概述
在之在此之前国上海开始的新型病原体性（2019-nCoV）挑起在随之蔓延，现已在多个国家政府胃癌。我们研究课题报告了在美国政府表明的首度2019-nCoV病菌SARS，并详细描述了该SARS的鉴定，临床，临床研究课题现实生活和管理者，之皆病征在病情第9天同上现为心脏病时的原先轻度癫痫状。
该例子合理化了临床研究课题牙医与人口众多，一个州和美国政府联邦各级医疗医疗卫生医疗卫生当局彼此之间密切联系协作的重要性，以及必须慢速广泛传播与这种新得病菌病征的医疗卫生有关的临床研究课题的资讯的期望。
2019年12月底31日，之在此之前国研究课题报告了与湖南省上海市华中海产批发在有关的一些人之在此之前的心脏病SARS。
2020年1月底7日，之在此之前国医疗卫生当局表明该簇与新型病原体性2019-nCoV有关。尽管原先华盛顿邮报的SARS与上海市海产商品的暴露有关，但当在此之前的药理学数据同上明，打算引发在2019-nCoV人际广泛传播。
截至2020年1月底30日，在将近21个国家政府/沿海地区研究课题报告了9976例SARS，之皆2020年1月底20日华盛顿邮报的美国政府首度胃癌的2019-nCoV病菌SARS。
全都球性范围内打算顺利进行追查，以愈来愈好地洞察广泛传播快照和临床研究课题营养不良范围。本研究课题报告详细描述了在美国政府表明的首度2019-nCoV病菌的药理学和临床研究课题形态。
例子研究课题报告
2020年1月底19日，一名35岁的男子借助于现在纽约一个州罗宾逊霍米巴加的一家门诊门诊，有4天的肠胃和有意识新陈代谢困难日本史。病患到门诊健康检查时，在候诊室戴上口罩。等待约20分钟后，他被带到健康检查室拒绝接受了发在放者的评估。
他透露，他在之在此之前国上海探望家人时为1月底15日返回纽约一个州。该病征同上示，他已从美国政府营养不良高度集之在此之前与预防性之在此之前心（CDC）收到有关之在此之前国新型病原体性暴发在的健康台风，由于他的癫痫状和近来的之旅，他重新考虑去看牙医。
示意图1-2020年1月底19日（营养不良第4天）的后背部和皆侧胸片
除了高三酸酯血癫痫的病因皆，该病征还是其他健康的不吸烟者。体格健康检查发在掘出病征新陈代谢环境气体时，血流量为37.2°C，血压为134/87 mm Hg，颤抖为每分钟110次，新陈代谢振幅为每分钟16次，氢相对于为96％。气管听诊表明有支气管炎，并顺利进行了胸片健康检查，据华盛顿邮报未发在掘出持续性（示意图1）。
甲型和九一SARS的慢速基因突变物质增量试验中（NAAT）为复数。获取了楔咽拭子新种，并通过NAAT将其送去侦测病原体性口腔病原体。
据华盛顿邮报在48星期内对所有试验中的病原体外深褐色复数，之皆甲型和九一SARS，副SARS，口腔合胞病原体，楔病原体，腺病原体和已知就会引致人类营养不良的四种少见病原体性株（HKU1，NL63、229E和OC43） ）。根据病征的之旅近现代，立即知就会人口众多和一个州当地政府。纽约该医院与紧急状况医疗卫生临床研究课题牙医三人知就会了CDC紧急状况行动之在此之前心。
尽管该病征研究课题报告却说他很难去过华中海产商品，也很难研究课题报告在去之在此之前国之旅期间与卧床者有任何碰触，但营养不良预防性高度集之在此之前之在此之前心的工作医护人员同意有必要根据当在此之前的营养不良预防性高度集之在此之前之在此之前心对病征顺利进行2019-nCoV试验中。
根据CDC最新查阅了8个新种，之皆小鼠，楔咽和口咽拭子新种。新种采集后，病征被送去中产阶级隔绝，并由当地当地政府顺利进行致力再次出现持续性。
2020年1月底20日，营养不良预防性高度集之在此之前之在此之前心（CDC）表明病征的楔咽和口咽拭子通过即时丝氨酸-一氧化氮羧化（rRT-PCR）侦测为2019-nCoV白血病。
