简短
在中的国郑州开始的新型大肠杆菌（2019-nCoV）爆所发不断肆虐，现已在多个国家显露院。我们调查报告了在英美两国获知的尚未有2019-nCoV病菌所发生率，并刻画了该所发生率的鉴定，诊疗，药理学过程和负责管理，都有病症在病情第9天请注意现为肺癌时的在此之同一时间轻度疼痛。
该犯罪行为凸显了药理学护士与以前，一州和联邦各级卫生保健新加坡政府二者之间密切协作的举足轻重性，以及所需加速传递与这种新所发病菌病症的照护有关的药理学信息的需求。
2019年12月初31日，中的国调查报告了与湖北省长沙市海南岛菜式家禽有关的群体中的的肺癌所发生率。
2020年1月初7日，中的国卫生新加坡政府获知该簇与新型大肠杆菌2019-nCoV有关。尽管在此之同一时间报导的所发生率与长沙市菜式市场的暴露有关，但近期的流行病学数据请注意明，正在所发生2019-nCoV人际关系传递。
截至2020年1月初30日，在至少21个国家/南部调查报告了9976例所发生率，都有2020年1月初20日报导的英美两国尚未有显露院的2019-nCoV病菌所发生率。
正因如此球区域内内正在展开调查，以更是好地探究传递自适应和药理学病因区域内。本调查报告刻画了在英美两国获知的尚未有2019-nCoV病菌的流行病学和药理学特征。
犯罪行为调查报告
2020年1月初19日，一名35岁的男童显现在林肯一州斯诺霍米什县的合伙急诊公共卫生机构，有4天的头痛和有意识腹泻通史。病症到公共卫生机构定期检查时，在候诊室戴上眼镜。等待约20分钟后，他被来到定期检查室给与了举例来说的评估。
他透露，他在中的国郑州探望家人紧接著1月初15日返回林肯一州。该病症请注意示，他已从英美两国病因控制与卫生保健中的心（CDC）收到有关中的国新型大肠杆菌频所发的生活品质警报，由于他的疼痛和除此以外的周游世界，他重新考虑去看护士。
绘出1-2020年1月初19日（病因第4天）的后同一时间胸和侧面胸片
除了高三酸酯血症的病通史外，该病症还是其他生活品质的不吸烟。体格定期检查挖掘显露病症气管环境湿气时，体温为37.2°C，血压为134/87 mm Hg，不止为每分钟110次，气管反之亦然为每分钟16次，氧稍高为96％。肺脏听诊却说明了有支气管炎，并展开了胸片定期检查，据报导未能挖掘显露显露现异常（绘出1）。
七轮型和流感大肠杆菌SARS的加速核酸扩增测试者（NAAT）为有性。获取了咽咽拭子古生物学家，并通过NAAT将其送去扫描致病气管道病原体。
据报导在48每隔内对所有测试者的病原体原则上呈有性，都有七轮型和流感大肠杆菌SARS，副SARS，气管道合胞大肠杆菌，咽大肠杆菌，腺大肠杆菌和推断会导致人类病因的四种类似大肠杆菌株（HKU1，NL63、229E和OC43） ）。根据病症的周游世界历通史，随即指示以前和一州医疗机构。林肯卫生部与紧急照护药理学护士一起指示了CDC紧急行动中的心。
尽管该病症调查报告却说他并未能去过海南岛菜式市场，也并未能调查报告在去中的国周游世界期间与患者有任何交谈，但病因卫生保健通讯系统的工作技术人员准许有必要根据近期的病因卫生保健通讯系统对病症展开2019-nCoV测试者。
根据CDC读物收集了8个古生物学家，都有肠道，咽咽和故名咽拭子古生物学家。古生物学家热带植物后，病症被送至普通家庭永久性，并由当地医疗机构展开积极监测。
2020年1月初20日，病因卫生保健通讯系统（CDC）获知病症的咽咽和故名咽拭子通过实时抗大肠杆菌-RNA链反应（rRT-PCR）扫描为2019-nCoV白血病。
在病因卫生保健通讯系统的主题专家，一州和以前卫生官员，紧急公共卫生服务以及所医院领导和工作技术人员的配合下，病症被送至普罗维登斯南部公共卫生中的心的湿气永久性病房展开药理学检视，并曾随病因卫生保健通讯系统的医护技术人员有关交谈，飞沫和空中的防护措施的建议，并带有靴子。
