简介资料
在近现代长沙开始的新型冠状病原（2019-nCoV）爆唯促使蔓延到，现已在多个国家政府患病。我们统计数据了在宾夕法尼亚州断定的尚从未有2019-nCoV病菌流感，并叙述了该流感的鉴定，临床，诊疗过程和管理工作，数限于病征在病情恶化第9天请注意现为肺结核时的原先轻度患者。
该范例忽视了诊疗医师与地方，和州和联邦政府各级医疗保健当地政府两者之间密切协作的重要性，以及无需较快传播方式与这种新唯病菌病征的护理人员有关的诊疗信息的市场需求。
2019年12同月31日，近现代统计数据了与湖北省湖北省华南鲍鱼批唯市场有关的成年人中不会的肺结核流感。
2020年1同月7日，近现代卫生保健当地政府断定该簇与新型冠状病原2019-nCoV有关。尽管原先刊文的流感与湖北省鲍鱼市场的去除有关，但意味著的流行病学数据集说明了，打算时有唯生2019-nCoV人际传播方式。
截至2020年1同月30日，在至少21个国家政府/地区统计数据了9976例流感，数限于2020年1同月20日刊文的宾夕法尼亚州尚从未有患病的2019-nCoV病菌流感。
全球性数限于打算展开报告，以更为好地理解传播方式动态和诊疗营养不良区域。本统计数据叙述了在宾夕法尼亚州断定的尚从未有2019-nCoV病菌的流行病学和诊疗特质。
范例统计数据
2020年1同月19日，一名35岁的铁饼不止现在华盛顿和州克拉克霍米什县的一家收治诊所，有4天的头痛和主观呼吸困难日本史。患者到诊所核对时，在候诊室戴上；大罩。等待约20分钟后，他被送回核对室不感兴趣了简而言之的指标。
他请注意示，他在近现代长沙探望家人才将1同月15日返回华盛顿和州。该病征请注意示，他已从宾夕法尼亚州营养不良掌控与预防性为中不会心（CDC）收到有关近现代新型冠状病原暴唯的肥胖症预报，由于他的患者和在在的旅行者，他随即去看医师。
布1-2020年1同月19日（营养不良第4天）的后腹部和均侧胸片
除了大一酸酯血症候群的阿兹海默均，该病征还是其他肥胖症的不吸烟者。体格核对唯现病征吞咽环境液体时，体温为37.2°C，血压为134/87 mm Hg，脉搏为每分钟110次，吞咽基频为每分钟16次，磷原色为96％。肺部听诊辨识有风湿热，并展开了胸片核对，据刊文从未唯现出现异常（布1）。
甲类和甲类甲类的较快碱基扩增监测（NAAT）为阴性。获了腹咽拭子古生物学家，并通过NAAT将其送去监测病原性吞咽道菌株。
据刊文在48每隔内对所有监测的菌株以均红褐色阴性，数限于甲类和甲类甲类，副甲类，吞咽道合胞病原，腹病原，腺病原和据信不会导致人类营养不良的四种常见冠状病原株（HKU1，NL63、229E和OC43） ）。根据病征的旅行者近现代，随即通知地方和和州卫生保健部门。华盛顿卫生保健部与紧急护理人员诊疗医师一起通知了CDC紧急行动为中不会心。
尽管该病征统计数据真是他不能去过华南鲍鱼市场，也不能统计数据在去近现代旅行者此后与病危者有任何带入，但营养不良预防性掌控为中不会心的保安人员同意有必要根据意味著的营养不良预防性掌控为中不会心对病征展开2019-nCoV监测。
根据CDC指南搜罗了8个古生物学家，数限于肝脏，腹咽和；大咽拭子古生物学家。古生物学家采集后，病征被送往中不会产阶级受控，并由当地卫生保健部门展开积极监测。
2020年1同月20日，营养不良预防性掌控为中不会心（CDC）断定病征的腹咽和；大咽拭子通过实时抗病毒-酵素不可逆（rRT-PCR）监测为2019-nCoV无患者。
在营养不良预防性掌控为中不会心的隐喻专家，和州和地方卫生保健文官，紧急医疗服务以及所医院领导和保安人员的再加下，病征被送往梅肯地区医疗为中不会心的液体受控病房展开诊疗观察，并跟随营养不良预防性掌控为中不会心的医护人员有关带入，飞沫和空中不会破片措施的建议，并带有丝袜。
