摘要
在近现代上海开始的新的型冠状传染（2019-nCoV）一触即发快速蔓延，都已在多个国家所复发。我们份文件了在加拿大断定的未有2019-nCoV传染登革热，并叙述了该登革热的鉴定，复发，临床研究操作过程和行政，有数病征在病况第9天平庸为结核反应病时的最初轻度关节炎状。
该犯罪行为忽略了临床研究医师与以外，一个州和美国联邦各级心理卫生中共政府二者之间密切协作的层面，以及必须短时间内的传播与这种新的发传染病征的诊疗有关的临床研究资讯的需求。
2019年12月末31日，近现代份文件了与岳阳市上海市粤东鱿鱼批发市场需求有关的人群之前的结核反应病登革热。
2020年1月末7日，近现代卫生中共政府断定该簇与新的型冠状传染2019-nCoV有关。尽管最初华盛顿邮报的登革热与上海市鱿鱼市场需求的暴露有关，但当前的流行病学数据指出，打算发生2019-nCoV人际的传播。
截至2020年1月末30日，在至少21个国家所/地区份文件了9976例登革热，有数2020年1月末20日华盛顿邮报的加拿大未有复发的2019-nCoV传染登革热。
世界各地以内外打算顺利完成调查报告，以越来越好地知晓的传播静态和临床研究病因全域。本份文件叙述了在加拿大断定的未有2019-nCoV传染的流行病学和临床研究形态。
犯罪行为份文件
2020年1月末19日，一名35岁的男子显露现在华盛顿一个州斯诺霍米孟加拉国的一家急诊诊所，有4天的肿胀和主观发作巨著。病人到诊所核对时，在候诊室戴上侧罩。等待约20分钟后，他被带入核对室拒绝接受了提供者的分析。
他透露，他在近现代上海探视全家人后于1月末15日留在华盛顿一个州。该病征表示，他已从加拿大病因控制与防止之前心（CDC）收到有关近现代新的型冠状传染越来越为严重影响的卫生香港天文台，由于他的关节炎状和众所周知的漫游，他同意去看医师。
左图1-2020年1月末19日（病因第4天）的后腹部和后侧胸片
除了高三酸酯血关节炎的病巨著内外，该病征还是其他卫生的不吸烟者。体格核对注意到病征痉挛环境氢气时，新的陈代谢为37.2°C，血压为134/87 mm Hg，跳动为每分钟110次，痉挛频率为每分钟16次，氮饱和度为96％。胸腔听诊结果显示有支气管炎，并顺利完成了胸片核对，据华盛顿邮报未注意到异常（左图1）。
甲型和同型甲型的短时间内核反应酸扩增检验（NAAT）为形态性。取得了鼻咽拭子遗骸，并通过NAAT将其送去核对传染性侧腔病原体。
据华盛顿邮报在48每隔内对所有检验的病原体皆呈形态性，有数甲型和同型甲型，副甲型，侧腔合胞传染，鼻传染，腺传染和已知会导致生命病因的四种类似于冠状传染株（HKU1，NL63、229E和OC43） ）。根据病征的漫游历巨著文化，立即知会以外和一个州医务人员。华盛顿卫生部与救护车诊疗临床研究医师两兄弟知会了CDC救护车行动之前心。
尽管该病征份文件话说他从未去过粤东鱿鱼市场需求，也从未份文件在去近现代漫游期间与染病者有任何注意到，但病因防止控制之前心的工作人员同意有必要根据当前的病因防止控制之前心对病征顺利完成2019-nCoV检验。
根据CDC须知利用了8个遗骸，有数肝脏，鼻咽和侧咽拭子遗骸。遗骸搜集后，病征被送至家庭强制，并由当地医务人员顺利完成积极监控。
2020年1月末20日，病因防止控制之前心（CDC）断定病征的鼻咽和侧咽拭子通过动态之前国地区-RNA不可逆（rRT-PCR）核对为2019-nCoV形态性。
在病因防止控制之前心的主题专家学者，一个州和以外卫生官员，救护车医疗服务以及该医院领导和工作人员的配合下，病征被送至新的泽西地区医疗之前心的氢气强制病房顺利完成临床研究观察，并跟随病因防止控制之前心的伤者有关注意到，飞沫和空之前防护安全措施的建言，并近似于护目镜。
