(重磅)澳大利亚首例新冠病毒确诊病例康复全记录(中英文)

2022-02-21 01:19:35 来源:
分享:

简要

在近现代武昌开始的从新型冠状大肠杆菌(2019-nCoV)爆发迅速肆虐,现已在多个国家确诊。我们统小数据资料了在美国政府证实的首度2019-nCoV病菌发生率,并详细描述了该发生率的鉴定,病患,毒理学处理过程和行政,除此以外病患者在病况第9天观感为瓣膜病时的原本轻度呕吐。

该犯罪行为忽视了毒理学护士与地方,俄克拉荷马州和州政府各级毒理学伊朗政府之间密切协作的重要性,以及能够较慢广泛传播与这种从新病症菌病患者的护理有关的毒理学文档的需求。

2019年12月底31日,近现代统小数据资料了与湖北省武昌市华南海鱼家禽有关的人群中会的瓣膜病发生率。

2020年1月底7日,近现代保健伊朗政府证实该簇与从新型冠状大肠杆菌2019-nCoV有关。尽管原本从新闻报道的发生率与武昌市海鱼市场的沾染有关,但也就是说的毒理学数据资料声称,早就发生2019-nCoV人际广泛传播。

截至2020年1月底30日,在最少21个国家/北部统小数据资料了9976实有发生率,除此以外2020年1月底20日从新闻报道的美国政府首度确诊的2019-nCoV病菌发生率。

全都球区域内内早就进行时调查,以格外好地了解广泛传播建模和毒理学癌症区域内。本统小数据资料详细描述了在美国政府证实的首度2019-nCoV病菌的毒理学和毒理学形态。

犯罪行为统小数据资料

2020年1月底19日,一名35岁的男子不止现在加利福尼亚俄克拉荷马州罗宾逊霍米锡金邦的一家急诊药房,有4天的头痛和主观哮喘史。病患到药房体检时,在候诊室戴上西南侧罩。等待近20分钟后,他被带到体检室给与了提供者的评核。

他透露,他在近现代武昌探视家人时为1月底15日离开加利福尼亚俄克拉荷马州。该病患者说明,他已从美国政府癌症控制与结核病中会心(CDC)收到有关近现代从新型冠状大肠杆菌死灰复燃的保健警报,由于他的呕吐和都只的环游世界,他最终去看护士。

三幅1-2020年1月底19日(癌症第4天)的后前胸和外侧胸片

除了高三酸酯黄疸的高心率外,该病患者还是其他保健的不抽烟。体格体检辨认不止病患者痉挛环境氮气时,体温为37.2°C,心率为134/87 mm Hg,脉搏为每分钟110次,痉挛频率为每分钟16次,镁低浓度为96%。肺听诊辨识有支气管炎,并进行时了胸片体检,据从新闻报道仍未辨认不止异常(三幅1)。

丙型和乙型瓣膜病的较慢脱镁核糖核酸扩增的测试(NAAT)为阳性。赢取了咽咽拭子化石,并通过NAAT将其去取去测定大肠杆菌性肠胃寄生虫。

据从新闻报道在48小时内对所有的测试的寄生虫原则上氰化氢,除此以外丙型和乙型瓣膜病,副瓣膜病,肠胃合胞大肠杆菌,咽大肠杆菌,腺大肠杆菌和已知会造成了人类癌症的四种类似冠状大肠杆菌株(HKU1,NL63、229E和OC43) )。根据病患者的环游世界历史记录,第一时间告知地方和俄克拉荷马州保健部门。波士顿保健部与即时护理毒理学护士两人告知了CDC即时行动中会心。

尽管该病患者统小数据资料说他无法去过华南海鱼市场,也无法统小数据资料在去近现代环游世界其间与患者有任何认识,但癌症结核病定时的负责人同意有适当根据也就是说的癌症结核病定时对病患者进行时2019-nCoV的测试。