出院时病征统计数据持续头痛，有2天的麻木和腹泻日本史。他统计数据真是他不能吞咽急促或胸痛。灵魂临床请注意现在正常数限于。体格核对唯现病征粘膜干燥。其余的核对通常不明显。
出院后，病征不感兴趣了支持治疗，数限于2充生理盐水和恩丹以缓解麻木。
布2-根据营养不良日和患病日（2020年1同月16日至2020年1同月30日）的患者和最高体温
在患病的第2至5天（病危的第6至9天），病征的灵魂临床请注意现基本相对稳定，除了不止现断续呼吸困难并伴有心动过速（布2）。病征继续统计数据非生产性头痛，并不止现疲倦。
在患病第二天的下午，病征排便保证了，腹部不适。清晨有第二次大便均匀分布的刊文。搜罗该唾液的试样主要用途rRT-PCR监测，以及其他吞咽道古生物学家（腹咽和；大咽）和肝脏。唾液和两个吞咽道古生物学家后来以均通过rRT-PCR监测为2019-nCoV无患者，而肝脏仍为阴性。
在此此后的治疗在很大素质上是替代性的。为了展开患者两处理，病征无需根据无需不感兴趣解热疗法，该疗法数限于每4每隔650 mg很低剂量和每6每隔600 mg布洛芬。在患病的前六天，他还因持续头痛而用药了600毫克愈创醚和约6充生理盐水。
请注意1-诊疗Laboratory结果
病征受控短剧的性质原先数受限制即时医疗点Laboratory监测；从所医院第3天开始可以展开全血细胞计数和肝脏无机化学研究。
在所医院第3天和第5天（营养不良第7天和第9天）的Laboratory结果反映不止血小板减少症候群，轻度血小板减少症候群和肌酸激酶水准充高（请注意1）。此均，肝功能指标也或多或少改变：溶激酶（每充68 U），骆驼氨基转移酶（每充105 U），天冬氨酸氨基转移酶（每充77 U）和乳酸脱氢酶（每充465 U）的水准则有：在患病的第5天所有充高。鉴于病征反复呼吸困难，在第4天获血清培养；在世界上，这些都不能激增。
布3-2020年1同月22日（头部第7天，所医院第3天）的后腹部和均侧胸片
布4-2020年1同月24日（头部第5天，所医院第9天）的后腹部X线片
据刊文，在所医院第3天（病危第7天）开拍的头部X光片从未辨识浸润或出现异常痕迹（布3）。
但是，从所医院第5天清晨（病危第9天）清晨展开的第二次头部X光片核对辨识，左肺下叶有肺结核（布4）。
这些影像学唯现与从所医院第5天清晨开始的吞咽精神状态改变相吻合，当时病征在吞咽均围液体时通过脉搏血磷原色测定的血磷原色参数减到90％。
在第6天，病征开始不感兴趣补充压缩液体，该压缩液体由腹毛细管以每分钟2充的速度输送。考虑到诊疗请注意现的改变和对所医院获性肺结核的关心，开始使用万古霉素（1750 mg耗损剂量，然后每8每隔很低剂量1 g）和萘吡苯基（每8每隔很低剂量）治疗。
布5-前后头部X光片，2020年1同月26日（营养不良第十天，所医院第六天）
在所医院第6天（病危第10天），第四次头部X射线照片辨识两个肺中不会都有举例来真是条状混浊，这一唯现与非相比较肺结核相符（布5），并且在听诊时在两个肺中不会都不止现了罗音。鉴于放射影像学唯现，随即拒绝不感兴趣压缩液体补充，病征持续呼吸困难，多个部位持续无患者的2019-nCoV RNA无患者，以及刊出了与放射性肺结核其唯展相一致的严重影响肺结核在该病征中不会，诊疗医师充满活力同情心地使用了自然科学抗病原治疗。
很低剂量日本史考特昔韦（一种打算整合的新型核苷酸甘氨酸前药）在第7天清晨开始，但从未观察到与减压有关的过多事件。在对乙磷西林致病的金黄色芽孢展开了紧接著的降钙素原水准和腹PCR监测后，在第7天清晨废弃万古霉素，并在第二天废弃萘吡苯基。
在所医院第8天（病危第12天），病征的诊疗现况给予改善。停止补充压缩液体，他在吞咽均围液体时的磷原色参数增加到94％至96％。无论如何的双侧下叶罗音以后长期存在。他的血清素给予改善，除了断续干咳和腹漏均，他不能患者。
