简短
在当近现代上海开始的新型冠状感染（2019-nCoV）爆发急剧肆虐，如今在多个第三世界就医。我们份文件了在澳大利亚推定的首创2019-nCoV病菌就医，并描述了该就医的鉴定，病症，诊疗过程和政府机构，之以外病人在身体健康原因第9天此表现为肺癌时的早先轻度副作用。
该案则有特别强调了诊疗医师与大都，的县和联邦各级公共公共卫生新加坡政府之间密切协作的普遍性，以及所需慢速扩散与这种新得病菌病人的护理人员有关的诊疗数据的效益。
2019年12月底31日，当近现代份文件了与湖北省上海市华南海鲜批发产品有关的人群当中的肺癌就医。
2020年1月底7日，当近现代公共卫生新加坡政府推定该簇与新型冠状感染2019-nCoV有关。尽管早先新闻报道的就医与上海市海鲜产品的暴露有关，但显然的毒理学统计数据此问道明，正要发生2019-nCoV人际扩散。
截至2020年1月底30日，在大概21个第三世界/地区份文件了9976则有就医，之以外2020年1月底20日新闻报道的澳大利亚首创就医的2019-nCoV病菌就医。
全都球区域内正要同步进行深入调查，以更高地了解扩散实时和诊疗病因区域。本份文件描述了在澳大利亚推定的首创2019-nCoV病菌的毒理学和诊疗外观上。
案则有份文件
2020年1月底19日，一名35岁的青年组用到在华盛顿的县怀特霍米什县的一家急诊诊所，有4天的肿胀和主观排便困难史。病人到诊所健康检查时，在候诊室戴上；大罩。等待约20分钟后，他被带到健康检查室拒绝接受了提供者的评估。
他暗示，他在当近现代上海探望家人才将1月底15日赶回华盛顿的县。该病人此表示，他已从澳大利亚病因压制与防范当一个中心（CDC）收到有关当近现代新型冠状感染暴发的身体健康警报，由于他的副作用和早先的之旅，他最终去看医师。
由此可知1-2020年1月底19日（病因第4天）的后前胸和前端胸片
除了高三酸酯血症的家族史以外，该病人还是其他身体健康的不吸烟者。体格健康检查注意到病人排便环境热气时，体温为37.2°C，血压为134/87 mm Hg，节律为每分钟110次，排便频率为每分钟16次，氧原色为96％。肺听诊推断有哮喘，并同步进行了胸片健康检查，据新闻报道没注意到异常（由此可知1）。
肺炎和乙型肺炎的慢速核分裂酸扩增测试者（NAAT）为形容词。授予了钝咽拭子新种，并通过NAAT将其去取去检验感染性发炎病原体。
据新闻报道在48天内内对所有测试者的病原体原则上呈圆形形容词，之以外肺炎和乙型肺炎，副肺炎，发炎合胞感染，钝感染，腺感染和已知会导致人类所病因的四种常见冠状感染株（HKU1，NL63、229E和OC43） ）。根据病人的之旅历史，立即通告大都和的县当地政府。华盛顿公共卫生部门与应急护理人员诊疗医师一起通告了CDC应急行动当一个中心。
尽管该病人份文件问道他并未去过华南海鲜产品，也并未份文件在去当近现代之旅此后与年老者有任何交谈，但病因防范压制当一个中心的工作人员同意有必要根据显然的病因防范压制当一个中心对病人同步进行2019-nCoV测试者。
根据CDC指南利用了8个新种，之以外人体内，钝咽和；大咽拭子新种。新种挖掘借助于后，病人被去取往父母亲分开，并由当地当地政府同步进行积极几率评估。
2020年1月底20日，病因防范压制当一个中心（CDC）推定病人的钝咽和；大咽拭子通过即时逆转录酶-聚合酶链反应（rRT-PCR）检验为2019-nCoV无副作用。
在病因防范压制当一个中心的隐喻专家，的县和大都公共卫生地方官吏，应急医疗服务以及该医院为首和工作人员的配合下，病人被去取往普罗维登斯地区医疗当一个中心的热气分开病房同步进行诊疗观察，并跟随病因防范压制当一个中心的医护有关交谈，飞沫和空当中防护措施的建议，并带有护目镜。
中风时病人份文件持续肿胀，有2天的白痴和呕吐史。他份文件问道他并未排便急促或胸痛。新生命病状在正常区域内。体格健康检查注意到病人粘膜湿。其余的健康检查往往不突出。
中风后，病人拒绝接受了支持以外科手术，之以外2再降生理盐水和恩丹以减轻白痴。
由此可知2-根据病因日和当中风日（2020年1月底16日至2020年1月底30日）的副作用和三高体温
在当中风的第2至5天（年老的第6至9天），病人的新生命病状基本保持一致，除了用到间歇性排便困难并伴有心动过速（由此可知2）。病人继续份文件非生产性肿胀，并用到疲乏。
在当中风第二天的早上，病人排便不畅，腹部不适。傍晚有第二次尿稀疏的新闻报道。利用该粪便的样品运用于rRT-PCR测试者，以及其他发炎新种（钝咽和；大咽）和人体内。粪便和两个发炎新种后来原则上通过rRT-PCR检验为2019-nCoV无副作用，而人体内仍为形容词。
在此此后的以外科手术在很大素质上是非典型的。为了同步进行副作用不远处理，病人所需根据所需拒绝接受解热疗法，该疗法之以外每4天内650 mg对乙酰甲醇基酚和每6天内600 mg非甾体。在当中风的前六天，他还因持续肿胀而服用了600毫克愈创醚和约6再降生理盐水。
此表1-诊疗研究团队结果
病人分开各别的物理性质早先仅有允许即时医疗点研究团队测试者；从该医院第3天开始可以同步进行全都肝细胞计数和人体内药理学研究工作。
在该医院第3天和第5天（病因第7天和第9天）的研究团队结果反映借助于白细胞缩减症，轻度血小板缩减症和肌酸激酶低水平再降高（此表1）。此以外，肝功能指标也有所变化：碱性磷酸酶（每再降68 U），丙甲醇酸甲醇基转移酶（每再降105 U），赖甲醇酸甲醇基转移酶（每再降77 U）和乳酸激酶（每再降465 U）的低水平共五：在当中风的第5天所有再降高。鉴于病人反复排便困难，在第4天授予血液培养；迄今为止，这些都并未增长。
由此可知3-2020年1月底22日（颈部第7天，该医院第3天）的后前胸和前端胸片
由此可知4-2020年1月底24日（颈部第5天，该医院第9天）的后前胸X线片
据新闻报道，在该医院第3天（年老第7天）外景的颈部X光片没推断显现出来或异常迹象（由此可知3）。
但是，从该医院第5天傍晚（年老第9天）傍晚同步进行的第二次颈部X光片健康检查推断，左肺下叶有肺癌（由此可知4）。
这些医学影像注意到与从该医院第5天傍晚开始的排便稳定状态变化亦然，当时病人在排便周围热气时通过节律血氧原色测定的血氧原色系数降至90％。
在第6天，病人开始拒绝接受足量氢气，该氢气由钝腹腔以每分钟2再降的速度输去取。考虑到诊疗此表现的变化和对该医院授予性肺癌的关注，开始用作万古霉素（1750 mg负荷剂量，然后每8天内制剂1 g）和头孢吡苯酚（每8天内制剂）以外科手术。
由此可知5-前后颈部X光片，2020年1月底26日（病因第十天，该医院第六天）
在该医院第6天（年老第10天），第四次颈部X射线照片推断两个肺当中都有基底薄片混浊，这一注意到与非典型肺癌相符（由此可知5），并且在听诊时在两个肺当中都用到了罗音。鉴于辐射线医学影像注意到，最终给予氢气足量，病人持续排便困难，多个胸部持续无副作用的2019-nCoV RNA无副作用，以及发此表了与辐射线性肺癌发展一致的严重影响肺癌在该病人当中，诊疗医师富有才智地用作了研究工作性抗感染以外科手术。
制剂瑞德昔韦（一种正要技术开发的新型核分裂苷酸类似物前药）在第7天傍晚开始，但没观察到与输注有关的不良事件。在对甲氧西林耐药的金黄色葡萄球菌同步进行了连续的降钙素原低水平和钝PCR检验后，在第7天傍晚停止使用万古霉素，并在第二天停止使用头孢吡苯酚。
在该医院第8天（年老第12天），病人的诊疗原因得到强化。停止足量氢气，他在排便周围热气时的氧原色系数更高到94％至96％。无论如何的双侧下叶罗音不再存在。他的食欲得到强化，除了间歇性干咳和钝漏以外，他并未副作用。
截至2020年1月底30日，病人仍当中风。他有呼吸困难，除肿胀以外，所有副作用原则上已减轻，肿胀的素质正要降低。
方法
新种挖掘借助于
根据CDC指南授予运用于2019-nCoV病症测试者的诊疗新种。用合成纤维拭子利用了12个钝咽和；大咽拭子新种。
将每个拭子放入包含2至3 ml感染转运介质的单独无菌管当中。将血集在人体内转化管当中，然后根据CDC指南同步进行离心。尿液和粪便新种分别利用在无菌新种容器当中。样品在2°C至8°C之间备份，直到准备运去取至CDC。
在病因的第7、11和12天利用了重复同步进行的2019-nCoV测试者的新种，之以外钝咽和；大咽拭子，人体内以及尿液和粪便试样。
2019-NCOV的病症测试者
用作从公开发表新闻公开发表的感染核分裂苷酸发展而来的rRT-PCR分析法测试者了诊疗新种。与无论如何针对诊治急性排便综合症冠状感染（SARS-CoV）和当中东排便综合症冠状感染（MERS-CoV）的病症方法相近，它较强三个核分裂衣壳基因化学合成和一个无副作用对照化学合成。该测定的描述为RRT-PCR面板引物和探针和核分裂苷酸数据当中可用的CDC研究团队数据博客2019-nCoV上。
性状人类所真核生物计划
2020年1月底7日，当近现代研究工作人员通过澳大利亚国立公共卫生研究工作院GenBank检索和全都球资源共享所有肺炎统计数据积极支持（GISAID）检索资源共享了2019-nCoV的完整基因核分裂苷酸；随后公开发表了有关分开2019-nCoV的份文件。
从rRT-PCR无副作用新种（；大咽和钝咽）当中提取核分裂酸，并在Sanger和下一代人类所真核生物计划平台（Illumina和MinIon）上运用于全都真核生物人类所真核生物计划。用作5.4.6版的Sequencher操作系统（Sanger）启动了核分裂苷酸组装。minimap操作系统，旧版2.17（MinIon）；和freebayes操作系统1.3.1版（MiSeq）。将完整真核生物与可用的2019-nCoV参考核分裂苷酸（GenBank登录号NC_045512.2）同步进行比较。
结果
2019-NCOV的新种测试者
此表2-2019年新型冠状感染（2019-nCoV）的即时逆转录酶-聚合酶-链反应测试者结果
该病人在年老第4秦人授予的初始发炎试样（钝咽拭子和；大咽拭子）在2019-nCoV呈圆形无副作用（此表2）。
尽管病人早先此表现为轻度副作用，但在病因第4天的低循环阈系数（Ct）系数（钝咽新种当中为18至20，；大咽新种当中为21至22）此问道明这些新种当中感染低水平较高。
在病因第7天授予的两个上发炎新种在2019-nCoV仍保持无副作用，之以外钝咽拭子新种当中持续高低水平（Ct系数23至24）。在病因第7天授予的粪便在2019-nCoV当中也呈圆形无副作用（Ct系数为36至38）。两种挖掘借助于日期的人体内试样在2019-nCoV原则上为形容词。
在病因第11天和第12天授予的钝咽和；大咽新种推断借助于感染低水平下滑的趋势。
；大咽新种在年老第12天的2019-nCoV测试者呈圆形形容词。在这些日期授予的人体内的rRT-PCR结果仍没定。
性状人类所真核生物计划
；大咽和钝咽新种的完整真核生物核分裂苷酸彼此大致相同，并且与其他可用的2019-nCoV核分裂苷酸仍然大致相同。
该病人的感染与2019-nCoV参考核分裂苷酸（NC_045512.2）在开放学习者框8不远处仅有有3个核分裂苷酸和1个不同。该核分裂苷酸可通过GenBank授予（登录号MN985325）。
讨论区
我们关于澳大利亚首创2019-nCoV就医就医的份文件阐明这一新兴病因的几个上都尚没无论如何都了解，之以外扩散实时和诊疗病因的全都部区域。
我们的就医病人曾去过当近现代上海，但份文件问道他在上海此后并未去过海鲜批发产品或医疗机构，也并未得病的交谈。尽管他的2019-nCoV病菌的来源尚不吻合，但已公开发表新闻了人对人扩散的证据。
到2020年1月底30日，尚没注意到与此就医相关的2019-nCoV继发就医，但仍在密切监视下。
在病因的第4天和第7天从上发炎新种当中检验到较强低Ct系数的2019-nCoV RNA，此问道明感染量高且较强扩散潜力。
系数得特别注意的是，我们还在病人年老第7天利用的粪便试样当中检验到了2019-nCoV RNA。尽管我们就医病人的人体内新种反复用到2019-nCoV形容词，但在当近现代诊治病人的血液当中仍检验到感染RNA。然而，肺以外检验感染RNA并不一定显然存在传染性感染，目前尚不吻合在发炎以外部检验感染RNA的诊疗意义。
目前，我们对2019-nCoV病菌的诊疗区域的了解非常有限。在当近现代，仍然新闻报道了诸如严重影响的肺癌，排便衰竭，急性排便窘迫综合症（ARDS）和心脏损伤等并发症，之以外致命的负面影响。然而，重要的是要特别注意，这些就医是根据其肺癌病症确认的，因此或许会使份文件偏向更严重影响的结果。
我们的就医病人早先此表现为轻度肿胀和低度间歇性排便困难，在年老的第4天并未颈部X光健康检查的肺癌迹象，而在年老第9天发展为肺癌之前，这些非特异性病状和副作用在20世纪在诊疗上，2019-nCoV病菌的诊疗过程或许与许多其他常见传染病并未突出不同之处，特别是在冬季发炎感染季节。
另以外，本就医病人在病因的第9天发展为肺癌的时机与近期排便困难的心脏病（得病后当中位数为8天）一致。尽管根据病人的诊疗原因好转最终确实给予remdesivir喜乐的用作，但仍所需同步进行随机对照试验以确认remdesivir和任何其他研究工作抑制剂以外科手术2019-nCoV病菌的安全都性和有效性。
我们份文件了澳大利亚首创份文件的2019-nCoV病菌病人的诊疗外观上。
该就医的关键上都之以外病人在学习者有关暴发的公共公共卫生无视后最终寻求医疗；由当地医疗服务提供者推定病人早先到上海的之旅历史，随后在当地，的县和联邦公共公共卫生地方官吏之间同步进行密切合作；并确认或许的2019-nCoV病菌，从而可以急剧分开病人并随后对2019-nCoV同步进行研究团队推定，并允许病人中风进一步评估和政府机构。
该就医份文件特别强调了诊疗医师对于任何用到急性病因副作用的就医病人，要概括借助于早先的之旅经历或交谈家族史的普遍性，为了适当确实识别和及早分开或许遭遇2019-nCoV病菌几率的病人，并帮助缩减进一步的扩散。
最后，本份文件特别强调所需确认与2019-nCoV病菌相关的诊疗病因，得病机理和感染脱落持续时间的
全都部区域和自然现象历史，以为诊疗政府机构和公共公共卫生决策提供依据。
都有为英文版
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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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