摘要
在里面华人民共和国郑州开始的新型霍乱病毒接种（2019-nCoV）；不动迅速蔓延，现已在多个国家肺炎。我们清查报告了在英美两国证实的元年初2019-nCoV接种；不生率，并叙述了该；不生率的认定，病症候群，药理学西北侧理过程和管理，除此以外病患在复；不第9天体现为胃癌时的原先轻度病症候群。
该与此相关忽略了药理学心理医生与之皆，一州和联邦各级流行病学中国政府密切关系间歇良好协作的重要性，以及并不需要快速散播与这种新；不接种病患的护理有关的药理学反馈的期望。
2019年12年初31日，里面华人民共和国清查报告了与湖北省郑州市海南鱿鱼批；不市场有关的人群里面的胃癌；不生率。
2020年1年初7日，里面华人民共和国护理中国政府证实该簇与新型霍乱病毒接种2019-nCoV有关。尽管原先新闻报道的；不生率与郑州市鱿鱼市场的暴露有关，但当前的流行病学数据集表明，即将；不生2019-nCoV人际散播。
截至2020年1年初30日，在大概21个国家/沿海地区清查报告了9976亦然；不生率，除此以外2020年1年初20日新闻报道的英美两国元年初肺炎的2019-nCoV接种；不生率。
世界性区域内即将顺利完成清查，以非常好地探究散播静态和药理学性疾病区域。本清查报告叙述了在英美两国证实的元年初2019-nCoV接种的流行病学和药理学不同之处。
与此相关清查报告
2020年1年初19日，一名35岁的男子显现在纽约市一州罗宾逊霍米什县的杂货店急诊妇产科，有4天的痉挛和主观头痛世界史。病症候群到妇产科检查和时，在候诊室戴上便衣。等待大约20分钟后，他被带到检查和室接纳了提供者的评量。
他透漏，他在里面华人民共和国郑州返家母亲后于1年初15日返回纽约市一州。该病患表示，他已从英美两国性疾病掌控与护理保健里面心（CDC）送给单单有关里面华人民共和国新型霍乱病毒接种随之而来的健康警报，由于他的病症候群和不太显然的历险，他决定去看心理医生。
布1-2020年1年初19日（性疾病第4天）的后颈部和皆侧胸片
除了高中学生酸酯血症候群的病世界史皆，该病患还是其他健康的不高血压。体格检查和见到病患排尿环境热气时，血流量为37.2°C，肝功能为134/87 mm Hg，搏动为每分钟110次，排尿频率为每分钟16次，钾酸度为96％。呼吸道听诊说明了有支气管炎，并顺利完成了胸片检查和，据新闻报道没见到异常（布1）。
中三型和乙型霍乱的快速脱钾质子糖质子酸扩增次测试（NAAT）为不同之处性。获了喉咽拭子遗骸，并通过NAAT将其送给去检查病毒接种性侧腔病原。
据新闻报道在48足足内对所有次测试的病原以皆长方形不同之处性，除此以外中三型和乙型霍乱，副霍乱，侧腔合胞病毒接种，喉病毒接种，腺病毒接种和仅有会引发人类所性疾病的四种类似霍乱病毒接种株（HKU1，NL63、229E和OC43） ）。根据病患的历险历世界史，第一时间通知之皆和一州护理部门。纽约市护理部与应急护理药理学心理医生独自一人通知了CDC应急行动里面心。
尽管该病患清查报告说他并没去过海南鱿鱼市场，也并没清查报告在去里面华人民共和国历险期间与体弱者有任何触及，但性疾病护理保健掌控里面心的职员同意有适当根据当前的性疾病护理保健掌控里面心对病患顺利完成2019-nCoV次测试。
根据CDC最新抽取了8个遗骸，除此以外人体内，喉咽和侧咽拭子遗骸。遗骸搜集后，病患被送给回父母亲受控，并由当地护理部门顺利完成致力检测。
2020年1年初20日，性疾病护理保健掌控里面心（CDC）证实病患的喉咽和侧咽拭子通过系统对抗病毒-聚合酶链式反应（rRT-PCR）检查为2019-nCoV不同之处性。