截至2020年1同月30日，病征仍患病。他有唯热，除头痛均，所有患者以均已缓解，头痛的素质打算减轻。
方法有
古生物学家采集
根据CDC指南获主要用途2019-nCoV临床监测的诊疗古生物学家。用聚酯拭子搜罗了12个腹咽和；大咽拭子古生物学家。
将每个拭子插入举例来真是2至3 ml病原水路介质的单独乳胶管中不会。将血集在肝脏分离管中不会，然后根据CDC指南展开离心。排泄物和唾液古生物学家分别搜罗在乳胶古生物学家容器中不会。试样在2°C至8°C两者之间储存，直到作准备运送至CDC。
在营养不良的第7、11和12天搜罗了重复展开的2019-nCoV监测的古生物学家，数限于腹咽和；大咽拭子，肝脏以及排泄物和唾液试样。
2019-NCOV的临床监测
使用从公开场合释出的病原脱磷核糖碱基其唯展而来的rRT-PCR分析法监测了诊疗古生物学家。与无论如何针对重症候群急性吞咽症候群冠状病原（SARS-CoV）和中不会东吞咽症候群冠状病原（MERS-CoV）的临床方法有相似，它具有三个核衣壳蛋白质特异性和一个无患者对应特异性。该测定的叙述为RRT-PCR元件PCR和探针和脱磷核糖碱基信息中不会需用的CDCLaboratory信息网站2019-nCoV上。
性状脱氧核糖碱基
2020年1同月7日，近现代研究人员通过宾夕法尼亚州国立卫生保健研究生院GenBank数据集库和全球性共享所有甲类数据集倡议（GISAID）数据集库共享了2019-nCoV的完备蛋白质脱磷核糖碱基；随后释出了有关受控2019-nCoV的统计数据。
从rRT-PCR无患者古生物学家（；大咽和腹咽）中不会提取碱基，并在Sanger和下一代脱氧核糖碱基平台（Illumina和MinIon）上主要用途全蛋白质组脱氧核糖碱基。使用5.4.6英文版的Sequencher软件包（Sanger）完成了脱磷核糖碱基组装。minimap软件包，英文版本2.17（MinIon）；和freebayes软件包1.3.1英文版（MiSeq）。将完备蛋白质组与需用的2019-nCoV简介脱磷核糖碱基（GenBank登录号NC_045512.2）展开相对。
结果
2019-NCOV的古生物学家监测
请注意2-2019年新型冠状病原（2019-nCoV）的实时抗病毒-酵素-不可逆监测结果
该病征在病危第4天时获的初始吞咽道试样（腹咽拭子和；大咽拭子）在2019-nCoV红褐色无患者（请注意2）。
尽管病征原先请注意现为轻度患者，但在营养不良第4天的很低循环系统阈参数（Ct）参数（腹咽古生物学家中不会为18至20，；大咽古生物学家中不会为21至22）说明了这些古生物学家中不会病原水准较高。
在营养不良第7天获的两个上吞咽道古生物学家在2019-nCoV仍保持无患者，数限于腹咽拭子古生物学家中不会持续高水准（Ct参数23至24）。在营养不良第7天获的唾液在2019-nCoV中不会也红褐色无患者（Ct参数为36至38）。两种采集月份的肝脏试样在2019-nCoV以均为阴性。
在营养不良第11天和第12天获的腹咽和；大咽古生物学家辨识不止病原水准下降的近来。
；大咽古生物学家在病危第12天的2019-nCoV监测红褐色阴性。在这些月份获的肝脏的rRT-PCR结果仍从完全相一致。
性状脱氧核糖碱基
；大咽和腹咽古生物学家的完备蛋白质组脱磷核糖碱基彼此并不相同，并且与其他需用的2019-nCoV脱磷核糖碱基近乎并不相同。
该病征的病原与2019-nCoV简介脱磷核糖碱基（NC_045512.2）在新开书本板8两处极少3个核苷酸和1个不尽并不相同。该脱磷核糖碱基可通过GenBank获（登录号MN985325）。
网上