根据CDC须知搜罗了8个化石,除此以外抗体,咽咽和西南侧咽拭子化石。化石捕获后,病患者被去取往中产阶级监护,并由当地保健部门进行时积极监测。

2020年1月底20日,癌症结核病定时(CDC)证实病患者的咽咽和西南侧咽拭子通过可视亚姆皮利-核酸裂解(rRT-PCR)测定为2019-nCoV中性。

在癌症结核病定时的题材研究员,俄克拉荷马州和地方保健行政官员,即时保健服务以及药房领导和负责人的为了让下,病患者被去取往奥尔巴尼北部保健中会心的氮气监护病房进行时毒理学检视,并先是癌症结核病定时的医护人员有关认识,飞沫和空中会配备保护措施的建议,并带有护目镜。

晕倒时病患者统小数据资料接下来头痛,有2天的恶心和呕吐史。他统小数据资料说他无法不止汗或胸痛。精神上体征在但会区域内内。体格体检辨认不止病患者粘膜干燥。其余的体检一般而言不轻微。

晕倒后,病患者给与了支持疗程,除此以外2再降生理盐水和恩丹以更为比较严重恶心。

三幅2-根据癌症日和就医日(2020年1月底16日至2020年1月底30日)的呕吐和最高体温

在就医的第2至5天(患的第6至9天),病患者的精神上体征基本维持稳定,除了不止现暂时性哮喘并伴有心动过速(三幅2)。病患者继续统小数据资料非生产性头痛,并不止现疲倦。

在就医第二天的上午,病患者阴部通畅,腹部不适。午夜有第二次大便稀疏的从新闻报道。搜罗该异味的试管主要用途rRT-PCR的测试,以及其他肠胃化石(咽咽和西南侧咽)和抗体。异味和两个肠胃化石自此原则上通过rRT-PCR测定为2019-nCoV中性,而抗体仍为阳性。

在此其间的疗程在很大素质上是支持性的。为了进行时呕吐处理,病患者能够根据能够给与解热制剂,该制剂除此以外每4小时650 mg对乙酰吡啶基酚和每6小时600 mg布洛芬。在就医的前六天,他还因接下来头痛而过量了600毫克少创醚和近6再降生理盐水。

表格1-毒理学科学实验结果

病患者监护单元的性质原本仅必需即时保健点科学实验的测试;从药房第3天开始可以进行时全都血细胞小数和抗体化学数据资料分析。

在药房第3天和第5天(癌症第7天和第9天)的科学实验结果看不止不止白细胞增大症,轻度白血球增大症和肌酸激酶高度再降高(表格1)。此外,肝功能指标也有所叠加:酸性天冬氨酸(每再降68 U),丙吡啶酸吡啶基转移酶(每再降105 U),乙酰吡啶基转移酶(每再降77 U)和果糖脱氢酶(每再降465 U)的高度分列:在就医的第5天所有再降高。鉴于病患者不停哮喘,在第4天赢取尿液养成;在此之前,这些都无法增长。

三幅3-2020年1月底22日(腰部第7天,药房第3天)的后前胸和外侧胸片

三幅4-2020年1月底24日(腰部第5天,药房第9天)的后前胸X线片

据从新闻报道,在药房第3天(患第7天)拍摄的腰部X光片仍未辨识诱发或异常征兆(三幅3)。

但是,从药房第5天午夜(患第9天)午夜进行时的第二次腰部X光片体检辨识,左肺下叶有瓣膜病(三幅4)。

这些CT辨认不止与从药房第5天午夜开始的痉挛状态叠加相吻合,之前病患者在痉挛周围氮气时通过脉搏泌尿系统低浓度推算不止的泌尿系统低浓度最大值减到90%。

在第6天,病患者开始给与补充一镁化碳,该一镁化碳由咽支架以每分钟2再降的速度输去取。考虑到毒理学观感的叠加和对药房赢取性瓣膜病的关切,开始用到万古霉素(1750 mg负荷施打,然后每8小时制剂1 g)和类抗生素联赛杯肟(每8小时制剂)疗程。

三幅5-前后腰部X光片,2020年1月底26日(癌症第十天,药房第六天)

在药房第6天(患第10天),第四次腰部X射线拍下辨识两个肺中会都有大块条状浅色,这一辨认不止与非相比较瓣膜病相符(三幅5),并且在听诊时在两个肺中会都不止现了罗音。鉴于来将CT辨认不止,最终给予一镁化碳补充,病患者接下来哮喘,多个部位接下来中性的2019-nCoV RNA中性,以及发表格文章了与来将性瓣膜病转型原则上的比较严重瓣膜病在该病患者中会,毒理学护士富有冷漠地用到了数据资料分析性抗大肠杆菌疗程。

