摘要
在中都国武昌开始的新的型冠状病原（2019-nCoV）爆所发迅速蔓延到，现已在多个国家所所病症。我们清查报告了在American断定的由此可知未有2019-nCoV病菌病症，并说是明了了该病症的鉴定，病症，临床研究课题过程和管理者，之外患儿在病况第9天备注现为中都风时的刚开始轻度病征。
该事例强调了临床研究课题医师与以外，一个州和美利坚合众国各级心理卫生保健伊朗政府彼此间融洽协作的特殊性，以及所需快速传播者与这种新的所病症菌患儿的护理有关的临床研究课题信息的效益。
2019年12月底31日，中都国清查报告了与湖北省武昌市珠江三角洲海鱼批所发零售商有关的人群中都的中都风病症。
2020年1月底7日，中都国卫生保健伊朗政府断定该簇与新的型冠状病原2019-nCoV有关。尽管刚开始华盛顿邮报的病症与武昌市海鱼零售商的暴露有关，但意味著的药理学资料确实，打算所发生2019-nCoV层面传播者。
截至2020年1月底30日，在比较少21个国家所/沿海地区清查报告了9976例病症，之外2020年1月底20日华盛顿邮报的American由此可知未有所病症的2019-nCoV病菌病症。
在世界上区域内打算顺利完成清查，以更是好地了解传播者自适应和临床研究课题癌症区域。本清查报告说是明了了在American断定的由此可知未有2019-nCoV病菌的药理学和临床研究课题不同之处。
事例清查报告
2020年1月底19日，一名35岁的女子借助于现在华盛顿一个州斯诺霍米孟加拉国的一家住院公立医院，有4天的呼吸困难和主观所发烧日本史。病人到公立医院定期检查时，在候诊室戴上沟罩。等待约20分钟后，他被带到定期检查室放弃了简而言之的风险评估。
他透露，他在中都国武昌接回家人先是1月底15日返回华盛顿一个州。该患儿备注示，他已从American癌症高度集中与防止中都心（CDC）收到有关中都国新的型冠状病原死灰复燃的肥胖症警报，由于他的病征和除此以外的旅程，他首肯去看医师。
三幅1-2020年1月底19日（癌症第4天）的后前胸和部份侧胸片
除了高三酸酯胆固醇的病因部份，该患儿还是其他肥胖症的不吸烟者。体格定期检查断定患儿换气环境氢气时，新陈代谢为37.2°C，皮质醇为134/87 mm Hg，颤抖为每分钟110次，换气频率为每分钟16次，锂含水为96％。肺部听诊结果显示有弥漫性，并顺利完成了胸片定期检查，据华盛顿邮报未断定极度（三幅1）。
流行性感冒和甲型流行性感冒的快速核酸扩增检测（NAAT）为中都性。获了颊咽拭子骨骸，并通过NAAT将其送去检验病原性所发炎病原。
据华盛顿邮报在48两星期内对所有检测的病原仅有深褐色中都性，之外流行性感冒和甲型流行性感冒，副流行性感冒，所发炎合胞病原，颊病原，腺病原和迄今为止都会导致人类癌症的四种常见于冠状病原株（HKU1，NL63、229E和OC43） ）。根据患儿的旅程历日本史，立即接到以外和一个州公立医院。华盛顿卫生保健部与应急护理临床研究课题医师一起接到了CDC应急行动中都心。
尽管该患儿清查报告说是他无法去过珠江三角洲海鱼零售商，也无法清查报告在去中都国旅程前夕与生病者有任何保持联系，但癌症防止高度集中中都心的工作人员首肯有应该根据意味著的癌症防止高度集中中都心对患儿顺利完成2019-nCoV检测。
根据CDC范本搜集了8个骨骸，之外肾脏，颊咽和沟咽拭子骨骸。骨骸采自后，患儿被送往父母亲隔绝，并由当地公立医院顺利完成尽力监测。
2020年1月底20日，癌症防止高度集中中都心（CDC）断定患儿的颊咽和沟咽拭子通过动态逆转录酶-转录羧化（rRT-PCR）检验为2019-nCoV非众所周知。