在营养不良预防性高度集之在此之前之在此之前心的主题技术人员，一个州和人口众多医疗卫生文官，紧急状况医疗医疗卫生服务以及疗养院领导和工作医护人员的定位下，病征被送去康涅狄格州沿海地区医疗医疗卫生之在此之前心的气体隔绝病房顺利进行临床研究课题观察，并跟著营养不良预防性高度集之在此之前之在此之前心的医护医护人员有关碰触，飞沫和空之在此之前防盗措施的建议，并带有护目镜。
病情恶化时病征研究课题报告接下来肠胃，有2天的眩晕和呕吐日本史。他研究课题报告却说他很难新陈代谢急促或胸痛。生命病症在正常范围内。体格健康检查发在掘出病征牙龈潮湿。其余的健康检查通常不值得注意。
病情恶化后，病征拒绝接受了支持治医学上，之皆2天和生理盐水和恩丹以大大降低眩晕。
示意图2-根据营养不良日和开刀日（2020年1月底16日至2020年1月底30日）的癫痫状和最高血流量
在开刀的第2至5天（卧床的第6至9天），病征的生命病症基本维持，除了借助于现间歇新陈代谢困难并伴有心动过速（示意图2）。病征之后研究课题报告非生产性肠胃，并借助于现筋疲力尽。
在开刀第二天的下午，病征进食通畅，腹部不适。早晨有第二次屁股稀疏的华盛顿邮报。查阅该排泄物的探针用以rRT-PCR试验中，以及其他口腔新种（楔咽和口咽）和小鼠。排泄物和两个口腔新种之后外通过rRT-PCR侦测为2019-nCoV白血病，而小鼠仍为复数。
在此期间的治医学上在非常大高度上是支持性的。为了顺利进行癫痫状妥善处理，病征必须根据必须拒绝接受镇痛药医学上，该医学上之皆每4星期650 mg片剂和每6星期600 mg不良反应。在开刀的在此之前六天，他还因接下来肠胃而服用了600毫克愈创醚盟约6天和生理盐水。
同上1-临床研究课题研究课题所结果
病征隔绝区块的性质原先仅并不必须定时医疗医疗卫生点研究课题所试验中；从疗养院第3天开始可以顺利进行全都血细胞总和和小鼠无机化学研究课题。
在疗养院第3天和第5天（营养不良第7天和第9天）的研究课题所结果揭示借助于红细胞降低癫痫，轻度血小板降低癫痫和肌酸激酶总体天和高（同上1）。此皆，肝功能指标也有所变动：碱性糖类（每天和68 U），丙氨酸氨基转移酶（每天和105 U），天冬氨酸氨基转移酶（每天和77 U）和乳酸脱氢酶（每天和465 U）的总体大致相同：在开刀的第5天所有天和高。鉴于病征反复新陈代谢困难，在第4天获取肾脏培养；在此之在此之前，这些都很难增长。
示意图3-2020年1月底22日（面部第7天，疗养院第3天）的后背部和皆侧胸片
示意图4-2020年1月底24日（面部第5天，疗养院第9天）的后背部X线片
据华盛顿邮报，在疗养院第3天（卧床第7天）拍摄的面部X光片未表明灌注或持续性都还（示意图3）。
但是，从疗养院第5天早晨（卧床第9天）早晨顺利进行的第二次面部X光片健康检查表明，左肺下叶有心脏病（示意图4）。
这些影像学发在掘出与从疗养院第5天早晨开始的新陈代谢状态变动密切联系相关，当时病征在新陈代谢附近气体时通过颤抖磁共振相对于检测的磁共振相对于值降至90％。
在第6天，病征开始拒绝接受不足之处缺氢，该缺氢由楔导管以每分钟2天和的反应速度输送。考虑到临床研究课题同上现的变动和对疗养院获取性心脏病的关注，开始可视阿司匹林（1750 mg负荷剂量，然后每8星期肌肉注射1 g）和唑吡甲苯（每8星期肌肉注射）治医学上。
示意图5-在此之前后面部X光片，2020年1月底26日（营养不良第十天，疗养院第六天）
在疗养院第6天（卧床第10天），第四次面部X射线拍下表明两个肺之在此之前都有一个大条状混浊，这一发在掘出与非典型心脏病相符合（示意图5），并且在听诊时在两个肺之在此之前都借助于现了罗音。鉴于放射影像学发在掘出，重新考虑赋予缺氢不足之处，病征接下来新陈代谢困难，多个手部接下来白血病的2019-nCoV RNA白血病，以及发在同上了与放射性心脏病其发在展相符的不堪重负心脏病在该病征之在此之前，临床研究课题牙医极富渴望地可视了研究课题性抗病原体治医学上。
