(破天荒)美国首例新冠病毒确诊病例康复全记录(中英文)

2022-02-07 04:57:58 来源:
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概述

在中的国上海开始的新型冠状流感病毒(2019-nCoV)爆放进一步死灰复燃,业已在多个国家所患病。我们通报了在澳大利亚确认的尚未有2019-nCoV病毒病症候群,并揭示了该病症候群的鉴定,治疗,药理学过程和负责管理,之以外患儿在病情第9天体现为胃癌时的刚开始轻度腹泻。

该案例忽略了药理学药剂师与人口众多,的州和州政府各级公共医疗当地政府彼此间深厚协作的效用,以及只能短时间传播方式与这种新放病毒患儿的眼科有关的药理学反馈的供给。

2019年12同月31日,中的国通报了与武汉市南昌市华南海产批放零售商有关的成年人中的的胃癌病症候群。

2020年1同月7日,中的国医疗当地政府确认该簇与新型冠状流感病毒2019-nCoV有关。尽管刚开始媒体报道的病症候群与南昌市海产零售商的暴露有关,但这两项的流行病学样本注记明,悄悄放生2019-nCoV人际传播方式。

截至2020年1同月30日,在仅仅21个国家所/地区通报了9976例病症候群,之以外2020年1同月20日媒体报道的澳大利亚尚未有患病的2019-nCoV病毒病症候群。

全部都是球以内内悄悄透过清查,以不够好地了解传播方式动态和药理学癌症候群以内。本通报揭示了在澳大利亚确认的尚未有2019-nCoV病毒的流行病学和药理学不同之处。

案例通报

2020年1同月19日,一名35岁的女子注意到在华盛顿的州斯诺霍米什县的一家急诊诊所,有4天的呕吐和主观放烧简史。病人到诊所体检时,在候诊室戴上口内罩。继续前进约20分钟后,他被带回体检室拒绝接受了提供者者的评估。

他透露,他在中的国上海探望家人才将1同月15日返回华盛顿的州。该患儿注记示,他已从澳大利亚癌症候群操纵与防治中的心(CDC)收到有关中的国新型冠状流感病毒暴放的肥胖中央气象局,由于他的腹泻和早先的环游世界,他最终去看药剂师。

所示1-2020年1同月19日(癌症候群第4天)的后前额和后侧胸片

除了高三酸酯缺乏症候群的病简史以外,该患儿还是其他肥胖的不尼古丁。体格体检推断出患儿肺部环境二氧化碳时,血浆循环为37.2°C,眼压为134/87 mm Hg,发烧为每分钟110次,肺部频率为每分钟16次,锂原色为96%。肺部听诊推测有支气管炎,并透过了胸片体检,据媒体报道并未推断出诱发(所示1)。

及第型和甲类流感的短时间核酸扩增飞行测试(NAAT)为阳性。授予了颈咽拭子头颅骨,并通过NAAT将其送来去监测流感病毒性肺部微生物。

据媒体报道在48每隔内对所有飞行测试的微生物原则上深褐色阳性,之以外及第型和甲类流感,副流感,肺部合胞流感病毒,颈流感病毒,腺流感病毒和已知都会导致生命体癌症候群的四种类似冠状流感病毒株(HKU1,NL63、229E和OC43) )。根据患儿的环游世界文化简史,立即汇报人口众多和的州医疗部门。华盛顿医疗部与紧急眼科药理学药剂师朋友们汇报了CDC紧急行动中的心。

尽管该患儿通报说是他没去过华南海产零售商,也没通报在去中的国环游世界之后与病危者有任何受伤害,但癌症候群防治操纵中的心的负责人同意有必要根据这两项的癌症候群防治操纵中的心对患儿透过2019-nCoV飞行测试。

根据CDC须知搜集了8个头颅骨,之以外血浆,颈咽和口内咽拭子头颅骨。头颅骨通过观察后,患儿被送来回家庭隔绝,并由当地医疗部门透过积极监测。

2020年1同月20日,癌症候群防治操纵中的心(CDC)确认患儿的颈咽和口内咽拭子通过实时遗传物质-酵素链反应(rRT-PCR)监测为2019-nCoV非典型。

在癌症候群防治操纵中的心的主题领域专家,的州和人口众多医疗行政官员,紧急诊疗服务以及该医院领导和负责人的配合下,患儿被送来回普罗维登斯地区诊疗中的心的二氧化碳隔绝病房透过药理学注意到,并跟随癌症候群防治操纵中的心的医务人员有关受伤害,飞沫和空中的防护措施的同意,并带有靴子。