在癌症防止高度集中中都心的题材专家，一个州和以外卫生保健官吏，应急医疗卫生保健服务以及病房领导和工作人员的配合下，患儿被送往普罗维登斯沿海地区医疗卫生保健中都心的氢气隔绝病房顺利完成临床研究课题掩蔽，并随同癌症防止高度集中中都心的医护人员有关保持联系，飞沫和空中都破片措施的备注示首肯，并带有护目镜。
入院时患儿清查报告持续呼吸困难，有2天的恶心和呕吐日本史。他清查报告说是他无法换气急促或心悸。永生征状在正常区域内。体格定期检查断定患儿上皮干燥。其余的定期检查通常不微小。
入院后，患儿放弃了赞同治疗，之外2升生理盐水和恩丹以更为严重恶心。
三幅2-根据癌症日和入院日（2020年1月底16日至2020年1月底30日）的病征和最高新陈代谢
在入院的第2至5天（生病的第6至9天），患儿的永生征状基本维持，除了借助于现间歇性所发烧并伴有心动过速（三幅2）。患儿继续清查报告非生产性呼吸困难，并借助于现疲累。
在入院第二天的晚间，患儿排便不畅，腹部不适。清晨有第二次小便仅有匀分布的华盛顿邮报。搜集该粪便的样品运用于rRT-PCR检测，以及其他所发炎骨骸（颊咽和沟咽）和肾脏。粪便和两个所发炎骨骸此后仅有通过rRT-PCR检验为2019-nCoV非众所周知，而肾脏仍为中都性。
在此前夕的治疗在不大相对上是赞同性的。为了顺利完成病征执行，患儿所需根据所需放弃解热治疗，该治疗之外每4两星期650 mg药物和每6两星期600 mg布洛芬。在入院的前六天，他还因持续呼吸困难而过量了600毫克够创醚和约6升生理盐水。
备注1-临床研究课题研究课题所结果
患儿隔绝单元的性质刚开始比较少意味着即时医疗卫生保健点研究课题所检测；从病房第3天开始可以顺利完成全血细胞计数器和肾脏化学研究课题。
在病房第3天和第5天（癌症第7天和第9天）的研究课题所结果反映借助于白血球增加症，轻度血小板增加症和肌酸激酶相对升高（备注1）。此部份，肺功能指标也有所叠加：酸性赖氯酸（每升68 U），丙氯酸氯基转移酶（每升105 U），天冬氯酸氯基转移酶（每升77 U）和乳糖天冬氯酸（每升465 U）的相对共有：在入院的第5天所有升高。鉴于患儿有规律所发烧，在第4天获肾脏人才；迄今为止，这些都无法上涨。
三幅3-2020年1月底22日（脸部第7天，病房第3天）的后前胸和部份侧胸片
三幅4-2020年1月底24日（脸部第5天，病房第9天）的后前胸X线片
据华盛顿邮报，在病房第3天（生病第7天）拍摄的脸部X光片未结果显示浸润或极度迹象（三幅3）。
但是，从病房第5天清晨（生病第9天）清晨顺利完成的第二次脸部X光片定期检查结果显示，左肺下叶有中都风（三幅4）。
这些影像学断定与从病房第5天清晨开始的换气正常叠加相吻合，以后患儿在换气区域内氢气时通过颤抖血锂含水测出的血锂含水最大值降至90％。
在第6天，患儿开始放弃补足水蒸气，该水蒸气由颊毛细管以每分钟2升的速度输送。尽量避免临床研究课题备注现的叠加和对病房获性中都风的关注，开始应运用于万古霉素（1750 mg负重剂量，然后每8两星期静脉注射1 g）和唑爆冷醛（每8两星期静脉注射）治疗。
三幅5-前后脸部X光片，2020年1月底26日（癌症第十天，病房第六天）
在病房第6天（生病第10天），第四次脸部X射线录像结果显示两个肺中都都有基底夹混浊，这一断定与非众所周知中都风相符（三幅5），并且在听诊时在两个肺中都都借助于现了罗音。鉴于辐射线影像学断定，首肯给予水蒸气补足，患儿持续所发烧，多个部位持续非众所周知的2019-nCoV RNA非众所周知，以及所发备注了与辐射线性中都风的所发展一致的致使中都风在该患儿中都，临床研究课题医师富有渴望地应运用于了研究课题性抑制剂治疗。
静脉注射史考特昔韦（一种打算共同开所发的新的型核苷酸萘前药）在第7天清晨开始，但未掩蔽到与减压有关的缺失事件。在对甲锂西林细菌性的深红色病原顺利完成了连续的降钙素原相对和颊PCR检验后，在第7天清晨废止万古霉素，并在第二天废止唑爆冷醛。
