概述
在华南地区内陆地区宜昌开始的新型冠状菌株（2019-nCoV）愈演愈烈快速蔓延，现已在多个国家肺癌。我们通报了在American断定的仍没有2019-nCoV感染者患者，并叙述了该患者的鉴定，病人，以外科反复和管理，以以外病症在病情恶化第9天平庸为肺癌时的在此之后轻度呕吐。
该案实有强调了以外科药剂师与地方，和州和合众国各级公共环境卫生当局两者之间密切协作的重要性，以及能够快速传递与这种新发感染者病症的护理人员有关的以外科个人信息的需求。
2019年12年底31日，华南地区内陆地区通报了与岳阳市岳阳市华南地区紫菜批发零售商有关的人群中会的肺癌患者。
2020年1年底7日，华南地区内陆地区环境卫生当局断定该簇与新型冠状菌株2019-nCoV有关。尽管在此之后华盛顿邮报的患者与岳阳市紫菜零售商的暴露有关，但意味著的流行病学信息表格明，正在发生2019-nCoV人际传递。
截至2020年1年底30日，在至少21个国家/内陆地区通报了9976实有患者，以以外2020年1年底20日华盛顿邮报的American仍没有肺癌的2019-nCoV感染者患者。
全世界各内陆地区正在顺利进行调查，以更好地认识到传递实时和以外科营养不良范围。本通报叙述了在American断定的仍没有2019-nCoV感染者的流行病学和以外科基本特征。
案实有通报
2020年1年底19日，一名35岁的男子显现出有在华盛顿和州怀特霍米孟加拉国的一家急诊医疗机构，有4天的肠胃和主观高烧史。病人到医疗机构体检时，在候诊室戴上口以外罩。才会平均20分钟后，他被带到体检室给与了提供者的评核。
他透露，他在华南地区内陆地区宜昌陪伴家人时为1年底15日返回华盛顿和州。该病症表格示，他已从American营养不良控制与卫生中会心（CDC）收到有关华南地区内陆地区新型冠状菌株暴发的健康强台风，由于他的呕吐和除此以以外的环游世界，他尽快去看药剂师。
布1-2020年1年底19日（营养不良第4天）的后肩部和以外侧胸片
除了高三酸酯血症的家族史以外，该病症还是其他健康的不成年人。体格体检见到病症排尿环境湿气时，心率为37.2°C，体温为134/87 mm Hg，脉搏为每分钟110次，排尿频率为每分钟16次，硫一般来说是为96％。心脏听诊标示出有有脑膜炎，并顺利进行了胸片体检，据华盛顿邮报没见到异常（布1）。
的大型和丙型疫情的快速蛋白质扩增次测试（NAAT）为比如说是。拿到了鼻咽拭子骨骼，并通过NAAT将其送到去探针菌株性排尿道免疫。
据华盛顿邮报在48不间断内对所有次测试的免疫均圆形比如说是，以以外的大型和丙型疫情，副疫情，排尿道合胞菌株，鼻菌株，腺菌株和已知就会导致人类营养不良的四种少用冠状菌株株（HKU1，NL63、229E和OC43） ）。根据病症的环游世界演进史，立即通告地方和和州环境政务院门。华盛顿环境政务院与紧急护理人员以外科药剂师一起通告了CDC紧急行动中会心。
尽管该病症通报说是他没有去过华南地区紫菜零售商，也没有通报在去华南地区内陆地区环游世界期间与卧床者有任何带入，但营养不良卫生指挥中会心的现场同意有必要根据意味著的营养不良卫生指挥中会心对病症顺利进行2019-nCoV次测试。
根据CDC读物收集了8个骨骼，以以外血浆，鼻咽和口以外咽拭子骨骼。骨骼采集后，病症被送到往家庭受控，并由当地环境政务院门顺利进行积极监测。
2020年1年底20日，营养不良卫生指挥中会心（CDC）断定病症的鼻咽和口以外咽拭子通过实时逆转录酶-一氧化氮链反应（rRT-PCR）探针为2019-nCoV比如说是。
