(重磅)美国政府首例新冠病毒确诊病例康复全记录(中英文)

2022-01-10 06:18:31 来源:
分享:

摘要

在当中华人民共和国上海开始的新型大肠杆菌(2019-nCoV)爆所发短时间内蔓延,现已在多个转型中华人民共和国家复所发。我们分析报告了在American断定的唯一未2019-nCoV病菌病事例,并所述了该病事例的鉴别,病症,病理操作过程和管理制度,都有病征在病情第9天此展现出为结质子病时的以在此之前轻度病征。

该案事例强调了病理眼科医生与地方,州和联邦议会各级卫生新加坡政府二者之间密切联系协作的益处,以及须要短时间内传布与这种新所发病菌病征的诊疗有关的病理接收者的需求。

2019年12年底31日,当中华人民共和国分析报告了与宜昌襄阳市广东紫菜批所发的产品有关的许多人当中的结质子病病事例。

2020年1年底7日,当中华人民共和国卫生新加坡政府断定该簇与新型大肠杆菌2019-nCoV有关。尽管以在此之前另据的病事例与襄阳市紫菜的产品的曝露有关,但当在此之前的流行病学资料此指出,打算所发生2019-nCoV人际传布。

截至2020年1年底30日,在至少21个转型中华人民共和国家/内陆地区分析报告了9976事例病事例,都有2020年1年底20日另据的American唯一未复所发的2019-nCoV病菌病事例。

全世界全域内打算展开报告,以更为好地理解传布特性和病理营养不良全域。本分析报告所述了在American断定的唯一未2019-nCoV病菌的流行病学和病理特性。

案事例分析报告

2020年1年底19日,一名35岁的铁饼造浮现在华盛顿州斯诺霍米塔奇拉州的的公司急诊诊疗机构,有4天的腹痛和理性头晕史。病人到诊疗机构体检时,在候诊室戴上朝天罩。下次约20分钟后,他被带往体检室遵从了透过者的审计。

他透露,他在当中华人民共和国上海探望家人时为1年底15日返回华盛顿州。该病征此回应,他已从American营养不良掌控与疟疾当为中心(CDC)收到有关当中华人民共和国新型大肠杆菌暴所发的卫生警报,由于他的病征和都有的环游,他暂时去看眼科医生。

绘造出1-2020年1年底19日(营养不良第4天)的后颈部和部份侧胸片

除了年级酸酯果糖的病史部份,该病征还是其他卫生的不吸烟者。体格体检所推断出病征排尿环境水蒸气时,体液循环为37.2°C,皮质醇为134/87 mm Hg,脉搏为每分钟110次,排尿频率为每分钟16次,镁一般来说为96%。肺部听诊此指出有脑膜炎,并展开了胸片体检,据另据未曾所推断出异常(绘造出1)。

亚型和九一亚型的短时间内质子酸扩增验证(NAAT)为同义。获了背咽拭子头颅骨,并通过NAAT将其送去定量感染性排尿道微生物。

据另据在48星期内对所有验证的微生物外呈同义,都有亚型和九一亚型,副亚型,排尿道合胞感染,背感染,腺感染和已知就会导致人类营养不良的四种常见大肠杆菌株(HKU1,NL63、229E和OC43) )。根据病征的环游在历史上,即刻指示地方和州卫生部门。华盛顿卫生部与应急诊疗病理眼科医生一起指示了CDC应急行动当为中心。

尽管该病征分析报告却说他无法去过广东紫菜的产品,也无法分析报告在去当中华人民共和国环游其间与体弱者有任何带入,但营养不良疟疾掌控当为中心的第一时间准许有必要根据当在此之前的营养不良疟疾掌控当为中心对病征展开2019-nCoV验证。

根据CDC范本收集了8个头颅骨,都有抗体,背咽和朝天咽拭子头颅骨。头颅骨收集后,病征被送到家庭强制,并由当地卫生部门展开积极检测。

2020年1年底20日,营养不良疟疾掌控当为中心(CDC)断定病征的背咽和朝天咽拭子通过系统对丝一镁化氮酸-聚合酶裂解(rRT-PCR)定量为2019-nCoVHIV。

在营养不良疟疾掌控当为中心的隐喻领域专家,州和地方卫生官员,应急诊疗服务以及养老院领导和第一时间的配合下,病征被送到普罗维登斯内陆地区诊疗当为中心的水蒸气强制病房展开病理注意到,并跟随营养不良疟疾掌控当为中心的医护其他部门有关带入,飞沫和空当中防护应急措施的决定,并带有护目镜。

造出院时病征分析报告短时间腹痛,有2天的羞耻和咳嗽史。他分析报告却说他无法排尿急促或胸痛。生命哮喘在较长时间全域内。体格体检所推断出病征粘膜高温。其余的体检有时候不轻微。

造出院后,病征遵从了支持疗程,都有2天和生理盐水和恩丹以缓解羞耻。

绘造出2-根据营养不良日和患病日(2020年1年底16日至2020年1年底30日)的病征和最高体液循环

在患病的第2至5天(体弱的第6至9天),病征的生命哮喘基本依然稳定,除了造浮现经年累月头晕并;还有心动过速(绘造出2)。病征独自分析报告非生产性腹痛,并造浮现疲倦。

在患病第二天的凌晨,病征排尿在行,腹部不适。傍晚有第二次饱密集的另据。收集该粪的样品主要用途rRT-PCR验证,以及其他排尿道头颅骨(背咽和朝天咽)和抗体。粪和两个排尿道头颅骨后来外通过rRT-PCR定量为2019-nCoVHIV,而抗体仍为同义。

在此其间的疗程在很大持续性上是支持性的。为了展开病征处理,病征须要根据须要遵从功效疗法,该疗法都有每4星期650 mg对乙酰一镁化氮基酚和每6星期600 mg布洛芬。在患病的在此之前六天,他还因短时间腹痛而摄入了600毫克渐创醚和约6天和生理盐水。

此表1-病理研究中心结果

病征强制单元的性质以在此之前大部分受限制即时诊疗点研究中心验证;从养老院第3天开始可以展开全淋巴结枚举和抗体化学深入研究。

在养老院第3天和第5天(营养不良第7天和第9天)的研究中心结果反映造出炎症减少症,轻度血小板减少症和肌酸激酶水平天和高(此表1)。此部份,肝功能指标也相当持续性改变:碱性磷酸酶(每天和68 U),丙一镁化氮酸一镁化氮基转移酶(每天和105 U),糖类一镁化氮基转移酶(每天和77 U)和乳酸天冬一镁化氮酸(每天和465 U)的水平分别为:在患病的第5天所有天和高。鉴于病征反复头晕,在第4天获体液培植;迄今为止,这些都无法增长。

绘造出3-2020年1年底22日(面部第7天,养老院第3天)的后颈部和部份侧胸片

绘造出4-2020年1年底24日(面部第5天,养老院第9天)的后颈部X线片

据另据,在养老院第3天(体弱第7天)制作的面部X光片未曾此指出伴生或异常确实(绘造出3)。

但是,从养老院第5天傍晚(体弱第9天)傍晚展开的第二次面部X光片体检此指出,左肺下叶有结质子病(绘造出4)。

这些影像学所推断出与从养老院第5天傍晚开始的排尿状态改变角度看,之在此之前病征在排尿外围水蒸气时通过脉搏高血压一般来说定量的高血压一般来说个数降至90%。

在第6天,病征开始遵从必需水蒸气,该水蒸气由背静脉以每分钟2天和的速度输送。难以实现病理此展现出的改变和对养老院获溃疡的关注,开始可用低剂量(1750 mg负荷药品,然后每8星期肌肉注射1 g)和唑吡吡啶(每8星期肌肉注射)疗程。

绘造出5-在此之前后面部X光片,2020年1年底26日(营养不良第十天,养老院第六天)

在养老院第6天(体弱第10天),第四次面部X射线剧照此指出两个肺当中都有大块条状浑浊,这一所推断出与非的现代结质子病完全一致(绘造出5),并且在听诊时在两个肺当中都造浮现了罗音。鉴于质子辐射影像学所推断出,暂时给与水蒸气必需,病征短时间头晕,多个部位短时间HIV的2019-nCoV RNAHIV,以及所发此表了与质子辐射溃疡转型一致的更为为严重结质子病在该病征当中,病理眼科医生富有同情心地可用了深入研究性抗感染疗程。

肌肉注射凯西昔韦(一种打算联合开所发的新型质子苷酸萘在此之前药)在第7天傍晚开始,但未曾注意到到与朝天服有关的不良惨剧。在对以次镁西林耐药的淡黄色革兰氏展开了连续的降钙素原水平和背PCR定量后,在第7天傍晚转用低剂量,并在第二天转用唑吡吡啶。

在养老院第8天(体弱第12天),病征的病理境况取得改善。暂时必需水蒸气,他在排尿外围水蒸气时的镁一般来说个数大大提高到94%至96%。当初的双侧下叶罗音仍然存在。他的食欲取得改善,除了经年累月干咳和背漏部份,他无法病征。

截至2020年1年底30日,病征仍患病。他有气喘,除腹痛部份,所有病征外已缓解,腹痛的持续性打算减轻。

步骤

头颅骨收集

根据CDC范本获主要用途2019-nCoV病症验证的病理头颅骨。用合成橡胶拭子收集了12个背咽和朝天咽拭子头颅骨。

将每个拭子接在包含2至3 ml感染转运介质的除此以部份杀菌管当中。将血集在抗体分离管当中,然后根据CDC范本展开离心。血浆和粪头颅骨分别收集在杀菌头颅骨密封当中。样品在2°C至8°C二者之间内含,直到准备好运送至CDC。

在营养不良的第7、11和12天收集了重复展开的2019-nCoV验证的头颅骨,都有背咽和朝天咽拭子,抗体以及血浆和粪抽样。

2019-NCOV的病症验证

可用从公联合开所发行的感染质子苷酸转型而来的rRT-PCR新方法验证了病理头颅骨。与当初针对诊治急性排尿综合症大肠杆菌(SARS-CoV)和当中东排尿综合症大肠杆菌(MERS-CoV)的病症步骤十分相似,它不具备三个质子核糖体基因靶标和一个HIV完全一致合靶标。该定量的所述为RRT-PCR面板引物和遮罩和质子苷酸接收者当中可用的CDC研究中心接收者主页2019-nCoV上。

基因型人类基因组计划

2020年1年底7日,当中华人民共和国深入研究其他部门通过American国立卫生深入该中心GenBank资料库和全世界共享所有亚型资料首倡(GISAID)资料库共享了2019-nCoV的零碎比对;随后所发行了有关强制2019-nCoV的分析报告。

从rRT-PCRHIV头颅骨(朝天咽和背咽)当中提取质子酸,并在Sanger和新一代人类基因组计划平台(Illumina和MinIon)上主要用途全DNA人类基因组计划。可用5.4.6国际版的Sequencher软件(Sanger)顺利进行了质子苷酸零件。minimap软件,国际版本2.17(MinIon);和freebayes软件1.3.1国际版(MiSeq)。将零碎DNA与可用的2019-nCoV参考质子苷酸(GenBank登录号NC_045512.2)展开相比较。

结果

2019-NCOV的头颅骨验证

此表2-2019年新型大肠杆菌(2019-nCoV)的系统对丝一镁化氮酸-聚合酶-裂解验证结果

该病征在体弱第4四海获的初始排尿道抽样(背咽拭子和朝天咽拭子)在2019-nCoV呈HIV(此表2)。

尽管病征以在此之前此展现出为轻度病征,但在营养不良第4天的较低循环阈个数(Ct)个数(背咽头颅骨当中为18至20,朝天咽头颅骨当中为21至22)此指出这些头颅骨当中感染水平极高。

在营养不良第7天获的两个上排尿道头颅骨在2019-nCoV仍依然HIV,都有背咽拭子头颅骨当中短时间上佳(Ct个数23至24)。在营养不良第7天获的粪在2019-nCoV当中也呈HIV(Ct个数为36至38)。两种收集日期的抗体抽样在2019-nCoV外为同义。

在营养不良第11天和第12天获的背咽和朝天咽头颅骨此指出造出感染水平下降的近来。

朝天咽头颅骨在体弱第12天的2019-nCoV验证呈同义。在这些日期获的抗体的rRT-PCR结果仍未曾定。

基因型人类基因组计划

朝天咽和背咽头颅骨的零碎DNA质子苷酸彼此相异,并且与其他可用的2019-nCoV质子苷酸几乎相异。

该病征的感染与2019-nCoV参考质子苷酸(NC_045512.2)在免费阅读框8处大部分有3个质子苷酸和1个不同。该质子苷酸可通过GenBank获(登录号MN985325)。

facebook

我们关于American唯一未2019-nCoV复所发病事例的分析报告却说明了这一新兴营养不良的几个方面未曾曾完全理解,都有传布特性和病理营养不良的全部全域。

我们的病事例病征曾去过当中华人民共和国上海,但分析报告却说他在上海其间无法去过紫菜批所发的产品或诊疗机构,也无法病重的带入。尽管他的2019-nCoV病菌的比如说尚不吻合,但已匿名了人对人传布的确实。

到2020年1年底30日,未曾曾所推断出与此病事例涉及的2019-nCoV全身性病事例,但仍在密切联系监视下。

在营养不良的第4天和第7天从上排尿道头颅骨当中定量到不具备较低Ct个数的2019-nCoV RNA,此指出感染负重高且不具备传布商业价值。

个数得注意的是,我们还在病征体弱第7天收集的粪抽样当中定量到了2019-nCoV RNA。尽管我们病事例病征的抗体头颅骨反复造浮现2019-nCoV同义,但在当中华人民共和国诊治病征的体液当中仍定量到感染RNA。然而,肺部份定量感染RNA比如说意味着存在传染性感染,目在此之前尚不吻合在排尿道部份部定量感染RNA的病理意义。

目在此之前,我们对2019-nCoV病菌的病理全域的理解十分有限。在当中华人民共和国,不太可能另据了诸如更为为严重的结质子病,排尿衰竭,急性排尿窘迫综合症(ARDS)和心脏烧伤等并所发症,都有致命的必然。然而,重要的是要注意,这些病事例是根据其结质子病病症明确的,因此也许就会使分析报告偏重更为更为为严重的结果。

我们的病事例病征以在此之前此展现出为轻度腹痛和较低度经年累月头晕,在体弱的第4天无法面部X光体检的结质子病确实,而在体弱第9天转型为结质子病之在此之前,这些非特异性哮喘和病征在早期在病理上,2019-nCoV病菌的病理操作过程也许与许多其他常见疟疾无法轻微区隔,尤其是在夏天排尿道感染季节性。

另部份,本病事例病征在营养不良的第9天转型为结质子病的时机与未来会排尿困难的所发作(所发病后当中位数为8天)一致。尽管根据病征的病理境况恶化暂时是否给与remdesivir至诚的可用,但仍须要展开随机完全一致合试验车以明确remdesivir和任何其他深入研究药品疗程2019-nCoV病菌的相容性和有效性。

我们分析报告了American唯一未分析报告的2019-nCoV病菌病征的病理特性。

该病事例的这两项方面都有病征在阅读有关暴所发的卫生强制执行后暂时促使诊疗;由当地诊疗服务透过者断定病征都有到上海的环游在历史上,随后在当地,州和联邦议会卫生官员二者之间展开协调;并明确也许的2019-nCoV病菌,从而可以短时间内强制病征并随后对2019-nCoV展开研究中心断定,并受限制病征造出院实质性审计和管理制度。

该病事例分析报告强调了病理眼科医生对于任何造浮现急性营养不良病征的就诊病征,要却说明了造出都有的环游经历或带入病史的益处,为了确保正确地识别和幸而强制也许面对2019-nCoV病菌风险的病征,并帮助减少实质性的传布。

之在此之前,本分析报告强调须要明确与2019-nCoV病菌涉及的病理营养不良,所发病机理和感染穿孔短时间时间的

全部全域和自然在历史上,以为病理管理制度和卫生决策透过依据。

以下为译者

——————

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.

分享: