摘要
在东亚重庆开始的新型冠状病原（2019-nCoV）爆发急剧蔓延，现已在多个国家政府确诊。我们调查结果了在英国断定的年初所2019-nCoV受到感染病患，并说明了了该病患的鉴定，诊断，除此以外科现实生活和管理，除此以除此以外病患在病情第9天请注意现为心脏病时的以前轻度肠胃。
该案实有忽视了除此以外科精神科与大都，俄克拉荷马州和州政府各级医疗中国政府里间密切协作的重要性，以及能够较快传播与这种新发受到感染病患的看护有关的除此以外科信息的需求。
2019年12年初31日，东亚调查结果了与湖北省重庆市海南岛海鲜批发市场有关的人群里的心脏病病患。
2020年1年初7日，东亚保健中国政府断定该簇与新型冠状病原2019-nCoV有关。尽管以前华盛顿邮报的病患与重庆市海鲜市场的暴露有关，但近期的微生物学图表得显露结论，正在发生2019-nCoV社会关系传播。
截至2020年1年初30日，在仅仅21个国家政府/北部调查结果了9976实有病患，除此以除此以外2020年1年初20日华盛顿邮报的英国年初所确诊的2019-nCoV受到感染病患。
同类型球在世界上正在进行时调查，以更好地探究传播动态和除此以外科营养过多适用范围。本调查结果说明了了在英国断定的年初所2019-nCoV受到感染的微生物学和除此以外科特征。
案实有调查结果
2020年1年初19日，一名35岁的女选手显露现在华盛顿俄克拉荷马州斯诺霍米什县的一家急诊诊所，有4天的肠胃和主观呼吸困难史。病患到诊所体检时，在候诊室戴上故名罩。等待约20分钟后，他被带到体检室给与了举实有来知道的评估。
他声称，他在东亚重庆拜访家人先于1年初15日返回华盛顿俄克拉荷马州。该病患请注意示，他已从英国营养过多控制与传染病里心（CDC）收到有关东亚新型冠状病原接踵而来的肥胖日本气象厅，由于他的肠胃和已经有的历险，他重新考虑去看精神科。
所示1-2020年1年初19日（营养过多第4天）的后腰部和除此以一侧胸片
除了高三酸酯血性疾病的病因除此以外，该病患还是其他肥胖的不成年人。体格体检辨认出病患新陈代谢环境湿气时，血流量为37.2°C，眼压为134/87 mm Hg，脉搏为每分钟110次，新陈代谢频率为每分钟16次，氧一般而言为96％。肺部听诊标示出有支气管炎，并进行时了胸片体检，据华盛顿邮报未曾辨认出异常（所示1）。
甲型和甲类心脏病的较快大分子扩增验证（NAAT）为特征性。给以了喉咽拭子骨骼，并通过NAAT将其送到去侦测病原性新陈代谢道病原体。
据华盛顿邮报在48时长内对所有验证的病原体仅有呈特征性，除此以除此以外甲型和甲类心脏病，副心脏病，新陈代谢道合胞病原，喉病原，腺病原和已知会致使人类营养过多的四种常见冠状病原株（HKU1，NL63、229E和OC43） ）。根据病患的历险近现代，第一时间通报大都和俄克拉荷马州商务部门。华盛顿商务部与救护车看护除此以外科精神科一起通报了CDC救护车行动里心。
尽管该病患调查结果知道他未曾去过海南岛海鲜市场，也未曾调查结果在去东亚历险过后与卧床者有任何沾染，但营养过多传染病控制里心的负责人同意有必要根据近期的营养过多传染病控制里心对病患进行时2019-nCoV验证。
根据CDC指南整理了8个骨骼，除此以除此以外肝细胞，喉咽和故名咽拭子骨骼。骨骼搜集后，病患被送到往家庭强制，并由当地商务部门进行时积极监测。
2020年1年初20日，营养过多传染病控制里心（CDC）断定病患的喉咽和故名咽拭子通过同步逆转录酶-聚合酶链式反应（rRT-PCR）侦测为2019-nCoV非典型。
在营养过多传染病控制里心的主题专家，俄克拉荷马州和大都保健官吏，救护车医疗服务以及所医院领导和负责人的配合下，病患被送到往普罗维登斯北部医疗里心的湿气强制病房进行时除此以外科观察，并跟随营养过多传染病控制里心的医护人员有关沾染，飞沫和空里防爆控制措施的建议，并含有护目镜。
病倒时病患调查结果长时间肠胃，有2天的恶心和肠胃史。他调查结果知道他未曾新陈代谢急促或病症。人类征状在正常在世界上。体格体检辨认出病患粘膜寒冷。其余的体检通常不微小。
病倒后，病患给与了支持治疗，除此以除此以外2升生理盐水和恩丹以缓解恶心。
所示2-根据营养过多日和开刀日（2020年1年初16日至2020年1年初30日）的肠胃和最高血流量
在开刀的第2至5天（卧床的第6至9天），病患的人类征状也就是知道保持稳定，除了显露现经年累月呼吸困难并伴有心动过速（所示2）。病患一直调查结果非生产性肠胃，并显露现舒服。
在开刀第二天的中午，病患排便通畅，腹部不适。午夜有第二次大便稀疏的华盛顿邮报。整理该排泄的试样用以rRT-PCR验证，以及其他新陈代谢道骨骼（喉咽和故名咽）和肝细胞。排泄和两个新陈代谢道骨骼在此之后仅有通过rRT-PCR侦测为2019-nCoV非典型，而肝细胞仍为特征性。
先后的治疗在相当大程度上是支持性的。为了进行时肠胃检视，病患能够根据能够给与镇痛药制剂，该制剂除此以除此以外每4时长650 mg对乙酰吡啶基酚和每6时长600 mg非甾体。在开刀的前六天，他还因长时间肠胃而过量了600毫克愈创醚和约6升生理盐水。
请注意1-除此以外科Laboratory结果
病患强制单元的性质以前仅必需即时医疗点Laboratory验证；从所医院第3天开始可以进行时同类型血细胞总和和肝细胞化学深入研究。
在所医院第3天和第5天（营养过多第7天和第9天）的Laboratory结果反映显露白细胞增大性疾病，轻度血小板增大性疾病和肌酸激酶水准增大（请注意1）。此除此以外，肾脏指标也有所发生变化：碱性糖类（每升68 U），丙吡啶酸吡啶基转移酶（每升105 U），天冬吡啶酸吡啶基转移酶（每升77 U）和乳糖脱氢酶（每升465 U）的水准分别为：在开刀的第5天所有增大。鉴于病患反复呼吸困难，在第4天给以肝脏人才；为数不多，这些都未曾增长。
所示3-2020年1年初22日（腿部第7天，所医院第3天）的后腰部和除此以一侧胸片
所示4-2020年1年初24日（腿部第5天，所医院第9天）的后腰部X线片
据华盛顿邮报，在所医院第3天（卧床第7天）拍摄的腿部X光片未曾标示出浸润或异常迹象（所示3）。
但是，从所医院第5天午夜（卧床第9天）午夜进行时的第二次腿部X光片体检标示出，左肺下叶有心脏病（所示4）。
这些医学影像辨认出与从所医院第5天午夜开始的新陈代谢状态发生变化相吻合，初期病患在新陈代谢周围湿气时通过脉搏血氧一般而言测定的血氧一般而言最大值降至90％。
在第6天，病患开始给与知道明氢气，该氢气由喉导管以每分钟2升的速度输送到。考虑到除此以外科请注意现的发生变化和对所医院给以性心脏病的关注，开始常用水杨酸（1750 mg负重施打，然后每8时长肌肉注射1 g）和头孢吡肟（每8时长肌肉注射）治疗。
所示5-前后腿部X光片，2020年1年初26日（营养过多第十天，所医院第六天）
在所医院第6天（卧床第10天），第四次腿部X射线照片标示出两个肺里都有基底条状混浊，这一辨认出与非相比较心脏病相符（所示5），并且在听诊时在两个肺里都显露现了罗音。鉴于放射源医学影像辨认出，重新考虑给以氢气知道明，病患长时间呼吸困难，多个部位长时间非典型的2019-nCoV RNA非典型，以及发请注意了与放射源性心脏病拓展恰当的轻微心脏病在该病患里，除此以外科精神科富有责任感地常用了深入研究性抗病原治疗。
肌肉注射瑞德昔韦（一种正在开发的新型连锁反应苷酸N-前药）在第7天午夜开始，但未曾观察到与用药有关的过多暴力事件。在对甲氧大白耐药的金黄色绿脓杆菌进行时了连续的降钙素原水准和喉PCR侦测后，在第7天午夜关闭水杨酸，并在第二天关闭头孢吡肟。
在所医院第8天（卧床第12天），病患的除此以外科境况给以改善。里止知道明氢气，他在新陈代谢周围湿气时的氧一般而言最大值提高到94％至96％。在此之后的双侧下叶罗音依然不存在。他的食欲给以改善，除了经年累月干咳和喉漏除此以外，他未曾肠胃。
截至2020年1年初30日，病患仍开刀。他有发热，除肠胃除此以外，所有肠胃仅有已缓解，肠胃的程度正在减轻。
分析方法
骨骼搜集
根据CDC指南给以用以2019-nCoV诊断验证的除此以外科骨骼。用尼龙拭子整理了12个喉咽和故名咽拭子骨骼。
将每个拭子插入相关联2至3 ml病原转运介质的除此以外杀菌管里。将血集在肝细胞分离管里，然后根据CDC指南进行时离心。尿液和排泄骨骼分别整理在杀菌骨骼容器里。试样在2°C至8°C里间储存，直到准备好运送到至CDC。
在营养过多的第7、11和12天整理了重复进行时的2019-nCoV验证的骨骼，除此以除此以外喉咽和故名咽拭子，肝细胞以及尿液和排泄试样。
2019-NCOV的诊断验证
常用从公开披露的病原碱基拓展而来的rRT-PCR分析法验证了除此以外科骨骼。与在此之后针对重性疾病急性新陈代谢囊肿冠状病原（SARS-CoV）和里东新陈代谢囊肿冠状病原（MERS-CoV）的诊断分析方法相似，它较强三个连锁反应衣壳基因化学合成和一个非典型印证化学合成。该测定的说明了为RRT-PCR面板引物和间隙和碱基信息里可视的CDCLaboratory信息com2019-nCoV上。
遗传DNA
2020年1年初7日，东亚深入研究人员通过英国国立保健深入研究生院GenBank资料库和同类型球提供者所有心脏病图表倡议（GISAID）资料库提供者了2019-nCoV的完备基因碱基；随后披露了有关强制2019-nCoV的调查结果。
从rRT-PCR非典型骨骼（故名咽和喉咽）里提取大分子，并在Sanger和新一代DNA平台（Illumina和MinIon）上用以同类型遗传物质DNA。常用5.4.6英文版的Sequencher软件（Sanger）启动了碱基装配。minimap软件，英文版2.17（MinIon）；和freebayes软件1.3.1英文版（MiSeq）。将完备遗传物质与可视的2019-nCoV简介碱基（GenBank登录号NC_045512.2）进行时比较。
结果
2019-NCOV的骨骼验证
请注意2-2019年新型冠状病原（2019-nCoV）的同步逆转录酶-聚合酶-链式反应验证结果
该病患在卧床第4而所给以的初始新陈代谢道试样（喉咽拭子和故名咽拭子）在2019-nCoV过量（请注意2）。
尽管病患以前请注意现为轻度肠胃，但在营养过多第4天的较差循环阈最大值（Ct）最大值（喉咽骨骼里为18至20，故名咽骨骼里为21至22）得显露结论这些骨骼里病原水准较差。
在营养过多第7天给以的两个上新陈代谢道骨骼在2019-nCoV仍保持非典型，除此以除此以外喉咽拭子骨骼里长时间较差水准（Ct最大值23至24）。在营养过多第7天给以的排泄在2019-nCoV里也过量（Ct最大值为36至38）。两种搜集定于的肝细胞试样在2019-nCoV仅有为特征性。
在营养过多第11天和第12天给以的喉咽和故名咽骨骼标示出显露病原水准下降的趋势。
故名咽骨骼在卧床第12天的2019-nCoV验证呈特征性。在这些定于给以的肝细胞的rRT-PCR结果仍未曾定。
遗传DNA
故名咽和喉咽骨骼的完备遗传物质碱基彼此相同，并且与其他可视的2019-nCoV碱基几乎相同。