肌肉注射珍妮昔韦（一种打算开发在设计的新型核糖衍生物在此之前药）在第7天早晨开始，但未观察到与减压有关的不良事件。在对甲氢霖青霉素的暗红色抗生素顺利进行了连续的降钙素原总体和楔PCR侦测后，在第7天早晨改用阿司匹林，并在第二天改用唑吡甲苯。
在疗养院第8天（卧床第12天），病征的临床研究课题状况得到更佳。中断不足之处缺氢，他在新陈代谢附近气体时的氢相对于值提高到94％至96％。先在此之前的双侧下叶罗音不再共存。他的食欲得到更佳，除了间歇干咳和楔漏皆，他很难癫痫状。
截至2020年1月底30日，病征仍开刀。他有发在热，除肠胃皆，所有癫痫状外已大大降低，肠胃的高度打算减轻。
方法
新种采集
根据CDC最新获取用以2019-nCoV临床试验中的临床研究课题新种。用合成树脂拭子查阅了12个楔咽和口咽拭子新种。
将每个拭子断开还包括2至3 ml病原体转运介质的单独无菌管之在此之前。将血集在小鼠分离管之在此之前，然后根据CDC最新顺利进行离心。尿液和排泄物新种分别查阅在无菌新种容器之在此之前。探针在2°C至8°C彼此之间储存，直到准备好运送至CDC。
在营养不良的第7、11和12天查阅了重复顺利进行的2019-nCoV试验中的新种，之皆楔咽和口咽拭子，小鼠以及尿液和排泄物取样。
2019-NCOV的临床试验中
可视从公开发表发在设计布的病原体基因序列其发在展而来的rRT-PCR分析方法试验中了临床研究课题新种。与先在此之前针对重癫痫急性新陈代谢囊肿病原体性（SARS-CoV）和之在此之前东新陈代谢囊肿病原体性（MERS-CoV）的临床方法相似，它具备三个核衣壳基因索科利夫卡和一个白血病解读索科利夫卡。该检测的详细描述为RRT-PCR面板引物和探针和基因序列的资讯之在此之前可视的CDC研究课题所的资讯网站2019-nCoV上。
基因突变动学合成
2020年1月底7日，之在此之前国研究课题医护人员通过美国政府国立医疗卫生研究课题院GenBank检索和全都球性共享所有SARS数据倡议（GISAID）检索共享了2019-nCoV的原始基因基因序列；随后发在布了有关隔绝2019-nCoV的研究课题报告。
从rRT-PCR白血病新种（口咽和楔咽）之在此之前提炼基因突变物质，并在Sanger和更进一步化学合成平台（Illumina和MinIon）上用以全都基因组化学合成。可视5.4.6海外版的Sequencher软件（Sanger）未完成了基因序列拆解。minimap软件，海外版2.17（MinIon）；和freebayes软件1.3.1海外版（MiSeq）。将原始基因组与可视的2019-nCoV参考基因序列（GenBank登录号NC_045512.2）顺利进行比较。
结果
2019-NCOV的新种试验中
同上2-2019年新型病原体性（2019-nCoV）的即时丝氨酸-一氧化氮-羧化试验中结果
该病征在卧床第4天时获取的初始口腔取样（楔咽拭子和口咽拭子）在2019-nCoV深褐色白血病（同上2）。
尽管病征原先同上现为轻度癫痫状，但在营养不良第4天的低循环接下来性（Ct）值（楔咽新种之在此之前为18至20，口咽新种之在此之前为21至22）同上明这些新种之在此之前病原体总体较高。
在营养不良第7天获取的两个上口腔新种在2019-nCoV仍保有白血病，之皆楔咽拭子新种之在此之前接下来高总体（Ct值23至24）。在营养不良第7天获取的排泄物在2019-nCoV之在此之前也深褐色白血病（Ct值为36至38）。两种采集日期的小鼠取样在2019-nCoV外为复数。
在营养不良第11天和第12天获取的楔咽和口咽新种表明借助于病原体总体下降的趋势。
口咽新种在卧床第12天的2019-nCoV试验中深褐色复数。在这些日期获取的小鼠的rRT-PCR结果仍综观。
基因突变动学合成
口咽和楔咽新种的原始基因组基因序列彼此相同，并且与其他可视的2019-nCoV基因序列几乎相同。
该病征的病原体与2019-nCoV参考基因序列（NC_045512.2）在新开读到框8处仅有3个核糖和1个不同。该基因序列可通过GenBank获取（登录号MN985325）。
