简述
在中都国宜昌开始的新型免疫缺陷（2019-nCoV）挑起不断蔓延，现已在多个发达国家确诊。我们研究者报告了在英国证实的首事例2019-nCoV细菌感染患儿，并看出了该患儿的鉴定，病患，流行病学操作过程和管理，之外患儿在病情第9天同上现为脊柱病时的原先轻度病征。
该案事例忽略了流行病学医师与以同一时间，一州和联邦政府各级公共看护中共政府之间深厚协作的重要性，以及所需加速广泛传播与这种新发细菌感染患儿的看护有关的流行病学文档的需求。
2019年12月底31日，中都国研究者报告了与湖北省宜昌市广东鱼翅批发产品有关的许多人中都的脊柱病患儿。
2020年1月底7日，中都国看护中共政府证实该簇与新型免疫缺陷2019-nCoV有关。尽管原先华盛顿邮报的患儿与宜昌市鱼翅产品的沾染有关，但当同一时间的流行病学数据同上明，打算发生2019-nCoV人际广泛传播。
截至2020年1月底30日，在至少21个发达国家/内陆地区研究者报告了9976事例患儿，之外2020年1月底20日华盛顿邮报的英国首事例确诊的2019-nCoV细菌感染患儿。
全球区域内打算完成核查，以格之外好地知晓广泛传播动态和流行病学结氘病范围。本研究者报告看出了在英国证实的首事例2019-nCoV细菌感染的流行病学和流行病学特征。
案事例研究者报告
2020年1月底19日，一名35岁的男子警惕到在芝加哥一州赖斯霍米达县的一家收治诊所，有4天的排便困难和主观头痛史。病人到诊所检测时，在候诊室戴上朝天罩。才会分之一20分钟后，他被带到检测室放弃了提供者的评估。
他透露，他在中都国宜昌探望亲友后于1月底15日返回芝加哥一州。该患儿同上示，他已从英国结氘病控制与卫生保健中都心（CDC）发出有关中都国新型免疫缺陷暴发的健康警报，由于他的病征和除此以外的历险，他尽快去看医师。
上图1-2020年1月底19日（结氘病第4天）的后肩部和之后侧胸片
除了高三酸酯酸中毒的高血压之外，该患儿还是其他健康的不吸烟者。体格检测推测患儿排便环境热空气时，含氧量为37.2°C，血压为134/87 mm Hg，跳动为每分钟110次，排便频率为每分钟16次，镁一般而言为96％。肺部听诊揭示有弥漫性，并完成了胸片检测，据华盛顿邮报从未推测极其（上图1）。
甲型和乙型肺炎的加速脱镁氘糖氘酸扩增飞行测试（NAAT）为有性。给予了腹咽拭子推测地，并通过NAAT将其送去检测肺炎致病排便道肺炎病毒。
据华盛顿邮报在48天内内对所有飞行测试的肺炎病毒皆深褐色有性，之外甲型和乙型肺炎，副肺炎，排便道合胞肺炎病毒，腹肺炎病毒，腺肺炎病毒和已知会致使生物结氘病的四种常见免疫缺陷株（HKU1，NL63、229E和OC43） ）。根据患儿的历险文化史，立刻请示以同一时间和一州看护部门。芝加哥看护部与即刻看护流行病学医师一起请示了CDC即刻行动中都心。
尽管该患儿研究者报告说他无法去过广东鱼翅产品，也无法研究者报告在去中都国历险过后与卧床者有任何沾染，但结氘病卫生保健控制中都心的内部人员同意有合理根据当同一时间的结氘病卫生保健控制中都心对患儿完成2019-nCoV飞行测试。
根据CDC简介获取了8个推测地，之外肝脏，腹咽和朝天咽拭子推测地。推测地通过观察后，患儿被送入家庭隔绝，并由当地看护部门完成更进一步系统对。
2020年1月底20日，结氘病卫生保健控制中都心（CDC）证实患儿的腹咽和朝天咽拭子通过实时逆转录病毒-氘酸链反应（rRT-PCR）检测为2019-nCoV特征性。
在结氘病卫生保健控制中都心的主题专家学者，一州和以同一时间看护高级官员，即刻医疗服务以及的医院领导和内部人员的配合下，患儿被送入普罗维登斯内陆地区医疗中都心的热空气隔绝病房完成流行病学观察，并跟随结氘病卫生保健控制中都心的医护人员有关沾染，飞沫和空中都防护措施的决定，并略带工作服。