中风时患儿通报停滞呕吐,有2天的白痴和呕吐简史。他通报说是他没肺部急促或胸痛。生命征象在正常人以内内。体格体检推断出患儿粘膜干燥。其余的体检通常不相对来说。

中风后,患儿拒绝接受了支持病患,之以外2改授生理盐水和恩丹以大大降很低白痴。

所示2-根据癌症候群日和中风日(2020年1同月16日至2020年1同月30日)的腹泻和极高血浆循环

在中风的第2至5天(病危的第6至9天),患儿的生命征象基本保持稳定,除了注意到间歇放烧并;还有心动过速(所示2)。患儿继续通报非生产性呕吐,并注意到疲倦。

在中风第二天的下午,患儿排便通畅,腹部不适。凌晨有第二次大便稀疏的媒体报道。搜集该异味的样品用于rRT-PCR飞行测试,以及其他肺部头颅骨(颈咽和口内咽)和血浆。异味和两个肺部头颅骨后来原则上通过rRT-PCR监测为2019-nCoV非典型,而血浆仍为阳性。

在此之后的病患在很小相对上是支持性的。为了透过腹泻附近理,患儿只能根据只能拒绝接受镇痛治疗法,该治疗法之以外每4每隔650 mg咖啡因和每6每隔600 mg不良反应。在中风的前六天,他还因停滞呕吐而服用了600毫克愈来愈创醚和约6改授生理盐水。

注记1-药理学麻省理工学院结果

患儿隔绝各别的性质刚开始仅允许将都会诊疗点麻省理工学院飞行测试;从该医院第3天开始可以透过全部都是血细胞计数和血浆化学研究工作。

在该医院第3天和第5天(癌症候群第7天和第9天)的麻省理工学院结果反映出白细胞减少症候群,轻度粒细胞减少症候群和肌酸激酶高水平改授高(注记1)。此以外,肝脏指标也稍稍推移:还原性脂质(每改授68 U),丙氨酸氨基转移酶(每改授105 U),谷胱甘肽氨基转移酶(每改授77 U)和脂肪酸脱氢酶(每改授465 U)的高水平分别为:在中风的第5天所有改授高。鉴于患儿连续不断放烧,在第4天授予血浆培养;迄今为止,这些都没增长。

所示3-2020年1同月22日(头部第7天,该医院第3天)的后前额和后侧胸片

所示4-2020年1同月24日(头部第5天,该医院第9天)的后前额X线片

据媒体报道,在该医院第3天(病危第7天)拍摄的头部X光片并未推测灌注或诱发有可能(所示3)。

但是,从该医院第5天凌晨(病危第9天)凌晨透过的第二次头部X光片体检推测,左肺下叶有胃癌(所示4)。

这些某类推断出与从该医院第5天凌晨开始的肺部稳定状态推移相吻合,当时患儿在肺部附近二氧化碳时通过发烧侵入性原色推算出的侵入性原色系数降至90%。

在第6天,患儿开始拒绝接受缺少氮气,该氮气由颈导管以每分钟2改授的平原则上速度输送来。毕竟药理学体现的推移和对该医院授予性胃癌的注意,开始用于水杨酸(1750 mg负荷施打,然后每8每隔制剂1 g)和萘威尔顿醛(每8每隔制剂)病患。

所示5-前后头部X光片,2020年1同月26日(癌症候群第十天,该医院第六天)

在该医院第6天(病危第10天),第四次头部X射线拍下推测两个肺中的都有一组条状变黑,这一推断出与非相较为胃癌大相径庭(所示5),并且在听诊时在两个肺中的都注意到了罗音。鉴于核辐射某类推断出,最终得到氮气缺少,患儿停滞放烧,多个部位停滞非典型的2019-nCoV RNA非典型,以及放注记了与核辐射性胃癌工业放展一致的严重胃癌在该患儿中的,药理学药剂师富有同情心地用于了自然科学抗流感病毒病患。

制剂瑞德昔韦(一种悄悄开放的新型多肽抗病毒前药)在第7天凌晨开始,但并未注意到到与口服有关的经常性意外事件。在对及第锂霖MRSA的金黄色葡萄球菌透过了连续的降钙素原高水平和颈PCR监测后,在第7天凌晨关闭水杨酸,并在第二天关闭萘威尔顿醛。

在该医院第8天(病危第12天),患儿的药理学现况给与改善。中断缺少氮气,他在肺部附近二氧化碳时的锂原色系数提改授到94%至96%。原先的内侧下叶罗音取而代之发挥作用。他的食欲给与改善,除了间歇干咳和颈漏以外,他没腹泻。

截至2020年1同月30日,患儿仍中风。他有放热,除呕吐以外,所有腹泻原则上已大大降很低,呕吐的相对悄悄缓解。

方法

头颅骨通过观察

根据CDC须知授予用于2019-nCoV治疗飞行测试的药理学头颅骨。用塑胶拭子搜集了12个颈咽和口内咽拭子头颅骨。

将每个拭子插入包含2至3 ml流感病毒转运颗粒的单独无害水银的。将血集在血浆除去水银的,然后根据CDC须知透过离心。排泄物和异味头颅骨分别搜集在无害头颅骨容器中的。样品在2°C至8°C彼此间储存,直到准备好运送来至CDC。

在癌症候群的第7、11和12天搜集了重复透过的2019-nCoV飞行测试的头颅骨,之以外颈咽和口内咽拭子,血浆以及排泄物和异味取样。

2019-NCOV的治疗飞行测试

用于从公开放布的流感病毒多肽工业放展而来的rRT-PCR分析法飞行测试了药理学头颅骨。与原先针对加护急性肺部性疾病冠状流感病毒(SARS-CoV)和中的东肺部性疾病冠状流感病毒(MERS-CoV)的治疗方法十分相似,它具有三个核双链基因组贝克曼和一个非典型相比较贝克曼。该推算出的揭示为RRT-PCR面板引物和探针和多肽反馈中的能用的CDC麻省理工学院反馈网上2019-nCoV上。

遗传化学合成

2020年1同月7日,中的国研究工作人员通过澳大利亚国立医疗研究工作部GenBank样本库和全部都是球协作所有流感样本倡议(GISAID)样本库协作了2019-nCoV的基本基因组多肽;随后放布了有关隔绝2019-nCoV的通报。

从rRT-PCR非典型头颅骨(口内咽和颈咽)中的提取核酸,并在Sanger和下一代化学合成应用应用程序(Illumina和MinIon)上用于全部都是基因组组化学合成。用于5.4.6版的Sequencher应用程序(Sanger)启动了多肽组装。minimap应用程序,版本2.17(MinIon);和freebayes应用程序1.3.1版(MiSeq)。将基本基因组组与能用的2019-nCoV概述多肽(GenBank登录号NC_045512.2)透过较为。

结果

2019-NCOV的头颅骨飞行测试

注记2-2019年新型冠状流感病毒(2019-nCoV)的实时遗传物质-酵素-链反应飞行测试结果

该患儿在病危第4天时授予的初始肺部取样(颈咽拭子和口内咽拭子)在2019-nCoV深褐色非典型(注记2)。

尽管患儿刚开始体现为轻度腹泻,但在癌症候群第4天的很低循环阈系数(Ct)系数(颈咽头颅骨中的为18至20,口内咽头颅骨中的为21至22)注记明这些头颅骨中的流感病毒高水平较差。

在癌症候群第7天授予的两个上肺部头颅骨在2019-nCoV仍保持非典型,之以外颈咽拭子头颅骨中的停滞高高水平(Ct系数23至24)。在癌症候群第7天授予的异味在2019-nCoV中的也深褐色非典型(Ct系数为36至38)。两种通过观察一月的血浆取样在2019-nCoV原则上为阳性。

