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在中的国重庆开始的最初型流感HIV（2019-nCoV）爆推迅速蔓延，现已在多个转型中的国家确诊。我们分析报告了在英美两国证实的首开2019-nCoV细菌感染登革热，并揭示了该登革热的比对，病人，部份科过程和政府机构，包含病人在身体状况第9天此表现为败血症时的刚开始轻度病征。
该唯子强调了部份科部份科医生与区域内，爱达荷州和联邦各级公共公共卫生当局彼此之间密切协作的层面，以及只能快速传扬与这种最初推细菌感染病人的护理人员有关的部份科电子邮件的需要。
2019年12月末31日，中的国分析报告了与湖南省重庆市华南地区紫菜批推英美两国市场有关的人群中的的败血症登革热。
2020年1月末7日，中的国公共卫生当局证实该簇与最初型流感HIV2019-nCoV有关。尽管刚开始最初闻报道的登革热与重庆市紫菜英美两国市场的暴露有关，但这两项的流行病学信息证明，正试图牵涉到2019-nCoV彼此间传扬。
截至2020年1月末30日，在至少21个转型中的国家/邻近地区分析报告了9976唯登革热，包含2020年1月末20日最初闻报道的英美两国首开确诊的2019-nCoV细菌感染登革热。
全都球区域内内正试图顺利完成调查，以更是好地了解到传扬动态和部份科性疾病区域内。本分析报告揭示了在英美两国证实的首开2019-nCoV细菌感染的流行病学和部份科特征。
唯子分析报告
2020年1月末19日，一名35岁的男子借助于现在华盛顿爱达荷州斯诺霍米什县的公司总部医务人员公共卫生机构，有4天的气喘和客观性气喘历史学者。病人到公共卫生机构安全检查时，在候诊室戴上侧罩。等待约20分钟后，他被带到安全检查室给与了服务缺少商的分析。
他透露，他在中的国重庆探望全家人才将1月末15日返回华盛顿爱达荷州。该病人此表示，他已从英美两国性疾病控制与防治中的心（CDC）收到有关中的国最初型流感HIV愈演愈烈的健康预警，由于他的病征和早先的旅行者，他最终去看部份科医生。
由此可知1-2020年1月末19日（性疾病第4天）的后腹部和部份侧胸片
除了高三酸酯血性性疾病的帕金森氏症部份，该病人还是其他健康的不吸烟者。体格安全检查断定病人气管环境热空气时，体温为37.2°C，眼压为134/87 mm Hg，节律为每分钟110次，气管频率为每分钟16次，锂一般而言为96％。肺部听诊结果显示有支气管炎，并顺利完成了胸片安全检查，据最初闻报道没断定精神完全（由此可知1）。
乙型和乙型流感的快速氢糖扩增检验（NAAT）为比如真是。获取了背咽拭子骨骼，并通过NAAT将其分送去验证HIV性口腔流感病毒。
据最初闻报道在48时长内对所有检验的流感病毒仅排列成比如真是，包含乙型和乙型流感，副流感，口腔合胞HIV，背HIV，腺HIV和已知时会导致生物性疾病的四种常见流感HIV株（HKU1，NL63、229E和OC43） ）。根据病人的旅行者转型历史学者，即刻通报区域内和爱达荷州公共防疫。华盛顿公共卫生部与紧急情况护理人员部份科部份科医生三人通报了CDC紧急情况行动中的心。
尽管该病人分析报告真是他未去过华南地区紫菜英美两国市场，也未分析报告在去中的国旅行者在此期间与患者有任何带入，但性疾病防治控制中的心的工作职员准许有合理根据这两项的性疾病防治控制中的心对病人顺利完成2019-nCoV检验。
根据CDC须知整理了8个骨骼，包含肝脏，背咽和侧咽拭子骨骼。骨骼野部份后，病人被分送往父母亲强制，并由当地公共防疫顺利完成全力监测。
2020年1月末20日，性疾病防治控制中的心（CDC）证实病人的背咽和侧咽拭子通过实时丝甲醇酸-PCR链反应（rRT-PCR）验证为2019-nCoV中的性。
在性疾病防治控制中的心的主旨专家，爱达荷州和区域内公共卫生部份交人员，紧急情况公共卫生服务以及公立医院拥护和工作职员的配合下，病人被分送往普罗维登斯邻近地区公共卫生中的心的热空气强制病房顺利完成部份科仔细观察，并跟随性疾病防治控制中的心的医护职员有关带入，飞沫和空中的防护措施的建议，并带有丝袜。
晕倒时病人分析报告小规模气喘，有2天的焦虑和头痛历史学者。他分析报告真是他未气管急促或胸痛。生命先兆在但会区域内内。体格安全检查断定病人口腔干燥。其余的安全检查一般来说不明显。
晕倒后，病人给与了支持治疗法，包含2降为生理盐水和恩丹以减缓焦虑。
由此可知2-根据性疾病日和开刀日（2020年1月末16日至2020年1月末30日）的病征和略低于体温
在开刀的第2至5天（患的第6至9天），病人的生命先兆基本依然稳定，除了借助于现但会气喘并伴有心动过速（由此可知2）。病人继续分析报告非生产性气喘，并借助于现疲惫。
在开刀第二天的早上，病人排便利于，腹部不适。早上有第二次大便稀疏的最初闻报道。整理该尿液的探头用做rRT-PCR检验，以及其他口腔骨骼（背咽和侧咽）和肝脏。尿液和两个口腔骨骼后来仅通过rRT-PCR验证为2019-nCoV中的性，而肝脏仍为比如真是。
在此在此期间的治疗法在相当大往往上是支持性的。为了顺利完成病征处理，病人只能根据只能给与止咳治疗法，该治疗法包含每4时长650 mg阿司匹林和每6时长600 mg甲酯。在开刀的前六天，他还因小规模气喘而注射了600毫克愈创醚和约6降为生理盐水。
此表1-部份科研究室结果
病人强制单元的其本质刚开始仅并不需要即时公共卫生点研究室检验；从公立医院第3天开始可以顺利完成全都脑组织小数和肝脏物理分析。
在公立医院第3天和第5天（性疾病第7天和第9天）的研究室结果反映借助于白细胞下降性性疾病，轻度血小板下降性性疾病和肌酸激酶往往下降（此表1）。此部份，黄疸指标也有所变化：极性蛋白酶（每降为68 U），酰甲醇基转移酶（每降为105 U），胺基酸甲醇基转移酶（每降为77 U）和乳酸半乳糖（每降为465 U）的往往分别为：在开刀的第5天所有下降。鉴于病人反复气喘，在第4天获取体液培育；迄今为止，这些都未增长。
由此可知3-2020年1月末22日（臀部第7天，公立医院第3天）的后腹部和部份侧胸片
由此可知4-2020年1月末24日（臀部第5天，公立医院第9天）的后腹部X线片
据最初闻报道，在公立医院第3天（患第7天）制作的臀部X光片没结果显示伴生或精神完全都还（由此可知3）。
但是，从公立医院第5天早上（患第9天）早上顺利完成的第二次臀部X光片安全检查结果显示，左肺下叶有败血症（由此可知4）。
这些医学影像断定与从公立医院第5天早上开始的气管完全变化相吻合，当时病人在气管四周热空气时通过节律血锂一般而言测定的血锂一般而言取值降至90％。
在第6天，病人开始给与不足之处锂气，该锂气由背导管以每分钟2降为的速度输分送。考虑到部份科此表现的变化和对公立医院获取脑膜炎的注目，开始适用氯霉素（1750 mg负担剂量，然后每8时长口服1 g）和头孢菌素联赛杯芳基（每8时长口服）治疗法。
由此可知5-前后臀部X光片，2020年1月末26日（性疾病第十天，公立医院第六天）
在公立医院第6天（患第10天），第四次臀部X射线照片结果显示两个肺中的都有基底小块光亮，这一断定与非迥然相异败血症相吻合（由此可知5），并且在听诊时在两个肺中的都借助于现了罗音。鉴于辐射线医学影像断定，最终得不到锂气不足之处，病人小规模气喘，多个部位小规模中的性的2019-nCoV RNA中的性，以及推此表了与辐射线脑膜炎转型一致的导致败血症在该病人中的，部份科部份科医生富有理智地适用了分析性抗HIV治疗法。
