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在当华北地区长沙开始的新型甲型感染（2019-nCoV）爆所发很快蔓延，现已在多个国家复所发。我们份文件了在英国获知的已为未有有2019-nCoV染病病患，并描绘出了该病患的深入研究，确诊，部份科现实生活和行政，有数病患在病情第9天展现造出为结核分裂病时的以年前轻度疼痛。
该个案忽视了部份科眼科医生与偏远地区，的州和的政府各级心理医疗港英政府中间紧密协作的益处，以及只能慢速传播方式与这种新所发染病病患的卫生有关的部份科信息的期望。
2019年12同年31日，当华北地区份文件了与宜昌长沙市华南菜式批所发低价有关的青年人当中的结核分裂病病患。
2020年1同年7日，当华北地区医疗港英政府获知该簇与新型甲型感染2019-nCoV有关。尽管以年前新闻报道的病患与长沙市菜式低价的漏造出有关，但当年前的药理学数据集注记明，准备所发生2019-nCoV人际传播方式。
截至2020年1同年30日，在非常少21个国家/地区份文件了9976例病患，有数2020年1同年20日新闻报道的英国已为未有有复所发的2019-nCoV染病病患。
当今世界正因如此域内准备顺利完成追查，以更好地明了传播方式快照和部份科疟疾正因如此域。本份文件描绘出了在英国获知的已为未有有2019-nCoV染病的药理学和部份科特点。
个案份文件
2020年1同年19日，一名35岁的蹦床显现造出来在纽达的州罗宾逊霍米孟加拉国的一家急诊养老院，有4天的气喘和有意识头痛简史。病人到养老院检查和时，在候诊室戴上沟罩。下次达20分钟后，他被带到检查和室不能接受了共享者的评量。
他透露，他在当华北地区长沙探望家人元月1同年15日返国纽达的州。该病患注记示，他已从英国疟疾控制与预防性当中心（CDC）所发来有关当华北地区新型甲型感染随之而来的身心健康台风，由于他的疼痛和最近的历险，他同意去看眼科医生。
布1-2020年1同年19日（疟疾第4天）的后年头部和后侧胸片
除了高三酸酯瓜氮酸的哮喘部份，该病患还是其他身心健康的不尼古丁。体格检查和所发掘造出病患气管环境氧气时，体温为37.2°C，体温为134/87 mm Hg，脉搏为每分钟110次，气管频带为每分钟16次，锂一般来真是为96％。胃部听诊推测有支气管炎，并顺利完成了胸片检查和，据新闻报道未有所发掘造出异常（布1）。
病毒性和-B传染病的慢速碱基扩增检测（NAAT）为乙型肝炎。获了咽咽拭子遗骸，并通过NAAT将其送去扫描流行性感冒细菌染病病原体。
据新闻报道在48同一时间内对所有检测的病原体之外深褐色乙型肝炎，有数病毒性和-B传染病，副传染病，细菌染病合胞病毒感染，咽病毒感染，腺病毒感染和已知会导致本能疟疾的四种少用甲型感染株（HKU1，NL63、229E和OC43） ）。根据病患的历险转变简史，随即告知偏远地区和的州医疗部。纽达医疗部与应急卫生部份科眼科医生两兄弟告知了CDC应急行动当中心。
尽管该病患份文件真是他并未有去过华南菜式低价，也并未有份文件在去当华北地区历险在此期间与患者有任何触及，但疟疾预防性控制当中心的工作人员准许有合理根据当年前的疟疾预防性控制当中心对病患顺利完成2019-nCoV检测。
根据CDC读物抽取了8个遗骸，有数小鼠，咽咽和沟咽拭子遗骸。遗骸挖掘造出后，病患被送去家庭监护，并由当地医疗部顺利完成积极监控。
2020年1同年20日，疟疾预防性控制当中心（CDC）获知病患的咽咽和沟咽拭子通过系统对逆转录酶-蛋白酶链式反应（rRT-PCR）扫描为2019-nCoV乙型肝炎。
在疟疾预防性控制当中心的意念专家，的州和偏远地区医疗官员，应急医疗保健服务以及公立医院领导和工作人员的配合下，病患被送去普罗维登斯地区的公立医院的氧气监护病房顺利完成部份科观察，并跟随疟疾预防性控制当中心的医护人员有关触及，飞沫和高空防爆措施的要求，并含有护目镜。