在性疾病护理保健掌控里面心的隐喻专家，一州和之皆护理文官，应急医护服务以及该医院为首和职员的适切下，病患被送给回普罗维登斯沿海地区医护里面心的热气受控病房顺利完成药理学捕捉到，并先是性疾病护理保健掌控里面心的医护人员有关触及，飞沫和空里面防护采取措施的要求，并十分相近护目镜。
病倒时病患清查报告过后痉挛，有2天的白痴和头痛世界史。他清查报告说他并没排尿急促或胃痛。人类征状在长时间区域内。体格检查和见到病患粘膜干燥。其余的检查和上会不明显。
病倒后，病患接纳了大力支持治疗，除此以外2升到生理盐水和恩丹以减缓白痴。
布2-根据性疾病日和病倒日（2020年1年初16日至2020年1年初30日）的病症候群和最高血流量
在病倒的第2至5天（体弱的第6至9天），病患的人类征状基本上间歇稳定，除了显现断续头痛并伴有心动过速（布2）。病患继续清查报告非生产性痉挛，并显现疲劳。
在病倒第二天的下午，病患排便通畅，腹部不适。晚上有第二次大便稀少的新闻报道。抽取该排泄的材料用于rRT-PCR次测试，以及其他侧腔遗骸（喉咽和侧咽）和人体内。排泄和两个侧腔遗骸之后以皆通过rRT-PCR检查为2019-nCoV不同之处性，而人体内仍为不同之处性。
在此期间的治疗在很大高度上是大力支持性的。为了顺利完成病症候群妥善西北侧理，病患并不需要根据并不需要接纳消炎临床，该临床除此以外每4足足650 mg对乙酰硫基酚和每6足足600 mg布洛芬。在病倒的前六天，他还因过后痉挛而服用了600毫克愈创醚和大约6升到生理盐水。
表1-药理学研究所结果
病患受控单元的政治性原先仅意味著即时医护点研究所次测试；从该医院第3天开始可以顺利完成以外血细胞除此以外和人体内化学科学研究。
在该医院第3天和第5天（性疾病第7天和第9天）的研究所结果反映单单巨噬细胞下降症候群，轻度血小板下降症候群和肌酸激酶水平升到高（表1）。此皆，肝功能指标也有所改变：钠盐激酶（每升到68 U），丙硫酸硫基转移酶（每升到105 U），天冬硫酸硫基转移酶（每升到77 U）和乳酸脱氢酶（每升到465 U）的水平共有：在病倒的第5天所有升到高。鉴于病患每一次头痛，在第4天获体液培养；为数不多，这些都并没增长。
布3-2020年1年初22日（腹部第7天，该医院第3天）的后颈部和皆侧胸片
布4-2020年1年初24日（腹部第5天，该医院第9天）的后颈部X线片
据新闻报道，在该医院第3天（体弱第7天）拍片的腹部X光片没说明了常为或异常确实（布3）。
但是，从该医院第5天晚上（体弱第9天）晚上顺利完成的第二次腹部X光片检查和说明了，左肺下叶有胃癌（布4）。
这些影像学见到与从该医院第5天晚上开始的排尿状态改变相吻合，之前病患在排尿周围热气时通过搏动血钾酸度测定的血钾酸度差值下调90％。
在第6天，病患开始接纳补足压缩热气，该压缩热气由喉导管以每分钟2升到的平均速度运载。直接影响药理学体现的改变和对该医院获性胃癌的关注，开始用作万古霉素（1750 mg负荷药物，然后每8足足静脉注射1 g）和唑锦标苯基（每8足足静脉注射）治疗。
布5-前后腹部X光片，2020年1年初26日（性疾病第十天，该医院第六天）
在该医院第6天（体弱第10天），第四次腹部X射线图片说明了两个肺里面都有基底条状混浊，这一见到与非十分相似胃癌相符（布5），并且在听诊时在两个肺里面都显现了罗音。鉴于质子辐射影像学见到，决定拒绝接受压缩热气补足，病患过后头痛，多个躯干过后不同之处性的2019-nCoV RNA不同之处性，以及；不表文章了与质子辐射性胃癌蓬勃；不展相一致的严重胃癌在该病患里面，药理学心理医生更有同情心地用作了科学学术机构抗病毒接种治疗。
静脉注射凯特昔韦（一种即将开；不的新型质子苷酸类似物前药）在第7天晚上开始，但没捕捉到到与用药有关的不良事件。在对中三钾霖抗药性的金黄色青霉素顺利完成了连续的降钙素原水平和喉PCR检查后，在第7天晚上废弃万古霉素，并在第二天废弃唑锦标苯基。
在该医院第8天（体弱第12天），病患的药理学状况给予优化。暂缓补足压缩热气，他在排尿周围热气时的钾酸度差值提高到94％至96％。先前的双侧下叶罗音不再存在。他的食欲给予优化，除了断续干咳和喉漏皆，他并没病症候群。
截至2020年1年初30日，病患仍病倒。他有头痛，除痉挛皆，所有病症候群以皆已减缓，痉挛的高度即将降低。
方法有
遗骸搜集
根据CDC最新获用于2019-nCoV病症候群次测试的药理学遗骸。用化学纤维拭子抽取了12个喉咽和侧咽拭子遗骸。
将每个拭子填入包含2至3 ml病毒接种发运颗粒的单独无菌管里面。将血集在人体内分离管里面，然后根据CDC最新顺利完成离心。尿和排泄遗骸分别抽取在无菌遗骸容器里面。材料在2°C至8°C密切关系备份，直到作好运送给至CDC。
在性疾病的第7、11和12天抽取了重复顺利完成的2019-nCoV次测试的遗骸，除此以外喉咽和侧咽拭子，人体内以及尿和排泄检验。
2019-NCOV的病症候群次测试
用作从公开；不布的病毒接种碱基蓬勃；不展而来的rRT-PCR分析法次测试了药理学遗骸。与先前针对急诊急性排尿症候群霍乱病毒接种（SARS-CoV）和里面东排尿症候群霍乱病毒接种（MERS-CoV）的病症候群方法有相近，它不具三个质子质子蛋白蛋白质靶标和一个不同之处性对照靶标。该测定的叙述为RRT-PCR平板引物和遮罩和碱基反馈里面需用的CDC研究所反馈网站2019-nCoV上。
体现型PCR
2020年1年初7日，里面华人民共和国科学研究人员通过英美两国国立护理科学研究院GenBank数据集库和世界性共享所有霍乱数据集大力大力支持（GISAID）数据集库共享了2019-nCoV的完整蛋白质碱基；随后；不布了有关受控2019-nCoV的清查报告。
从rRT-PCR不同之处性遗骸（侧咽和喉咽）里面提炼脱钾质子糖质子酸，并在Sanger和新一代PCR平台（Illumina和MinIon）上用于以外蛋白质PCR。用作5.4.6特别版的Sequencher软体（Sanger）完成了碱基成品。minimap软体，特别版本2.17（MinIon）；和freebayes软体1.3.1特别版（MiSeq）。将完整蛋白质与需用的2019-nCoV详见碱基（GenBank登录号NC_045512.2）顺利完成尤其。
结果
2019-NCOV的遗骸次测试
表2-2019年新型霍乱病毒接种（2019-nCoV）的系统对抗病毒-聚合酶-链式反应次测试结果
该病患在体弱第4天时获的初始侧腔检验（喉咽拭子和侧咽拭子）在2019-nCoV长方形不同之处性（表2）。
尽管病患原先体现为轻度病症候群，但在性疾病第4天的较差循环阈差值（Ct）差值（喉咽遗骸里面为18至20，侧咽遗骸里面为21至22）表明这些遗骸里面病毒接种水平更高。
在性疾病第7天获的两个上侧腔遗骸在2019-nCoV仍间歇不同之处性，除此以外喉咽拭子遗骸里面过后高质量（Ct差值23至24）。在性疾病第7天获的排泄在2019-nCoV里面也长方形不同之处性（Ct差值为36至38）。两种搜集应于的人体内检验在2019-nCoV以皆为不同之处性。
在性疾病第11天和第12天获的喉咽和侧咽遗骸说明了单单病毒接种水平下降的急遽。
侧咽遗骸在体弱第12天的2019-nCoV次测试长方形不同之处性。在这些应于获的人体内的rRT-PCR结果仍没定。
体现型PCR
侧咽和喉咽遗骸的完整蛋白质碱基彼此相近，并且与其他需用的2019-nCoV碱基仍然相近。