在病房第8天（生病第12天），患儿的临床研究课题原因得到提高。停止补足水蒸气，他在换气区域内氢气时的锂含水最大值提高到94％至96％。在此之后的双侧下叶罗音早已依赖于。他的食欲得到提高，除了间歇性干咳和颊漏部份，他无法病征。
截至2020年1月底30日，患儿仍入院。他有所发热，除呼吸困难部份，所有病征仅有已更为严重，呼吸困难的相对打算消除。
法则
骨骸采自
根据CDC范本获运用于2019-nCoV病症检测的临床研究课题骨骸。用聚酯拭子搜集了12个颊咽和沟咽拭子骨骸。
将每个拭子插入最大比如说是2至3 ml病原河运颗粒的单独无菌泵都。将血集在肾脏受控泵都，然后根据CDC范本顺利完成离心。尿和粪便骨骸分别搜集在无菌骨骸容器中都。样品在2°C至8°C彼此间储存，直到准备好运送至CDC。
在癌症的第7、11和12天搜集了重复顺利完成的2019-nCoV检测的骨骸，之外颊咽和沟咽拭子，肾脏以及尿和粪便样本。
2019-NCOV的病症检测
应运用于从公共同开所发布的病原脱氧核糖核酸的所发展而来的rRT-PCR分析法检测了临床研究课题骨骸。与在此之后针对重症急性换气症冠状病原（SARS-CoV）和中都东换气症冠状病原（MERS-CoV）的病症法则相近，它兼具三个核衣壳基因核酸和一个非众所周知对照核酸。该测出的说是明了为RRT-PCR面板引物和剪切和脱氧核糖核酸信息中都需用的CDC研究课题所信息com2019-nCoV上。
基因测序
2020年1月底7日，中都国研究课题人员通过American国立卫生保健研究课题院GenBank索引和在世界上共享所有流行性感冒资料倡议（GISAID）索引共享了2019-nCoV的比较简单基因脱氧核糖核酸；随后所发布了有关隔绝2019-nCoV的清查报告。
从rRT-PCR非众所周知骨骸（沟咽和颊咽）中都提取核酸，并在Sanger和世代测序平台（Illumina和MinIon）上运用于全原核生物测序。应运用于5.4.6版的Sequencher软件（Sanger）完成了脱氧核糖核酸组装。minimap软件，版本2.17（MinIon）；和freebayes软件1.3.1版（MiSeq）。将比较简单原核生物与需用的2019-nCoV参考脱氧核糖核酸（GenBank登录号NC_045512.2）顺利完成比较。
结果
2019-NCOV的骨骸检测
备注2-2019年新的型冠状病原（2019-nCoV）的动态逆转录酶-转录-羧化检测结果
该患儿在生病第4秦人获的初始所发炎样本（颊咽拭子和沟咽拭子）在2019-nCoV检出（备注2）。
尽管患儿刚开始备注现为轻度病征，但在癌症第4天的极低重复阈最大值（Ct）最大值（颊咽骨骸中都为18至20，沟咽骨骸中都为21至22）确实这些骨骸中都病原相对极低。
在癌症第7天获的两个上所发炎骨骸在2019-nCoV仍保持非众所周知，之外颊咽拭子骨骸中都持续高层次（Ct最大值23至24）。在癌症第7天获的粪便在2019-nCoV中都也检出（Ct最大值为36至38）。两种采自日期的肾脏样本在2019-nCoV仅有为中都性。
在癌症第11天和第12天获的颊咽和沟咽骨骸结果显示借助于病原相对增高的趋势。
沟咽骨骸在生病第12天的2019-nCoV检测深褐色中都性。在这些日期获的肾脏的rRT-PCR结果仍就其。
基因测序
沟咽和颊咽骨骸的比较简单原核生物脱氧核糖核酸彼此相同，并且与其他需用的2019-nCoV脱氧核糖核酸大部分相同。
该患儿的病原与2019-nCoV参考脱氧核糖核酸（NC_045512.2）在对外开放读者框8处比较少有3个核苷酸和1个不同。该脱氧核糖核酸可通过GenBank获（登录号MN985325）。
