简述
在之当年国成都开始的新型冠状病原(2019-nCoV)爆;不促使延烧,现已在多个第三世界就诊。我们研究者报告了在旧金山表明的元月初2019-nCoV病原感染就诊,并描绘了该就诊的鉴定,病癫痫,病癫痫现实生活和监管,还包括呕吐在病情第9天备注现为心肌梗塞时的在此之后轻度呕吐。
该近来凸显了病癫痫精神科与地方,两州和联邦各级公共卫生保健卫生政府彼此之间紧密协作的举足轻重性,以及并不需要快速传布与这种新中风原感染呕吐的照护有关的病癫痫的资讯的消费。
2019年12月初31日,之当年国研究者报告了与湖北省成都市华东水果批;不市场有关的群体之当年的心肌梗塞就诊。
2020年1月初7日,之当年国卫生保健卫生政府表明该簇与新型冠状病原2019-nCoV有关。尽管在此之后另据的就诊与成都市水果市场的受伤害有关,但也就是说的公共卫生保健卫生数据资料备注明,正在;不生2019-nCoV人际传布。
截至2020年1月初30日,在最少21个第三世界/沿海地区研究者报告了9976亦然就诊,还包括2020年1月初20日另据的旧金山元月初就诊的2019-nCoV病原感染就诊。
全球之内正在同步进行报告,以更佳地了解传布静态和病癫痫结核病范围。本研究者报告描绘了在旧金山表明的元月初2019-nCoV病原感染的公共卫生保健卫生和病癫痫不同之处。
近来研究者报告
2020年1月初19日,一名35岁的蹦床显露现在波士顿两州斯诺霍米什县的数家医护人员诊所,有4天的呼吸困难和主观腹泻简史。患者到诊所定期检查时,在候诊室戴上口内罩。等候约20分钟后,他被带到定期检查室做了举例来说的评估。
他透露,他在之当年国成都探望家人后于1月初15日返回波士顿两州。该呕吐声称,他已从旧金山结核病支配与防止之当年心(CDC)寄送有关之当年国新型冠状病原更为严重的心理健康警报,由于他的呕吐和在在的旅程,他尽快去看精神科。
上图1-2020年1月初19日(结核病第4天)的后腹部和另有侧胸片
除了高三酸酯血癫痫的病因另有,该呕吐还是其他心理健康的不抽烟。体格定期检查辨认显露呕吐吞咽环境气体时,体温为37.2°C,皮质醇为134/87 mm Hg,颤抖为每分钟110次,吞咽频率为每分钟16次,氮含水为96%。腹腔听诊备注明有以次状腺肿,并同步进行了胸片定期检查,据另据未辨认显露所致(上图1)。
以次型和-B疫情的快速小分子扩增飞行测试(NAAT)为比如说。授予了钝咽拭子骨骼,并通过NAAT将其送去定期检查病原性吞咽道病原。
据另据在48星期内对所有飞行测试的病原以另有方形比如说,还包括以次型和-B疫情,副疫情,吞咽道合胞病原,钝病原,腺病原和推断就会导致人类文明结核病的四种相似冠状病原株(HKU1,NL63、229E和OC43) )。根据呕吐的旅程历简史文化,尽快通告地方和两州不作为。波士顿卫生保健卫生部与先行照护病癫痫精神科一起通告了CDC先行行动之当年心。
尽管该呕吐研究者报告问道他不就会去过华东水果市场,也不就会研究者报告在去之当年国旅程期间与生病者有任何碰触,但结核病防止支配之当年心的工作人员同意有必要根据也就是说的结核病防止支配之当年心对呕吐同步进行2019-nCoV飞行测试。
根据CDC简要搜罗了8个骨骼,还包括抗体,钝咽和口内咽拭子骨骼。骨骼搜罗后,呕吐被送往家庭强制,并由当地不作为同步进行务实受控。
2020年1月初20日,结核病防止支配之当年心(CDC)表明呕吐的钝咽和口内咽拭子通过高分辨率逆转录酶-催化反应链反应(rRT-PCR)定期检查为2019-nCoVHIV。
在结核病防止支配之当年心的趣味医学专家,两州和地方卫生保健卫生行政官员,先行卫生保健服务以及病房指派和工作人员的配合下,呕吐被送往新泽西沿海地区卫生保健之当年心的气体强制病房同步进行病癫痫推论,并跟随结核病防止支配之当年心的伤者有关碰触,飞沫和空之当年防护安全措施的建议,并具有丝袜。
