摘录
在中所国成都开始的新型病原性（2019-nCoV）爆发促使席卷，现已在多个国际组织就诊。我们统个数据集了在英美两国获知的月所2019-nCoV传染患者，并描绘出了该患者的认定，病因，针灸现实生活和管理者，之以外病病征在病情第9天列于现为心肌梗塞时的起初轻度痉挛。
该犯罪行为合理化了针灸医师与；也，和州和美利坚合众国各级护理保健新加坡政府相互间密切协作的层面，以及必需快速传递与这种新发传染病病征的护理有关的针灸信息的需求。
2019年12年底31日，中所国统个数据集了与湖北省岳阳市华南鲍鱼批发消费市场有关的人群中所的心肌梗塞患者。
2020年1年底7日，中所国护理新加坡政府获知该簇与新型病原性2019-nCoV有关。尽管起初刊文的患者与岳阳市鲍鱼消费市场的暴露有关，但当前的流行病学数据集列于明，正试图再次发生2019-nCoV人际传递。
截至2020年1年底30日，在至少21个国际组织/邻近地区统个数据集了9976例患者，之以外2020年1年底20日刊文的英美两国月所就诊的2019-nCoV传染患者。
以以外球区域正试图开展惨案调查，以格外高地明了传递自适应和针灸疟疾之内。本统个数据集描绘出了在英美两国获知的月所2019-nCoV传染的流行病学和针灸不同之处。
犯罪行为统个数据集
2020年1年底19日，一名35岁的铁饼显露现在华盛顿和州斯诺霍米什县的服装店收治诊所，有4天的发烧和单纯哮喘史。病人到诊所检测时，在候诊室戴上故名罩。等候约20分钟后，他被送到检测室接纳了之以外联的评估。
他透露，他在中所国成都探望家人后于1年底15日返回华盛顿和州。该病病征列于示，他已从英美两国疟疾掌控与防治中所心（CDC）发给有关中所国新型病原性随之而来的健康中央气象局，由于他的痉挛和早先的环游，他最终去看医师。
平面图1-2020年1年底19日（疟疾第4天）的后前额和下方胸片
除了大一酸酯血病征的帕金森氏病征以外，该病病征还是其他健康的不吸烟者。体格检测推断出病病征吞咽环境氢气时，代谢率为37.2°C，血压为134/87 mm Hg，----为每分钟110次，吞咽频率为每分钟16次，锂相对于为96％。肺部听诊结果显示有支气管炎，并开展了胸片检测，据刊文亦然未推断出持续性（平面图1）。
亚型和乙型传染病的快速核苷酸扩充试验（NAAT）为比如话说。赢得了喉咽拭子头颅骨，并通过NAAT将其送去侦测病原性吞咽道免疫。
据刊文在48星期内对所有试验的免疫原则上黄绿色比如话说，之以外亚型和乙型传染病，副传染病，吞咽道合胞病原，喉病原，腺病原和已知就会导致全人类疟疾的四种常用病原性株（HKU1，NL63、229E和OC43） ）。根据病病征的环游近代，立刻接到；也和和州护理部门。华盛顿护理部与紧急护理针灸医师一同接到了CDC紧急行动中所心。
尽管该病病征统个数据集话说他并亦然未去过华南鲍鱼消费市场，也并亦然未统个数据集在去中所国环游长期与体弱者有任何认识，但疟疾防治掌控中所心的管理人员同意有应该根据当前的疟疾防治掌控中所心对病病征开展2019-nCoV试验。
根据CDC读物查阅了8个头颅骨，之以外小鼠，喉咽和故名咽拭子头颅骨。头颅骨查阅后，病病征被送往家庭强制，并由当地护理部门开展不遗余力监测。
2020年1年底20日，疟疾防治掌控中所心（CDC）获知病病征的喉咽和故名咽拭子通过实时逆转录病毒-聚合酶链式反应（rRT-PCR）侦测为2019-nCoVHIV。
在疟疾防治掌控中所心的主旨技术人员，和州和；也护理行政官员，紧急医护服务以及的医院领导者和管理人员的配合下，病病征被送往新泽西和州邻近地区教育中所心的氢气强制病房开展针灸观察，并跟随疟疾防治掌控中所心的医护人员有关认识，飞沫和飞行中所防护防治措施的敦促，并带有防毒面具。
病情恶化时病病征统个数据集持续性发烧，有2天的烦躁和痉挛史。他统个数据集话说他并亦然未吞咽急促或胸痛。灵魂病病征在经常性区域。体格检测推断出病病征牙龈湿气。其余的检测不一定不微小。
病情恶化后，病病征接纳了支持放射治疗，之以外2升生理盐水和恩丹以减缓烦躁。
平面图2-根据疟疾日和就医日（2020年1年底16日至2020年1年底30日）的痉挛和略低于代谢率
在就医的第2至5天（体弱的第6至9天），病病征的灵魂病病征基本保持良好稳定，除了显露现但会哮喘并浸润心动过速（平面图2）。病病征继续统个数据集非生产性发烧，并显露现疲倦。
在就医第二天的下午，病病征手淫有利于，腹部不适。中所午有第二次大便稀疏的刊文。查阅该粪的试样用以rRT-PCR试验，以及其他吞咽道头颅骨（喉咽和故名咽）和小鼠。粪和两个吞咽道头颅骨日后原则上通过rRT-PCR侦测为2019-nCoVHIV，而小鼠仍为比如话说。
在此长期的放射治疗在很大程度上是支持性的。为了开展痉挛附近理，病病征必需根据必需接纳解热化学疗法，该化学疗法之以外每4星期650 mg对乙酰氨基酚和每6星期600 mg抗炎药。在就医的前六天，他还因持续性发烧而用药了600毫克愈好创醚条约6升生理盐水。
列于1-针灸研究成果所结果
病病征强制单元的不一定起初仅必需事前医护点研究成果所试验；从的医院第3天开始可以开展以以外血细胞个数和小鼠化学研究成果。
在的医院第3天和第5天（疟疾第7天和第9天）的研究成果所结果突显显露炎症减缓病征，轻度粒细胞减缓病征和肌酸激酶程度急剧下降（列于1）。此以外，肝功能测试方法也有所变异：水溶性磷酸酶（每升68 U），酰氨基转移酶（每升105 U），胺基酸氨基转移酶（每升77 U）和三酸甘油酯脱氢酶（每升465 U）的程度都为：在就医的第5天所有急剧下降。鉴于病病征有规律哮喘，在第4天赢得血浆培植；当今世界，这些都并亦然未增加。
平面图3-2020年1年底22日（臀部第7天，的医院第3天）的后前额和下方胸片
平面图4-2020年1年底24日（臀部第5天，的医院第9天）的后前额X线片
据刊文，在的医院第3天（体弱第7天）取景的臀部X光片亦然未结果显示浸润或持续性可能（平面图3）。
但是，从的医院第5天中所午（体弱第9天）中所午开展的第二次臀部X光片检测结果显示，左肺下叶有心肌梗塞（平面图4）。
这些医学影像推断出与从的医院第5天中所午开始的吞咽状态变异密切相关，当年病病征在吞咽四周氢气时通过----MRI相对于检测的MRI相对于系数降至90％。
在第6天，病病征开始接纳应该二锂化碳，该二锂化碳由喉导管以每分钟2升的格外快输送。受制于针灸列于现的变异和对的医院赢得性心肌梗塞的关注，开始采用布洛芬（1750 mg负担剂量，然后每8星期施打1 g）和类抗生素爆冷苯甲酸（每8星期施打）放射治疗。
平面图5-前后臀部X光片，2020年1年底26日（疟疾第十天，的医院第六天）
在的医院第6天（体弱第10天），第四次臀部X射线照片结果显示两个肺中所都有角化条状经年累年底，这一推断出与非典型心肌梗塞相符（平面图5），并且在听诊时在两个肺中所都显露现了罗音。鉴于放射线医学影像推断出，最终给予二锂化碳应该，病病征持续性哮喘，多个臀部持续性HIV的2019-nCoV RNAHIV，以及发列于了与放射线性心肌梗塞拓展相一致的严重心肌梗塞在该病病征中所，针灸医师极富同情心地采用了人文学科抗病原放射治疗。
施打史密斯昔韦（一种正试图开发新的新型核苷酸类似物前药）在第7天中所午开始，但亦然未观察到与输注有关的不良惨案。在对甲锂霖耐药的金黄色细菌性开展了连续的降钙素原程度和喉PCR侦测后，在第7天中所午撤除布洛芬，并在第二天撤除类抗生素爆冷苯甲酸。
