摘要
在近现代汉口开始的新型病原菌株（2019-nCoV）爆样促使蔓延，现已在多个国家政府就诊。我们年度报告了在American证实的首度2019-nCoV细菌感染登革热，并描述了该登革热的比对，病因，医学流程和管理，举例来说病患在病情第9天所列现为白血病时的刚开始轻度患者。
该案唯重申了医学内科医生与以外，州和美国联邦政府各级公共医疗卫生新加坡政府中所间密切协作的效用，以及必须短时间传递与这种新样细菌感染病患的医疗有关的医学讯息的需求。
2019年12同年31日，近现代年度报告了与湖北省汉口市珠江三角洲海产批样市场需求有关的人群中所的白血病登革热。
2020年1同年7日，近现代医疗卫生新加坡政府证实该簇与新型病原菌株2019-nCoV有关。尽管刚开始芝加哥邮报的登革热与汉口市海产市场需求的暴露有关，但当在此之前的临床数据所列明，正要样生2019-nCoV社但会群体传递。
截至2020年1同年30日，在至少21个国家政府/周边地区年度报告了9976唯登革热，举例来说2020年1同年20日芝加哥邮报的American首度就诊的2019-nCoV细菌感染登革热。
全球之内正要展开调查，以更好地洞察传递快照和医学病癫痫区域。本年度报告描述了在American证实的首度2019-nCoV细菌感染的临床和医学构造。
案唯年度报告
2020年1同年19日，一名35岁的男子显现显现出来在芝加哥州华莱士霍米什县的一家急诊门诊，有4天的呕吐和主观样烧近代史。病患到门诊核查时，在候诊室戴上背心。等待约20分钟后，他被带到核查室不能接受了相关联的分析。
他透露，他在近现代汉口养病家人后于1同年15日留在芝加哥州。该病患所列示，他已从American病癫痫控制与预防性中所心（CDC）寄出有关近现代新型病原菌株暴样的身心健康警报，由于他的患者和早先的旅途，他暂时去看内科医生。
左图1-2020年1同年19日（病癫痫第4天）的后腹部和外侧胸片
除了高三酸酯血癫痫的病近代史外，该病患还是其他身心健康的不吸烟者。体格核查样现病患气管环境湿气时，含氧量为37.2°C，血压为134/87 mm Hg，脉搏为每分钟110次，气管频率为每分钟16次，硫相对于为96％。气管听诊推断有高血压，并展开了胸片核查，据芝加哥邮报仍未样现异常（左图1）。
病毒性和-A病原的短时间连锁反应酸扩增试验性中所（NAAT）为中所性。得不到了钝咽拭子遗骸，并通过NAAT将其送去扫描菌株性肺部病原。
据芝加哥邮报在48不间断内对所有试验性中所的病原之外呈中所性，举例来说病毒性和-A病原，副病原，肺部合胞菌株，钝菌株，腺菌株和已知但会致使人类病癫痫的四种常见病原菌株株（HKU1，NL63、229E和OC43） ）。根据病患的旅途历近代史，立即通知以外和州医务人员。芝加哥医疗该医院与即刻医疗医学内科医生四人通知了CDC即刻行动中所心。
尽管该病患年度报告时说他不能去过珠江三角洲海产市场需求，也不能年度报告在去近现代旅途期间与病重者有任何带入，但病癫痫预防性机房的工作人员同意有必要根据当在此之前的病癫痫预防性机房对病患展开2019-nCoV试验性中所。
根据CDC读物搜罗了8个遗骸，举例来说毒素，钝咽和沟咽拭子遗骸。遗骸野外后，病患被送进家庭永久性，并由当地医务人员展开尽力风险分析。
2020年1同年20日，病癫痫预防性机房（CDC）证实病患的钝咽和沟咽拭子通过数据处理丝氨酸-核酸链式反应（rRT-PCR）扫描为2019-nCoV中所性。
在病癫痫预防性机房的题材专家，州和以外医疗卫生官员，即刻医疗服务以及医务人员积极支持者和工作人员的立体化下，病患被送进普罗维登斯周边地区活动中所心的湿气永久性病房展开医学观察，并曾随病癫痫预防性机房的医护人员有关带入，飞沫和机群防护措施的促请，并带有丝袜。
入院时病患年度报告过后呕吐，有2天的恶心和呕吐近代史。他年度报告时说他不能气管急促或胸痛。全人类先兆在经常性之内。体格核查样现病患粘膜干燥。其余的核查通常不值得注意。
入院后，病患不能接受了支持者病患，举例来说2升到生理盐水和恩丹以消除恶心。
左图2-根据病癫痫日和康复日（2020年1同年16日至2020年1同年30日）的患者和最高含氧量
在康复的第2至5天（病重的第6至9天），病患的全人类先兆基本保持稳定，除了显现显现出来断续样烧并伴有心动过速（左图2）。病患此后年度报告非生产性呕吐，并显现显现出来疲惫。
在康复第二天的凌晨，病患排便有利于，腹部不适。午夜有第二次尿稀少的芝加哥邮报。搜罗该腐肉的容器常用rRT-PCR试验性中所，以及其他肺部遗骸（钝咽和沟咽）和毒素。腐肉和两个肺部遗骸后来之外通过rRT-PCR扫描为2019-nCoV中所性，而毒素仍为中所性。
在此期间的病患在很大相对上是支持者性的。为了展开患者附近理，病患必须根据必须不能接受镇痛疗法，该疗法举例来说每4不间断650 mg对乙酰硫酸基酚和每6不间断600 mg胺类。在康复的在此之前六天，他还因过后呕吐而施打了600毫克极创醚友好条约6升到生理盐水。
所列1-医学研究工作小组结果
病患永久性单元的性质刚开始仅容许事在此之前医疗点研究工作小组试验性中所；从医务人员第3天开始可以展开全血细胞计数和毒素化学研究工作。
在医务人员第3天和第5天（病癫痫第7天和第9天）的研究工作小组结果总结显现出白细胞减少癫痫，轻度血小板减少癫痫和肌酸激酶水准下降时（所列1）。此外，酸中所毒指标也或多或少波动：碱性糖类（每升到68 U），丙硫酸酸硫酸基转移酶（每升到105 U），天冬硫酸酸硫酸基转移酶（每升到77 U）和糖类脱氢酶（每升到465 U）的水准共五：在康复的第5天所有下降时。鉴于病患反复样烧，在第4天得不到体液培养；迄今，这些都不能上涨。
左图3-2020年1同年22日（背部第7天，医务人员第3天）的后腹部和外侧胸片
左图4-2020年1同年24日（背部第5天，医务人员第9天）的后腹部X线片
据芝加哥邮报，在医务人员第3天（病重第7天）拍下的背部X光片仍未推断灌注或异常痕迹（左图3）。
但是，从医务人员第5天午夜（病重第9天）午夜展开的第二次背部X光片核查推断，左肺下叶有白血病（左图4）。
这些影像学样现与从医务人员第5天午夜开始的气管状态波动相吻合，当时病患在气管周边湿气时通过脉搏血硫相对于精确测量的血硫相对于倍数回落90％。
在第6天，病患开始不能接受足量二硫化碳，该二硫化碳由钝导管以每分钟2升到的速率运送。考虑到医学所列现的波动和对医务人员得不到性白血病的关心，开始用到水杨酸（1750 mg损耗剂量，然后每8不间断麻醉1 g）和唑足总杯芳基（每8不间断麻醉）病患。
左图5-在此之前后背部X光片，2020年1同年26日（病癫痫第十天，医务人员第六天）
在医务人员第6天（病重第10天），第四次背部X射线照片推断两个肺中所都有复合条状混浊，这一样现与非典型白血病相符（左图5），并且在听诊时在两个肺中所都显现显现出来了罗音。鉴于人沟为120人影像学样现，暂时得不到二硫化碳足量，病患过后样烧，多个部位过后中所性的2019-nCoV RNA中所性，以及样所列了与人沟为120人性白血病样展保持一致的比较严重白血病在该病患中所，医学内科医生富有冷漠地用到了各学科抗菌株病患。
麻醉瑞德昔韦（一种正要开样的新型多肽类似物在此之前药）在第7天午夜开始，但仍未观察到与输液有关的不良血案。在对甲硫朱家致病的金黄色葡萄球菌展开了连续的降钙素原水准和钝PCR扫描后，在第7天午夜停用水杨酸，并在第二天停用唑足总杯芳基。
在医务人员第8天（病重第12天），病患的医学原因得到改善。中所断足量二硫化碳，他在气管周边湿气时的硫相对于倍数提升到到94％至96％。先在此之前的双侧下叶罗音不再发挥作用。他的嗜睡得到改善，除了断续干咳和钝漏外，他不能患者。
截至2020年1同年30日，病患仍康复。他有样热，除呕吐外，所有患者之外已消除，呕吐的相对正要减轻。
分析方法
遗骸野外
根据CDC读物得不到常用2019-nCoV病因试验性中所的医学遗骸。用橡胶拭子搜罗了12个钝咽和沟咽拭子遗骸。
将每个拭子嵌入举例来说2至3 ml菌株船运介质的除此以外新鲜胸腔所。将血集在毒素分离胸腔所，然后根据CDC读物展开离心。尿液和腐肉遗骸分别搜罗在新鲜遗骸容器中所。容器在2°C至8°C中所间储藏，直到准备好运送至CDC。
在病癫痫的第7、11和12天搜罗了单调展开的2019-nCoV试验性中所的遗骸，举例来说钝咽和沟咽拭子，毒素以及尿液和腐肉比对。
2019-NCOV的病因试验性中所
用到从公开场合样布的菌株脱氧连锁反应糖连锁反应酸样展而来的rRT-PCR分析法试验性中所了医学遗骸。与先在此之前针对高血压急性气管癫痫病原菌株（SARS-CoV）和中所东气管癫痫病原菌株（MERS-CoV）的病因分析方法相似，它具有三个连锁反应衣壳等位基因特异性和一个中所性对照特异性。该精确测量的描述为RRT-PCR背光程序但会和容器和脱氧连锁反应糖连锁反应酸讯息中所比如时说的CDC研究工作小组讯息网站2019-nCoV上。
遗传高通量
2020年1同年7日，近现代研究工作人员通过American国立医疗卫生研究工作院GenBank数据库系统和全球构建所有病原数据倡议（GISAID）数据库系统构建了2019-nCoV的比较简单等位基因脱氧连锁反应糖连锁反应酸；随后样布了有关永久性2019-nCoV的年度报告。
从rRT-PCR中所性遗骸（沟咽和钝咽）中所分离显现出连锁反应酸，并在Sanger和下一代高通量平台（Illumina和MinIon）上常用全等位遗传物质高通量。用到5.4.6版本的Sequencher软件包（Sanger）完毕了脱氧连锁反应糖连锁反应酸组装。minimap软件包，版本本2.17（MinIon）；和freebayes软件包1.3.1版本（MiSeq）。将比较简单等位遗传物质与比如时说的2019-nCoV概述脱氧连锁反应糖连锁反应酸（GenBank登录号NC_045512.2）展开比较。
结果
2019-NCOV的遗骸试验性中所
所列2-2019年新型病原菌株（2019-nCoV）的数据处理丝氨酸-核酸-链式反应试验性中所结果
该病患在病重第4四海得不到的初始肺部比对（钝咽拭子和沟咽拭子）在2019-nCoV呈中所性（所列2）。
尽管病患刚开始所列现为轻度患者，但在病癫痫第4天的更高重复也就是时说（Ct）倍数（钝咽遗骸中所为18至20，沟咽遗骸中所为21至22）所列明这些遗骸中所菌株水准较高。
在病癫痫第7天得不到的两个上肺部遗骸在2019-nCoV仍保持中所性，举例来说钝咽拭子遗骸中所过后高层次（Ct倍数23至24）。在病癫痫第7天得不到的腐肉在2019-nCoV中所也呈中所性（Ct倍数为36至38）。两种野外日期的毒素比对在2019-nCoV之外为中所性。
在病癫痫第11天和第12天得不到的钝咽和沟咽遗骸推断显现出菌株水准下降的趋势。
沟咽遗骸在病重第12天的2019-nCoV试验性中所呈中所性。在这些日期得不到的毒素的rRT-PCR结果仍仍未确定。
遗传高通量
沟咽和钝咽遗骸的比较简单等位遗传物质脱氧连锁反应糖连锁反应酸彼此不尽相同，并且与其他比如时说的2019-nCoV脱氧连锁反应糖连锁反应酸几乎不尽相同。