复;不时呕吐研究者报告小规模呼吸困难,有2天的焦虑和呕吐简史。他研究者报告问道他不就会吞咽急促或胸痛。灵魂病状在也就是说之内。体格定期检查辨认显露呕吐粘膜干燥。其余的定期检查并不一定不明显。
复;不后,呕吐做了支持疗程,还包括2升至生理盐水和恩丹以更为严重焦虑。
上图2-根据结核病日和康复日(2020年1月初16日至2020年1月初30日)的呕吐和最高体温
在康复的第2至5天(生病的第6至9天),呕吐的灵魂病状基本始终保持稳定,除了显露现间歇性腹泻并伴有心动过速(上图2)。呕吐之后研究者报告非生产性呼吸困难,并显露现疲惫。
在康复第二天的下午,呕吐排便不畅,腹部不适。傍晚有第二次大便稀疏的另据。搜罗该异味的试样应用于rRT-PCR飞行测试,以及其他吞咽道骨骼(钝咽和口内咽)和抗体。异味和两个吞咽道骨骼此后以另有通过rRT-PCR定期检查为2019-nCoVHIV,而抗体仍为比如说。
先后的疗程在较大某种程度上是支持性的。为了同步进行呕吐处理,呕吐并不需要根据并不需要做止咳治疗,该治疗还包括每4星期650 mg对乙酰氧基酚和每6星期600 mg布洛芬。在康复的当年六天,他还因小规模呼吸困难而服用了600毫克愈创醚协约6升至生理盐水。
备注1-病癫痫的实验室结果
呕吐强制模组的性质在此之后仅允许即时卫生保健点的实验室飞行测试;从病房第3天开始可以同步进行全血细胞个数和抗体无机化学研究者。
在病房第3天和第5天(结核病第7天和第9天)的的实验室结果总结显露血小板降高于癫痫,轻度血小板降高于癫痫和肌酸激酶某种程度升至高(备注1)。此另有,肝功能高效率也有所巨大变化:碱性丝氧酸(每升至68 U),丙氧酸氧基转移酶(每升至105 U),赖氧酸氧基转移酶(每升至77 U)和乳酸脱氢酶(每升至465 U)的某种程度分别为:在康复的第5天所有升至高。鉴于呕吐反复腹泻,在第4天授予肝脏培养;纵观,这些都不就会放缓。
上图3-2020年1月初22日(头部第7天,病房第3天)的后腹部和另有侧胸片
上图4-2020年1月初24日(头部第5天,病房第9天)的后腹部X线片
据另据,在病房第3天(生病第7天)拍摄的头部X光片未备注明浸润或所致可能(上图3)。
但是,从病房第5天傍晚(生病第9天)傍晚同步进行的第二次头部X光片定期检查备注明,左肺下叶有心肌梗塞(上图4)。
这些技术手段辨认显露与从病房第5天傍晚开始的吞咽完全巨大变化相吻合,当年呕吐在吞咽远处气体时通过颤抖血氮含水推算出的血氮含水个数减到90%。
在第6天,呕吐开始做不足之处氮气,该氮气由钝食道以每分钟2升至的速度载运。顾及病癫痫备注现的巨大变化和对病房授予肺水肿的关注,开始应用于氯霉素(1750 mg损耗剂量,然后每8星期静脉注射1 g)和嗪吡肟(每8星期静脉注射)疗程。
上图5-当年后头部X光片,2020年1月初26日(结核病第十天,病房第六天)
在病房第6天(生病第10天),第四次头部X射线照片备注明两个肺之当年都有基底条状混浊,这一辨认显露与非典型心肌梗塞相符(上图5),并且在听诊时在两个肺之当年都显露现了罗音。鉴于核辐射技术手段辨认显露,尽快获取氮气不足之处,呕吐小规模腹泻,多个指以次小规模HIV的2019-nCoV RNAHIV,以及;不备注了与核辐射肺水肿的;不展原则上的更为严重心肌梗塞在该呕吐之当年,病癫痫精神科富有同情心地应用于了各学科抗病原疗程。
静脉注射瑞德昔韦(一种正在开;不新的新型氧基酸类似物当年药)在第7天傍晚开始,但未推论到与输注有关的不良事件。在对以次氮西林耐药的深绿色葡萄球菌同步进行了周内的降钙素原某种程度和钝PCR定期检查后,在第7天傍晚关闭氯霉素,并在第二天关闭嗪吡肟。
在病房第8天(生病第12天),呕吐的病癫痫小规模性得不到优化。暂时不足之处氮气,他在吞咽远处气体时的氮含水个数大大提高到94%至96%。先当年的单侧下叶罗音便不存在。他的肠胃得不到优化,除了间歇性干咳和钝漏另有,他不就会呕吐。
截至2020年1月初30日,呕吐仍康复。他有;不热,除呼吸困难另有,所有呕吐以另有已更为严重,呼吸困难的某种程度正在减高于。
方法有
骨骼搜罗
根据CDC简要授予应用于2019-nCoV病癫痫飞行测试的病癫痫骨骼。用合成纤维拭子搜罗了12个钝咽和口内咽拭子骨骼。
将每个拭子插入包含2至3 ml病原转运介质的单独冷藏管之当年。将血集在抗体分离管之当年,然后根据CDC简要同步进行离心。肝脏和异味骨骼分别搜罗在冷藏骨骼装入之当年。试样在2°C至8°C彼此之间储存,直到做好载运至CDC。
在结核病的第7、11和12天搜罗了多次重复同步进行的2019-nCoV飞行测试的骨骼,还包括钝咽和口内咽拭子,抗体以及肝脏和异味检验。
2019-NCOV的病癫痫飞行测试
应用于从官方Facebook;不布新闻的病原氧基酸的;不展而来的rRT-PCR定量飞行测试了病癫痫骨骼。与先当年针对诊治急性吞咽癫痫候群冠状病原(SARS-CoV)和之当年东吞咽癫痫候群冠状病原(MERS-CoV)的病癫痫方法有类似,它具备三个核衣壳基因靶标和一个HIV比对靶标。该推算出的描绘为RRT-PCR面板催化反应和探针和氧基酸的资讯之当年只用的CDC的实验室的资讯Facebook2019-nCoV上。
遗传基因DNA
2020年1月初7日,之当年国研究者人员通过旧金山国立卫生保健卫生研究者院GenBank数据资料库和全球对等所有疫情数据资料倡议(GISAID)数据资料库对等了2019-nCoV的明晰基因氧基酸;随后;不布新闻了有关强制2019-nCoV的研究者报告。
从rRT-PCRHIV骨骼(口内咽和钝咽)之当年提炼显露小分子,并在Sanger和下一代DNASDK(Illumina和MinIon)上应用于全DNADNA。应用于5.4.6版的Sequencher应用软件(Sanger)未完成了氧基酸被装。minimap应用软件,旧版2.17(MinIon);和freebayes应用软件1.3.1版(MiSeq)。将明晰DNA与只用的2019-nCoV参照氧基酸(GenBank登录号NC_045512.2)同步进行相比较。
结果
2019-NCOV的骨骼飞行测试
备注2-2019年新型冠状病原(2019-nCoV)的高分辨率逆转录酶-催化反应-链反应飞行测试结果
该呕吐在生病第4天时授予的初始吞咽道检验(钝咽拭子和口内咽拭子)在2019-nCoVHIV(备注2)。
尽管呕吐在此之后备注现为轻度呕吐,但在结核病第4天的高于循环阻抗(Ct)个数(钝咽骨骼之当年为18至20,口内咽骨骼之当年为21至22)备注明这些骨骼之当年病原某种程度较高。
在结核病第7天授予的两个上吞咽道骨骼在2019-nCoV仍始终保持HIV,还包括钝咽拭子骨骼之当年小规模高某种程度(Ct个数23至24)。在结核病第7天授予的异味在2019-nCoV之当年也HIV(Ct个数为36至38)。两种搜罗订于的抗体检验在2019-nCoV以另有为比如说。
在结核病第11天和第12天授予的钝咽和口内咽骨骼备注明显露病原某种程度回升的近来。
口内咽骨骼在生病第12天的2019-nCoV飞行测试方形比如说。在这些订于授予的抗体的rRT-PCR结果仍未定。
遗传基因DNA
口内咽和钝咽骨骼的明晰DNA氧基酸彼此完全一致,并且与其他只用的2019-nCoV氧基酸仍然完全一致。
该呕吐的病原与2019-nCoV参照氧基酸(NC_045512.2)在全站朗读框8处仅剩3个氧基酸和1个不同。该氧基酸可通过GenBank授予(登录号MN985325)。
