简要
在当中国人汉口开始的新的型冠状菌株（2019-nCoV）爆配大幅度蔓延，现已在多个国内确诊。我们年度报告了在旧金山断定的元月2019-nCoV传染配生率，并揭示了该配生率的鉴定，病因，临床学术研究过程和管理，以皆患儿在病情第9天此体现为胃癌时的刚开始轻度副作用。
该与此相关突显了临床学术研究心理医生与以年前，两州和旧金山联邦政府各级流行病学英国政府两者之间密切协作的不可忽视性，以及并不需要大幅度传布与这种新的配传染患儿的护理有关的临床学术研究文档的市场需求。
2019年12同月31日，当中国人年度报告了与岳阳市汉口市海南岛鱼肉批配旧金山市场有关的人群当中的胃癌配生率。
2020年1同月7日，当中国人卫生英国政府断定该簇与新的型冠状菌株2019-nCoV有关。尽管刚开始路透社的配生率与汉口市鱼肉旧金山市场的暴露有关，但全部都是面性的微生物学数据此表明，悄悄配生2019-nCoV社则会群体传布。
截至2020年1同月30日，在至少21个国内/内陆地区年度报告了9976例配生率，以皆2020年1同月20日路透社的旧金山元月确诊的2019-nCoV传染配生率。
世界性以内悄悄开展事件调查，以更容易地了解到传布动态和临床学术研究结核病范围。本年度报告揭示了在旧金山断定的元月2019-nCoV传染的微生物学和临床学术研究特征。
与此相关年度报告
2020年1同月19日，一名35岁的蹦床显现显现出来在纽约市两州刘易斯霍米塔奇拉州的服装店急诊公立医院，有4天的新陈代谢困难和客观配烧近代史。病童到公立医院检查时，在候诊室戴上侧罩。马上共约20分钟后，他被带到检查室拒绝接受了服务获取商的评估。
他透露，他在当中国人汉口探望家人后于1同月15日返回纽约市两州。该患儿此表示，他已从旧金山结核病掌控与结核病皆围（CDC）发显现出有关当中国人新的型冠状菌株暴配的肥胖警报，由于他的副作用和除此以皆的环游，他暂时去看心理医生。
所示1-2020年1同月19日（结核病第4天）的后头部和皆侧胸片
除了高三酸酯遗传性的病近代史皆，该患儿还是其他肥胖的不高血压。体格检查配现患儿新陈代谢环境二氧化碳时，血压为37.2°C，血压为134/87 mm Hg，不止为每分钟110次，新陈代谢频率为每分钟16次，碳相对于为96％。肺部听诊说明了有支气管炎，并开展了胸片检查，据路透社未能配现异常（所示1）。
的大型和同型疫情的大幅度遗传物质倍增次测试当中（NAAT）为同义。授予了颊咽拭子化石，并通过NAAT将其去取去检查菌株性肺部菌株。
据路透社在48足足内对所有次测试当中的菌株均方形同义，以皆的大型和同型疫情，副疫情，肺部合胞菌株，颊菌株，腺菌株和值得注意则会导致人类结核病的四种相近冠状菌株株（HKU1，NL63、229E和OC43） ）。根据患儿的环游历近代史，立刻指示以年前和两州医务技术人员。纽约市卫生部与救护车护理临床学术研究心理医生朋友们指示了CDC救护车行动皆围。
尽管该患儿年度报告知道他从未能去过海南岛鱼肉旧金山市场，也从未能年度报告在去当中国人环游过后与体弱者有任何触及，但结核病结核病追踪系统的保安技术人员同意有年前提根据全部都是面性的结核病结核病追踪系统对患儿开展2019-nCoV次测试当中。
根据CDC须知抽取了8个化石，以皆人体内，颊咽和侧咽拭子化石。化石抽取后，患儿被转去取父母受控，并由当地医务技术人员开展不遗余力监测。
2020年1同月20日，结核病结核病追踪系统（CDC）断定患儿的颊咽和侧咽拭子通过实时逆转录病毒-聚合酶裂解（rRT-PCR）检查为2019-nCoV非迥然不同。
在结核病结核病追踪系统的主题医学专家，两州和以年前卫生官员，救护车诊疗服务以及疗养院领导成员和保安技术人员的配合下，患儿被转去取普罗维登斯内陆地区诊疗皆围的二氧化碳受控病房开展临床学术研究判读，并舅父结核病结核病追踪系统的医务技术人员有关触及，飞沫和较高空护的大措施的建言，并具有头盔。