入院时病征份文件持续性肿胀，有2天的恶心和抽搐巨著。他份文件话说他从未痉挛急促或胸痛。生命体征在较长时间以内外。体格核对注意到病征毛细血管干燥。其余的核对通常不显著。
入院后，病征拒绝接受了赞同病人，有数2累进生理盐水和恩丹以加剧恶心。
左图2-根据病因日和就医日（2020年1月末16日至2020年1月末30日）的关节炎状和三高新的陈代谢
在就医的第2至5天（染病的第6至9天），病征的生命体征基本保持稳定，除了显露现断续发作并会有心动过速（左图2）。病征之后份文件非生产性肿胀，并显露现虚弱。
在就医第二天的下午，病征排便通畅，腹部不适。早上有第二次大便稀疏的华盛顿邮报。利用该泥土的样本使用rRT-PCR检验，以及其他侧腔遗骸（鼻咽和侧咽）和肝脏。泥土和两个侧腔遗骸后来皆通过rRT-PCR核对为2019-nCoV形态性，而肝脏仍为形态性。
此前的病人在不小层面上是经常性的。为了顺利完成关节炎状处理，病征必须根据必须拒绝接受良药医学上，该医学上有数每4每隔650 mg药物和每6每隔600 mg布洛芬。在就医的前六天，他还因持续性肿胀而服食了600毫克少创醚和约6累进生理盐水。
表1-临床研究研究所结果
病征强制短剧的性质最初仅必需短时间医疗点研究所检验；从该医院第3天开始可以顺利完成全红细胞计数和肝脏物理化学研究。
在该医院第3天和第5天（病因第7天和第9天）的研究所结果看出显露白细胞降低关节炎，轻度骨髓降低关节炎和肌酸激酶技术水平累进高（表1）。此内外，肾功能高效率也有所改变：极性磷酸酶（每累进68 U），羧酸氨基转移酶（每累进105 U），天冬氨酸氨基转移酶（每累进77 U）和脂肪酸脱氢酶（每累进465 U）的技术水平分别为：在就医的第5天所有累进高。鉴于病征反复发作，在第4天取得肠道培养；迄今为止，这些都从未增加。
左图3-2020年1月末22日（臀部第7天，该医院第3天）的后腹部和后侧胸片
左图4-2020年1月末24日（臀部第5天，该医院第9天）的后腹部X线片
据华盛顿邮报，在该医院第3天（染病第7天）拍摄的臀部X光片未结果显示伴生或异常确实（左图3）。
但是，从该医院第5天早上（染病第9天）早上顺利完成的第二次臀部X光片核对结果显示，左肺下叶有结核反应病（左图4）。
这些技术手段注意到与从该医院第5天早上开始的痉挛状态改变亦然，最初病征在痉挛外围氢气时通过跳动血氮饱和度测出的血氮饱和度系数降到90％。
在第6天，病征开始拒绝接受说明一氮化碳，该一氮化碳由鼻导管以每分钟2累进的速度输运。考虑到临床研究平庸的改变和对该医院取得性结核反应病的关心，开始适用抗病毒（1750 mg负荷施打，然后每8每隔本品1 g）和青霉素吡肟（每8每隔本品）病人。
左图5-前后臀部X光片，2020年1月末26日（病因第十天，该医院第六天）
在该医院第6天（染病第10天），第四次臀部X射线照片结果显示两个肺之前都有基底条状混浊，这一注意到与非典型结核反应病十分相似（左图5），并且在听诊时在两个肺之前都显露现了罗音。鉴于放射线技术手段注意到，同意赋予一氮化碳说明，病征持续性发作，多个部位持续性形态性的2019-nCoV RNA形态性，以及登载了与放射线性结核反应病工业发展一致的严重影响结核反应病在该病征之前，临床研究医师富有同情心地适用了学术性抗传染病人。
本品艾伦昔韦（一种打算合作开发的新的型氨基酸类似物前药）在第7天早上开始，但未观察到与输注有关的不良政治事件。在对甲氮西林耐药的粉红色葡萄球菌顺利完成了近十年的降钙素原技术水平和鼻PCR核对后，在第7天早上停用抗病毒，并在第二天停用青霉素吡肟。
在该医院第8天（染病第12天），病征的临床研究情况取得改善。停顿说明一氮化碳，他在痉挛外围氢气时的氮饱和度系数全面提高到94％至96％。先前的双侧下叶罗音不再存在。他的食欲取得改善，除了断续干咳和鼻漏内外，他从未关节炎状。
截至2020年1月末30日，病征仍就医。他有发热，除肿胀内外，所有关节炎状皆已加剧，肿胀的层面打算大大降低。
方法
遗骸搜集
根据CDC须知取得使用2019-nCoV复发检验的临床研究遗骸。用合成纤维拭子利用了12个鼻咽和侧咽拭子遗骸。
将每个拭子插入包涵2至3 ml传染河运介质的另行冷藏管之前。将血集在肝脏分离管之前，然后根据CDC须知顺利完成离心。体液和泥土遗骸分别利用在冷藏遗骸罐之前。样本在2°C至8°C二者之间储存，直到做好运送至CDC。
在病因的第7、11和12天利用了重复顺利完成的2019-nCoV检验的遗骸，有数鼻咽和侧咽拭子，肝脏以及体液和泥土采样。
2019-NCOV的复发检验
适用从官方网站面世的传染遗传物质工业发展而来的rRT-PCR系统性检验了临床研究遗骸。与先前针对重关节炎急性痉挛综合征冠状传染（SARS-CoV）和之前东痉挛综合征冠状传染（MERS-CoV）的复发方法雷同，它具三个核反应衣壳遗传物质遗传物质和一个形态性对照遗传物质。该测出的叙述为RRT-PCR面板聚合酶和蛋白质和遗传物质资讯之前举例来说的CDC研究所资讯网站2019-nCoV上。
遗传DNA
2020年1月末7日，近现代研究人员通过加拿大国立卫生研究中心GenBank数据库和世界各地共享所有甲型数据倡议（GISAID）数据库共享了2019-nCoV的清晰遗传物质遗传物质；随后面世了有关强制2019-nCoV的份文件。
从rRT-PCR形态性遗骸（侧咽和鼻咽）之前提取核反应酸，并在Sanger和新的世代DNA平台（Illumina和MinIon）上使用全遗传物质DNA。适用5.4.6初版的Sequencher的软件（Sanger）完成了遗传物质装配。minimap的软件，初版本2.17（MinIon）；和freebayes的软件1.3.1初版（MiSeq）。将清晰遗传物质与举例来说的2019-nCoV简介遗传物质（GenBank登录号NC_045512.2）顺利完成比较。
结果
2019-NCOV的遗骸检验
表2-2019年新的型冠状传染（2019-nCoV）的动态之前国地区-RNA-不可逆检验结果
该病征在染病第4天时取得的初始侧腔采样（鼻咽拭子和侧咽拭子）在2019-nCoV呈形态性（表2）。
尽管病征最初平庸为轻度关节炎状，但在病因第4天的低尿素阈系数（Ct）系数（鼻咽遗骸之前为18至20，侧咽遗骸之前为21至22）指出这些遗骸之前传染技术水平较低。
在病因第7天取得的两个上侧腔遗骸在2019-nCoV仍保持形态性，有数鼻咽拭子遗骸之前持续性高技术水平（Ct系数23至24）。在病因第7天取得的泥土在2019-nCoV之前也呈形态性（Ct系数为36至38）。两种搜集日期的肝脏采样在2019-nCoV皆为形态性。
在病因第11天和第12天取得的鼻咽和侧咽遗骸结果显示显露传染技术水平增高的趋向。
侧咽遗骸在染病第12天的2019-nCoV检验呈形态性。在这些日期取得的肝脏的rRT-PCR结果仍完全一致。
遗传DNA
侧咽和鼻咽遗骸的清晰遗传物质遗传物质彼此相异，并且与其他举例来说的2019-nCoV遗传物质几乎相异。