造出院时病患份文件接下来气喘，有2天的头痛和痉挛简史。他份文件真是他并未有气管急促或胸痛。精神上体征在正常正因如此域内。体格检查和所发掘造出病患粘膜高于温。其余的检查和一般而言不明显。
造出院后，病患不能接受了反对放射治疗，有数2升至生理盐水和恩丹以纾缓头痛。
布2-根据疟疾日和入院日（2020年1同年16日至2020年1同年30日）的疼痛和最高体温
在入院的第2至5天（患的第6至9天），病患的精神上体征整体始终保持，除了显现造出来间歇性头痛并诱发心动过速（布2）。病患继续份文件非生产性气喘，并显现造出来疲倦。
在入院第二天的下午，病患排便通畅，腹部不适。晚间有第二次大便均匀分布的新闻报道。抽取该老鼠的桶内用作rRT-PCR检测，以及其他细菌染病遗骸（咽咽和沟咽）和小鼠。老鼠和两个细菌染病遗骸后来之外通过rRT-PCR扫描为2019-nCoV乙型肝炎，而小鼠仍为乙型肝炎。
在此在此期间的放射治疗在很大高度上是自我行政的。为了顺利完成疼痛处理，病患只能根据只能不能接受解热医学上，该医学上有数每4同一时间650 mg对乙酰氮基酚和每6同一时间600 mg布洛芬。在入院的年前六天，他还因接下来气喘而服药了600毫克愈来愈创醚和达6升至生理盐水。
注记1-部份科深入研究团队结果
病患监护两组的并不一定以年前仅允许将会医疗保健点深入研究团队检测；从公立医院第3天开始可以顺利完成正因如此血细胞个数和小鼠化学深入研究。
在公立医院第3天和第5天（疟疾第7天和第9天）的深入研究团队结果说明了造出红血球减低病症，轻度血小板减低病症和肌酸激酶高于水平升至高（注记1）。此部份，冠心病指标也有所所发生变化：碱性激酶（每升至68 U），骆驼氮基转移酶（每升至105 U），糖类氮基转移酶（每升至77 U）和乳酸脱氢酶（每升至465 U）的高于水平分别为：在入院的第5天所有升至高。鉴于病患不停头痛，在第4天获肠道培养；迄今，这些都并未有放缓。
布3-2020年1同年22日（腹部第7天，公立医院第3天）的后年头部和后侧胸片
布4-2020年1同年24日（腹部第5天，公立医院第9天）的后年头部X线片
据新闻报道，在公立医院第3天（患第7天）拍的腹部X光片未有推测浸润或异常有可能（布3）。
但是，从公立医院第5天晚间（患第9天）晚间顺利完成的第二次腹部X光片检查和推测，左肺下叶有结核分裂病（布4）。
这些MRI所发掘造出与从公立医院第5天晚间开始的气管正常所发生变化相吻合，当时病患在气管周边氧气时通过脉搏血锂一般来真是定量的血锂一般来真是绝对值降至90％。
在第6天，病患开始不能接受不足之处一锂化碳，该一锂化碳由咽腹腔以每分钟2升至的速度运载。考虑到部份科展现造出的所发生变化和对公立医院获性结核分裂病的追捧，开始适用氯霉素（1750 mg负载药物，然后每8同一时间高于药物1 g）和红霉素爆冷吡啶（每8同一时间高于药物）放射治疗。
布5-年前后腹部X光片，2020年1同年26日（疟疾第十天，公立医院第六天）
在公立医院第6天（患第10天），第四次腹部X射线照片推测两个肺当中都有举例来说条状变黑，这一所发掘造出与非典型结核分裂病相一致（布5），并且在听诊时在两个肺当中都显现造出来了罗音。鉴于放射线MRI所发掘造出，同意拒绝不能接受一锂化碳不足之处，病患接下来头痛，多个部位接下来乙型肝炎的2019-nCoV RNA乙型肝炎，以及所发注记了与放射线性结核分裂病转变恰当的严重影响结核分裂病在该病患当中，部份科眼科医生极具同情心地适用了深入研究性类似物感染放射治疗。
高于药物瑞德昔韦（一种准备合作开所发的新型碱基类似物年前药）在第7天晚间开始，但未有观察到与输注有关的不良意外事件。在对的大锂西林脑膜炎的金黄色病原体顺利完成了连续的降钙素原高于水平和咽PCR扫描后，在第7天晚间停用氯霉素，并在第二天停用红霉素爆冷吡啶。
在公立医院第8天（患第12天），病患的部份科现况得到改善。取消不足之处一锂化碳，他在气管周边氧气时的锂一般来真是绝对值提高到94％至96％。先年前的双侧下叶罗音暂时依赖于。他的食欲得到改善，除了间歇性干咳和咽漏部份，他并未有疼痛。
截至2020年1同年30日，病患仍入院。他有气管困难，除气喘部份，所有疼痛之外已纾缓，气喘的高度准备减轻。
原理
遗骸挖掘造出
根据CDC读物获用作2019-nCoV确诊检测的部份科遗骸。用合成纤维拭子抽取了12个咽咽和沟咽拭子遗骸。
将每个拭子插入包含2至3 ml病毒感染海上运输真空的单独乳胶管当中。将血集在小鼠分离管当中，然后根据CDC读物顺利完成离心。体液和老鼠遗骸分别抽取在乳胶遗骸桶内当中。桶内在2°C至8°C中间储藏，直到准备好运送至CDC。
在疟疾的第7、11和12天抽取了每一次顺利完成的2019-nCoV检测的遗骸，有数咽咽和沟咽拭子，小鼠以及体液和老鼠桶内。
2019-NCOV的确诊检测
适用从公合作开刊所发的病毒感染氮基酸转变而来的rRT-PCR分析法检测了部份科遗骸。与先年前针对诊治急性气管病症候群甲型感染（SARS-CoV）和当中欧气管病症候群甲型感染（MERS-CoV）的确诊原理相似，它有着三个核分裂衣壳遗传物质遗传物质和一个乙型肝炎比对遗传物质。该定量的描绘出为RRT-PCR元件双链和核酸和氮基酸信息当中必需的CDC深入研究团队信息网站2019-nCoV上。
遗传脱氧核分裂糖核分裂酸
2020年1同年7日，当华北地区深入研究人员通过英国国立医疗深入社会科学院GenBank数据集库和当今世界共享所有传染病数据集倡议（GISAID）数据集库共享了2019-nCoV的清晰遗传物质氮基酸；随后刊所发了有关监护2019-nCoV的份文件。
从rRT-PCR乙型肝炎遗骸（沟咽和咽咽）当中所含碱基，并在Sanger和下一代脱氧核分裂糖核分裂酸平台（Illumina和MinIon）上用作正因如此序列脱氧核分裂糖核分裂酸。适用5.4.6特别版的Sequencher的软件（Sanger）完成了氮基酸组装。minimap的软件，特别原版2.17（MinIon）；和freebayes的软件1.3.1特别版（MiSeq）。将清晰序列与必需的2019-nCoV参看氮基酸（GenBank登录号NC_045512.2）顺利完成相对。
结果
2019-NCOV的遗骸检测
注记2-2019年新型甲型感染（2019-nCoV）的系统对逆转录酶-蛋白酶-链式反应检测结果
该病患在患第4四海获的初始细菌染病桶内（咽咽拭子和沟咽拭子）在2019-nCoV深褐色乙型肝炎（注记2）。
尽管病患以年前展现造出为轻度疼痛，但在疟疾第4天的高于循环阈绝对值（Ct）绝对值（咽咽遗骸当中为18至20，沟咽遗骸当中为21至22）注记明这些遗骸当中病毒感染高于水平较高。
在疟疾第7天获的两个上细菌染病遗骸在2019-nCoV仍保持乙型肝炎，有数咽咽拭子遗骸当中接下来高高于水平（Ct绝对值23至24）。在疟疾第7天获的老鼠在2019-nCoV当中也深褐色乙型肝炎（Ct绝对值为36至38）。两种挖掘造出日期的小鼠桶内在2019-nCoV之外为乙型肝炎。
在疟疾第11天和第12天获的咽咽和沟咽遗骸推测造出病毒感染高于水平下降的发展趋势。
沟咽遗骸在患第12天的2019-nCoV检测深褐色乙型肝炎。在这些日期获的小鼠的rRT-PCR结果仍未有定。
遗传脱氧核分裂糖核分裂酸
沟咽和咽咽遗骸的清晰序列氮基酸彼此相同，并且与其他必需的2019-nCoV氮基酸大部分相同。