该病患的病原与2019-nCoV简介碱基（NC_045512.2）在开放阅读框8处仅有3个连锁反应苷酸和1个不同。该碱基可通过GenBank给以（登录号MN985325）。
讨论区
我们关于英国年初所2019-nCoV确诊病患的调查结果看出这一新兴营养过多的几个方面未曾完同类型探究，除此以除此以外传播动态和除此以外科营养过多的同类型部适用范围。
我们的病患病患曾去过东亚重庆，但调查结果知道他在重庆过后未曾去过海鲜批发市场或医疗机构，也未曾生病的沾染。尽管他的2019-nCoV受到感染的来源已为不似乎，但已公开了人对人传播的结论。
到2020年1年初30日，未曾辨认出与此病患就其的2019-nCoV神经性病患，但仍在密切警卫下。
在营养过多的第4天和第7天从上新陈代谢道骨骼里侦测到较强较差Ct最大值的2019-nCoV RNA，得显露结论病原载量高且较强传播潜力。
最大值得注意的是，我们还在病患卧床第7天整理的排泄试样里侦测到了2019-nCoV RNA。尽管我们病患病患的肝细胞骨骼反复显露现2019-nCoV特征性，但在东亚重性疾病病患的肝脏里仍侦测到病原RNA。然而，肺除此以外侦测病原RNA这不意味着不存在传染性病原，目前已为不似乎在新陈代谢道除此以外部侦测病原RNA的除此以外科意义。
目前，我们对2019-nCoV受到感染的除此以外科适用范围的探究非常有限。在东亚，已经华盛顿邮报了诸如轻微的心脏病，新陈代谢衰竭，急性新陈代谢窘迫囊肿（ARDS）和心脏挫伤等并发性疾病，除此以除此以外致命的不可避免。然而，重要的是要注意，这些病患是根据其心脏病诊断确定的，因此不太可能会使调查结果偏向更轻微的结果。
我们的病患病患以前请注意现为轻度肠胃和较差度经年累月呼吸困难，在卧床的第4天未曾腿部X光体检的心脏病迹象，而在卧床第9天拓展为心脏病之前，这些非特异性征状和肠胃在一时期在除此以外科上，2019-nCoV受到感染的除此以外科现实生活不太可能与许多其他常见传染病未曾微小区别于，尤其是在冬季新陈代谢道病原干季。
另除此以外，本病患病患在营养过多的第9天拓展为心脏病的时机与近期新陈代谢困难的心脏病（发病后里位数为8天）恰当。尽管根据病患的除此以外科境况恶化重新考虑到底给以remdesivir赐福的常用，但仍能够进行时随机印证试验以确定remdesivir和任何其他深入研究药品治疗2019-nCoV受到感染的安同类型性和精确性。
我们调查结果了英国年初所调查结果的2019-nCoV受到感染病患的除此以外科特征。
该病患的关键方面除此以除此以外病患在阅读有关接踵而来的医疗发出后重新考虑借此医疗；由当地医疗IMS断定病患已经有到重庆的历险近现代，随后在当地，俄克拉荷马州和州政府医疗官吏里间进行时协调；并确定不太可能的2019-nCoV受到感染，从而可以急剧强制病患并随后对2019-nCoV进行时Laboratory断定，并必需病患病倒有利于评估和管理。
该病患调查结果忽视了除此以外科精神科对于任何显露现急性营养过多肠胃的就诊病患，要总结显露已经有的历险经历或沾染病因的重要性，为了确保正确识别和幸而强制不太可能陷入2019-nCoV受到感染风险的病患，并帮助增大有利于的传播。
最后，本调查结果忽视能够确定与2019-nCoV受到感染就其的除此以外科营养过多，发病机理和病原脱落长时间时间的
同类型部适用范围和自然近现代，以为除此以外科管理和医疗决断提供依据。
以下为译者
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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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