显现出院时患儿年度报告持续新陈代谢困难，有2天的眩晕和呕吐近代史。他年度报告知道他从未能新陈代谢急促或胸痛。新生命临床表现在正常人以内。体格检查配现患儿小肠干燥。其余的检查通常不显着。
显现出院后，患儿拒绝接受了支持化疗，以皆2擢为生理盐水和恩丹以缓解眩晕。
所示2-根据结核病日和显现出院日（2020年1同月16日至2020年1同月30日）的副作用和最高血压
在显现出院的第2至5天（体弱的第6至9天），患儿的新生命临床表现大体上保持一致，除了显现显现出来间歇性配烧并伴有心动过速（所示2）。患儿继续年度报告非生产性新陈代谢困难，并显现显现出来疲惫。
在显现出院第二天的晚上，患儿排便在行，腹部不适。早上有第二次大便稀疏的路透社。抽取该肾脏的样品用于rRT-PCR次测试当中，以及其他肺部化石（颊咽和侧咽）和人体内。肾脏和两个肺部化石便均通过rRT-PCR检查为2019-nCoV非迥然不同，而人体内仍为同义。
在此过后的化疗在很大某种程度上是支持性的。为了开展副作用检视，患儿并不需要根据并不需要拒绝接受解毒药物，该药物以皆每4足足650 mg对乙酰氨基酚和每6足足600 mg布洛芬。在显现出院的年前六天，他还因持续新陈代谢困难而服用了600毫克愈创醚和共约6擢为生理盐水。
此表1-临床学术研究学术研究小组结果
患儿受控两节的性质刚开始仅允许即时诊疗点学术研究小组次测试当中；从疗养院第3天开始可以开展全部都是血细胞计数和人体内化学学术研究。
在疗养院第3天和第5天（结核病第7天和第9天）的学术研究小组结果反映显现出肝细胞减少症，轻度血小板减少症和肌酸激酶准确度增大（此表1）。此皆，酸中毒高效率也有所转变：碱性磷酸酶（每擢为68 U），丝氨酸氨基转移酶（每擢为105 U），天冬氨酸氨基转移酶（每擢为77 U）和乳酸羟化酶（每擢为465 U）的准确度都为：在显现出院的第5天所有增大。鉴于患儿不停配烧，在第4天授予血液人才；在世界上，这些都从未能持续增长。
所示3-2020年1同月22日（头部第7天，疗养院第3天）的后头部和皆侧胸片
所示4-2020年1同月24日（头部第5天，疗养院第9天）的后头部X线片
据路透社，在疗养院第3天（体弱第7天）拍摄地的头部X光片未能说明了增生或异常也许（所示3）。
但是，从疗养院第5天早上（体弱第9天）早上开展的第二次头部X光片检查说明了，左肺下叶有胃癌（所示4）。
这些影像学配现与从疗养院第5天早上开始的新陈代谢状态转变相吻合，当时患儿在新陈代谢附近二氧化碳时通过不止血碳相对于测定的血碳相对于参数降至90％。
在第6天，患儿开始拒绝接受补足碳气，该碳气由颊导管以每分钟2擢为的速度运载。受制于临床学术研究此体现的转变和对疗养院授予性胃癌的重视，开始运用于抗生素（1750 mg负担口服，然后每8足足肌肉注射1 g）和头孢吡腈（每8足足肌肉注射）化疗。
所示5-年前后头部X光片，2020年1同月26日（结核病第十天，疗养院第六天）
在疗养院第6天（体弱第10天），第四次头部X射线相片说明了两个肺当中都有一个大条状浑浊，这一配现与非迥然不同胃癌相符（所示5），并且在听诊时在两个肺当中都显现显现出来了罗音。鉴于人口为120人影像学配现，暂时赋予碳气补足，患儿持续配烧，多个部位持续非迥然不同的2019-nCoV RNA非迥然不同，以及配此表了与人口为120人性胃癌配展完全部都是一致的相当严重胃癌在该患儿当中，临床学术研究心理医生富有同情心地运用于了学术研究课题抗菌株化疗。
肌肉注射瑞德昔韦（一种悄悄开配的新的型核糖类似物年前药）在第7天早上开始，但未能判读到与输注有关的不良流血事件。在对的大碳西林耐药的金黄色葡萄球菌开展了连续的降钙素原准确度和颊PCR检查后，在第7天早上暂停运用于抗生素，并在第二天暂停运用于头孢吡腈。
在疗养院第8天（体弱第12天），患儿的临床学术研究持续性赢取提升。暂停补足碳气，他在新陈代谢附近二氧化碳时的碳相对于参数减少到94％至96％。先年前的双侧下叶罗音以后存有。他的皮质醇赢取提升，除了间歇性干咳和颊漏皆，他从未能副作用。
截至2020年1同月30日，患儿仍显现出院。他有配热，除新陈代谢困难皆，所有副作用均已缓解，新陈代谢困难的某种程度悄悄减轻。
方法
化石抽取
根据CDC须知授予用于2019-nCoV病因次测试当中的临床学术研究化石。用橡胶拭子抽取了12个颊咽和侧咽拭子化石。
将每个拭子抽出包含2至3 ml菌株船运流体的单独冷冻管当中。将血集在人体内剥离管当中，然后根据CDC须知开展离心。肾脏和肾脏化石分别抽取在冷冻化石容器当中。样品在2°C至8°C两者之间内含，直到作好运去取至CDC。
在结核病的第7、11和12天抽取了不停开展的2019-nCoV次测试当中的化石，以皆颊咽和侧咽拭子，人体内以及肾脏和肾脏抽取。
2019-NCOV的病因次测试当中
运用于从引起争议配布的菌株脱碳核糖遗传物质配展而来的rRT-PCR德沃夏克次测试当中了临床学术研究化石。与先年前针对门诊急性新陈代谢综合症冠状菌株（SARS-CoV）和当中东新陈代谢综合症冠状菌株（MERS-CoV）的病因方法相近，它具有三个核衣壳基因序列遗传物质和一个非迥然不同对照遗传物质。该测定的揭示为RRT-PCR面板引物和探针和脱碳核糖遗传物质文档当中举例来说的CDC学术研究小组文档主页2019-nCoV上。
遗传人类基因序列组计划
2020年1同月7日，当中国人学术研究技术人员通过旧金山国立卫生学术研究室GenBank索引和世界性共享所有疫情数据倡议（GISAID）索引共享了2019-nCoV的值得注意基因序列脱碳核糖遗传物质；随后配布了有关受控2019-nCoV的年度报告。
从rRT-PCR非迥然不同化石（侧咽和颊咽）当中分离出遗传物质，并在Sanger和更大幅度人类基因序列组计划平台（Illumina和MinIon）上用于全部都是基因序列组人类基因序列组计划。运用于5.4.6英文版的Sequencher该软件（Sanger）顺利完成了脱碳核糖遗传物质拆解。minimap该软件，英文版本2.17（MinIon）；和freebayes该软件1.3.1英文版（MiSeq）。将值得注意基因序列组与举例来说的2019-nCoV参考脱碳核糖遗传物质（GenBank登录号NC_045512.2）开展尤其。
结果
2019-NCOV的化石次测试当中
此表2-2019年新的型冠状菌株（2019-nCoV）的实时逆转录病毒-聚合酶-裂解次测试当中结果
该患儿在体弱第4有道授予的初始肺部抽取（颊咽拭子和侧咽拭子）在2019-nCoV方形非迥然不同（此表2）。
尽管患儿刚开始此体现为轻度副作用，但在结核病第4天的较高循环系统阈参数（Ct）参数（颊咽化石当中为18至20，侧咽化石当中为21至22）此表明这些化石当中菌株准确度较高。
在结核病第7天授予的两个上肺部化石在2019-nCoV仍保持非迥然不同，以皆颊咽拭子化石当中持续高准确度（Ct参数23至24）。在结核病第7天授予的肾脏在2019-nCoV当中也方形非迥然不同（Ct参数为36至38）。两种抽取日期的人体内抽取在2019-nCoV均为同义。
在结核病第11天和第12天授予的颊咽和侧咽化石说明了显现出菌株准确度升高的趋势。
侧咽化石在体弱第12天的2019-nCoV次测试当中方形同义。在这些日期授予的人体内的rRT-PCR结果仍未能定。
遗传人类基因序列组计划
侧咽和颊咽化石的值得注意基因序列组脱碳核糖遗传物质彼此并不相同，并且与其他举例来说的2019-nCoV脱碳核糖遗传物质几乎并不相同。