我们关于宾夕法尼亚州尚从未有2019-nCoV患病流感的统计数据真是明了这一新兴营养不良的几个方面从未曾完全理解，数限于传播方式动态和诊疗营养不良的全部区域。
我们的流感病征曾去过近现代长沙，但统计数据真是他在长沙此后不能去过鲍鱼批唯市场或该医院，也不能得病的带入。尽管他的2019-nCoV病菌的来源亦然不清楚，但已公开场合了人对人传播方式的证据。
到2020年1同月30日，从未曾唯现与此流感系统性的2019-nCoV继唯流感，但仍在密切监视下。
在营养不良的第4天和第7天从上吞咽道古生物学家中不会监测到具有很低Ct参数的2019-nCoV RNA，说明了病原乘载高且具有传播方式潜力。
参数得注意的是，我们还在病征病危第7天搜罗的唾液试样中不会监测到了2019-nCoV RNA。尽管我们流感病征的肝脏古生物学家反复不止现2019-nCoV阴性，但在近现代重症候群病征的血清中不会仍监测到病原RNA。然而，肺均监测病原RNA并不一定反之亦然长期存在传染性病原，目前为止亦然不清楚在吞咽道均部监测病原RNA的诊疗意义。
目前为止，我们对2019-nCoV病菌的诊疗区域的理解极其需用。在近现代，已经刊文了诸如严重影响的肺结核，吞咽衰竭，急性吞咽窘迫症候群（ARDS）和肺脏损伤等肺炎，数限于致命的后果。然而，重要的是要注意，这些流感是根据其肺结核临床断定的，因此意味著不会使统计数据相对于更为严重影响的结果。
我们的流感病征原先请注意现为轻度头痛和很低度断续呼吸困难，在病危的第4天不能头部X光核对的肺结核痕迹，而在病危第9天其唯展为肺结核之前，这些非特异性临床请注意现和患者在早期在诊疗上，2019-nCoV病菌的诊疗过程意味著与许多其他常见霍乱不能明显区别，众所周知是在冬季吞咽道病原季节。
另均，本流感病征在营养不良的第9天其唯展为肺结核的良机与近期吞咽困难的唯作（唯病后家庭收入为8天）相一致。尽管根据病征的诊疗现况恶化随即是不是拒绝不感兴趣remdesivir诚心的使用，但仍无需展开随机对应试验以断定remdesivir和任何其他研究药物治疗2019-nCoV病菌的稳定性和实证。
我们统计数据了宾夕法尼亚州尚从未有统计数据的2019-nCoV病菌病征的诊疗特质。
该流感的关键方面数限于病征在书本有关暴唯的医疗保健警告后随即寻求医疗；由当地医疗服务简而言之断定病征在在到长沙的旅行者近现代，随后在当地，和州和联邦政府医疗保健文官两者之间展开密切合作；并断定意味著的2019-nCoV病菌，从而可以促使受控病征并随后对2019-nCoV展开Laboratory断定，并受限制病征出院全面指标和管理工作。
该流感统计数据忽视了诊疗医师对于任何不止现急性营养不良患者的就诊病征，要总结不止在在的旅行者经历或带入阿兹海默的重要性，为了保障正确标识和随即受控意味著面对着2019-nCoV病菌不确定性的病征，并帮助减少全面的传播方式。
再一，本统计数据忽视无需断定与2019-nCoV病菌系统性的诊疗营养不良，唯病机理和病原穿孔持续时间的
全部区域和自然近现代，以为诊疗管理工作和医疗保健决策提供依据。
请注意列为英文英文版
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Summary
An outbreak of novel coronirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
On December 31, 2019, China reported a cluster of cases of pneumonia in people associated with the Huanan Seafood Wholesale Market in Wuhan, Hubei Province.
On January 7, 2020, Chinese health authorities confirmed that this cluster was associated with a novel coronirus, 2019-nCoV.
Although cases were originally reported to be associated with exposure to the seafood market in Wuhan, current epidemiologic data indicate that person-to-person transmission of 2019-nCoV is occurring.
As of January 30, 2020, a total of 9976 cases had been reported in at least 21 countries,including the first confirmed case of 2019-nCoV infection in the United States, reported on January 20, 2020.
Investigations are under way worldwide to better understand transmission dynamics and the spectrum of clinical illness.
This report describes the epidemiologic and clinical features of the first case of 2019-nCoV infection confirmed in the United States.
Case Report
On January 19, 2020, a 35-year-old man presented to an urgent care clinic in Snohomish County, Washington, with a 4-day history of cough and subjective fever.
On checking into the clinic, the patient put on a mask in the waiting room. After waiting approximately 20 minutes, he was taken into an examination room and underwent evaluation by a provider. He disclosed that he had returned to Washington State on January 15 after treling to visit family in Wuhan, China.
The patient stated that he had seen a health alert from the U.S. Centers for Disease Control and Prevention (CDC) about the novel coronirus outbreak in China and, because of his symptoms and recent trel, decided to see a health care provider.
Figure 1.Posteroanterior and Lateral Chest Radiographs, January 19, 2020 (Illness Day 4).
Apart from a history of hypertriglyceridemia, the patient was an otherwise healthy nonsmoker. The physical examination revealed a body temperature of 37.2°C, blood pressure of 134/87 mm Hg, pulse of 110 beats per minute, respiratory rate of 16 breaths per minute, and oxygen saturation of 96% while the patient was breathing ambient air. Lung auscultation revealed rhonchi, and chest radiography was performed, which was reported as showing no abnormalities (Figure 1).
A rapid nucleic acid amplification test (NAAT) for influenza A and B was negative. A nasopharyngeal swab specimen was obtained and sent for detection of viral respiratory pathogens by NAAT; this was reported back within 48 hours as negative for all pathogens tested, including influenza A and B, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, and four common coronirus strains known to cause illness in humans (HKU1, NL63, 229E, and OC43).
Given the patient’s trel history, the local and state health departments were immediately notified. Together with the urgent care clinician, the Washington Department of Health notified the CDC Emergency Operations Center.
Although the patient reported that he had not spent time at the Huanan seafood market and reported no known contact with ill persons during his trel to China, CDC staff concurred with the need to test the patient for 2019-nCoV on the basis of current CDC “persons under investigation” case definitions.
Specimens were collected in accordance with CDC guidance and included serum and nasopharyngeal and oropharyngeal swab specimens. After specimen collection, the patient was discharged to home isolation with active monitoring by the local health department.
On January 20, 2020, the CDC confirmed that the patient’s nasopharyngeal and oropharyngeal swabs tested positive for 2019-nCoV by real-time reverse-transcriptase–polymerase-chain-reaction (rRT-PCR) assay.
In coordination with CDC subject-matter experts, state and local health officials, emergency medical services, and hospital leadership and staff, the patient was admitted to an airborne-isolation unit at Providence Regional Medical Center for clinical observation, with health care workers following CDC recommendations for contact, droplet, and airborne precautions with eye protection.