制剂史考特昔韦(一种早就联合开发的从新型胺基酸小分子前药)在第7天午夜开始,但仍未检视到与输液有关的缺失事件真相。在对丙镁霖耐药的粉红色葡萄球菌进行时了连续的降钙素原高度和咽PCR测定后,在第7天午夜转用万古霉素,并在第二天转用类抗生素联赛杯肟。

在药房第8天(患第12天),病患者的毒理学情况给与更佳。终止补充一镁化碳,他在痉挛周围氮气时的镁低浓度最大值提高到94%至96%。无论如何的泌尿下叶罗音以后长期存在。他的食欲给与更佳,除了暂时性干咳和咽漏外,他无法呕吐。

截至2020年1月底30日,病患者仍就医。他有发热,除头痛外,所有呕吐原则上已更为比较严重,头痛的素质早就减轻。

从新方法

化石捕获

根据CDC须知赢取主要用途2019-nCoV病患的测试的毒理学化石。用合成纤维拭子搜罗了12个咽咽和西南侧咽拭子化石。

将每个拭子嵌入包含2至3 ml大肠杆菌转运电磁场的单独无菌循环系统会。将血集在抗体分离循环系统会,然后根据CDC须知进行时离心。尿液和异味化石分别搜罗在无菌化石试管中会。试管在2°C至8°C之间储藏,直到准备运去取至CDC。

在癌症的第7、11和12天搜罗了每一次进行时的2019-nCoV的测试的化石,除此以外咽咽和西南侧咽拭子,抗体以及尿液和异味试管。

2019-NCOV的病患的测试

用到从匿名刊发的大肠杆菌碱基转型而来的rRT-PCR德沃夏克的测试了毒理学化石。与无论如何针对住院治疗急性痉挛基因序列突变性冠状大肠杆菌(SARS-CoV)和中会东痉挛基因序列突变性冠状大肠杆菌(MERS-CoV)的病患从新方法相似,它很强三个核球状基因序列靶标和一个中性相符合靶标。该推算不止的详细描述为RRT-PCR面板引物和探针和碱基文档中会可视的CDC科学实验文档网站2019-nCoV上。

基因序列突变分子生物学

2020年1月底7日,近现代数据资料分析人员通过美国政府国立保健数据资料分析院GenBank数据资料库和全都球提供者所有瓣膜病数据资料发起者(GISAID)数据资料库提供者了2019-nCoV的比较简单基因序列碱基;随后刊发了有关监护2019-nCoV的统小数据资料。

从rRT-PCR中性化石(西南侧咽和咽咽)中会提取脱镁核糖核酸,并在Sanger和下一代分子生物学平台(Illumina和MinIon)上主要用途全都线粒体分子生物学。用到5.4.6版的Sequencher软件(Sanger)进行时了碱基组装。minimap软件,版本2.17(MinIon);和freebayes软件1.3.1版(MiSeq)。将比较简单线粒体与可视的2019-nCoV参考碱基(GenBank登录号NC_045512.2)进行时尤其。

结果

2019-NCOV的化石的测试

表格2-2019年从新型冠状大肠杆菌(2019-nCoV)的可视亚姆皮利-核酸-裂解的测试结果

该病患者在患第4有道赢取的初始肠胃试管(咽咽拭子和西南侧咽拭子)在2019-nCoV呈中性(表格2)。

尽管病患者原本观感为轻度呕吐,但在癌症第4天的低循环阈最大值(Ct)最大值(咽咽化石中会为18至20,西南侧咽化石中会为21至22)声称这些化石中会大肠杆菌高度极高。

在癌症第7天赢取的两个上肠胃化石在2019-nCoV仍维持中性,除此以外咽咽拭子化石中会接下来高高度(Ct最大值23至24)。在癌症第7天赢取的异味在2019-nCoV中会也呈中性(Ct最大值为36至38)。两种捕获日期的抗体试管在2019-nCoV原则上为阳性。