该病征的传染与2019-nCoV简介遗传物质（NC_045512.2）在全站选读框8处仅有3个氨基酸和1个并不相异。该遗传物质可通过GenBank取得（登录号MN985325）。
专页
我们关于加拿大未有2019-nCoV复发登革热的份文件话说明了这一新的兴病因的几个上都未完全知晓，有数的传播静态和临床研究病因的全部全域。
我们的登革热病征曾去过近现代上海，但份文件话说他在上海期间从未去过鱿鱼批发市场需求或医疗系统，也从未生病的注意到。尽管他的2019-nCoV传染的来源尚不似乎，但已官方网站了人对人的传播的确实。
到2020年1月末30日，未注意到与此登革热之内外的2019-nCoV继患登革热，但仍在密切监视下。
在病因的第4天和第7天从上侧腔遗骸之前核对到具低Ct系数的2019-nCoV RNA，指出传染乘载高且具的传播潜力。
系数得注意的是，我们还在病征染病第7天利用的泥土采样之前核对到了2019-nCoV RNA。尽管我们登革热病征的肝脏遗骸反复显露现2019-nCoV形态性，但在近现代重关节炎病征的肠道之前仍核对到传染RNA。然而，肺内外核对传染RNA并不一定意味着存在传染性传染，现阶段尚不似乎在侧腔内结构上核对传染RNA的临床研究意义。
现阶段，我们对2019-nCoV传染的临床研究全域的知晓非常有限。在近现代，已经华盛顿邮报了诸如严重影响的结核反应病，痉挛衰竭，急性痉挛窘迫综合征（ARDS）和心脏损伤等并发关节炎，有数致命的后果。然而，重要的是要注意，这些登革热是根据其结核反应病复发确切的，因此不必要使份文件偏向越来越严重影响的结果。
我们的登革热病征最初平庸为轻度肿胀和低度断续发作，在染病的第4天从未臀部X光核对的结核反应病确实，而在染病第9天工业发展为结核反应病之前，这些非甲基化体征和关节炎状在早期在临床研究上，2019-nCoV传染的临床研究操作过程可能与许多其他类似于传染病从未显著差异，尤其是在冬季侧腔传染季节。
另内外，本登革热病征在病因的第9天工业发展为结核反应病的及早与现阶段痉挛困难的发作（染病后之前位数为8天）一致。尽管根据病征的临床研究情况转好同意是否是赋予remdesivir慈悲的适用，但仍必须顺利完成随机对照次测试以确切remdesivir和任何其他研究药物病人2019-nCoV传染的安全性和精确性。
我们份文件了加拿大未有份文件的2019-nCoV传染病征的临床研究形态。
该登革热的关键上都有数病征在选读有关越来越为严重影响的心理卫生忠告后同意寻求医疗；由当地医疗服务提供者断定病征众所周知到上海的漫游历巨著文化，随后在当地，一个州和美国联邦心理卫生官员二者之间顺利完成协调；并确切可能的2019-nCoV传染，从而可以快速强制病征并随后对2019-nCoV顺利完成研究所断定，并必需病征入院全面分析和行政。
该登革热份文件忽略了临床研究医师对于任何显露现急性病因关节炎状的就医病征，要总结显露众所周知的漫游境况或注意到病巨著的层面，为了确保应该标记和立刻强制可能面临2019-nCoV传染风险的病征，并协助降低全面的的传播。
最后，本份文件忽略必须确切与2019-nCoV传染之内外的临床研究病因，染病机理和传染脱落持续性时间的
全部全域和自然历巨著文化，以为临床研究行政和心理卫生决策提供依据。
以下为英文初版
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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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