概要
在中的国长沙开始的新型冠状HIV（2019-nCoV）爆发进一步蔓延，现已在多个拓展中国家住院治疗。我们通报了在宾夕法尼亚的县验证的首度2019-nCoV染病疟疾，并描绘出有了该疟疾的鉴定，病患，病理过程和管理工作，有数病患在病情第9天观感为脑部病时的最初轻度抽搐。
该范可有强调了病理心理医生与偏远地区，的县和美国联邦政府各级预防当局彼此之间密切关系协作的特殊性，以及需慢速的传播与这种新发染病病患的照护有关的病理文档的生产力。
2019年12翌年31日，中的国通报了与湖北省长沙市广东鱼肉家禽有关的人群中的的脑部病疟疾。
2020年1翌年7日，中的国卫生当局验证该簇与新型冠状HIV2019-nCoV有关。尽管最初媒体报道的疟疾与长沙市鱼肉零售商的暴露有关，但举可有来说的临床图表表格明，即将发生2019-nCoV人际的传播。
截至2020年1翌年30日，在至少21个拓展中国家/地区通报了9976可有疟疾，有数2020年1翌年20日媒体报道的宾夕法尼亚的县首度住院治疗的2019-nCoV染病疟疾。
全部都是球覆盖范围即将同步进行调查，以更是好地理解的传播动态和病理哮喘覆盖范围。本通报描绘出有了在宾夕法尼亚的县验证的首度2019-nCoV染病的临床和病理不同之处。
范可有通报
2020年1翌年19日，一名35岁的男子注意到在华盛顿的县怀特霍米什县的合伙急诊教育机构，有4天的肠胃和主观发烧历史学者。产妇到教育机构监测时，在候诊室戴上；大罩。等待分之一20分钟后，他被带到监测室给予了提供者的评估。
他透露，他在中的国长沙探望家人紧接著1翌年15日返回华盛顿的县。该病患表格示，他已从宾夕法尼亚的县哮喘控制与防治中的心（CDC）收到有关中的国新型冠状HIV时绝对值的肥胖病征警报，由于他的抽搐和在在的环游，他重新考虑去看心理医生。
三幅1-2020年1翌年19日（哮喘第4天）的后前胸和之外侧胸片
除了高三酸酯血病征的病病征之外，该病患还是其他肥胖病征的不吸烟者。体格监测挖掘出有病患颤动环境热气时，体温为37.2°C，心率为134/87 mm Hg，发烧为每分钟110次，颤动振幅为每分钟16次，氧原色为96％。肺部听诊显示有支气管炎，并同步进行了胸片监测，据媒体报道未有挖掘出有诱发（三幅1）。
亚型和甲类流行性感冒的慢速小分子扩增测试者（NAAT）为有性。取得了颊咽拭子遗骸，并通过NAAT将其送给去监测HIV性颤动系统寄生虫。
据媒体报道在48全部都是程内对所有测试者的寄生虫原则上呈有性，有数亚型和甲类流行性感冒，副流行性感冒，颤动系统合胞HIV，颊HIV，腺HIV和已知会导致全人类哮喘的四种类似冠状HIV株（HKU1，NL63、229E和OC43） ）。根据病患的环游历历史学者，立即汇报偏远地区和的县政务院门。华盛顿政务院与紧急照护病理心理医生一起汇报了CDC紧急行动中的心。
尽管该病患通报感叹他不会去过广东鱼肉零售商，也不会通报在去中的国环游期间与病重者有任何接触，但哮喘防治控制中的心的现场首肯有必需根据举可有来说的哮喘防治控制中的心对病患同步进行2019-nCoV测试者。
根据CDC指南抽取了8个遗骸，有数胰岛素，颊咽和；大咽拭子遗骸。遗骸采集后，病患被送给往贫穷强制，并由当地政务院门同步进行大力监测。
2020年1翌年20日，哮喘防治控制中的心（CDC）验证病患的颊咽和；大咽拭子通过实时逆转录酶-聚合酶裂解（rRT-PCR）监测为2019-nCoV非类似。
在哮喘防治控制中的心的主题专家，的县和偏远地区卫生官员，紧急照护服务以及医务人员领导和现场的配合下，病患被送给往普罗维登斯地区照护中的心的热气强制病房同步进行病理仔细观察，并先是哮喘防治控制中的心的医护人员有关接触，飞沫和气球的防护措施的建议，并有着护目镜。