On admission, the patient reported persistent dry cough and a 2-day history of nausea and vomiting; he reported that he had no shortness of breath or chest pain. Vital signs were within normal ranges. On physical examination, the patient was found to he dry mucous membranes. The remainder of the examination was generally unremarkable. After admission, the patient received supportive care, including 2 liters of normal saline and ondansetron for nausea.
Figure 2.Symptoms and Maximum Body Temperatures According to Day of Illness and Day of Hospitalization, January 16 to January 30, 2020.
On days 2 through 5 of hospitalization (days 6 through 9 of illness), the patient’s vital signs remained largely stable, apart from the development of intermittent fevers accompanied by periods of tachycardia (Figure 2).
The patient continued to report a nonproductive cough and appeared fatigued. On the afternoon of hospital day 2, the patient passed a loose bowel movement and reported abdominal discomfort. A second episode of loose stool was reported overnight; a sample of this stool was collected for rRT-PCR testing, along with additional respiratory specimens (nasopharyngeal and oropharyngeal) and serum.
The stool and both respiratory specimens later tested positive by rRT-PCR for 2019-nCoV, whereas the serum remained negative.
Treatment during this time was largely supportive. For symptom management, the patient received, as needed, antipyretic therapy consisting of 650 mg of acetaminophen every 4 hours and 600 mg of ibuprofen every 6 hours. He also received 600 mg of guaifenesin for his continued cough and approximately 6 liters of normal saline over the first 6 days of hospitalization.
Table 1.Clinical Laboratory Results.
The nature of the patient isolation unit permitted only point-of-care laboratory testing initially; complete blood counts and serum chemical studies were ailable starting on hospital day 3.
Laboratory results on hospital days 3 and 5 (illness days 7 and 9) reflected leukopenia, mild thrombocytopenia, and elevated levels of creatine kinase (Table 1).
In addition, there were alterations in hepatic function measures: levels of alkaline phosphatase (68 U per liter), alanine aminotransferase (105 U per liter), aspartate aminotransferase (77 U per liter), and lactate dehydrogenase (465 U per liter) were all elevated on day 5 of hospitalization.
Given the patient’s recurrent fevers, blood cultures were obtained on day 4; these he shown no growth to date.
Figure 3.Posteroanterior and Lateral Chest Radiographs, January 22, 2020 (Illness Day 7, Hospital Day 3).
Figure 4.Posteroanterior Chest Radiograph, January 24, 2020 (Illness Day 9, Hospital Day 5).
A chest radiograph taken on hospital day 3 (illness day 7) was reported as showing no evidence of infiltrates or abnormalities (Figure 3).
However, a second chest radiograph from the night of hospital day 5 (illness day 9) showed evidence of pneumonia in the lower lobe of the left lung (Figure 4).
These radiographic findings coincided with a change in respiratory status starting on the evening of hospital day 5, when the patient’s oxygen saturation values as measured by pulse oximetry dropped to as low as 90% while he was breathing ambient air.
On day 6, the patient was started on supplemental oxygen, delivered by nasal cannula at 2 liters per minute.
Given the changing clinical presentation and concern about hospital-acquired pneumonia, treatment with vancomycin (a 1750-mg loading dose followed by 1 g administered intrenously every 8 hours) and cefepime (administered intrenously every 8 hours) was initiated.
Figure 5.Anteroposterior and Lateral Chest Radiographs, January 26, 2020 (Illness Day 10, Hospital Day 6).
On hospital day 6 (illness day 10), a fourth chest radiograph showed basilar streaky opacities in both lungs, a finding consistent with atypical pneumonia (Figure 5), and rales were noted in both lungs on auscultation.
Given the radiographic findings, the decision to administer oxygen supplementation, the patient’s ongoing fevers, the persistent positive 2019-nCoV RNA at multiple sites, and published reports of the development of severe pneumonia at a period consistent with the development of radiographic pneumonia in this patient, clinicians pursued compassionate use of an investigational antiviral therapy.