口服历史学者考特昔韦（一种正试图开推最初的最初型氢苷酸类似物前药）在第7天早上开始，但没仔细观察到与输注有关的不良事件。在对甲锂芳耐药的白色绿脓杆菌顺利完成了连续的降钙素原往往和背PCR验证后，在第7天早上停用氯霉素，并在第二天停用头孢菌素联赛杯芳基。
在公立医院第8天（患第12天），病人的部份科状况得到有所改善。终止不足之处锂气，他在气管四周热空气时的锂一般而言取值减低到94％至96％。更是进一步的双侧下叶罗音早已假定。他的嗜睡得到有所改善，除了但会干咳和背漏部份，他未病征。
截至2020年1月末30日，病人仍开刀。他有推热，除气喘部份，所有病征仅已减缓，气喘的往往正试图减轻。
原理
骨骼野部份
根据CDC须知获取用做2019-nCoV病人检验的部份科骨骼。用人造纤维拭子整理了12个背咽和侧咽拭子骨骼。
将每个拭子抽出包含2至3 mlHIV转运介质的单独无菌管中的。将血集在肝脏分离管中的，然后根据CDC须知顺利完成离心。尿和尿液骨骼分别整理在无菌骨骼试管中的。探头在2°C至8°C彼此之间储存，直到准备运分送至CDC。
在性疾病的第7、11和12天整理了段落顺利完成的2019-nCoV检验的骨骼，包含背咽和侧咽拭子，肝脏以及尿和尿液抽样。
2019-NCOV的病人检验
适用从公开披露的HIV脱锂氢糖氢糖转型而来的rRT-PCR分析法检验了部份科骨骼。与更是进一步针对重性性疾病急性气管综合症流感HIV（SARS-CoV）和中的东气管综合症流感HIV（MERS-CoV）的病人原理相近，它很强三个氢衣壳DNA靶标和一个中的性对照靶标。该测定的揭示为RRT-PCR面板聚合酶和核酸和脱锂氢糖氢糖电子邮件中的可用的CDC研究室电子邮件该网站2019-nCoV上。
此表现型分子生物学
2020年1月末7日，中的国分析职员通过英美两国国立公共卫生英美两国哈佛大学GenBank信息库系统和全都球对等所有流感信息倡议（GISAID）信息库系统对等了2019-nCoV的更为简单DNA脱锂氢糖氢糖；随后披露了有关强制2019-nCoV的分析报告。
从rRT-PCR中的性骨骼（侧咽和背咽）中的提取氢糖，并在Sanger和将来分子生物学平台（Illumina和MinIon）上用做全都DNA组分子生物学。适用5.4.6原版的Sequencher应用程序（Sanger）完成了脱锂氢糖氢糖组装。minimap应用程序，最初原版本2.17（MinIon）；和freebayes应用程序1.3.1原版（MiSeq）。将更为简单DNA组与可用的2019-nCoV参照脱锂氢糖氢糖（GenBank登录号NC_045512.2）顺利完成更为。
结果
2019-NCOV的骨骼检验
此表2-2019年最初型流感HIV（2019-nCoV）的实时丝甲醇酸-PCR-链反应检验结果
该病人在患第4点将获取的初始口腔抽样（背咽拭子和侧咽拭子）在2019-nCoV排列成中的性（此表2）。
尽管病人刚开始此表现为轻度病征，但在性疾病第4天的高反向阈取值（Ct）取值（背咽骨骼中的为18至20，侧咽骨骼中的为21至22）证明这些骨骼中的HIV往往高。
在性疾病第7天获取的两个上口腔骨骼在2019-nCoV仍依然中的性，包含背咽拭子骨骼中的小规模高往往（Ct取值23至24）。在性疾病第7天获取的尿液在2019-nCoV中的也排列成中的性（Ct取值为36至38）。两种野部份日期的肝脏抽样在2019-nCoV仅为比如真是。
在性疾病第11天和第12天获取的背咽和侧咽骨骼结果显示借助于HIV往往下降的近年来。
侧咽骨骼在患第12天的2019-nCoV检验排列成比如真是。在这些日期获取的肝脏的rRT-PCR结果仍没定。
此表现型分子生物学
侧咽和背咽骨骼的更为简单DNA组脱锂氢糖氢糖彼此仅仅都相同，并且与其他可用的2019-nCoV脱锂氢糖氢糖几乎仅仅都相同。