讨论区
我们关于美国政府首度2019-nCoV胃癌SARS的研究课题报告暗示这一新兴营养不良的几个特别之在此之前基本上洞察，之皆广泛传播快照和临床研究课题营养不良的全都部范围。
我们的SARS病征曾去过之在此之前国上海，但研究课题报告却说他在上海期间很难去过海产批发在或医疗医疗卫生机构，也很难得病的碰触。尽管他的2019-nCoV病菌的来源不明尚不确实，但已公开发表了人对人广泛传播的确凿。
到2020年1月底30日，之在此之前发在掘出与此SARS特别的2019-nCoV心绞痛在SARS，但仍在密切联系监视下。
在营养不良的第4天和第7天从上口腔新种之在此之前侦测到具备低Ct值的2019-nCoV RNA，同上明病原体载量高且具备广泛传播潜力。
或多或少的是，我们还在病征卧床第7天查阅的排泄物取样之在此之前侦测到了2019-nCoV RNA。尽管我们SARS病征的小鼠新种反复借助于现2019-nCoV复数，但在之在此之前国重癫痫病征的肾脏之在此之前仍侦测到病原体RNA。然而，肺皆侦测病原体RNA未必这样一来共存传染性病原体，迄今尚不确实在口腔皆部侦测病原体RNA的临床研究课题意义。
迄今，我们对2019-nCoV病菌的临床研究课题范围的洞察非常有限。在之在此之前国，之在此之前华盛顿邮报了诸如不堪重负的心脏病，新陈代谢衰竭，急性新陈代谢窘迫囊肿（ARDS）和心脏损坏等并发在癫痫，之皆灾难性的后果。然而，重要的是要同样，这些SARS是根据其心脏病临床断定的，因此有可能就会使研究课题报告偏向愈来愈不堪重负的结果。
我们的SARS病征原先同上现为轻度肠胃和低度间歇新陈代谢困难，在卧床的第4天很难面部X光健康检查的心脏病都还，而在卧床第9天其发在展为心脏病之在此之前，这些非特异性病症和癫痫状在早期在临床研究课题上，2019-nCoV病菌的临床研究课题现实生活有可能与许多其他少见传染病很难值得注意区分，偏爱是在夏季口腔病原体时节。
另皆，本SARS病征在营养不良的第9天其发在展为心脏病的才就会与近期新陈代谢困难的发在作（得病后之在此之前位数为8天）相符。尽管根据病征的临床研究课题状况衰弱重新考虑是不是赋予remdesivir愿的可视，但仍必须顺利进行随机解读试验以断定remdesivir和任何其他研究课题用药治医学上2019-nCoV病菌的安全都性和持续性。
我们研究课题报告了美国政府首度研究课题报告的2019-nCoV病菌病征的临床研究课题形态。
该SARS的关键特别之皆病征在读到有关暴发在的医疗医疗卫生医疗卫生警告后重新考虑争取医疗医疗卫生；由当地医疗医疗卫生服务发在放者表明病征近来到上海的之旅近现代，随后在当地，一个州和美国政府联邦医疗医疗卫生医疗卫生文官彼此之间顺利进行协调；并断定有可能的2019-nCoV病菌，从而可以随之隔绝病征并随后对2019-nCoV顺利进行研究课题所表明，并并不必须病征病情恶化进一步评估和管理者。
该SARS研究课题报告合理化了临床研究课题牙医对于任何借助于现急性营养不良癫痫状的门诊病征，要论述借助于近来的之旅境遇或碰触病因的重要性，为了保证正确识别和及时隔绝有可能面对2019-nCoV病菌安全都性的病征，并协助降低进一步的广泛传播。
最后，本研究课题报告合理化必须断定与2019-nCoV病菌特别的临床研究课题营养不良，得病机理和病原体断裂接下来时间的
全都部范围和共存近现代，以为临床研究课题管理者和医疗医疗卫生医疗卫生决策发在放依据。
以下为修订本
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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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