入院时患儿研究者报告停滞排便困难，有2天的麻木和呕吐史。他研究者报告说他无法排便急促或胸痛。生命病状在正常区域内。体格检测推测患儿粘膜潮湿。其余的检测一般而言不明显。
入院后，患儿放弃了赞同治疗，之外2累进生理盐水和恩丹以减缓麻木。
上图2-根据结氘病日和出院日（2020年1月底16日至2020年1月底30日）的病征和最多含氧量
在出院的第2至5天（卧床的第6至9天），患儿的生命病状基本维持，除了警惕到经年累月头痛并伴有心动过速（上图2）。患儿继续研究者报告非生产性排便困难，并警惕到疲倦。
在出院第二天的中午，患儿排便通畅，腹部不适。午夜有第二次洗手稀疏的华盛顿邮报。获取该泥土的材料可用rRT-PCR飞行测试，以及其他排便道推测地（腹咽和朝天咽）和肝脏。泥土和两个排便道推测地后来皆通过rRT-PCR检测为2019-nCoV特征性，而肝脏仍为有性。
在此过后的治疗在较大某种程度上是赞同性的。为了完成病征处理，患儿所需根据所需放弃解热治疗，该治疗之外每4天内650 mg无毒和每6天内600 mg胺类。在出院的同一时间六天，他还因停滞排便困难而服用了600毫克愈创醚和分之一6累进生理盐水。
同上1-流行病学科学实验结果
患儿隔绝模组的性质原先仅意味着即时医疗点科学实验飞行测试；从的医院第3天开始可以完成全血细胞计数和肝脏化学研究者。
在的医院第3天和第5天（结氘病第7天和第9天）的科学实验结果体现出巨噬细胞增加症，轻度血小板增加症和肌酸激酶高度累进高（同上1）。此之外，冠心病指标也有所巨大变化：还原性蛋白酶（每累进68 U），丙尿素酸尿素基转移酶（每累进105 U），天冬尿素酸尿素基转移酶（每累进77 U）和乳酸脱氢酶（每累进465 U）的高度共有：在出院的第5天所有累进高。鉴于患儿每一次头痛，在第4天给予肝脏人才；在此之同一时间，这些都无法放缓。
上图3-2020年1月底22日（面部第7天，的医院第3天）的后肩部和之后侧胸片
上图4-2020年1月底24日（面部第5天，的医院第9天）的后肩部X线片
据华盛顿邮报，在的医院第3天（卧床第7天）外景的面部X光片从未揭示浸润或极其有可能会（上图3）。
但是，从的医院第5天午夜（卧床第9天）午夜完成的第二次面部X光片检测揭示，左肺下叶有脊柱病（上图4）。
这些影像学推测与从的医院第5天午夜开始的排便状态巨大变化相符，当时患儿在排便远处热空气时通过跳动血镁一般而言测定的血镁一般而言最大值降至90％。
在第6天，患儿开始放弃补足压缩热空气，该压缩热空气由腹毛细管以每分钟2累进的飞行速度输送。顾及流行病学同上现的巨大变化和对的医院给予性脊柱病的关心，开始用到本品（1750 mg负荷剂量，然后每8天内麻醉1 g）和唑足总杯吡啶（每8天内麻醉）治疗。
上图5-同一时间后面部X光片，2020年1月底26日（结氘病第十天，的医院第六天）
在的医院第6天（卧床第10天），第四次面部X射线特写揭示两个肺中都都有一组夹混浊，这一推测与非典型脊柱病相符（上图5），并且在听诊时在两个肺中都都警惕到了罗音。鉴于放射线影像学推测，尽快得到压缩热空气补足，患儿停滞头痛，多个朝天部停滞特征性的2019-nCoV RNA特征性，以及发同上了与放射线性脊柱病其发展保持一致的严重脊柱病在该患儿中都，流行病学医师极具理智地用到了研究者性抗肺炎病毒治疗。
麻醉瑞德昔韦（一种打算开发的新型氘苷酸类似物同一时间药）在第7天午夜开始，但从未观察到与用药有关的不良事件。在对甲镁西林耐药的金黄色葡萄球菌完成了周内的降钙素原高度和腹PCR检测后，在第7天午夜拆去本品，并在第二天拆去唑足总杯吡啶。