在癌症第11天和第12天赢取的咽咽和西南侧咽化石辨识不止大肠杆菌高度下降的态势。

西南侧咽化石在患第12天的2019-nCoV的测试氰化氢。在这些日期赢取的抗体的rRT-PCR结果仍仍确定。

基因序列突变分子生物学

西南侧咽和咽咽化石的比较简单线粒体碱基彼此多种不同,并且与其他可视的2019-nCoV碱基几乎多种不同。

该病患者的大肠杆菌与2019-nCoV参考碱基(NC_045512.2)在开放写出侧边8处全部都是3个胺基酸和1个多种不同。该碱基可通过GenBank赢取(登录号MN985325)。

专页

我们关于美国政府首度2019-nCoV确诊发生率的统小数据资料说明了这一从新兴癌症的几个上都唯仍未完全都了解,除此以外广泛传播建模和毒理学癌症的全都部区域内。

我们的发生率病患者曾去过近现代武昌,但统小数据资料说他在武昌其间无法去过海鱼家禽或保健机构,也无法重病的认识。尽管他的2019-nCoV病菌的来源唯不清楚,但已匿名了人对人广泛传播的事实。

到2020年1月底30日,唯仍未辨认不止与此发生率相关的2019-nCoV继发发生率,但仍在密切监视下。

在癌症的第4天和第7天从上肠胃化石中会测定到很强低Ct最大值的2019-nCoV RNA,声称大肠杆菌载量高且很强广泛传播潜力。

在在的是,我们还在病患者患第7天搜罗的异味试管中会测定到了2019-nCoV RNA。尽管我们发生率病患者的抗体化石不停不止现2019-nCoV阳性,但在近现代住院治疗病患者的尿液中会仍测定到大肠杆菌RNA。然而,肺外测定大肠杆菌RNA并不一定显然长期存在传染性大肠杆菌,在此之前唯不清楚在肠胃直接测定大肠杆菌RNA的毒理学意义。

在此之前,我们对2019-nCoV病菌的毒理学区域内的了解非常极少。在近现代,现在从新闻报道了诸如比较严重的瓣膜病,痉挛衰竭,急性痉挛窘迫基因序列突变性(ARDS)和瓣膜损伤等并发症,除此以外致命的后果。然而,重要的是要注意,这些发生率是根据其瓣膜病病患明确的,因此或许会使统小数据资料偏向格外比较严重的结果。

我们的发生率病患者原本观感为轻度头痛和低度暂时性哮喘,在患的第4天无法腰部X光体检的瓣膜病征兆,而在患第9天转型为瓣膜病之前,这些非酪吡啶酸体征和呕吐在早期在毒理学上,2019-nCoV病菌的毒理学处理过程或许与许多其他类似结核病无法轻微区别,尤其是在冬季肠胃大肠杆菌季节。

另外,本发生率病患者在癌症的第9天转型为瓣膜病的意图与近期痉挛困难的发作(病症后人原则上收入为8天)原则上。尽管根据病患者的毒理学情况紧张最终有否给予remdesivir诚心的用到,但仍能够进行时随机相符合的测试以明确remdesivir和任何其他数据资料分析药物疗程2019-nCoV病菌的安全都性和确实。

我们统小数据资料了美国政府首度统小数据资料的2019-nCoV病菌病患者的毒理学形态。

该发生率的关键上都除此以外病患者在写出有关死灰复燃的毒理学发不止后最终寻求保健;由当地保健IP证实病患者都只到武昌的环游世界历史记录,随后在当地,俄克拉荷马州和州政府毒理学行政官员之间进行时协调;并明确或许的2019-nCoV病菌,从而可以迅速监护病患者并随后对2019-nCoV进行时科学实验证实,并必需病患者晕倒全面性评核和行政。

该发生率统小数据资料忽视了毒理学护士对于任何不止现急性癌症呕吐的就诊病患者,要总结不止都只的环游世界经历或认识高心率的重要性,为了确保安全错误鉴别和及时监护或许面临2019-nCoV病菌风险的病患者,并尽力增大全面性的广泛传播。

最后,本统小数据资料忽视能够明确与2019-nCoV病菌相关的毒理学癌症,病症机理和大肠杆菌脱落接下来时间的

全都部区域内和自然历史记录,以为毒理学行政和毒理学执行者提供依据。

所列为日文版

——————

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: