内容可
在我国上海开始的新近型SARS大肠杆菌（2019-nCoV）发生随之蔓延，现已在多个国家政府就诊。我们份文件了在新近泽西州说明的月所2019-nCoV受到感染SARS，并阐述了该SARS的鉴定，临床，流行病学处理过程和负责管理，都有综合征状在病状第9天此乏善可陈为心脏病时的原先轻度综合征状。
该犯罪行为务实了流行病学精神科与；也，一州和美国联邦各级预防控制措施新近加坡政府相互间密切联系协作的优越性，以及必需快速传播方式与这种新近发受到感染综合征状的医疗有关的流行病学资讯的需求量。
2019年12月底31日，我国份文件了与常德市上海市珠江三角洲菜式商铺有关的人群之前的心脏病SARS。
2020年1月底7日，我国环境卫生新近加坡政府说明该簇与新近型SARS大肠杆菌2019-nCoV有关。尽管原先华盛顿邮报的SARS与上海市菜式产品的暴露有关，但当前的流行病学数据资料此说明，正在发生2019-nCoV人际传播方式。
截至2020年1月底30日，在仅仅21个国家政府/地区份文件了9976例SARS，都有2020年1月底20日华盛顿邮报的新近泽西州月所就诊的2019-nCoV受到感染SARS。
全世界区域内内正在展开核查，以更好地探究传播方式动态和流行病学哮喘区域内。本份文件阐述了在新近泽西州说明的月所2019-nCoV受到感染的流行病学和流行病学也就是说特征。
犯罪行为份文件
2020年1月底19日，一名35岁的男子显现不止在华盛顿一州斯诺霍米喀什地区的合伙急诊托儿所，有4天的肿胀和客观性感冒通史。病人到托儿所核对时，在候诊室戴上口罩。等待平均20分钟后，他被带到核对室遵从了举例来说的审计。
他披露，他在我国上海看望家人后于1月底15日返回华盛顿一州。该综合征状此问到，他已从新近泽西州哮喘控制与预防控制措施之前心（CDC）收到有关我国新近型SARS大肠杆菌暴发的健康警报系统，由于他的综合征状和值得肯定的旅程，他立即去看精神科。
由此可知1-2020年1月底19日（哮喘第4天）的后颈部和内内侧胸片
除了初中酸酯血综合症的帕金森氏症内外，该综合征状还是其他健康的不吸烟者。体格核对推断不止综合征状新近陈代谢环境液体时，体温为37.2°C，血糖为134/87 mm Hg，颤抖为每分钟110次，新近陈代谢kHz为每分钟16次，磷原色为96％。心脏听诊推断有脑膜炎，并展开了胸片核对，据华盛顿邮报唯未推断不止精神状态（由此可知1）。
流感和流感SARS的快速氢酸扩增次测试（NAAT）为有性。获得了钝咽拭子古生物学家，并通过NAAT将其送去测定大肠杆菌性新近陈代谢道病菌。
据华盛顿邮报在48星期内对所有次测试的病菌之内外椭圆形有性，都有流感和流感SARS，副SARS，新近陈代谢道合胞大肠杆菌，钝大肠杆菌，腺大肠杆菌和已知就会导致生命哮喘的四种少用SARS大肠杆菌株（HKU1，NL63、229E和OC43） ）。根据综合征状的旅程历通史，立即通知；也和一州环境卫生部门。华盛顿环境卫生部与紧急医疗流行病学精神科三人通知了CDC紧急行动之前心。
尽管该综合征状份文件说道他不会去过珠江三角洲菜式产品，也不会份文件在去我国旅程长期与体弱者有任何触及，但哮喘预防控制措施控制之前心的管理医务人员提议有必要根据当前的哮喘预防控制措施控制之前心对综合征状展开2019-nCoV次测试。
根据CDC概要采自了8个古生物学家，都有胰岛素，钝咽和口咽拭子古生物学家。古生物学家采自后，综合征状被送入家庭可避免，并由当地环境卫生部门展开积极测定。
2020年1月底20日，哮喘预防控制措施控制之前心（CDC）说明综合征状的钝咽和口咽拭子通过短时间核苷-催化反应链反应（rRT-PCR）测定为2019-nCoV受到感染性。
在哮喘预防控制措施控制之前心的主题专业人士，一州和；也环境卫生行政官员，紧急医疗服务以及所医院领导和管理医务人员的为了让下，综合征状被送入新近泽西地区医疗之前心的液体可避免病房展开流行病学通过观察，并跟随哮喘预防控制措施控制之前心的医护医务人员有关触及，飞沫和空之前护甲控制措施的提议，并含有护目镜。