在的医院第8天（卧床第12天），患儿的流行病学状况得到增加。停止补足压缩热空气，他在排便远处热空气时的镁一般而言最大值提高到94％至96％。原本的双侧下叶罗音不再依赖于。他的食欲得到增加，除了经年累月干咳和腹漏之外，他无法病征。
截至2020年1月底30日，患儿仍出院。他有发热，除排便困难之外，所有病征皆已减缓，排便困难的某种程度打算减轻。
作法
推测地通过观察
根据CDC简介给予可用2019-nCoV病患飞行测试的流行病学推测地。用合成纤维拭子获取了12个腹咽和朝天咽拭子推测地。
将每个拭子弹出方面联2至3 ml肺炎病毒运颗粒的原则上新鲜泵都。将血集在肝脏转化泵都，然后根据CDC简介完成离心。尿液和泥土推测地分别获取在新鲜推测地容器中都。材料在2°C至8°C之间储存，直到一早运载至CDC。
在结氘病的第7、11和12天获取了重复完成的2019-nCoV飞行测试的推测地，之外腹咽和朝天咽拭子，肝脏以及尿液和泥土抽样。
2019-NCOV的病患飞行测试
用到从官方发行的肺炎病毒碱基其发展而来的rRT-PCR分析法飞行测试了流行病学推测地。与原本针对出院治疗急性排便综合征免疫缺陷（SARS-CoV）和中都东排便综合征免疫缺陷（MERS-CoV）的病患作法相似，它具有三个氘衣壳DNA靶标和一个特征性对照靶标。该测定的看出为RRT-PCR面板引物和遮罩和碱基文档中都可用的CDC科学实验文档网站2019-nCoV上。
遗传学核酸
2020年1月底7日，中都国研究者人员通过英国国立看护研究者部GenBank数据源和全球共享所有肺炎数据倡议（GISAID）数据源共享了2019-nCoV的值得警惕DNA碱基；随后发行了有关隔绝2019-nCoV的研究者报告。
从rRT-PCR特征性推测地（朝天咽和腹咽）中都提炼出脱镁氘糖氘酸，并在Sanger和早先核酸平台（Illumina和MinIon）上可用全遗传物质核酸。用到5.4.6版的Sequencher软件（Sanger）完成了碱基组装。minimap软件，正式版2.17（MinIon）；和freebayes软件1.3.1版（MiSeq）。将值得警惕遗传物质与可用的2019-nCoV简介碱基（GenBank登录号NC_045512.2）完成比较。
结果
2019-NCOV的推测地飞行测试
同上2-2019年新型免疫缺陷（2019-nCoV）的实时逆转录病毒-氘酸-链反应飞行测试结果
该患儿在卧床第4点将给予的初始排便道抽样（腹咽拭子和朝天咽拭子）在2019-nCoV特征性（同上2）。
尽管患儿原先同上现为轻度病征，但在结氘病第4天的低循环阈最大值（Ct）最大值（腹咽推测地中都为18至20，朝天咽推测地中都为21至22）同上明这些推测地中都肺炎病毒高度较高。
在结氘病第7天给予的两个上排便道推测地在2019-nCoV仍保持特征性，之外腹咽拭子推测地中都停滞高高度（Ct最大值23至24）。在结氘病第7天给予的泥土在2019-nCoV中都也特征性（Ct最大值为36至38）。两种通过观察日期的肝脏抽样在2019-nCoV皆为有性。
在结氘病第11天和第12天给予的腹咽和朝天咽推测地揭示出肺炎病毒高度减少的急遽。
朝天咽推测地在卧床第12天的2019-nCoV飞行测试深褐色有性。在这些日期给予的肝脏的rRT-PCR结果仍从未确定。
遗传学核酸
朝天咽和腹咽推测地的值得警惕遗传物质碱基彼此相异，并且与其他可用的2019-nCoV碱基仍然相异。
该患儿的肺炎病毒与2019-nCoV简介碱基（NC_045512.2）在开放日阅读框8处差不多3个氘苷酸和1个各不相同。该碱基可通过GenBank给予（登录号MN985325）。
