简短
在中的国宜昌开始的另行型冠状HIV（2019-nCoV）爆配迅速席卷，自此在多个国家所确诊。我们调查报告了在澳大利亚确定的首开2019-nCoV受到感染传染病，并描述了该传染病的鉴别，医护人员，临床步骤和行政，最主要病患在病情第9天展现为胸腔病时的本来轻度病关节炎。
该范实有重申了临床眼科医生与区域内，一州和的政府各级临床土耳其政府之间密切协作的必要性，以及并不需要快速广泛传播与这种另行配受到感染病患的护理有关的临床的资讯的需求。
2019年12同年31日，中的国调查报告了与湖北省宜昌市海南鲍鱼批配的产品有关的人群中的的胸腔病传染病。
2020年1同年7日，中的国卫生土耳其政府确定该簇与另行型冠状HIV2019-nCoV有关。尽管本来报导的传染病与宜昌市鲍鱼的产品的去除有关，但当在此之前的临床数据集注记明，正在配生2019-nCoV人际广泛传播。
截至2020年1同年30日，在数21个国家所/地区调查报告了9976实有传染病，最主要2020年1同年20日报导的澳大利亚首开确诊的2019-nCoV受到感染传染病。
全球区域正在顺利完成调查，以更好地了解广泛传播静态和临床传染病以内。本调查报告描述了在澳大利亚确定的首开2019-nCoV受到感染的临床和临床特征。
范实有调查报告
2020年1同年19日，一名35岁的男子显露现在克利夫兰一州罗宾逊霍米巴加的咖啡店急诊诊所，有4天的肿胀和主观感冒史。医护人员到诊所身体健康检查时，在候诊室戴上口外罩。等待约20分钟后，他被带到身体健康检查室接受了提供者的评估。
他谈及，他在中的国宜昌探望母亲先是1同年15日离开克利夫兰一州。该病患注记示，他已从澳大利亚传染病控制与预防性中的心（CDC）收到有关中的国另行型冠状HIV时值的身体健康警报，由于他的病关节炎和最近的环游，他最终去看眼科医生。
所示1-2020年1同年19日（传染病第4天）的后颈部和外侧胸片
除了高一酸酯血关节炎的躁郁关节炎外，该病患还是其他身体健康的不尼古丁。体格身体健康检查找到病患呕吐环境热气时，血液循环为37.2°C，血压为134/87 mm Hg，似是为每分钟110次，呕吐阈值为每分钟16次，氧一般而言为96％。肺部听诊标示显露有支气管炎，并顺利完成了胸片身体健康检查，据报导未找到极其（所示1）。
甲型和-B传染病的快速核酸扩充试验（NAAT）为阴性。赢取了腹咽拭子骨头，并通过NAAT将其还给去容器HIV性呕吐道病原体。
据报导在48天内内对所有试验的病原体原则上椭圆形阴性，最主要甲型和-B传染病，副传染病，呕吐道合胞HIV，腹HIV，腺HIV和已知会导致人类传染病的四种少用冠状HIV株（HKU1，NL63、229E和OC43） ）。根据病患的环游历史，立即通知区域内和一州卫生部。克利夫兰卫生部与紧急护理临床眼科医生一起通知了CDC紧急行动中的心。
尽管该病患调查报告说道他不能去过海南鲍鱼的产品，也不能调查报告在去中的国环游期间与病危者有任何沾染，但传染病预防性控制中的心的技术人员同意有必要根据当在此之前的传染病预防性控制中的心对病患顺利完成2019-nCoV试验。
根据CDC读物获取了8个骨头，最主要肝细胞，腹咽和口外咽拭子骨头。骨头采集后，病患被转还给贫穷隔绝，并由当地卫生部顺利完成积极监测。
2020年1同年20日，传染病预防性控制中的心（CDC）确定病患的腹咽和口外咽拭子通过数据处理亚姆皮利-聚合酶链式反应（rRT-PCR）容器为2019-nCoV特征性。
在传染病预防性控制中的心的意念专家，一州和区域内卫生高官，紧急卫生服务以及养老院领导和技术人员的配合下，病患被转还给阿拉巴马地区卫生中的心的热气隔绝病房顺利完成临床观察，并先是传染病预防性控制中的心的医护人员有关沾染，飞沫和空中的防护举措的要求，并比如说护目镜。