入院时综合征状份文件持续性肿胀，有2天的焦虑和腹痛通史。他份文件说道他不会新近陈代谢急促或便秘。新近生命体征在正常区域内内。体格核对推断不止综合征状口腔干燥。其余的核对通常不显着。
入院后，综合征状遵从了支持放射治疗，都有2改授生理盐水和恩丹以缓解焦虑。
由此可知2-根据哮喘日和不止院日（2020年1月底16日至2020年1月底30日）的综合征状和极高体温
在不止院的第2至5天（体弱的第6至9天），综合征状的新近生命体征也就是说发挥作用，除了显现不止出现精神状态感冒并间歇性心动过速（由此可知2）。综合征状再次份文件非生产性肿胀，并显现不止疲倦。
在不止院第二天的上午，综合征状排便利于，腹部不适。清晨有第二次小便稀疏的华盛顿邮报。采自该异味的容器用于rRT-PCR次测试，以及其他新近陈代谢道古生物学家（钝咽和口咽）和胰岛素。异味和两个新近陈代谢道古生物学家后来之内外通过rRT-PCR测定为2019-nCoV受到感染性，而胰岛素仍为有性。
在此长期的放射治疗在很大程度上是非典型的。为了展开综合征状处理，综合征状必需根据必需遵从镇痛疗法，该疗法都有每4星期650 mg对乙酰氨基酚和每6星期600 mg抗炎药。在不止院的前六天，他还因持续性肿胀而施打了600毫克愈创醚和平均6改授生理盐水。
此表1-流行病学研究团队结果
综合征状可避免单元的政治性原先并不少允许短时间医疗点研究团队次测试；从所医院第3天开始可以展开全血细胞计数和胰岛素分析化学科学研究。
在所医院第3天和第5天（哮喘第7天和第9天）的研究团队结果反映不止白细胞增大综合症，轻度白细胞增大综合症和肌酸激酶水准攀改授（此表1）。此内外，肝功能指标也大为变化：酸性磷酸酶（每改授68 U），酰氨基转移酶（每改授105 U），糖类氨基转移酶（每改授77 U）和甘油脱氢酶（每改授465 U）的水准分别为：在不止院的第5天所有攀改授。鉴于综合征状重复感冒，在第4天获得体液培养；现阶段为止，这些都不会增长。
由此可知3-2020年1月底22日（腹部第7天，所医院第3天）的后颈部和内内侧胸片
由此可知4-2020年1月底24日（腹部第5天，所医院第9天）的后颈部X线片
据华盛顿邮报，在所医院第3天（体弱第7天）拍摄的腹部X光片唯未推断显现出来或精神状态似乎（由此可知3）。
但是，从所医院第5天清晨（体弱第9天）清晨展开的第二次腹部X光片核对推断，左肺下叶有心脏病（由此可知4）。
这些CT推断不止与从所医院第5天清晨开始的新近陈代谢平衡状态变化相吻合，当时综合征状在新近陈代谢远处液体时通过颤抖血磷原色定量的血磷原色差值改授至90％。
在第6天，综合征状开始遵从补充磷气，该磷气由钝尿道以每分钟2改授的速度运输。受制于流行病学此乏善可陈的变化和对所医院获得性心脏病的非议，开始常用本品（1750 mg负荷血糖，然后每8星期静脉注射1 g）和吲哚日本杯甲苯（每8星期静脉注射）放射治疗。
由此可知5-前后腹部X光片，2020年1月底26日（哮喘第十天，所医院第六天）
在所医院第6天（体弱第10天），第四次腹部X射线照片推断两个肺之前都有基底面就会变黑，这一推断不止与非差相相比较心脏病十分相似（由此可知5），并且在听诊时在两个肺之前都显现不止了罗音。鉴于核辐射CT推断不止，立即获得磷气补充，综合征状持续性感冒，多个口腔持续性受到感染性的2019-nCoV RNA受到感染性，以及发此表了与核辐射性心脏病其发展一致的相当严重心脏病在该综合征状之前，流行病学精神科充满活力才智地常用了科学研究性抑制剂放射治疗。
静脉注射瑞德昔韦（一种正在开发的新近型氢苷酸类似物前药）在第7天清晨开始，但唯未通过观察到与减压有关的不好事件。在对甲磷芳细菌性的金黄色葡萄球菌展开了连续的降钙素原水准和钝PCR测定后，在第7天清晨停用本品，并在第二天停用吲哚日本杯甲苯。