在的医院第8天（体弱第12天），病病征的针灸状况得到增加。暂时中止应该二锂化碳，他在吞咽四周氢气时的锂相对于系数提高到94％至96％。原本的铰下叶罗音不再共存。他的激素得到增加，除了但会干咳和喉漏以外，他并亦然未痉挛。
截至2020年1年底30日，病病征仍就医。他有发热，除发烧以外，所有痉挛原则上已减缓，发烧的程度正试图加重。
方法
头颅骨查阅
根据CDC读物赢得用以2019-nCoV病因试验的针灸头颅骨。用橡胶拭子查阅了12个喉咽和故名咽拭子头颅骨。
将每个拭子嵌入还包括2至3 ml病原船运介质的实际上新鲜循环系统所。将血集在小鼠分离循环系统所，然后根据CDC读物开展离心。血浆和粪头颅骨分别查阅在新鲜头颅骨容器中所。试样在2°C至8°C相互间填充，直到作好运送至CDC。
在疟疾的第7、11和12天查阅了多次重复开展的2019-nCoV试验的头颅骨，之以外喉咽和故名咽拭子，小鼠以及血浆和粪试样。
2019-NCOV的病因试验
采用从未公开发新布的病原数列拓展而来的rRT-PCR分析法试验了针灸头颅骨。与原本针对重病征急性吞咽综合病征病原性（SARS-CoV）和中所东吞咽综合病征病原性（MERS-CoV）的病因方法完全相近，它很强三个核核蛋白基因化学合成和一个HIV对照化学合成。该检测的描绘出为RRT-PCR元件引物和间隙和数列信息中所举例来说的CDC研究成果所信息网站2019-nCoV上。
遗传脱锂核糖核苷酸
2020年1年底7日，中所国研究成果人员通过英美两国国立护理研究成果院GenBank数据集库和以以外球包涵所有传染病数据集倡议（GISAID）数据集库包涵了2019-nCoV的比较简单基因数列；随后发布了有关强制2019-nCoV的统个数据集。
从rRT-PCRHIV头颅骨（故名咽和喉咽）中所提取核苷酸，并在Sanger和亦然未来脱锂核糖核苷酸平台（Illumina和MinIon）上用以以以外基因脱锂核糖核苷酸。采用5.4.6版本的Sequencher软体（Sanger）完成了数列被装。minimap软体，版本本2.17（MinIon）；和freebayes软体1.3.1版本（MiSeq）。将比较简单基因与举例来说的2019-nCoV参考数列（GenBank登录号NC_045512.2）开展比较。
结果
2019-NCOV的头颅骨试验
列于2-2019年新型病原性（2019-nCoV）的实时逆转录病毒-聚合酶-链式反应试验结果
该病病征在体弱第4天时赢得的初始吞咽道试样（喉咽拭子和故名咽拭子）在2019-nCoV黄绿色HIV（列于2）。
尽管病病征起初列于现为轻度痉挛，但在疟疾第4天的高于循环阈系数（Ct）系数（喉咽头颅骨中所为18至20，故名咽头颅骨中所为21至22）列于明这些头颅骨中所病原程度较高。
在疟疾第7天赢得的两个上吞咽道头颅骨在2019-nCoV仍保持良好HIV，之以外喉咽拭子头颅骨中所持续性高程度（Ct系数23至24）。在疟疾第7天赢得的粪在2019-nCoV中所也黄绿色HIV（Ct系数为36至38）。两种查阅日前的小鼠试样在2019-nCoV原则上为比如话说。
在疟疾第11天和第12天赢得的喉咽和故名咽头颅骨结果显示显露病原程度下降的趋势。
故名咽头颅骨在体弱第12天的2019-nCoV试验黄绿色比如话说。在这些日前赢得的小鼠的rRT-PCR结果仍亦然未定。
遗传脱锂核糖核苷酸
故名咽和喉咽头颅骨的比较简单基因数列彼此相近，并且与其他举例来说的2019-nCoV数列依然相近。
该病病征的病原与2019-nCoV参考数列（NC_045512.2）在开放朗读上端8附近仅有3个核苷酸和1个不同。该数列可通过GenBank赢得（登录号MN985325）。
讨论区
我们关于英美两国月所2019-nCoV就诊患者的统个数据集话暗示这一新兴疟疾的几个各个方面亦然亦然未完以以外明了，之以外传递自适应和针灸疟疾的以以外部之内。
我们的患者病病征曾去过中所国成都，但统个数据集话说他在成都长期并亦然未去过鲍鱼批发消费市场或医护机构，也并亦然未年老的认识。尽管他的2019-nCoV传染的来源亦然不相符，但已未公开了人对人传递的证据。
到2020年1年底30日，亦然亦然未推断出与此患者之以外的2019-nCoV所致患者，但仍在密切跟踪下。
在疟疾的第4天和第7天从上吞咽道头颅骨中所侦测到很强高于Ct系数的2019-nCoV RNA，列于明病原载量高且很强传递潜质。
系数得注意的是，我们还在病病征体弱第7天查阅的粪试样中所侦测到了2019-nCoV RNA。尽管我们患者病病征的小鼠头颅骨有规律显露现2019-nCoV比如话说，但在中所国重病征病病征的血浆中所仍侦测到病原RNA。然而，肺以外侦测病原RNA不一定意味着共存传染性病原，现有亦然不相符在吞咽道以外部侦测病原RNA的针灸意义。
现有，我们对2019-nCoV传染的针灸之内的明了比较实际。在中所国，已经刊文了诸如严重的心肌梗塞，吞咽衰竭，急性吞咽窘迫综合病征（ARDS）和胸腔损伤等并发病征，之以外不幸的后果。然而，重要的是要注意，这些患者是根据其心肌梗塞病因考虑到的，因此可能就会使统个数据集相反格外严重的结果。
我们的患者病病征起初列于现为轻度发烧和高于度但会哮喘，在体弱的第4天并亦然未臀部X光检测的心肌梗塞可能，而在体弱第9天拓展为心肌梗塞之前，这些非特异性病病征和痉挛在20世纪在针灸上，2019-nCoV传染的针灸现实生活可能与许多其他常用传染病并亦然未微小区别，尤其是在冬季吞咽道病原夏天。
另以外，本患者病病征在疟疾的第9天拓展为心肌梗塞的必定会与早先吞咽困难的发作（就诊后中所位数为8天）相一致。尽管根据病病征的针灸状况恶化最终是否是给予remdesivir慈悲的采用，但仍必需开展人文学科飞行试验以考虑到remdesivir和任何其他研究成果药物放射治疗2019-nCoV传染的安以以外性和有效性。
我们统个数据集了英美两国月所统个数据集的2019-nCoV传染病病征的针灸不同之处。
该患者的关键各个方面之以外病病征在朗读有关随之而来的护理保健发出后最终寻求医护；由当地医护服务之以外联获知病病征早先到成都的环游近代，随后在当地，和州和美利坚合众国护理保健行政官员相互间开展协调；并考虑到可能的2019-nCoV传染，从而可以促使强制病病征并随后对2019-nCoV开展研究成果所获知，并必需病病征病情恶化促使评估和管理者。
该患者统个数据集合理化了针灸医师对于任何显露现急性疟疾痉挛的就诊病病征，要阐释显露早先的环游经历或认识帕金森氏病征的层面，为了尽可能正确标识和及早强制可能面临2019-nCoV传染风险的病病征，并帮助减缓促使的传递。
最后，本统个数据集合理化必需考虑到与2019-nCoV传染之以外的针灸疟疾，就诊衍生物和病原脱落持续性时间的
以以外部之内和其本质近代，以为针灸管理者和护理保健决策者提供依据。
请注意为英文版本
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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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