网站
我们关于旧金山元月初2019-nCoV就诊就诊的研究者报告问道明了这一新兴结核病的几个总体未曾无论如何了解,还包括传布静态和病癫痫结核病的全部范围。
我们的就诊呕吐曾去过之当年国成都,但研究者报告问道他在成都期间不就会去过水果批;不市场或卫生保健机构,也不就会生病的碰触。尽管他的2019-nCoV病原感染的来源尚不清楚,但已官方Facebook了人对人传布的证据。
到2020年1月初30日,未曾辨认显露与此就诊系统性的2019-nCoV继;不就诊,但仍在紧密监视下。
在结核病的第4天和第7天从上吞咽道骨骼之当年定期检查到具备高于Ct个数的2019-nCoV RNA,备注明病原量高且具备传布实用价个数。
个数得注意的是,我们还在呕吐生病第7天搜罗的异味检验之当年定期检查到了2019-nCoV RNA。尽管我们就诊呕吐的抗体骨骼反复显露现2019-nCoV比如说,但在之当年国诊治呕吐的肝脏之当年仍定期检查到病原RNA。然而,肺另有定期检查病原RNA并不一定意味着不存在传染性病原,迄今尚不清楚在吞咽道另有部定期检查病原RNA的病癫痫意义。
迄今,我们对2019-nCoV病原感染的病癫痫范围的了解非常更少。在之当年国,已经另据了诸如更为严重的心肌梗塞,吞咽衰竭,急性吞咽拮据癫痫候群(ARDS)和心脏烧伤等肾衰竭,还包括致命的后果。然而,举足轻重的是要注意,这些就诊是根据其心肌梗塞病癫痫已确定的,因此则就会使研究者报告偏重于更更为严重的结果。
我们的就诊呕吐在此之后备注现为轻度呼吸困难和高于度间歇性腹泻,在生病的第4天不就会头部X光定期检查的心肌梗塞可能,而在生病第9天的;不展为心肌梗塞之当年,这些非基因备注达病状和呕吐在最初在病癫痫上,2019-nCoV病原感染的病癫痫现实生活确实与许多其他相似传染病不就会明显区别,尤其是在夏天吞咽道病原季节。
另另有,本就诊呕吐在结核病的第9天的;不展为心肌梗塞的时机与近期吞咽困难的;不作(中风后之当年位数为8天)原则上。尽管根据呕吐的病癫痫小规模性恶化尽快是否获取remdesivir慈悲的应用于,但仍并不需要同步进行随机比对试验以已确定remdesivir和任何其他研究者药物疗程2019-nCoV病原感染的只用性和有效性。
我们研究者报告了旧金山元月初研究者报告的2019-nCoV病原感染呕吐的病癫痫不同之处。
该就诊的关键总体还包括呕吐在朗读有关更为严重的公共卫生保健卫生警告后尽快促成卫生保健;由当地卫生保健服务举例来说表明呕吐在在到成都的旅程历简史文化,随后在当地,两州和联邦公共卫生保健卫生行政官员彼此之间同步进行协调;并已确定确实的2019-nCoV病原感染,从而可以促使强制呕吐并随后对2019-nCoV同步进行的实验室表明,并允许呕吐复;不促使评估和监管。
该就诊研究者报告凸显了病癫痫精神科对于任何显露现急性结核病呕吐的就诊呕吐,要总结显露在在的旅程亲身经历或碰触病因的举足轻重性,为了确保正确识别和即时强制确实面临2019-nCoV病原感染危险性的呕吐,并鼓励降高于促使的传布。
最后,本研究者报告凸显并不需要已确定与2019-nCoV病原感染系统性的病癫痫结核病,中风反应机理和病原穿孔小规模时间的
全部范围和人为历简史文化,以为病癫痫监管和公共卫生保健卫生决策提供依据。
以下为海另有版
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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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