在所医院第8天（体弱第12天），综合征状的流行病学状况取得改善。停止补充磷气，他在新近陈代谢远处液体时的磷原色差值提高到94％至96％。先前的脊柱下叶罗音才会共存。他的激素取得改善，除了出现精神状态干咳和钝漏内外，他不会综合征状。
截至2020年1月底30日，综合征状仍不止院。他有发热，除肿胀内外，所有综合征状之内外已缓解，肿胀的程度正在减轻。
方法
古生物学家采自
根据CDC概要获得用于2019-nCoV临床次测试的流行病学古生物学家。用合成树脂拭子采自了12个钝咽和口咽拭子古生物学家。
将每个拭子插入相关联2至3 ml大肠杆菌运介质的直接无害循环系统。将血集在胰岛素分离循环系统，然后根据CDC概要展开离心。尿和异味古生物学家分别采自在无害古生物学家容器之前。容器在2°C至8°C相互间贮存，直到做好装载至CDC。
在哮喘的第7、11和12天采自了重复展开的2019-nCoV次测试的古生物学家，都有钝咽和口咽拭子，胰岛素以及尿和异味检验。
2019-NCOV的临床次测试
常用从官方发布的大肠杆菌数列其发展而来的rRT-PCR分析法次测试了流行病学古生物学家。与先前针对重综合症急性新近陈代谢肉瘤SARS大肠杆菌（SARS-CoV）和东欧新近陈代谢肉瘤SARS大肠杆菌（MERS-CoV）的临床方法相似，它不具三个氢核糖体蛋白质贝克曼和一个受到感染性对照贝克曼。该定量的阐述为RRT-PCR基板引物和探针和数列资讯之前需用的CDC研究团队资讯网站2019-nCoV上。
遗传蛋白质分析化学合成
2020年1月底7日，我国科学研究医务人员通过新近泽西州国立环境卫生科学研究室GenBank数据资料源和全世界协作所有SARS数据资料牵头（GISAID）数据资料源协作了2019-nCoV的比较简单蛋白质数列；随后发布了有关可避免2019-nCoV的份文件。
从rRT-PCR受到感染性古生物学家（口咽和钝咽）之前浓缩氢酸，并在Sanger和世代分析化学合成网络服务（Illumina和MinIon）上用于全蛋白质组分析化学合成。常用5.4.6特别版的Sequencher软件（Sanger）完成了数列制造。minimap软件，特别旧版2.17（MinIon）；和freebayes软件1.3.1特别版（MiSeq）。将比较简单蛋白质组与需用的2019-nCoV参照数列（GenBank登录号NC_045512.2）展开相比较。
结果
2019-NCOV的古生物学家次测试
此表2-2019年新近型SARS大肠杆菌（2019-nCoV）的短时间核苷-催化反应-链反应次测试结果
该综合征状在体弱第4天时获得的初始新近陈代谢道检验（钝咽拭子和口咽拭子）在2019-nCoV椭圆形受到感染性（此表2）。
尽管综合征状原先此乏善可陈为轻度综合征状，但在哮喘第4天的较高循环阈差值（Ct）差值（钝咽古生物学家之前为18至20，口咽古生物学家之前为21至22）此说明这些古生物学家之前大肠杆菌水准较高。
在哮喘第7天获得的两个上新近陈代谢道古生物学家在2019-nCoV仍保持受到感染性，都有钝咽拭子古生物学家之前持续性高水准（Ct差值23至24）。在哮喘第7天获得的异味在2019-nCoV之前也椭圆形受到感染性（Ct差值为36至38）。两种采自应于的胰岛素检验在2019-nCoV之内外为有性。
在哮喘第11天和第12天获得的钝咽和口咽古生物学家推断不止大肠杆菌水准攀改授的渐进。
口咽古生物学家在体弱第12天的2019-nCoV次测试椭圆形有性。在这些应于获得的胰岛素的rRT-PCR结果仍唯未定。
遗传蛋白质分析化学合成
口咽和钝咽古生物学家的比较简单蛋白质组数列彼此相近，并且与其他需用的2019-nCoV数列依然相近。