在癌症候群第11天和第12天授予的颈咽和口内咽头颅骨推测出流感病毒高水平下降的趋势。

口内咽头颅骨在病危第12天的2019-nCoV飞行测试深褐色阳性。在这些一月授予的血浆的rRT-PCR结果仍并确切。

遗传化学合成

口内咽和颈咽头颅骨的基本基因组组多肽彼此相近,并且与其他能用的2019-nCoV多肽几乎相近。

该患儿的流感病毒与2019-nCoV概述多肽(NC_045512.2)在开放学习者框8附近均3个多肽和1个不同。该多肽可通过GenBank授予(登录号MN985325)。

网上

我们关于澳大利亚尚未有2019-nCoV患病病症候群的通报说是明了这一新兴癌症候群的几个方面尚并未完全部都是了解,之以外传播方式动态和药理学癌症候群的全部都是部以内。

我们的病症候群患儿曾去过中的国上海,但通报说是他在上海之后没去过海产批放零售商或诊疗,也没病危的受伤害。尽管他的2019-nCoV病毒的可能尚不明确,但已公开了人对人传播方式的证据。

到2020年1同月30日,尚并未推断出与此病症候群无关的2019-nCoV继放病症候群,但仍在深厚监视下。

在癌症候群的第4天和第7天从上肺部头颅骨中的监测到具有很低Ct系数的2019-nCoV RNA,注记明流感病毒总重量高且具有传播方式发展潜力。

系数得一提的是的是,我们还在患儿病危第7天搜集的异味取样中的监测到了2019-nCoV RNA。尽管我们病症候群患儿的血浆头颅骨连续不断注意到2019-nCoV阳性,但在中的国加护患儿的血浆中的仍监测到流感病毒RNA。然而,肺以外监测流感病毒RNA并不一定假定发挥作用传染性流感病毒,目前尚不明确在肺部以外部监测流感病毒RNA的药理学意义。

目前,我们对2019-nCoV病毒的药理学以内的了解十分极少。在中的国,早已媒体报道了诸如严重的胃癌,肺部衰竭,急性肺部窘迫性疾病(ARDS)和肝脏损伤等并放症候群,之以外致命的后果。然而,重要的是要注意,这些病症候群是根据其胃癌治疗确切的,因此或许都会使通报倾向不够严重的结果。

我们的病症候群患儿刚开始体现为轻度呕吐和很低度间歇放烧,在病危的第4天没头部X光体检的胃癌有可能,而在病危第9天工业放展为胃癌之前,这些非免疫征象和腹泻在不够早在药理学上,2019-nCoV病毒的药理学过程或许与许多其他类似狂犬病没相对来说区别,尤其是在冬季肺部流感病毒季节性。

另以外,本病症候群患儿在癌症候群的第9天工业放展为胃癌的时机与近来肺部困难的放作(放病后中的位数为8天)一致。尽管根据患儿的药理学现况紧张最终是否得到remdesivir慈悲的用于,但仍只能透过探索性试验以确切remdesivir和任何其他研究工作药物病患2019-nCoV病毒的安全部都是性和理论上。

我们通报了澳大利亚尚未有通报的2019-nCoV病毒患儿的药理学不同之处。

该病症候群的关键方面之以外患儿在学习者有关暴放的公共医疗指示后最终借助诊疗;由当地诊疗服务提供者者确认患儿早先到上海的环游世界文化简史,随后在当地,的州和州政府公共医疗行政官员彼此间透过协调;并确切或许的2019-nCoV病毒,从而可以进一步隔绝患儿并随后对2019-nCoV透过麻省理工学院确认,并允许患儿中风进一步评估和负责管理。

该病症候群通报忽略了药理学药剂师对于任何注意到急性癌症候群腹泻的就诊患儿,要概括出早先的环游世界经历或受伤害病简史的效用,为了确保正确识别和立即隔绝或许面临2019-nCoV病毒高风险的患儿,并帮助减少进一步的传播方式。

仍要,本通报忽略只能确切与2019-nCoV病毒无关的药理学癌症候群,放病中间体和流感病毒脱落停滞时间的

全部都是部以内和自然文化简史,以为药理学负责管理和公共医疗决策提供者依据。

请注意为中文翻译

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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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