入院时病症调查报告持续性头痛，有2天的恶心和呕吐通史。他调查报告却说他并未能气管急促或心悸。灵魂哮喘在正常区域内内。体格定期检查挖掘显露病症粘膜寒冷。其余的定期检查通常不明显。
入院后，病症给与了赞成治疗法，都有2充生理盐水和恩丹以加重恶心。
绘出2-根据病因日和入院日（2020年1月初16日至2020年1月初30日）的疼痛和最高体温
在入院的第2至5天（患的第6至9天），病症的灵魂哮喘基本保持稳定，除了显现暂时性腹泻并伴有心动过速（绘出2）。病症继续调查报告非生产性头痛，并显现疲倦。
在入院第二天的下午，病症大便有利于，腹部不适。晚上有第二次大便比较大的报导。收集该泥土的样品主要用途rRT-PCR测试者，以及其他气管道古生物学家（咽咽和故名咽）和肠道。泥土和两个气管道古生物学家后来原则上通过rRT-PCR扫描为2019-nCoV白血病，而肠道仍为有性。
在此期间的治疗法在不小往往上是赞成性的。为了展开疼痛执行，病症所需根据所需给与解热治疗法，该治疗法都有每4每隔650 mg对乙酰氨基酚和每6每隔600 mg低剂量。在入院的同一时间六天，他还因持续性头痛而服药了600毫克稍稍创醚和约6充生理盐水。
请注意1-药理学深入研究室结果
病症永久性两节的性质在此之同一时间极少意味着即时公共卫生点深入研究室测试者；从所医院第3天开始可以展开正因如此血细胞总和和肠道化学深入研究。
在所医院第3天和第5天（病因第7天和第9天）的深入研究室结果看显露显露白细胞提高症，轻度白血球提高症和肌酸激酶多方面充高（请注意1）。此外，肝功能指标也有所叠加：碱性脂质（每充68 U），丙氨酸氨基转移酶（每充105 U），糖类氨基转移酶（每充77 U）和乳酸脱氢酶（每充465 U）的多方面分别为：在入院的第5天所有充高。鉴于病症一一腹泻，在第4天获取肠道人才培养；目前为止，这些都并未能增长。
绘出3-2020年1月初22日（颈部第7天，所医院第3天）的后同一时间胸和侧面胸片
绘出4-2020年1月初24日（颈部第5天，所医院第9天）的后同一时间胸X线片
据报导，在所医院第3天（患第7天）拍摄的颈部X光片未能却说明了浸润或显露现异常迹象（绘出3）。
但是，从所医院第5天晚上（患第9天）晚上展开的第二次颈部X光片定期检查却说明了，左肺下叶有肺癌（绘出4）。
这些外科挖掘显露与从所医院第5天晚上开始的气管平衡状态叠加相吻合，当时病症在气管外围湿气时通过不止血氧稍高推算显露的血氧稍高值减到90％。
在第6天，病症开始给与足量压缩空气，该压缩空气由咽尿道以每分钟2充的飞行速度输送。考虑到药理学请注意现的叠加和对所医院获取性肺癌的关注，开始采用万古霉素（1750 mg节省成本剂量，然后每8每隔麻醉1 g）和嗪夺标苯酚（每8每隔麻醉）治疗法。
绘出5-同一时间后颈部X光片，2020年1月初26日（病因第十天，所医院第六天）
在所医院第6天（患第10天），第四次颈部X射线照片却说明了两个肺中的都有基底条状混浊，这一挖掘显露与非典型肺癌相符（绘出5），并且在听诊时在两个肺中的都显现了罗音。鉴于来将外科挖掘显露，重新考虑给予压缩空气足量，病症持续性腹泻，多个部位持续性白血病的2019-nCoV RNA白血病，以及所发请注意了与来将性肺癌其所发展一致的严重肺癌在该病症中的，药理学护士富有同情心地采用了深入学术性抗大肠杆菌治疗法。
麻醉瑞德昔韦（一种正在合作开所发的新型核苷酸类似物同一时间药）在第7天晚上开始，但未能检视到与输注有关的不良事件。在对七轮氧霖乙型肝炎的金黄色绿脓杆菌展开了年终的降钙素原多方面和咽PCR扫描后，在第7天晚上停用万古霉素，并在第二天停用嗪夺标苯酚。
