摘录
在里面华人民共和国武汉开始的新型冠状菌株（2019-nCoV）爆发短时间散播，现已在多个国家出院。我们调查结果了在美国政府认定的首由此可知2019-nCoV受到感染登革热，并所述了该登革热的深入研究，产妇，药理学流程和管理工作，最主要病患在病情第9天请注意现为中风时的最初轻度疼痛。
该情形强调了药理学护士与地方，州和联邦各级公共医疗当局之间密切协作的更进一步，以及需要迅速传扬与这种新发受到感染病患的护理有关的药理学资讯的需求。
2019年12同年31日，里面华人民共和国调查结果了与湖北武汉市华南水果批发商品有关的人群里面的中风登革热。
2020年1同年7日，里面华人民共和国医疗当局认定该簇与新型冠状菌株2019-nCoV有关。尽管最初路透社的登革热与武汉市水果商品的曝露有关，但也就是真是的流行病学原始数据请注意明，正在发生2019-nCoV人际传扬。
截至2020年1同年30日，在至少21个国家/区域调查结果了9976由此可知登革热，最主要2020年1同年20日路透社的美国政府首由此可知出院的2019-nCoV受到感染登革热。
正因如此球仅限于内正在开展调查，以更好地探究传扬动态和药理学病因仅限于。本调查结果所述了在美国政府认定的首由此可知2019-nCoV受到感染的流行病学和药理学特征。
情形调查结果
2020年1同年19日，一名35岁的男子浮现在科罗拉多州斯诺霍米什县的一家住院诊所，有4天的痉挛和直觉感冒日本史。产妇到诊所检查时，在候诊室戴上口罩。准备好约20分钟后，他被带到检查室拒绝接受了获取者的分析报告。
他透露，他在里面华人民共和国武汉陪同母亲都于1同年15日返回科罗拉多州。该病患对此，他已从美国政府病因管控与防止里面心（CDC）收到有关里面华人民共和国新型冠状菌株暴发的肥胖症警报，由于他的疼痛和现在有的历险，他同意去看护士。
三幅1-2020年1同年19日（病因第4天）的后颈部和以外侧胸片
除了高三酸酯缺乏症的帕金森氏症以外，该病患还是其他肥胖症的不高血压。体格检查断定病患肺部环境二氧化碳时，血压为37.2°C，血压为134/87 mm Hg，跳动为每分钟110次，肺部Hz为每分钟16次，镁一般来说为96％。肺部听诊说明了有支气管炎，并开展了胸片检查，据路透社尚未断定诱发（三幅1）。
丙型和九一猪流感的迅速核酸扩增验证（NAAT）为复数。赢得了腹咽拭子化石，并通过NAAT将其送去检查菌株性细菌受到感染细菌。
据路透社在48星期内对所有验证的细菌大多黄绿色复数，最主要丙型和九一猪流感，副猪流感，细菌受到感染合胞菌株，腹菌株，腺菌株和已知都会导致人类所病因的四种常见冠状菌株株（HKU1，NL63、229E和OC43） ）。根据病患的历险历日本史，立即事先地方和州防疫。华盛顿医疗部与紧急护理药理学护士一同事先了CDC紧急行动里面心。
尽管该病患调查结果真是他尚未去过华南水果商品，也尚未调查结果在去里面华人民共和国历险之前与年老者有任何碰触，但病因防止管控里面心的工作医务人员同意有必要根据也就是真是的病因防止管控里面心对病患开展2019-nCoV验证。
根据CDC须知得来了8个化石，最主要血浆，腹咽和口咽拭子化石。化石采集后，病患被送至家庭隔离，并由当地防疫开展不遗余力监测。
2020年1同年20日，病因防止管控里面心（CDC）认定病患的腹咽和口咽拭子通过系统会中国地区-聚合酶裂解（rRT-PCR）检查为2019-nCoV白血病。
在病因防止管控里面心的主题专家学者，州和地方医疗行政官员，紧急公共医疗服务以及所医院领导和工作医务人员的配合下，病患被送至梅肯区域公共医疗里面心的二氧化碳隔离病房开展药理学观察，并跟随病因防止管控里面心的消防员有关碰触，飞沫和机群防护措施的建议，并含有工作服。
病情恶化时病患调查结果不间断痉挛，有2天的麻木和呕吐日本史。他调查结果真是他尚未肺部急促或胸痛。生命体征在情况下仅限于内。体格检查断定病患粘膜湿。其余的检查通常不明显。
病情恶化后，病患拒绝接受了支持以外科手术，最主要2充生理盐水和恩丹以减轻麻木。
三幅2-根据病因日和就医日（2020年1同年16日至2020年1同年30日）的疼痛和最高血压
在就医的第2至5天（年老的第6至9天），病患的生命体征基本长期保持，除了浮现间歇性感冒并；还有心动过速（三幅2）。病患之前调查结果非生产性痉挛，并浮现疲倦。
在就医第二天的下午，病患排便保证了，腹部不适。凌晨有第二次洗手零散的路透社。得来该泥土的样品运用于rRT-PCR验证，以及其他细菌受到感染化石（腹咽和口咽）和血浆。泥土和两个细菌受到感染化石日后大多通过rRT-PCR检查为2019-nCoV白血病，而血浆仍为复数。
在此之前的以外科手术在很大程度上是支持性的。为了开展疼痛处理，病患需要根据需要拒绝接受解热疗法，该疗法最主要每4星期650 mg对乙酰氨基酚和每6星期600 mg布洛芬。在就医的前六天，他还因不间断痉挛而服用了600毫克愈创醚和约6充生理盐水。
请注意1-药理学研究中心结果
病患隔离单元的性质最初仅有并不需要即时公共医疗点研究中心验证；从所医院第3天开始可以开展正因如此血细胞计数和血浆化学原始数据分析。
在所医院第3天和第5天（病因第7天和第9天）的研究中心结果反映出白细胞下降症，轻度肝细胞下降症和肌酸激酶水平充高（请注意1）。此以外，肝功能测试方法也不大变化：碱性磷酸酶（每充68 U），丙氨酸氨基转移酶（每充105 U），天冬氨酸氨基转移酶（每充77 U）和甘油脱氢酶（每充465 U）的水平分别为：在就医的第5天所有充高。鉴于病患反复感冒，在第4天赢得血液周而复始培训；迄今为止，这些都尚未增长。
三幅3-2020年1同年22日（头部第7天，所医院第3天）的后颈部和以外侧胸片
三幅4-2020年1同年24日（头部第5天，所医院第9天）的后颈部X线片
据路透社，在所医院第3天（年老第7天）拍摄的头部X光片尚未说明了浸润或诱发似乎（三幅3）。
但是，从所医院第5天凌晨（年老第9天）凌晨开展的第二次头部X光片检查说明了，左肺下叶有中风（三幅4）。
这些影像学断定与从所医院第5天凌晨开始的肺部精神状态变化相吻合，起初病患在肺部周围二氧化碳时通过跳动血镁一般来说测定的血镁一般来说系数降至90％。
在第6天，病患开始拒绝接受必需镁气，该镁气由腹导管以每分钟2充的速率输送。考虑到药理学请注意现的变化和对所医院赢得性中风的关注，开始采用低剂量（1750 mg负担剂量，然后每8星期用药1 g）和咪唑两场肟（每8星期用药）以外科手术。
三幅5-前后头部X光片，2020年1同年26日（病因第十天，所医院第六天）
在所医院第6天（年老第10天），第四次头部X射线照片说明了两个肺里面都有基底长条状混浊，这一断定与非典型中风相符（三幅5），并且在听诊时在两个肺里面都浮现了罗音。鉴于放射影像学断定，同意获得镁气必需，病患不间断感冒，多个部位不间断白血病的2019-nCoV RNA白血病，以及发请注意了与放射性中风转变一致的相当严重中风在该病患里面，药理学护士富有同情心地采用了原始数据分析性抗菌株以外科手术。
用药瑞德昔韦（一种正在研发的新型核糖类似物前药）在第7天凌晨开始，但尚未观察到与输注有关的不良事件。在对丙镁西林耐药的金黄色链球菌开展了倒数的降钙素原水平和腹PCR检查后，在第7天凌晨转用低剂量，并在第二天转用咪唑两场肟。
在所医院第8天（年老第12天），病患的药理学不间断性获得改善。暂缓必需镁气，他在肺部周围二氧化碳时的镁一般来说系数提高到94％至96％。之前的双侧下叶罗音暂时不存在。他的食欲获得改善，除了间歇性干咳和腹漏以外，他尚未疼痛。
截至2020年1同年30日，病患仍就医。他有头痛，除痉挛以外，所有疼痛大多已减轻，痉挛的程度正在过重。
新方法
化石采集
根据CDC须知赢得运用于2019-nCoV产妇验证的药理学化石。用合成纤维拭子得来了12个腹咽和口咽拭子化石。
将每个拭子接在包含2至3 ml菌株转运介质的原则上冷冻管里面。将血集在血浆分离管里面，然后根据CDC须知开展离心。血浆和泥土化石分别得来在冷冻化石容器里面。样品在2°C至8°C之间储存，直到准备好搬运至CDC。
在病因的第7、11和12天得来了减法开展的2019-nCoV验证的化石，最主要腹咽和口咽拭子，血浆以及血浆和泥土检验。
2019-NCOV的产妇验证
采用从公研面世的菌株基因序列转变而来的rRT-PCR分析验证了药理学化石。与之前针对病患急性肺部病症冠状菌株（SARS-CoV）和里面东肺部病症冠状菌株（MERS-CoV）的产妇新方法相似，它具有三个核单链遗传靶标和一个白血病对照靶标。该测定的所述为RRT-PCR面板引物和探针和基因序列资讯里面举例来说的CDC研究中心资讯网站2019-nCoV上。
遗传DNA
2020年1同年7日，里面华人民共和国原始数据分析医务人员通过美国政府国立医疗原始数据分析院GenBank原始数据源和正因如此球资源共享所有猪流感原始数据倡议（GISAID）原始数据源资源共享了2019-nCoV的零碎遗传基因序列；随后面世了有关隔离2019-nCoV的调查结果。
从rRT-PCR白血病化石（口咽和腹咽）里面提取核酸，并在Sanger和世代DNA平台（Illumina和MinIon）上运用于正因如此遗传组DNA。采用5.4.6国际版的Sequencher硬件（Sanger）收尾了基因序列组装。minimap硬件，国际版本2.17（MinIon）；和freebayes硬件1.3.1国际版（MiSeq）。将零碎遗传组与举例来说的2019-nCoV参考基因序列（GenBank登录号NC_045512.2）开展比较。
结果
2019-NCOV的化石验证
请注意2-2019年新型冠状菌株（2019-nCoV）的系统会中国地区-聚合酶-裂解验证结果
该病患在年老第4天时赢得的初始细菌受到感染检验（腹咽拭子和口咽拭子）在2019-nCoV黄绿色白血病（请注意2）。
尽管病患最初请注意现为轻度疼痛，但在病因第4天的低周而复始阈系数（Ct）系数（腹咽化石里面为18至20，口咽化石里面为21至22）请注意明这些化石里面菌株水平较高。
在病因第7天赢得的两个上细菌受到感染化石在2019-nCoV仍保持白血病，最主要腹咽拭子化石里面不间断多方面（Ct系数23至24）。在病因第7天赢得的泥土在2019-nCoV里面也黄绿色白血病（Ct系数为36至38）。两种采集应于的血浆检验在2019-nCoV大多为复数。
在病因第11天和第12天赢得的腹咽和口咽化石说明了出菌株水平下降的趋势。
口咽化石在年老第12天的2019-nCoV验证黄绿色复数。在这些应于赢得的血浆的rRT-PCR结果仍断定。
遗传DNA
口咽和腹咽化石的零碎遗传组基因序列彼此相近，并且与其他举例来说的2019-nCoV基因序列几乎相近。
该病患的菌株与2019-nCoV参考基因序列（NC_045512.2）在免费朗读框内8处仅有有3个核糖和1个不同。该基因序列可通过GenBank赢得（登录号MN985325）。
专页
我们关于美国政府首由此可知2019-nCoV出院登革热的调查结果真是明了这一新兴病因的几个不足之处亦然尚未完正因如此探究，最主要传扬动态和药理学病因的正因如此部仅限于。
我们的登革热病患曾去过里面华人民共和国武汉，但调查结果真是他在武汉之前尚未去过水果批发商品或公共医疗机构，也尚未生病的碰触。尽管他的2019-nCoV受到感染的来源亦然不相符，但已公开发表文章了人对人传扬的证据。
到2020年1同年30日，亦然尚未断定与此登革热相关的2019-nCoV继发登革热，但仍在密切警卫下。
在病因的第4天和第7天从上细菌受到感染化石里面检查到具有低Ct系数的2019-nCoV RNA，请注意明菌株载量高且具有传扬潜力。
系数得注意的是，我们还在病患年老第7天得来的泥土检验里面检查到了2019-nCoV RNA。尽管我们登革热病患的血浆化石反复浮现2019-nCoV复数，但在里面华人民共和国病年老患的血液周而复始里面仍检查到菌株RNA。然而，肺以外检查菌株RNA并不一定这样一来不存在传染性菌株，目前亦然不相符在细菌受到感染以内部检查菌株RNA的药理学意义。
目前，我们对2019-nCoV受到感染的药理学仅限于的探究并不举例来说。在里面华人民共和国，现在路透社了诸如相当严重的中风，肺部衰竭，急性肺部窘迫病症（ARDS）和心脏细菌感染等中风，最主要有可能的严重后果。然而，重要的是要注意，这些登革热是根据其中风产妇断定的，因此可能都会使调查结果偏向更相当严重的结果。
我们的登革热病患最初请注意现为轻度痉挛和低度间歇性感冒，在年老的第4天尚未头部X光检查的中风似乎，而在年老第9天转变为中风之前，这些非特异性体征和疼痛在早期在药理学上，2019-nCoV受到感染的药理学流程可能与许多其他常见传染病尚未明显区别，尤其是在冬季细菌受到感染菌株季节。
另以外，本登革热病患在病因的第9天转变为中风的适时与近期肺部困难的复发（中风后里面位数为8天）一致。尽管根据病患的药理学不间断性恶化同意是否获得remdesivir慈悲的采用，但仍需要开展探索性试验中以断定remdesivir和任何其他原始数据分析药品以外科手术2019-nCoV受到感染的安正因如此性和有效性。
我们调查结果了美国政府首由此可知调查结果的2019-nCoV受到感染病患的药理学特征。
该登革热的关键不足之处最主要病患在朗读有关暴发的公共医疗警告后同意寻求公共医疗；由当地公共医疗服务获取者认定病患现在有到武汉的历险历日本史，随后在当地，州和联邦公共医疗行政官员之间开展协商；并断定可能的2019-nCoV受到感染，从而可以短时间隔离病患并随后对2019-nCoV开展研究中心认定，并并不需要病年老情恶化进一步分析报告和管理工作。
该登革热调查结果强调了药理学护士对于任何浮现急性病因疼痛的就诊病患，要总结出现在有的历险经历或碰触帕金森氏症的更进一步，为了确保正确定位和第一时间隔离可能面临2019-nCoV受到感染风险的病患，并鼓励下降进一步的传扬。
最后，本调查结果强调需要断定与2019-nCoV受到感染相关的药理学病因，中风成因和菌株脱落不间断时间的
正因如此部仅限于和其本质历日本史，以为药理学管理工作和公共医疗决策获取依据。
以下为英文国际版
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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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