Treatment with intrenous remdesivir (a novel nucleotide ogue prodrug in development) was initiated on the evening of day 7, and no adverse events were observed in association with the infusion.
Vancomycin was discontinued on the evening of day 7, and cefepime was discontinued on the following day, after serial negative procalcitonin levels and negative nasal PCR testing for methicillin-resistant Staphylococcus aureus.
On hospital day 8 (illness day 12), the patient’s clinical condition improved. Supplemental oxygen was discontinued, and his oxygen saturation values improved to 94 to 96% while he was breathing ambient air.
The previous bilateral lower-lobe rales were no longer present. His appetite improved, and he was asymptomatic aside from intermittent dry cough and rhinorrhea.
As of January 30, 2020, the patient remains hospitalized. He is afebrile, and all symptoms he resolved with the exception of his cough, which is decreasing in severity.
Methods
SPECIMEN COLLECTIONClinical specimens for 2019-nCoV diagnostic testing were obtained in accordance with CDC guidelines. Nasopharyngeal and oropharyngeal swab specimens were collected with synthetic fiber swabs; each swab was inserted into a separate sterile tube containing 2 to 3 ml of viral transport medium. Serum was collected in a serum separator tube and then centrifuged in accordance with CDC guidelines. The urine and stool specimens were each collected in sterile specimen containers. Specimens were stored between 2°C and 8°C until ready for shipment to the CDC. Specimens for repeat 2019-nCoV testing were collected on illness days 7, 11, and 12 and included nasopharyngeal and oropharyngeal swabs, serum, and urine and stool samples.
DIAGNOSTIC TESTING FOR 2019-NCOV
Clinical specimens were tested with an rRT-PCR assay that was developed from the publicly released virus sequence. Similar to previous diagnostic assays for severe acute respiratory syndrome coronirus (SARS-CoV) and Middle East respiratory syndrome coronirus (MERS-CoV), it has three nucleocapsid gene targets and a positive control target.
A description of this assay and sequence information for the rRT-PCR panel primers and probes are ailable on the CDC Laboratory Information website for 2019-nCoV.
GENETIC SEQUENCING
On January 7, 2020, Chinese researchers shared the full genetic sequence of 2019-nCoV through the National Institutes of Health GenBank database and the Global Initiative on Sharing All Influenza Data (GISAID) database; a report about the isolation of 2019-nCoV was later published.
Nucleic acid was extracted from rRT-PCR–positive specimens (oropharyngeal and nasopharyngeal) and used for whole-genome sequencing on both Sanger and next-generation sequencing platforms (Illumina and MinIon).
Sequence assembly was completed with the use of Sequencher software, version 5.4.6 (Sanger); minimap software, version 2.17 (MinIon); and freebayes software, version 1.3.1 (MiSeq). Complete genomes were compared with the ailable 2019-nCoV reference sequence (GenBank accession number NC_045512.2).
Results
SPECIMEN TESTING FOR 2019-NCOV
Table 2.Results of Real-Time Reverse-Transcriptase–Polymerase-Chain-Reaction Testing for the 2019 Novel Coronirus (2019-nCoV).
The initial respiratory specimens (nasopharyngeal and oropharyngeal swabs) obtained from this patient on day 4 of his illness were positive for 2019-nCoV (Table 2).
The low cycle threshold (Ct) values (18 to 20 in nasopharyngeal specimens and 21 to 22 in oropharyngeal specimens) on illness day 4 suggest high levels of virus in these specimens, despite the patient’s initial mild symptom presentation.
Both upper respiratory specimens obtained on illness day 7 remained positive for 2019-nCoV, including persistent high levels in a nasopharyngeal swab specimen (Ct values, 23 to 24). Stool obtained on illness day 7 was also positive for 2019-nCoV (Ct values, 36 to 38).
Serum specimens for both collection dates were negative for 2019-nCoV. Nasopharyngeal and oropharyngeal specimens obtained on illness days 11 and 12 showed a trend toward decreasing levels of virus. The oropharyngeal specimen tested negative for 2019-nCoV on illness day 12. The rRT-PCR results for serum obtained on these dates are still pending.