病倒时病患通报接下来肠胃，有2天的恶心和抽搐历史学者。他通报感叹他不会颤动急促或胸痛。生命体征在较长时间覆盖范围。体格监测挖掘出有病患粘膜湿气。其余的监测通常不轻微。
病倒后，病患给予了支持治疗法，有数2擢为生理盐水和恩丹以纾缓恶心。
三幅2-根据哮喘日和住院治疗日（2020年1翌年16日至2020年1翌年30日）的抽搐和最高者体温
在住院治疗的第2至5天（病重的第6至9天），病患的生命体征原则上维持稳定，除了注意到间歇发烧并伴有心动过速（三幅2）。病患继续通报非生产性肠胃，并注意到疲倦。
在住院治疗第二天的下午，病患排便利于，腹部不适。早上有第二次水泡稀疏的媒体报道。抽取该排泄物的样品用作rRT-PCR测试者，以及其他颤动系统遗骸（颊咽和；大咽）和胰岛素。排泄物和两个颤动系统遗骸后来原则上通过rRT-PCR监测为2019-nCoV非类似，而胰岛素仍为有性。
其间的治疗法在很大某种程度上是支持性的。为了同步进行抽搐出有；大处理，病患需根据需给予解热疗法，该疗法有数每4全部都是程650 mg对乙酰硫酸基酚和每6全部都是程600 mg布洛芬。在住院治疗的前六天，他还因接下来肠胃而口服了600毫克稍创醚友好条分之一6擢为生理盐水。
表格1-病理的实验室结果
病患强制单元的性质最初仅无需即时照护点的实验室测试者；从医务人员第3天开始可以同步进行全部都是红细胞小数和胰岛素药理学数据分析。
在医务人员第3天和第5天（哮喘第7天和第9天）的的实验室结果揭示出有巨噬细胞减少病征，轻度血小板减少病征和肌酸激酶高水平擢为高（表格1）。此之外，肝功能指标也有所变化：碱性酪氨酸（每擢为68 U），丙硫酸酸硫酸基转移酶（每擢为105 U），天冬硫酸酸硫酸基转移酶（每擢为77 U）和乳酸脱氢酶（每擢为465 U）的高水平分别为：在住院治疗的第5天所有擢为高。鉴于病患反复发烧，在第4天取得血液循环培养；迄今为止，这些都不会增长。
三幅3-2020年1翌年22日（臀部第7天，医务人员第3天）的后前胸和之外侧胸片
三幅4-2020年1翌年24日（臀部第5天，医务人员第9天）的后前胸X线片
据媒体报道，在医务人员第3天（病重第7天）外景的臀部X光片未有显示浸润或诱发迹象（三幅3）。
但是，从医务人员第5天早上（病重第9天）早上同步进行的第二次臀部X光片监测显示，左肺下叶有脑部病（三幅4）。
这些之外科挖掘出有与从医务人员第5天早上开始的颤动正常变化相一致，当时病患在颤动周围热气时通过发烧MRI原色测定的MRI原色绝对值降至90％。
在第6天，病患开始给予必需水蒸气，该水蒸气由颊导管以每分钟2擢为的速度运输给。受制于病理观感的变化和对医务人员取得性脑部病的非议，开始运用作万古霉素（1750 mg耗损剂量，然后每8全部都是程静脉注射1 g）和青霉素威尔顿肟（每8全部都是程静脉注射）治疗法。
三幅5-前后臀部X光片，2020年1翌年26日（哮喘第十天，医务人员第六天）
在医务人员第6天（病重第10天），第四次臀部X射线拍照显示两个肺中的都有基底条状混浊，这一挖掘出有与非类似脑部病吻合（三幅5），并且在听诊时在两个肺中的都注意到了罗音。鉴于核辐射之外科挖掘出有，重新考虑给予水蒸气必需，病患接下来发烧，多个部位接下来非类似的2019-nCoV RNA非类似，以及发表格了与核辐射性脑部病拓展原则上的导致脑部病在该病患中的，病理心理医生充满活力同情心地运用作了自然科学抗HIV治疗法。
静脉注射瑞德昔韦（一种即将合作开发的新型蛋白质类似物前药）在第7天早上开始，但未有仔细观察到与输注有关的不良事件。在对甲氧丁耐药的紫色葡萄球菌同步进行了连续的降钙素原高水平和颊PCR监测后，在第7天早上停用万古霉素，并在第二天停用青霉素威尔顿肟。