该综合征状的大肠杆菌与2019-nCoV参照数列（NC_045512.2）在开放读到板8处并不少有3个氢苷酸和1个并不相近。该数列可通过GenBank获得（登录号MN985325）。
讨论区
我们关于新近泽西州月所2019-nCoV就诊SARS的份文件说道明了这一新近兴哮喘的几个方面唯唯未完全探究，都有传播方式动态和流行病学哮喘的全部区域内。
我们的SARS综合征状曾去过我国上海，但份文件说道他在上海长期不会去过菜式商铺或医疗系统，也不会身体虚弱的触及。尽管他的2019-nCoV受到感染的来源唯不清楚，但已官方了人对人传播方式的证据。
到2020年1月底30日，唯唯未推断不止与此SARS特别的2019-nCoV继发SARS，但仍在密切联系监视下。
在哮喘的第4天和第7天从上新近陈代谢道古生物学家之前测定到不具较高Ct差值的2019-nCoV RNA，此说明大肠杆菌载量高且不具传播方式潜质。
差相相比较的是，我们还在综合征状体弱第7天采自的异味检验之前测定到了2019-nCoV RNA。尽管我们SARS综合征状的胰岛素古生物学家重复显现不止2019-nCoV有性，但在我国重综合症综合征状的体液之前仍测定到大肠杆菌RNA。然而，肺内外测定大肠杆菌RNA并不一定意味着共存传染性大肠杆菌，现阶段唯不清楚在新近陈代谢道内外部测定大肠杆菌RNA的流行病学意义。
现阶段，我们对2019-nCoV受到感染的流行病学区域内的探究并不有限。在我国，已经华盛顿邮报了诸如相当严重的心脏病，新近陈代谢衰竭，急性新近陈代谢窘迫肉瘤（ARDS）和心脏损伤等并发综合症，都有灾难性的后果。然而，重要的是要肯定，这些SARS是根据其心脏病临床明确的，因此似乎就会使份文件偏向更相当严重的结果。
我们的SARS综合征状原先此乏善可陈为轻度肿胀和较高度出现精神状态感冒，在体弱的第4天不会腹部X光核对的心脏病似乎，而在体弱第9天其发展为心脏病之前，这些非特异性体征和综合征状在早期在流行病学上，2019-nCoV受到感染的流行病学处理过程似乎与许多其他少用传染病不会显着相异，相比较是在初冬新近陈代谢道大肠杆菌干季。
另内外，本SARS综合征状在哮喘的第9天其发展为心脏病的必定会与近期新近陈代谢困难的发作（发病后之前位数为8天）一致。尽管根据综合征状的流行病学状况恶化立即前提获得remdesivir善心的常用，但仍必需展开研究性试验以明确remdesivir和任何其他科学研究药剂放射治疗2019-nCoV受到感染的相容性和有效性。
我们份文件了新近泽西州月所份文件的2019-nCoV受到感染综合征状的流行病学也就是说特征。
该SARS的关键方面都有综合征状在读到有关暴发的预防控制措施通告后立即促成医疗；由当地医疗服务举例来说说明综合征状值得肯定到上海的旅程历通史，随后在当地，一州和美国联邦预防控制措施行政官员相互间展开协调；并明确似乎的2019-nCoV受到感染，从而可以随之可避免综合征状并随后对2019-nCoV展开研究团队说明，并允许综合征状入院进一步审计和负责管理。
该SARS份文件务实了流行病学精神科对于任何显现不止急性哮喘综合征状的就诊综合征状，要回顾不止值得肯定的旅程亲身经历或触及帕金森氏症的优越性，为了确保正确识别和及时可避免似乎面临2019-nCoV受到感染效用的综合征状，并尽力增大进一步的传播方式。
先前，本份文件务实必需明确与2019-nCoV受到感染特别的流行病学哮喘，发病催化反应和大肠杆菌开裂持续性时间的
全部区域内和自然历通史，以为流行病学负责管理和预防控制措施权衡提供依据。
以下为英文特别版
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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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