留言板
我们关于American由此可知未有2019-nCoV所病症病症的清查报告说是明了这一新的兴癌症的几个方面由此可知未完全了解，之外传播者自适应和临床研究课题癌症的全部区域。
我们的病症患儿曾去过中都国武昌，但清查报告说是他在武昌前夕无法去过海鱼批所发零售商或医疗卫生保健机构，也无法生病的保持联系。尽管他的2019-nCoV病菌的有可能由此可知不明确，但已引起争议了人对人传播者的证据。
到2020年1月底30日，由此可知未断定与此病症相关的2019-nCoV继所病症症，但仍在融洽搜查下。
在癌症的第4天和第7天从上所发炎骨骸中都检验到兼具极低Ct最大值的2019-nCoV RNA，确实病原载量高且兼具传播者潜力。
最大比如说是的是，我们还在患儿生病第7天搜集的粪便样本中都检验到了2019-nCoV RNA。尽管我们病症患儿的肾脏骨骸有规律借助于现2019-nCoV中都性，但在中都国重症患儿的肾脏中都仍检验到病原RNA。然而，肺部份检验病原RNA并不一定意味着依赖于传染性病原，迄今由此可知不明确在所发炎部份部检验病原RNA的临床研究课题意义。
迄今，我们对2019-nCoV病菌的临床研究课题区域的了解比较有限。在中都国，已经华盛顿邮报了诸如致使的中都风，换气衰竭，急性换气虚弱症（ARDS）和胸腔损伤等并所发症，之外有有可能的严重后果。然而，重要的是要注意，这些病症是根据其中都风病症断定的，因此有可能都会使清查报告偏向更是致使的结果。
我们的病症患儿刚开始备注现为轻度呼吸困难和极低度间歇性所发烧，在生病的第4天无法脸部X光定期检查的中都风迹象，而在生病第9天的所发展为中都风以后，这些非免疫征状和病征在晚期在临床研究课题上，2019-nCoV病菌的临床研究课题过程有可能与许多其他常见于传染病无法微小区别，尤其是在严寒所发炎病原季节。
另部份，本病症患儿在癌症的第9天的所发展为中都风的适时与近期换气困难的猝死（所病症后中都位数为8天）一致。尽管根据患儿的临床研究课题原因恶化首肯是否给予remdesivir慈悲的应运用于，但仍所需顺利完成随机对照试验以断定remdesivir和任何其他研究课题药物治疗2019-nCoV病菌的安全性和有效性。
我们清查报告了American由此可知未有清查报告的2019-nCoV病菌患儿的临床研究课题不同之处。
该病症的关键方面之外患儿在读者有关死灰复燃的心理卫生保健警告后首肯帮助医疗卫生保健；由当地医疗卫生保健简而言之断定患儿除此以外到武昌的旅程历日本史，随后在当地，一个州和美利坚合众国心理卫生保健官吏彼此间顺利完成协商；并断定有可能的2019-nCoV病菌，从而可以迅速隔绝患儿并随后对2019-nCoV顺利完成研究课题所断定，并意味着患儿入院进一步风险评估和管理者。
该病症清查报告强调了临床研究课题医师对于任何借助于现急性癌症病征的就诊患儿，要总结借助于除此以外的旅程经历或保持联系病因的特殊性，为了必需正确识别和第一时间隔绝有可能面临2019-nCoV病菌可能都会的患儿，并帮助增加进一步的传播者。
仍要，本清查报告强调所需断定与2019-nCoV病菌相关的临床研究课题癌症，所病症衍生物和病原脱落时间尺度的
全部区域和自然历日本史，以为临床研究课题管理者和心理卫生保健决策提供依据。
不限为英文版
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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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