GENETIC SEQUENCING
The full genome sequences from oropharyngeal and nasopharyngeal specimens were identical to one another and were nearly identical to other ailable 2019-nCoV sequences.
There were only 3 nucleotides and 1 amino acid that differed at open reading frame 8 between this patient’s virus and the 2019-nCoV reference sequence (NC_045512.2). The sequence is ailable through GenBank (accession number MN985325).
DISCUSSION
Our report of the first confirmed case of 2019-nCoV in the United States illustrates several aspects of this emerging outbreak that are not yet fully understood, including transmission dynamics and the full spectrum of clinical illness.
Our case patient had treled to Wuhan, China, but reported that he had not visited the wholesale seafood market or health care facilities or had any sick contacts during his stay in Wuhan. Although the source of his 2019-nCoV infection is unknown, evidence of person-to-person transmission has been published.
Through January 30, 2020, no secondary cases of 2019-nCoV related to this case he been identified, but monitoring of close contacts continues.
Detection of 2019-nCoV RNA in specimens from the upper respiratory tract with low Ct values on day 4 and day 7 of illness is suggestive of high viral loads and potential for transmissibility.
It is notable that we also detected 2019-nCoV RNA in a stool specimen collected on day 7 of the patient’s illness. Although serum specimens from our case patient were repeatedly negative for 2019-nCoV, viral RNA has been detected in blood in severely ill patients in China.
However, extrapulmonary detection of viral RNA does not necessarily mean that infectious virus is present, and the clinical significance of the detection of viral RNA outside the respiratory tract is unknown at this time.
Currently, our understanding of the clinical spectrum of 2019-nCoV infection is very limited. Complications such as severe pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), and cardiac injury, including fatal outcomes, he been reported in China.
However, it is important to note that these cases were identified on the basis of their pneumonia diagnosis and thus may bias reporting toward more severe outcomes.
Our case patient initially presented with mild cough and low-grade intermittent fevers, without evidence of pneumonia on chest radiography on day 4 of his illness, before hing progression to pneumonia by illness day 9.
These nonspecific signs and symptoms of mild illness early in the clinical course of 2019-nCoV infection may be indistinguishable clinically from many other common infectious diseases, particularly during the winter respiratory virus season. In addition, the timing of our case patient’s progression to pneumonia on day 9 of illness is consistent with later onset of dyspnea (at a median of 8 days from onset) reported in a recent publication.
Although a decision to administer remdesivir for compassionate use was based on the case patient’s worsening clinical status, randomized controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection.
We report the clinical features of the first reported patient with 2019-nCoV infection in the United States.
Key aspects of this case included the decision made by the patient to seek medical attention after reading public health warnings about the outbreak; recognition of the patient’s recent trel history to Wuhan by local providers, with subsequent coordination among local, state, and federal public health officials; and identification of possible 2019-nCoV infection, which allowed for prompt isolation of the patient and subsequent laboratory confirmation of 2019-nCoV, as well as for admission of the patient for further evaluation and management.
This case report highlights the importance of clinicians eliciting a recent history of trel or exposure to sick contacts in any patient presenting for medical care with acute illness symptoms, in order to ensure appropriate identification and prompt isolation of patients who may be at risk for 2019-nCoV infection and to help reduce further transmission.
Finally, this report highlights the need to determine the full spectrum and natural history of clinical disease, pathogenesis, and duration of viral shedding associated with 2019-nCoV infection to inform clinical management and public health decision making.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
This article was published on January 31, 2020, at NEJM.org.
We thank the patient; the nurses and clinical staff who are providing care for the patient; staff at the local and state health departments; staff at the Washington State Department of Health Public Health Laboratories and at the Centers for Disease Control and Prevention (CDC) Division of Viral Disease Laboratory; CDC staff at the Emergency Operations Center; and members of the 2019-nCoV response teams at the local, state, and national levels.
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