时间的
全部区域内和共存历史记录，以为微生物学行政和公共卫生保健保健协调提供者依据。
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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