在营养不良卫生指挥中会心的主题专家，和州和地方环境卫生官员，紧急医疗服务以及养老院领导和现场的配合下，病症被送到往普罗维登斯内陆地区医疗中会心的湿气受控病房顺利进行以外科观察，并跟随营养不良卫生指挥中会心的医护管理人员有关带入，飞沫和空中会防护举措的建议，并略带护目镜。
病倒时病症通报过后肠胃，有2天的焦虑和呕吐史。他通报说是他没有排尿急促或胸痛。永生病状在正常各内陆地区。体格体检见到病症粘膜干燥。其余的体检有时候不相对来说是。
病倒后，病症给与了支持疗程，以以外2升生理盐水和恩丹以缓解焦虑。
布2-根据营养不良日和开刀日（2020年1年底16日至2020年1年底30日）的呕吐和最高者心率
在开刀的第2至5天（卧床的第6至9天），病症的永生病状理论上保持稳定，除了显现出有但会高烧并伴有心动过速（布2）。病症继续通报非生产性肠胃，并显现出有疲惫。
在开刀第二天的下午，病症进食通畅，腹部不适。凌晨有第二次饱稀疏的华盛顿邮报。收集该老鼠的探针应用于rRT-PCR次测试，以及其他排尿道骨骼（鼻咽和口以外咽）和血浆。老鼠和两个排尿道骨骼后来均通过rRT-PCR探针为2019-nCoV比如说是，而血浆仍为比如说是。
在此期间的疗程在很大程度上是自我管理的。为了顺利进行呕吐处理，病症能够根据能够给与解毒疗法，该疗法以以外每4不间断650 mg对乙酰氨基酚和每6不间断600 mg不良反应。在开刀的前六天，他还因过后肠胃而服用了600毫克愈创醚和平均6升生理盐水。
表格1-以外科研究所结果
病症受控单元的物理性质在此之后仅允许须要医疗点研究所次测试；从养老院第3天开始可以顺利进行全病灶可用和血浆无机化学研究课题。
在养老院第3天和第5天（营养不良第7天和第9天）的研究所结果反映出有白细胞减少症，轻度血小板减少症和肌酸激酶水平升高（表格1）。此以外，败血症指标也有所叠加：碱性磷酸酶（每升68 U），丙氨酸氨基转移酶（每升105 U），谷胱甘肽氨基转移酶（每升77 U）和乳酸脱氢酶（每升465 U）的水平分别为：在开刀的第5天所有升高。鉴于病症反复高烧，在第4天拿到血液培养；迄今为止，这些都没有激增。
布3-2020年1年底22日（腹部第7天，养老院第3天）的后肩部和以外侧胸片
布4-2020年1年底24日（腹部第5天，养老院第9天）的后肩部X线片
据华盛顿邮报，在养老院第3天（卧床第7天）拍摄的腹部X光片没标示出有浸润或异常迹象（布3）。
但是，从养老院第5天凌晨（卧床第9天）凌晨顺利进行的第二次腹部X光片体检标示出有，左肺下叶有肺癌（布4）。
这些影像学见到与从养老院第5天凌晨开始的排尿状态叠加相吻合，当年病症在排尿周围湿气时通过脉搏血硫一般来说是测定的血硫一般来说是值减至90％。
在第6天，病症开始给与多余硫气，该硫气由鼻导管以每分钟2升的速度输送到。考虑到以外科平庸的叠加和对养老院拿到性肺癌的关注，开始应用于万古霉素（1750 mg负荷剂量，然后每8不间断静脉注射1 g）和嗪爆冷肟（每8不间断静脉注射）疗程。
布5-前后腹部X光片，2020年1年底26日（营养不良第十天，养老院第六天）
在养老院第6天（卧床第10天），第四次腹部X射线照片标示出有两个肺中会都有连续性大块较深，这一见到与非典型肺癌相符（布5），并且在听诊时在两个肺中会都显现出有了罗音。鉴于辐射影像学见到，尽快给与硫气多余，病症过后高烧，多个部位过后比如说是的2019-nCoV RNA比如说是，以及发表格了与辐射性肺癌演进保持一致的更为严重肺癌在该病症中会，以外科药剂师优雅真诚地应用于了研究课题性抗菌株疗程。
静脉注射瑞德昔韦（一种正在开发的新型质子苷酸类似物前药）在第7天凌晨开始，但没观察到与用药有关的不良重大事件。在对的大硫西林耐药的金黄色免疫顺利进行了连续的降钙素原水平和鼻PCR探针后，在第7天凌晨撤除万古霉素，并在第二天撤除嗪爆冷肟。