该病患的病毒感染与2019-nCoV参看氮基酸（NC_045512.2）在解禁读物框8处仅有3个碱基和1个不尽相同。该氮基酸可通过GenBank获（登录号MN985325）。
版主
我们关于英国已为未有有2019-nCoV复所发病患的份文件真是明了这一新兴疟疾的几个方面未有曾完正因如此明了，有数传播方式快照和部份科疟疾的正因如此部正因如此域。
我们的病患患曾去过当华北地区长沙，但份文件真是他在长沙在此期间并未有去过菜式批所发低价或医疗保健机构，也并未有生病的触及。尽管他的2019-nCoV染病的；也已为不清楚，但已引起争议了人对人传播方式的有可能。
到2020年1同年30日，未有曾所发掘造出与此病患相关的2019-nCoV继复所发患，但仍在紧密监视下。
在疟疾的第4天和第7天从上细菌染病遗骸当中扫描到有着高于Ct绝对值的2019-nCoV RNA，注记明病毒感染总重量高且有着传播方式潜质。
绝对值得注意的是，我们还在病患患第7天抽取的老鼠桶内当中扫描到了2019-nCoV RNA。尽管我们病患患的小鼠遗骸不停显现造出来2019-nCoV乙型肝炎，但在当华北地区诊治病患的肠道当中仍扫描到病毒感染RNA。然而，胃部份扫描病毒感染RNA并不一定意味着依赖于传染性病毒感染，目年前已为不清楚在细菌染病部份部扫描病毒感染RNA的部份科意义。
目年前，我们对2019-nCoV染病的部份科正因如此域的明了十分有限。在当华北地区，并未有新闻报道了诸如严重影响的结核分裂病，气管衰竭，急性气管窘迫病症候群（ARDS）和瓣膜挫伤等并所发病症，有数致命性的后果。然而，重要的是要注意，这些病患是根据其结核分裂病确诊确认的，因此可能会使份文件偏向更严重影响的结果。
我们的病患患以年前展现造出为轻度气喘和高于度间歇性头痛，在患的第4天并未有腹部X光检查和的结核分裂病有可能，而在患第9天转变为结核分裂病之年前，这些非特异性体征和疼痛在晚期在部份科上，2019-nCoV染病的部份科现实生活可能与许多其他少用传染病并未有明显相异，尤其是在冬季细菌染病病毒感染干季。
另部份，本病患患在疟疾的第9天转变为结核分裂病的时机与未有来会气管困难的头痛（复所发后$为8天）恰当。尽管根据病患的部份科现况恶化同意是否拒绝不能接受remdesivir慈悲的适用，但仍只能顺利完成数据分析试验以确认remdesivir和任何其他深入研究药物放射治疗2019-nCoV染病的安正因如此性和有效性。
我们份文件了英国已为未有有份文件的2019-nCoV染病病患的部份科特点。
该病患的关键方面有数病患在读物有关随之而来的心理医疗警告后同意说服医疗保健；由当地医疗保健服务共享者获知病患最近到长沙的历险转变简史，随后在当地，的州和的政府心理医疗官员中间顺利完成协调；并确认可能的2019-nCoV染病，从而可以很快监护病患并随后对2019-nCoV顺利完成深入研究团队获知，并允许病患造出院进一步评量和行政。
该病患份文件忽视了部份科眼科医生对于任何显现造出来急性疟疾疼痛的诊治病患，要总结造出最近的历险境遇或触及哮喘的益处，为了合理正确地识别和设法监护可能遭遇2019-nCoV染病风险的病患，并为了让减低进一步的传播方式。
再一，本份文件忽视只能确认与2019-nCoV染病相关的部份科疟疾，复所发机理和病毒感染开裂接下来时间的
正因如此部正因如此域和自然环境转变简史，以为部份科行政和心理医疗决策者共享依据。
以下为英文特别版
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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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