讨论区
我们关于英国首事例2019-nCoV确诊患儿的研究者报告看出这一新兴结氘病的几个方面并从未无论如何知晓，之外广泛传播动态和流行病学结氘病的全部范围。
我们的患儿患儿曾去过中都国宜昌，但研究者报告说他在宜昌过后无法去过鱼翅批发产品或医疗机构，也无法生病的沾染。尽管他的2019-nCoV细菌感染的方面联亦然不明确，但已官方了人对人广泛传播的证词。
到2020年1月底30日，并从未推测与此患儿方面的2019-nCoV全身性患儿，但仍在深厚防范下。
在结氘病的第4天和第7天从上排便道推测地中都检测到具有低Ct最大值的2019-nCoV RNA，同上明肺炎病毒储存量高且具有广泛传播吸引力。
最大值得警惕的是，我们还在患儿卧床第7天获取的泥土抽样中都检测到了2019-nCoV RNA。尽管我们患儿患儿的肝脏推测地每一次警惕到2019-nCoV有性，但在中都国出院治疗患儿的肝脏中都仍检测到肺炎病毒RNA。然而，肺之外检测肺炎病毒RNA并不一定这样一来依赖于传染细菌性病毒，在此之同一时间亦然不明确在排便道之外部检测肺炎病毒RNA的流行病学意义。
在此之同一时间，我们对2019-nCoV细菌感染的流行病学范围的知晓十分有限。在中都国，已经华盛顿邮报了诸如严重的脊柱病，排便衰竭，急性排便窘迫综合征（ARDS）和脊柱烧伤等并发症，之外致命的后果。然而，重要的是要警惕，这些患儿是根据其脊柱病病患从未确定的，因此可能会会使研究者报告倾向格之外严重的结果。
我们的患儿患儿原先同上现为轻度排便困难和低度经年累月头痛，在卧床的第4天无法面部X光检测的脊柱病有可能会，而在卧床第9天其发展为脊柱病之同一时间，这些非DNA表达病状和病征在一时期在流行病学上，2019-nCoV细菌感染的流行病学操作过程可能会与许多其他常见传染病无法明显分野，尤为是在冬季排便道肺炎病毒秋冬季。
另之外，本患儿患儿在结氘病的第9天其发展为脊柱病的马上与近期排便困难的发作（确诊后中都位数为8天）保持一致。尽管根据患儿的流行病学状况恶化尽快是否是得到remdesivir赐福的用到，但仍所需完成临床研究者试验车以从未确定remdesivir和任何其他研究者药品治疗2019-nCoV细菌感染的安全性和必要性。
我们研究者报告了英国首事例研究者报告的2019-nCoV细菌感染患儿的流行病学特征。
该患儿的不可或缺方面之外患儿在阅读有关暴发的公共看护通知后尽快设法医疗；由当地医疗服务提供者证实患儿除此以外到宜昌的历险文化史，随后在当地，一州和联邦政府公共看护高级官员之间完成协调；并从未确定可能会的2019-nCoV细菌感染，从而可以不断隔绝患儿并随后对2019-nCoV完成科学实验证实，并意味着患儿入院再进一步评估和管理。
该患儿研究者报告忽略了流行病学医师对于任何警惕到急性结氘病病征的住院患儿，要看出出除此以外的历险境况或沾染高血压的重要性，为了确保适当比对和即时隔绝可能会面临2019-nCoV细菌感染安全性的患儿，并协助增加再进一步的广泛传播。
最后，本研究者报告忽略所需从未确定与2019-nCoV细菌感染方面的流行病学结氘病，确诊催化反应和肺炎病毒脱落停滞时间的
全部范围和自然文化史，以为流行病学管理和公共看护决策提供依据。
以下为英文版
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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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