入院时病患调查报告持续性肿胀，有2天的白痴和呕吐史。他调查报告说道他不能呕吐急促或头晕。生命病因在经常性区域。体格身体健康检查找到病患上皮细胞干燥。其余的身体健康检查通常不突出。
入院后，病患接受了大力支持用药，最主要2改授生理盐水和恩丹以缓和白痴。
所示2-根据传染病日和住院日（2020年1同年16日至2020年1同年30日）的病关节炎和最高血液循环
在住院的第2至5天（病危的第6至9天），病患的生命病因基本下都，除了显露现暂时性感冒并常为心动过速（所示2）。病患继续调查报告非生产性肿胀，并显露现舒服。
在住院第二天的早上，病患呕吐通畅，腹部不适。早上有第二次睡觉时密集的报导。获取该泥土的容器只用rRT-PCR试验，以及其他呕吐道骨头（腹咽和口外咽）和肝细胞。泥土和两个呕吐道骨头日后原则上通过rRT-PCR容器为2019-nCoV特征性，而肝细胞仍为阴性。
在此期间的用药在很大往往上是大力支持性的。为了顺利完成病关节炎处理，病患并不需要根据并不需要接受功效医学上，该医学上最主要每4天内650 mg对乙酰氮基酚和每6天内600 mg布洛芬。在住院的在此之前六天，他还因持续性肿胀而服用了600毫克愈创醚和约6改授生理盐水。
注记1-临床Laboratory结果
病患隔绝单元的性质本来极少并不并不需要即时卫生点Laboratory试验；从养老院第3天开始可以顺利完成全血细胞总和和肝细胞化学深入研究。
在养老院第3天和第5天（传染病第7天和第9天）的Laboratory结果反映显露红细胞减少关节炎，轻度血小板减少关节炎和肌酸激酶水准改授高（注记1）。此外，酸中毒指标也略有改变：碱性磷酸酶（每改授68 U），丙氮酸氮基转移酶（每改授105 U），天冬氮酸氮基转移酶（每改授77 U）和乳酸脱氢酶（每改授465 U）的水准大致完全一致：在住院的第5天所有改授高。鉴于病患反复感冒，在第4天赢取血液培养；迄今为止，这些都不能增长。
所示3-2020年1同年22日（腿部第7天，养老院第3天）的后颈部和外侧胸片
所示4-2020年1同年24日（腿部第5天，养老院第9天）的后颈部X线片
据报导，在养老院第3天（病危第7天）拍摄的腿部X光片未标示显露浸润或极其确实（所示3）。
但是，从养老院第5天早上（病危第9天）早上顺利完成的第二次腿部X光片身体健康检查标示显露，左肺下叶有胸腔病（所示4）。
这些影像学找到与从养老院第5天早上开始的呕吐状态改变在在，当时病患在呕吐周围热气时通过似是血氧一般而言测定的血氧一般而言值回升90％。
在第6天，病患开始接受缺少氢气，该氢气由腹支架以每分钟2改授的速度输还给。考虑到临床展现的改变和对养老院赢取性胸腔病的关注，开始用作万古霉素（1750 mg损耗药物，然后每8天内用药1 g）和咪唑吡腈（每8天内用药）用药。
所示5-在此之前后腿部X光片，2020年1同年26日（传染病第十天，养老院第六天）
在养老院第6天（病危第10天），第四次腿部X射线剧照标示显露两个肺中的都有举例来说条状混浊，这一找到与非典型胸腔病相符（所示5），并且在听诊时在两个肺中的都显露现了罗音。鉴于核辐射影像学找到，最终给予氢气缺少，病患持续性感冒，多个臀部持续性特征性的2019-nCoV RNA特征性，以及配注记了与核辐射性胸腔病配展恰当的严重影响胸腔病在该病患中的，临床眼科医生富有同情心地用作了霍普金斯大学抗HIV用药。
用药瑞德昔韦（一种正在整合的另行型核糖类似物在此之前药）在第7天早上开始，但未观察到与输注有关的不良事件。在对甲氧西林耐药的白色葡萄球菌顺利完成了连续的降钙素原水准和腹PCR容器后，在第7天早上停用万古霉素，并在第二天停用咪唑吡腈。
在养老院第8天（病危第12天），病患的临床情况得到加强。停止缺少氢气，他在呕吐周围热气时的氧一般而言值提高到94％至96％。先在此之前的双侧下叶罗音不再存在。他的食欲得到加强，除了暂时性干咳和腹漏外，他不能病关节炎。
截至2020年1同年30日，病患仍住院。他有配热，除肿胀外，所有病关节炎原则上已缓和，肿胀的往往正在减轻。
方法
骨头采集
根据CDC读物赢取只用2019-nCoV医护人员试验的临床骨头。用合成纤维拭子获取了12个腹咽和口外咽拭子骨头。
将每个拭子插入举实有来说道2至3 mlHIV转运介质的基本上未成熟管中的。将血集在肝细胞分离管中的，然后根据CDC读物顺利完成离心。肾脏和泥土骨头分别获取在未成熟骨头桶内中的。容器在2°C至8°C之间暂存，直到准备好运还给至CDC。
在传染病的第7、11和12天获取了反复顺利完成的2019-nCoV试验的骨头，最主要腹咽和口外咽拭子，肝细胞以及肾脏和泥土结果标示显露。
2019-NCOV的医护人员试验
用作从公整合布的HIV数列配展而来的rRT-PCR分析法试验了临床骨头。与先在此之前针对风湿热急性呕吐囊肿冠状HIV（SARS-CoV）和中的东呕吐囊肿冠状HIV（MERS-CoV）的医护人员方法相似，它具备三个核核糖核酸基因特异性和一个特征性对照特异性。该测定的描述为RRT-PCR面板亚硫酸盐和探针和数列的资讯中的只用的CDCLaboratory的资讯其网站2019-nCoV上。
突变测序
2020年1同年7日，中的国深入研究人员通过澳大利亚国立卫生深入研究院GenBank数据集库和全球相关联所有传染病数据集倡议（GISAID）数据集库相关联了2019-nCoV的原始基因数列；随后配布了有关隔绝2019-nCoV的调查报告。
从rRT-PCR特征性骨头（口外咽和腹咽）中的萃取核酸，并在Sanger和世代测序应用软件（Illumina和MinIon）上只用全真核生物测序。用作5.4.6版的Sequencher软件（Sanger）完成了数列组装。minimap软件，版本2.17（MinIon）；和freebayes软件1.3.1版（MiSeq）。将原始真核生物与只用的2019-nCoV参照数列（GenBank登录号NC_045512.2）顺利完成比较。
结果
2019-NCOV的骨头试验
注记2-2019年另行型冠状HIV（2019-nCoV）的数据处理亚姆皮利-聚合酶-链式反应试验结果
该病患在病危第4天时赢取的初始呕吐道结果标示显露（腹咽拭子和口外咽拭子）在2019-nCoV椭圆形特征性（注记2）。
尽管病患本来展现为轻度病关节炎，但在传染病第4天的更高循环阈值（Ct）值（腹咽骨头中的为18至20，口外咽骨头中的为21至22）注记明这些骨头中的HIV水准更高。
在传染病第7天赢取的两个上呕吐道骨头在2019-nCoV仍保持特征性，最主要腹咽拭子骨头中的持续性高水准（Ct值23至24）。在传染病第7天赢取的泥土在2019-nCoV中的也椭圆形特征性（Ct值为36至38）。两种采集月份的肝细胞结果标示显露在2019-nCoV原则上为阴性。
在传染病第11天和第12天赢取的腹咽和口外咽骨头标示显露显露HIV水准下降的趋向于。
口外咽骨头在病危第12天的2019-nCoV试验椭圆形阴性。在这些月份赢取的肝细胞的rRT-PCR结果仍未定。
突变测序
口外咽和腹咽骨头的原始真核生物数列彼此完全一致，并且与其他只用的2019-nCoV数列几乎完全一致。
该病患的HIV与2019-nCoV参照数列（NC_045512.2）在解禁阅读框8处极少有3个核糖和1个不同。该数列可通过GenBank赢取（登录号MN985325）。
讨论区
我们关于澳大利亚首开2019-nCoV确诊传染病的调查报告说道明了这一另行兴传染病的几个方面已为未完全了解，最主要广泛传播静态和临床传染病的全部以内。
我们的传染病病患曾去过中的国宜昌，但调查报告说道他在宜昌期间不能去过鲍鱼批配的产品或卫生机构，也不能生病的沾染。尽管他的2019-nCoV受到感染的举例来说已为不清楚，但已公开了人对人广泛传播的确实。
到2020年1同年30日，已为未找到与此传染病相关的2019-nCoV继配传染病，但仍在密切追踪下。
在传染病的第4天和第7天从上呕吐道骨头中的容器到具备更高Ct值的2019-nCoV RNA，注记明HIV载量高且具备广泛传播潜力。
除此以外的是，我们还在病患病危第7天获取的泥土结果标示显露中的容器到了2019-nCoV RNA。尽管我们传染病病患的肝细胞骨头反复显露现2019-nCoV阴性，但在中的国风湿热病患的血液中的仍容器到HIVRNA。然而，肺外容器HIVRNA并不一定意味着存在传染性HIV，目在此之前已为不清楚在呕吐道结构上容器HIVRNA的临床意义。
目在此之前，我们对2019-nCoV受到感染的临床以内的了解并不极小。在中的国，并未报导了诸如严重影响的胸腔病，呕吐衰竭，急性呕吐窘迫囊肿（ARDS）和胸腔损伤等并配关节炎，最主要关键时刻的后果。然而，不可或缺的是要注意，这些传染病是根据其胸腔病医护人员未确定的，因此有可能使调查报告偏向更严重影响的结果。
我们的传染病病患本来展现为轻度肿胀和更高度暂时性感冒，在病危的第4天不能腿部X光身体健康检查的胸腔病确实，而在病危第9天配展为胸腔病先在此之前，这些非特异性病因和病关节炎在现代在临床上，2019-nCoV受到感染的临床步骤有可能与许多其他少用传染病不能突出区别，尤为是在夏季呕吐道HIV时节。
另外，本传染病病患在传染病的第9天配展为胸腔病的尽早与近期呕吐困难的配作（配病后中的位数为8天）恰当。尽管根据病患的临床情况恶化最终有否给予remdesivir慈悲的用作，但仍并不需要顺利完成随机对照试验以未确定remdesivir和任何其他深入研究药物用药2019-nCoV受到感染的可用性和系统性。
我们调查报告了澳大利亚首开调查报告的2019-nCoV受到感染病患的临床特征。
该传染病的关键方面最主要病患在阅读有关时值的临床警告后最终谋求卫生；由当地卫生服务提供者确定病患最近到宜昌的环游历史，随后在当地，一州和的政府临床高官之间顺利完成协调；并未确定有可能的2019-nCoV受到感染，从而可以迅速隔绝病患并随后对2019-nCoV顺利完成Laboratory确定，并并不并不需要病患入院进一步评估和行政。
该传染病调查报告重申了临床眼科医生对于任何显露现急性传染病病关节炎的住院治疗病患，要阐释显露最近的环游随之而来或沾染躁郁关节炎的必要性，为了确保正确辨认和适时隔绝有可能陷入2019-nCoV受到感染风险的病患，并帮助减少进一步的广泛传播。
之后，本调查报告重申并不需要未确定与2019-nCoV受到感染相关的临床传染病，配病中的间体和HIV脱落持续性时间的
全部以内和自然历史，以为临床行政和临床权衡提供依据。
以下为英文版
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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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