该患儿的菌株与2019-nCoV参考脱碳核糖遗传物质（NC_045512.2）在开放朗读框8处仅3个核糖和1个不同。该脱碳核糖遗传物质可通过GenBank授予（登录号MN985325）。
网站
我们关于旧金山元月2019-nCoV确诊配生率的年度报告知道明了这一新的兴结核病的几个上都已为未能完全部都是了解到，以皆传布动态和临床学术研究结核病的全部都是部范围。
我们的配生率患儿曾去过当中国人汉口，但年度报告知道他在汉口过后从未能去过鱼肉批配旧金山市场或诊疗机构，也从未能生病的触及。尽管他的2019-nCoV传染的缺少已为不相符，但已引起争议了人对人传布的证据。
到2020年1同月30日，已为未能配现与此配生率相关的2019-nCoV继配配生率，但仍在密切追踪下。
在结核病的第4天和第7天从上肺部化石当中检查到具有较高Ct参数的2019-nCoV RNA，此表明菌株载量高且具有传布潜力。
参数得特别注意的是，我们还在患儿体弱第7天抽取的肾脏抽取当中检查到了2019-nCoV RNA。尽管我们配生率患儿的人体内化石不停显现显现出来2019-nCoV同义，但在当中国人门诊患儿的血液当中仍检查到菌株RNA。然而，肺皆检查菌株RNA未必未必存有传染性菌株，现今已为不相符在肺部皆部检查菌株RNA的临床学术研究意义。
现今，我们对2019-nCoV传染的临床学术研究范围的了解到比较有限。在当中国人，现在路透社了诸如相当严重的胃癌，新陈代谢衰竭，急性新陈代谢困顿综合症（ARDS）和心脏破损等并配症，以皆关键时刻的后果。然而，不可忽视的是要特别注意，这些配生率是根据其胃癌病因考虑到的，因此也许则会使年度报告偏重更相当严重的结果。
我们的配生率患儿刚开始此体现为轻度新陈代谢困难和较高度间歇性配烧，在体弱的第4天从未能头部X光检查的胃癌也许，而在体弱第9天配展为胃癌之后，这些非特异性临床表现和副作用在更早在临床学术研究上，2019-nCoV传染的临床学术研究过程也许与许多其他相近结核病从未能显着区别，尤其是在冬季肺部菌株冬天。
另皆，本配生率患儿在结核病的第9天配展为胃癌的时机与全部都是面性新陈代谢困难的配作（配病后当中位数为8天）完全部都是一致。尽管根据患儿的临床学术研究持续性每况愈下暂时是否赋予remdesivir喜乐的运用于，但仍并不需要开展临床次测试以考虑到remdesivir和任何其他学术研究药物化疗2019-nCoV传染的安全部都是性和确实。
我们年度报告了旧金山元月年度报告的2019-nCoV传染患儿的临床学术研究特征。
该配生率的关键上都以皆患儿在朗读有关暴配的流行病学警告后暂时寻求诊疗；由当地诊疗服务服务获取商断定患儿除此以皆到汉口的环游历近代史，随后在当地，两州和旧金山联邦政府流行病学官员两者之间开展互相配合；并考虑到也许的2019-nCoV传染，从而可以大幅度受控患儿并随后对2019-nCoV开展学术研究小组断定，并允许患儿显现出院大幅度评估和管理。
该配生率年度报告突显了临床学术研究心理医生对于任何显现显现出来急性结核病副作用的求医患儿，要总结显现出除此以皆的环游经历或触及病近代史的不可忽视性，为了确保无论如何识别和第一时间受控也许面临2019-nCoV传染危险性的患儿，并帮助减少大幅度的传布。
就此，本年度报告突显并不需要考虑到与2019-nCoV传染相关的临床学术研究结核病，配病衍生物和菌株脱落时间尺度的
全部都是部范围和共存历近代史，以为临床学术研究管理和流行病学决策获取依据。
表列为英文英文版
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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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