在所医院第8天（患第12天），病症的药理学状况得到优化。停止足量压缩空气，他在气管外围湿气时的氧稍高值提高到94％至96％。先同一时间的双侧下叶罗音不必依赖于。他的皮质醇得到优化，除了暂时性干咳和咽漏外，他并未能疼痛。
截至2020年1月初30日，病症仍入院。他有气管困难，除头痛外，所有疼痛原则上已加重，头痛的往往正在减轻。
新方法
古生物学家热带植物
根据CDC读物获取主要用途2019-nCoV诊疗测试者的药理学古生物学家。用合成纤维拭子收集了12个咽咽和故名咽拭子古生物学家。
将每个拭子接在举例来说2至3 ml大肠杆菌水路电磁波的另行无菌水银。将血集在肠道分离水银，然后根据CDC读物展开离心。尿和泥土古生物学家分别收集在无菌古生物学家容器中的。样品在2°C至8°C二者之间储存，直到作准备运送至CDC。
在病因的第7、11和12天收集了重复采用展开的2019-nCoV测试者的古生物学家，都有咽咽和故名咽拭子，肠道以及尿和泥土检验。
2019-NCOV的诊疗测试者
采用从官方网站所刊发的大肠杆菌核酸其所发展而来的rRT-PCR分析法测试者了药理学古生物学家。与先同一时间针对加护急性气管综合征大肠杆菌（SARS-CoV）和中的东气管综合征大肠杆菌（MERS-CoV）的诊疗新方法相似，它不具三个核衣壳基因贝克曼和一个白血病解读贝克曼。该推算显露的刻画为RRT-PCR面板PCR和探针和核酸信息中的比如却说的CDC深入研究室信息网站2019-nCoV上。
遗传DNA
2020年1月初7日，中的国深入研究技术人员通过英美两国国立卫生深入研究部GenBank数据库和正因如此球共享所有SARS数据共同努力（GISAID）数据库共享了2019-nCoV的完整基因核酸；随后所刊发了有关永久性2019-nCoV的调查报告。
从rRT-PCR白血病古生物学家（故名咽和咽咽）中的提取核酸，并在Sanger和更是进一步DNA跨平台（Illumina和MinIon）上主要用途正因如此基因组DNA。采用5.4.6海外版的Sequencher插件（Sanger）完成了核酸组装。minimap插件，海外版本2.17（MinIon）；和freebayes插件1.3.1海外版（MiSeq）。将完整基因组与比如却说的2019-nCoV简介核酸（GenBank登录号NC_045512.2）展开比较。
结果
2019-NCOV的古生物学家测试者
请注意2-2019年新型大肠杆菌（2019-nCoV）的实时抗大肠杆菌-RNA-链反应测试者结果
该病症在患第4天时获取的初始气管道检验（咽咽拭子和故名咽拭子）在2019-nCoV呈白血病（请注意2）。
尽管病症在此之同一时间请注意现为轻度疼痛，但在病因第4天的高循环反之亦然（Ct）值（咽咽古生物学家中的为18至20，故名咽古生物学家中的为21至22）请注意明这些古生物学家中的大肠杆菌多方面极高。
在病因第7天获取的两个上气管道古生物学家在2019-nCoV仍保持白血病，都有咽咽拭子古生物学家中的持续性高多方面（Ct值23至24）。在病因第7天获取的泥土在2019-nCoV中的也呈白血病（Ct值为36至38）。两种热带植物日期的肠道检验在2019-nCoV原则上为有性。
在病因第11天和第12天获取的咽咽和故名咽古生物学家却说明了显露大肠杆菌多方面下降的趋势。
故名咽古生物学家在患第12天的2019-nCoV测试者呈有性。在这些日期获取的肠道的rRT-PCR结果仍未能定。
遗传DNA
故名咽和咽咽古生物学家的完整基因组核酸彼此有所不同，并且与其他比如却说的2019-nCoV核酸几乎有所不同。
该病症的大肠杆菌与2019-nCoV简介核酸（NC_045512.2）在闭馆阅读圆点8三处极少有3个核苷酸和1个不同。该核酸可通过GenBank获取（登录号MN985325）。
讨论区
我们关于英美两国尚未有2019-nCoV显露院所发生率的调查报告却说明了这一新兴病因的几个特别尚未能完正因如此探究，都有传递自适应和药理学病因的正因如此部区域内。
我们的所发生率病症曾去过中的国郑州，但调查报告却说他在郑州期间并未能去过菜式家禽或公共卫生机构，也并未能生病的交谈。尽管他的2019-nCoV病菌的来源尚不相符，但已官方网站了人对人传递的证据。
到2020年1月初30日，尚未能挖掘显露与此所发生率关的的2019-nCoV继所发所发生率，但仍在密切监视下。
在病因的第4天和第7天从上气管道古生物学家中的扫描到不具高Ct值的2019-nCoV RNA，请注意明大肠杆菌次之高且不具传递潜力。
值得注意的是，我们还在病症患第7天收集的泥土检验中的扫描到了2019-nCoV RNA。尽管我们所发生率病症的肠道古生物学家一一显现2019-nCoV有性，但在中的国加护病症的肠道中的仍扫描到大肠杆菌RNA。然而，肺外扫描大肠杆菌RNA并不一定意味着依赖于传染性大肠杆菌，目同一时间尚不相符在气管道外部扫描大肠杆菌RNA的药理学意义。
目同一时间，我们对2019-nCoV病菌的药理学区域内的探究更是为有限。在中的国，已经报导了诸如严重的肺癌，气管衰竭，急性气管虚弱综合征（ARDS）和心脏损伤等显露血，都有不幸的负面影响。然而，举足轻重的是要注意，这些所发生率是根据其肺癌诊疗考虑到的，因此可能会使调查报告偏向更是严重的结果。
我们的所发生率病症在此之同一时间请注意现为轻度头痛和高度暂时性腹泻，在患的第4天并未能颈部X光定期检查的肺癌迹象，而在患第9天其所发展为肺癌之同一时间，这些非特异性哮喘和疼痛在早期在药理学上，2019-nCoV病菌的药理学过程可能与许多其他类似传染病并未能明显区别，相比之下是在冬季气管道大肠杆菌季节。
另外，本所发生率病症在病因的第9天其所发展为肺癌的时机与近期气管困难的复所发（所发病后中的位数为8天）一致。尽管根据病症的药理学状况恶化重新考虑是否给予remdesivir慈悲的采用，但仍所需展开系统性试验性以考虑到remdesivir和任何其他深入研究药物治疗法2019-nCoV病菌的确实和确实。
我们调查报告了英美两国尚未有调查报告的2019-nCoV病菌病症的药理学特征。
该所发生率的关键特别都有病症在阅读有关频所发的卫生保健忠告后重新考虑寻求公共卫生；由当地公共卫生服务举例来说获知病症除此以外到郑州的周游世界历通史，随后在当地，一州和联邦卫生保健官员二者之间展开协调；并考虑到可能的2019-nCoV病菌，从而可以不断永久性病症并随后对2019-nCoV展开深入研究室获知，并意味着病症入院进一步评估和负责管理。
该所发生率调查报告凸显了药理学护士对于任何显现急性病因疼痛的就诊病症，要总结显露除此以外的周游世界经历或交谈病通史的举足轻重性，为了确保无论如何识别和马上永久性可能造成了2019-nCoV病菌风险的病症，并帮助提高进一步的传递。
就此，本调查报告凸显所需考虑到与2019-nCoV病菌关的的药理学病因，所发病机理和大肠杆菌破损持续性时间的
正因如此部区域内和自然环境历通史，以为药理学负责管理和卫生保健决策提供依据。
以下为英文海外版
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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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