在养老院第8天（卧床第12天），病症的以外科情形获取改善。停顿多余硫气，他在排尿周围湿气时的硫一般来说是值提高到94％至96％。更必要性的双侧下叶罗音依然实际上。他的食欲获取改善，除了但会干咳和鼻漏以外，他没有呕吐。
截至2020年1年底30日，病症仍开刀。他有发热，除肠胃以外，所有呕吐均已缓解，肠胃的程度正在减轻。
方法
骨骼采集
根据CDC读物拿到应用于2019-nCoV病人次测试的以外科骨骼。用化学纤维拭子收集了12个鼻咽和口以外咽拭子骨骼。
将每个拭子插入包含2至3 ml菌株水路介质的单独新鲜将水。将血集在血浆分离将水，然后根据CDC读物顺利进行离心。尿液和老鼠骨骼分别收集在新鲜骨骼器皿中会。探针在2°C至8°C两者之间可用，直到事先运往到至CDC。
在营养不良的第7、11和12天收集了重复顺利进行的2019-nCoV次测试的骨骼，以以外鼻咽和口以外咽拭子，血浆以及尿液和老鼠样本。
2019-NCOV的病人次测试
应用于从公开场合披露的菌株碱基演进而来的rRT-PCR分析法次测试了以外科骨骼。与更必要性针对心绞痛急性排尿病症冠状菌株（SARS-CoV）和地中会海内陆地区排尿病症冠状菌株（MERS-CoV）的病人方法相近，它具三个质子衣壳基因质子酸和一个比如说是对照质子酸。该测定的叙述为RRT-PCR元件引物和探针和碱基个人信息中会可用的CDC研究所个人信息的网站2019-nCoV上。
基因人类序列计划
2020年1年底7日，华南地区内陆地区研究课题管理人员通过American国立环境卫生研究课题院GenBank信息库和全世界共享所有疫情信息倡议（GISAID）信息库共享了2019-nCoV的完整基因碱基；随后披露了有关受控2019-nCoV的通报。
从rRT-PCR比如说是骨骼（口以外咽和鼻咽）中会提取蛋白质，并在Sanger和下一代人类序列计划游戏平台（Illumina和MinIon）上应用于全序列人类序列计划。应用于5.4.6原版的Sequencher该软件（Sanger）完成了碱基组装。minimap该软件，原版本2.17（MinIon）；和freebayes该软件1.3.1原版（MiSeq）。将完整序列与可用的2019-nCoV参见碱基（GenBank登录号NC_045512.2）顺利进行比较。
结果
2019-NCOV的骨骼次测试
表格2-2019年新型冠状菌株（2019-nCoV）的实时逆转录酶-一氧化氮-链反应次测试结果
该病症在卧床第4天时拿到的初始排尿道样本（鼻咽拭子和口以外咽拭子）在2019-nCoV圆形比如说是（表格2）。
尽管病症在此之后平庸为轻度呕吐，但在营养不良第4天的低循环阈值（Ct）值（鼻咽骨骼中会为18至20，口以外咽骨骼中会为21至22）表格明这些骨骼中会菌株水平较高。
在营养不良第7天拿到的两个上排尿道骨骼在2019-nCoV仍保持比如说是，以以外鼻咽拭子骨骼中会过后高水平（Ct值23至24）。在营养不良第7天拿到的老鼠在2019-nCoV中会也圆形比如说是（Ct值为36至38）。两种采集日期的血浆样本在2019-nCoV均为比如说是。
在营养不良第11天和第12天拿到的鼻咽和口以外咽骨骼标示出有出有菌株水平下降的趋势。
口以外咽骨骼在卧床第12天的2019-nCoV次测试圆形比如说是。在这些日期拿到的血浆的rRT-PCR结果仍没定。
基因人类序列计划
口以外咽和鼻咽骨骼的完整序列碱基彼此相异，并且与其他可用的2019-nCoV碱基几乎相异。
该病症的菌株与2019-nCoV参见碱基（NC_045512.2）在开放写出有框8处极少3个质子苷酸和1个不同。该碱基可通过GenBank拿到（登录号MN985325）。
网上
我们关于American仍没有2019-nCoV肺癌患者的通报说是明了这一新兴营养不良的几个方面仍没基本上认识到，以以外传递实时和以外科营养不良的全部范围。
我们的患者病症曾去过华南地区内陆地区宜昌，但通报说是他在宜昌期间没有去过紫菜批发零售商或附属养老院，也没有生病的带入。尽管他的2019-nCoV感染者的来源尚不吻合，但已公开场合了人对人传递的证据。
到2020年1年底30日，仍没见到与此患者相关的2019-nCoV继复发实有，但仍在密切情报搜集下。
在营养不良的第4天和第7天从上排尿道骨骼中会探针到具低Ct值的2019-nCoV RNA，表格明菌株载量高且具传递实用价值。
众所周知的是，我们还在病症卧床第7天收集的老鼠样本中会探针到了2019-nCoV RNA。尽管我们患者病症的血浆骨骼反复显现出有2019-nCoV比如说是，但在华南地区内陆地区心绞痛病症的血液中会仍探针到菌株RNA。然而，肺以外探针菌株RNA并不一定意味着实际上传染性菌株，迄今为止尚不吻合在排尿道以外部探针菌株RNA的以外科意义。
迄今为止，我们对2019-nCoV感染者的以外科范围的认识到非常受限。在华南地区内陆地区，已经华盛顿邮报了诸如更为严重的肺癌，排尿衰竭，急性排尿窘迫病症（ARDS）和心脏损伤等并发症，以以外致命的更为严重后果。然而，重要的是要注意，这些患者是根据其肺癌病人考虑到的，因此意味著就会使通报相反更更为严重的结果。
我们的患者病症在此之后平庸为轻度肠胃和低度但会高烧，在卧床的第4天没有腹部X光体检的肺癌迹象，而在卧床第9天演进为肺癌之前，这些非特异性病状和呕吐在晚期在以外科上，2019-nCoV感染者的以外科反复意味著与许多其他少用狂犬病没有相对来说是区别，相比较是在秋季排尿道菌株季节。
另以外，本患者病症在营养不良的第9天演进为肺癌的时机与全面性排尿困难的发作（复发后$为8天）保持一致。尽管根据病症的以外科情形恶化尽快是否给与remdesivir慈悲的应用于，但仍能够顺利进行以外科实验以考虑到remdesivir和任何其他研究课题药物疗程2019-nCoV感染者的安全性和有效性。
我们通报了American仍没有通报的2019-nCoV感染者病症的以外科基本特征。
该患者的关键方面以以外病症在写出有有关暴发的公共环境卫生警告后尽快设法医疗；由当地医疗服务提供者断定病症除此以以外到宜昌的环游世界演进史，随后在当地，和州和合众国公共环境卫生官员两者之间顺利进行协调；并考虑到意味著的2019-nCoV感染者，从而可以快速受控病症并随后对2019-nCoV顺利进行研究所断定，并允许病症病倒必要性评核和管理。
该患者通报强调了以外科药剂师对于任何显现出有急性营养不良呕吐的就医病症，要总结出有除此以以外的环游世界境遇或带入家族史的重要性，为了确保安全正确比对和幸而受控意味著导致2019-nCoV感染者风险的病症，并为了让减少必要性的传递。
最后，本通报强调能够考虑到与2019-nCoV感染者相关的以外科营养不良，复发机理和菌株裂开过后时间的
全部范围和自然演进史，以为以外科管理和公共环境卫生对政府提供依据。
以下为英文原版
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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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