在医务人员第8天（病重第12天），病患的病理状况取得改善。停止必需水蒸气，他在颤动周围热气时的氧原色绝对值更高到94％至96％。在此之后的双侧下叶罗音不再共存。他的食欲取得改善，除了间歇干咳和颊漏之外，他不会抽搐。
截至2020年1翌年30日，病患仍住院治疗。他有发热，除肠胃之外，所有抽搐原则上已纾缓，肠胃的某种程度即将减轻。
方法
遗骸采集
根据CDC指南取得用作2019-nCoV病患测试者的病理遗骸。用合成纤维拭子抽取了12个颊咽和；大咽拭子遗骸。
将每个拭子插入包含2至3 mlHIV运输介质的之外新鲜管中的。将血集在胰岛素分立管中的，然后根据CDC指南同步进行离心。排泄物和排泄物遗骸分别抽取在新鲜遗骸容器中的。样品在2°C至8°C彼此之间贮存，直到准备好载运给至CDC。
在哮喘的第7、11和12天抽取了重复同步进行的2019-nCoV测试者的遗骸，有数颊咽和；大咽拭子，胰岛素以及排泄物和排泄物抽取。
2019-NCOV的病患测试者
运用作从公合作开发布的HIV脱氧核糖小分子拓展而来的rRT-PCR分析法测试者了病理遗骸。与在此之后针对风湿热急性颤动综合征冠状HIV（SARS-CoV）和中的东颤动综合征冠状HIV（MERS-CoV）的病患方法类似，它有着三个核衣壳基因靶标和一个非类似对照靶标。该测定的描绘出有为RRT-PCR扬声器引物和探针和脱氧核糖小分子文档中的必需的CDC的实验室文档网站2019-nCoV上。
性状PCR
2020年1翌年7日，中的国数据分析人员通过宾夕法尼亚的县国立卫生数据分析院GenBank图表库和全部都是球相关联所有流行性感冒图表倡议（GISAID）图表库相关联了2019-nCoV的非常简单基因脱氧核糖小分子；随后发布了有关强制2019-nCoV的通报。
从rRT-PCR非类似遗骸（；大咽和颊咽）中的提取小分子，并在Sanger和下一代PCR和平台（Illumina和MinIon）上用作全部都是基因组PCR。运用作5.4.6原版的Sequencher软件（Sanger）进行时了脱氧核糖小分子出有厂。minimap软件，原版本2.17（MinIon）；和freebayes软件1.3.1原版（MiSeq）。将非常简单基因组与必需的2019-nCoV参照脱氧核糖小分子（GenBank登录号NC_045512.2）同步进行比起。
结果
2019-NCOV的遗骸测试者
表格2-2019年新型冠状HIV（2019-nCoV）的实时逆转录酶-聚合酶-裂解测试者结果
该病患在病重第4自是取得的初始颤动系统抽取（颊咽拭子和；大咽拭子）在2019-nCoV呈非类似（表格2）。
尽管病患最初观感为轻度抽搐，但在哮喘第4天的低循环阈绝对值（Ct）绝对值（颊咽遗骸中的为18至20，；大咽遗骸中的为21至22）表格明这些遗骸中的HIV高水平较高。
在哮喘第7天取得的两个上颤动系统遗骸在2019-nCoV仍维持非类似，有数颊咽拭子遗骸中的接下来高高水平（Ct绝对值23至24）。在哮喘第7天取得的排泄物在2019-nCoV中的也呈非类似（Ct绝对值为36至38）。两种采集月份的胰岛素抽取在2019-nCoV原则上为有性。
在哮喘第11天和第12天取得的颊咽和；大咽遗骸显示出有HIV高水平下降的趋势。
；大咽遗骸在病重第12天的2019-nCoV测试者呈有性。在这些月份取得的胰岛素的rRT-PCR结果仍未有定。
性状PCR
；大咽和颊咽遗骸的非常简单基因组脱氧核糖小分子彼此相同，并且与其他必需的2019-nCoV脱氧核糖小分子几乎相同。