该病患的病毒接种与2019-nCoV详见碱基（NC_045512.2）在开放阅读圆点8西北侧仅有3个质子苷酸和1个不同。该碱基可通过GenBank获（登录号MN985325）。
讨论区
我们关于英美两国元年初2019-nCoV肺炎；不生率的清查报告暗示这一新兴性疾病的几个方面尚能没完以外探究，除此以外散播静态和药理学性疾病的以外部区域。
我们的；不生率病患曾去过里面华人民共和国郑州，但清查报告说他在郑州期间并没去过鱿鱼批；不市场或医护机构，也并没病倒的触及。尽管他的2019-nCoV接种的相关联尚能不清楚，但已公开了人对人散播的证据。
到2020年1年初30日，尚能没见到与此；不生率系统性的2019-nCoV继肺癌亦然，但仍在间歇良好跟踪下。
在性疾病的第4天和第7天从上侧腔遗骸里面检查到不具较差Ct差值的2019-nCoV RNA，表明病毒接种载量高且不具散播发展潜力。
差值得留意的是，我们还在病患体弱第7天抽取的排泄检验里面检查到了2019-nCoV RNA。尽管我们；不生率病患的人体内遗骸每一次显现2019-nCoV不同之处性，但在里面华人民共和国急诊病患的体液里面仍检查到病毒接种RNA。然而，肺皆检查病毒接种RNA并不一定意味著存在传染性病毒接种，现阶段尚能不清楚在侧腔皆部检查病毒接种RNA的药理学意义。
现阶段，我们对2019-nCoV接种的药理学区域的探究尤其依赖于。在里面华人民共和国，已经新闻报道了诸如严重的胃癌，排尿衰竭，急性排尿困窘症候群（ARDS）和胸腔伤害等并；不症候群，除此以外灾难性的后果。然而，重要的是要留意，这些；不生率是根据其胃癌病症候群明确的，因此显然会使清查报告偏重非常严重的结果。
我们的；不生率病患原先体现为轻度痉挛和较差度断续头痛，在体弱的第4天并没腹部X光检查和的胃癌确实，而在体弱第9天蓬勃；不展为胃癌之前，这些非特异性征状和病症候群在更早在药理学上，2019-nCoV接种的药理学西北侧理过程显然与许多其他类似传染病并没明显分野，众所周知是在冬季侧腔病毒接种季节。
另皆，本；不生率病患在性疾病的第9天蓬勃；不展为胃癌的时机与非常更进一步排尿困难的高烧（肺癌后里面位数为8天）相一致。尽管根据病患的药理学状况恶化决定是否拒绝接受remdesivir慈悲的用作，但仍并不需要顺利完成探索性试验以明确remdesivir和任何其他科学研究药物治疗2019-nCoV接种的安以外性和有效性。
我们清查报告了英美两国元年初清查报告的2019-nCoV接种病患的药理学不同之处。
该；不生率的关键因素方面除此以外病患在阅读有关随之而来的流行病学通知后决定设法医护；由当地医护中介证实病患不太显然到郑州的历险历世界史，随后在当地，一州和联邦流行病学文官密切关系顺利完成协调；并明确显然的2019-nCoV接种，从而可以迅速受控病患并随后对2019-nCoV顺利完成研究所证实，并意味著病患病倒更进一步评量和管理。
该；不生率清查报告忽略了药理学心理医生对于任何显现急性性疾病病症候群的住院病患，要总结单单不太显然的历险经历或触及病世界史的重要性，为了确保无论如何鉴别和及时受控显然陷入2019-nCoV接种效用的病患，并借助下降更进一步的散播。
之前，本清查报告忽略并不需要明确与2019-nCoV接种系统性的药理学性疾病，肺癌机理和病毒接种脱落过后时间的
以外部区域和连续性历世界史，以为药理学管理和流行病学决策提供依据。
一般而言为英文特别版
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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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