该病患的菌株与2019-nCoV概述脱氧连锁反应糖连锁反应酸（NC_045512.2）在对外开放朗读凸8附近全部都是3个多肽和1个不同。该脱氧连锁反应糖连锁反应酸可通过GenBank得不到（登录号MN985325）。
讨论区
我们关于American首度2019-nCoV就诊登革热的年度报告时说明了这一新兴病癫痫的几个方面尚能仍未完全洞察，举例来说传递快照和医学病癫痫的全部区域。
我们的登革热病患曾去过近现代汉口，但年度报告时说他在汉口期间不能去过海产批样市场需求或该医务人员，也不能身体虚弱的带入。尽管他的2019-nCoV细菌感染的来源尚能不确切，但已公开场合了人对人传递的证据。
到2020年1同年30日，尚能仍未样现与此登革热之外的2019-nCoV继样登革热，但仍在密切监视下。
在病癫痫的第4天和第7天从上肺部遗骸中所扫描到具有更高Ct倍数的2019-nCoV RNA，所列明菌株载量高且具有传递吸引力。
倍数得注意的是，我们还在病患病重第7天搜罗的腐肉比对中所扫描到了2019-nCoV RNA。尽管我们登革热病患的毒素遗骸反复显现显现出来2019-nCoV中所性，但在近现代高血压病患的体液中所仍扫描到菌株RNA。然而，肺外扫描菌株RNA并不一定意味着发挥作用传染性菌株，目在此之前尚能不确切在肺部外部扫描菌株RNA的医学意义。
目在此之前，我们对2019-nCoV细菌感染的医学区域的洞察非常有限。在近现代，已经芝加哥邮报了诸如比较严重的白血病，气管衰竭，急性气管窘迫癫痫（ARDS）和心脏重击等并样癫痫，举例来说致命的后果。然而，重要的是要注意，这些登革热是根据其白血病病因考虑到的，因此有可能但会使年度报告取向更比较严重的结果。
我们的登革热病患刚开始所列现为轻度呕吐和更高度断续样烧，在病重的第4天不能背部X光核查的白血病痕迹，而在病重第9天样展为白血病之在此之前，这些非特异性先兆和患者在早期在医学上，2019-nCoV细菌感染的医学流程有可能与许多其他常见病原不能值得注意区别，相比较是在夏季时肺部菌株时节。
另外，本登革热病患在病癫痫的第9天样展为白血病的尽早与近期气管困难的样作（样病后中所位数为8天）保持一致。尽管根据病患的医学原因每况愈下暂时究竟得不到remdesivir慈悲的用到，但仍必须展开结果推断试验性以考虑到remdesivir和任何其他研究工作药物病患2019-nCoV细菌感染的安全性和有效性。
我们年度报告了American首度年度报告的2019-nCoV细菌感染病患的医学构造。
该登革热的关键性方面举例来说病患在朗读有关暴样的公共医疗卫生警告后暂时寻求医疗；由当地医疗服务相关联证实病患早先到汉口的旅途历近代史，随后在当地，州和美国联邦政府公共医疗卫生官员中所间展开协调；并考虑到有可能的2019-nCoV细菌感染，从而可以促使永久性病患并随后对2019-nCoV展开研究工作小组证实，并容许病患入院有利于分析和管理。
该登革热年度报告重申了医学内科医生对于任何显现显现出来急性病癫痫患者的就诊病患，要总结显现出早先的旅途年中或带入病近代史的效用，为了尽有可能确实定位和及时永久性有可能造成了2019-nCoV细菌感染风险的病患，并帮助减少有利于的传递。
最后，本年度报告重申必须考虑到与2019-nCoV细菌感染之外的医学病癫痫，样病机理和菌株脱落过后时间的
全部区域和自然环境历近代史，以为医学管理和公共医疗卫生决策包括依据。
以下为英文版本
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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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