该病患的HIV与2019-nCoV参照脱氧核糖小分子（NC_045512.2）在开放阅读上端8出有；大处极少3个蛋白质和1个不同。该脱氧核糖小分子可通过GenBank取得（登录号MN985325）。
版主
我们关于宾夕法尼亚的县首度2019-nCoV住院治疗疟疾的通报感叹明了这一新兴哮喘的几个各个方面唯未有完全部都是理解，有数的传播动态和病理哮喘的全部都是部覆盖范围。
我们的疟疾病患曾去过中的国长沙，但通报感叹他在长沙期间不会去过鱼肉家禽或照护机构，也不会病危的接触。尽管他的2019-nCoV染病的来源唯不清楚，但已公开了人对人的传播的确实。
到2020年1翌年30日，唯未有挖掘出有与此疟疾相关的2019-nCoV诱发疟疾，但仍在密切关系监视下。
在哮喘的第4天和第7天从上颤动系统遗骸中的监测到有着低Ct绝对值的2019-nCoV RNA，表格明HIV载量高且有着的传播潜力。
绝对值得注意的是，我们还在病患病重第7天抽取的排泄物抽取中的监测到了2019-nCoV RNA。尽管我们疟疾病患的胰岛素遗骸反复注意到2019-nCoV有性，但在中的国风湿热病患的血液循环中的仍监测到HIVRNA。然而，肺之外监测HIVRNA并不一定意味着共存传染性HIV，目前唯不清楚在颤动系统之外部监测HIVRNA的病理意义。
目前，我们对2019-nCoV染病的病理覆盖范围的理解非常受限制。在中的国，已经媒体报道了诸如导致的脑部病，肺气肿，急性颤动困顿综合征（ARDS）和脑部损伤等并发病征，有数致命的后果。然而，重要的是要注意，这些疟疾是根据其脑部病病患确定的，因此或许会使通报相反更是导致的结果。
我们的疟疾病患最初观感为轻度肠胃和低度间歇发烧，在病重的第4天不会臀部X光监测的脑部病迹象，而在病重第9天拓展为脑部病之前，这些非特异性体征和抽搐在早期在病理上，2019-nCoV染病的病理过程或许与许多其他类似疟疾不会轻微区别，偏爱是在夏季颤动系统HIV季节。
另之外，本疟疾病患在哮喘的第9天拓展为脑部病的适时与近期肠胃的猝死（病病征后中的位数为8天）原则上。尽管根据病患的病理状况恶化重新考虑前提给予remdesivir慈悲的运用作，但仍需同步进行随机对照次测试以确定remdesivir和任何其他数据分析药物治疗法2019-nCoV染病的安全部都是性和有效性。
我们通报了宾夕法尼亚的县首度通报的2019-nCoV染病病患的病理不同之处。
该疟疾的关键各个方面有数病患在阅读有关时绝对值的预防无视后重新考虑寻求照护；由当地照护服务提供者验证病患在在到长沙的环游历历史学者，随后在当地，的县和美国联邦政府预防官员彼此之间同步进行协调；并确定或许的2019-nCoV染病，从而可以进一步强制病患并随后对2019-nCoV同步进行的实验室验证，并无需病患病倒进一步评估和管理工作。
该疟疾通报强调了病理心理医生对于任何注意到急性哮喘抽搐的求诊病患，要总结出有在在的环游经历或接触病病征的特殊性，为了确保正确识别和及时强制或许面临2019-nCoV染病效用的病患，并帮助减少进一步的的传播。
就此，本通报强调需确定与2019-nCoV染病相关的病理哮喘，病病征机理和HIV穿孔接下来时间的
全部都是部覆盖范围和自然历历史学者，以为病理管理工作和预防决策提供依据。
下述为英文原版
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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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