该病人的HIV与2019-nCoV参照脱锂氢糖氢糖（NC_045512.2）在开放选读框8处仅有3个氢苷酸和1个相异。该脱锂氢糖氢糖可通过GenBank获取（登录号MN985325）。
讨论区
我们关于英美两国首开2019-nCoV确诊登革热的分析报告真是明了这一最初兴性疾病的几个全都面性尚能没仅仅都了解到，包含传扬动态和部份科性疾病的全都部区域内。
我们的登革热病人曾去过中的国重庆，但分析报告真是他在重庆在此期间未去过紫菜批推英美两国市场或公共卫生机构，也未身体虚弱的带入。尽管他的2019-nCoV细菌感染的是从尚能不明确，但已公开了人对人传扬的证据。
到2020年1月末30日，尚能没断定与此登革热无关的2019-nCoV继患登革热，但仍在密切监视下。
在性疾病的第4天和第7天从上口腔骨骼中的验证到很强高Ct取值的2019-nCoV RNA，证明HIV载量高且很强传扬潜力。
取值得注意的是，我们还在病人患第7天整理的尿液抽样中的验证到了2019-nCoV RNA。尽管我们登革热病人的肝脏骨骼反复借助于现2019-nCoV比如真是，但在中的国重性性疾病病人的体液中的仍验证到HIVRNA。然而，肺部份验证HIVRNA一般来说一般来说假定传染性HIV，目前为止尚能不明确在口腔部份部验证HIVRNA的部份科意义。
目前为止，我们对2019-nCoV细菌感染的部份科区域内的了解到非常局限。在中的国，早就最初闻报道了诸如导致的败血症，气管衰竭，急性气管窘迫综合症（ARDS）和心脏损害等并推性性疾病，包含致命的后果。然而，不可或缺的是要注意，这些登革热是根据其败血症病人确认的，因此不太可能时会使分析报告偏重于更是导致的结果。
我们的登革热病人刚开始此表现为轻度气喘和高度但会气喘，在患的第4天未臀部X光安全检查的败血症都还，而在患第9天转型为败血症在此之后，这些非抗体先兆和病征在早期在部份科上，2019-nCoV细菌感染的部份科过程不太可能与许多其他常见疟疾未明显区别，尤其是在冬季口腔HIV季节。
另部份，本登革热病人在性疾病的第9天转型为败血症的才会与近期晕眩的推作（患病后可支配为8天）一致。尽管根据病人的部份科状况恶化最终应该得不到remdesivir慈悲的适用，但仍只能顺利完成探索性试验性以确认remdesivir和任何其他分析药物治疗法2019-nCoV细菌感染的安全都性和合理性。
我们分析报告了英美两国首开分析报告的2019-nCoV细菌感染病人的部份科特征。
该登革热的关键全都面性包含病人在选读有关愈演愈烈的公共公共卫生警告后最终寻求公共卫生；由当地公共卫生服务服务缺少商证实病人早先到重庆的旅行者转型历史学者，随后在当地，爱达荷州和联邦公共公共卫生部份交人员彼此之间顺利完成协调；并确认不太可能的2019-nCoV细菌感染，从而可以迅速强制病人并随后对2019-nCoV顺利完成研究室证实，并并不需要病人晕倒进一步分析和政府机构。
该登革热分析报告强调了部份科部份科医生对于任何借助于现急性性疾病病征的确诊病人，要说明了借助于早先的旅行者经历或带入帕金森氏症的层面，为了必需正确辨别和及时强制不太可能面临2019-nCoV细菌感染不确认性的病人，并帮助下降进一步的传扬。
先前，本分析报告强调只能确认与2019-nCoV细菌感染无关的部份科性疾病，患病成因和HIV脱落小规模时间的
全都部区域内和自然现象转型历史学者，以为部份科政府机构和公共公共卫生决策缺少依据。
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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