摘录
在之在此之前国郑特拉华开始的新型冠状病原（2019-nCoV）爆发很快蔓延，现已在多个国家确诊。我们调查结果了在新泽西特拉华证实的月所2019-nCoV接种结核病，并描绘了该结核病的鉴别，病症，药理学管控过程和管理者，还包括病症在病情恶化第9天展现出为肾脏病时的起初轻度病症。
该情形合理化了药理学医生与人；大众多，特拉华和联邦各级公共环境卫生英国政府密切关系密切协作的最层面，以及需更快传播与这种新发接种病症的公共卫生有关的药理学资讯的生产力。
2019年12年底31日，之在此之前国调查结果了与长沙市郑特拉华市海南鱼翅批发产品有关的老年人之在此之前的肾脏病结核病。
2020年1年底7日，之在此之前国环境卫生英国政府证实该簇与新型冠状病原2019-nCoV有关。尽管起初美联社的结核病与郑特拉华市鱼翅产品的掩盖有关，但也就是说是的流行病学数据指出，正在死灰复燃2019-nCoV社会群体传播。
截至2020年1年底30日，在至少21个国家/南部调查结果了9976例结核病，还包括2020年1年底20日美联社的新泽西特拉华月所确诊的2019-nCoV接种结核病。
亚洲南部覆盖以外正在顺利完成调查，以很好地知晓传播动态和药理学传染病覆盖范围。本调查结果描绘了在新泽西特拉华证实的月所2019-nCoV接种的流行病学和药理学特征。
情形调查结果
2020年1年底19日，一名35岁的男子不止现在纽约市特拉华米勒霍米西孟加拉邦的一家医护人员药房，有4天的腹痛和主观发烧史。病人到药房定期检查时，在候诊室戴上眼罩。等待分之一20分钟后，他被送去定期检查室给予了之在此之前介的检验。
他透露，他在之在此之前国郑特拉华接回家人后于1年底15日返回纽约市特拉华。该病症列于示，他已从新泽西特拉华传染病控制与防范之在此之前心（CDC）收到有关之在此之前国新型冠状病原死灰复燃的保健警报，由于他的病症和近来的周游世界，他决定去看医生。
所示1-2020年1年底19日（传染病第4天）的后在此之前胸和侧面胸片
除了高年级酸酯血症的阿兹海默内外，该病症还是其他保健的不尼古丁。体格定期检查辨认出病症痉挛环境气体时，血流量为37.2°C，眼压为134/87 mm Hg，不止为每分钟110次，痉挛频率为每分钟16次，钾酸度为96％。呼吸道听诊标示出有细菌性，并顺利完成了胸片定期检查，据美联社未辨认出异常（所示1）。
甲型和乙型流感的更快核酸扩增试验（NAAT）为复数。取得了颊咽拭子骨骼，并通过NAAT将其送去电子束病原性溃疡病原。
据美联社在48同一时间内对所有试验的病原皆椭圆形复数，还包括甲型和乙型流感，副流感，溃疡合胞病原，颊病原，腺病原和目在此之前为止似乎会造成全人类传染病的四种类似于冠状病原株（HKU1，NL63、229E和OC43） ）。根据病症的周游世界历史文化，立即知似乎会人；大众多和特拉华湖北省人民政府门。纽约市湖北省人民政府与紧急公共卫生药理学医生三人知似乎会了CDC紧急行动之在此之前心。
尽管该病症调查结果说是他不似乎会去过海南鱼翅产品，也不似乎会调查结果在去之在此之前国周游世界其间与病重者有任何注意到，但传染病防范指挥之在此之前心的职员同意有必要根据也就是说是的传染病防范指挥之在此之前心对病症顺利完成2019-nCoV试验。
根据CDC简要采集了8个骨骼，还包括肝脏，颊咽和；大咽拭子骨骼。骨骼采自后，病症被送进父母永久性，并由当地湖北省人民政府门顺利完成不遗余力追踪。
2020年1年底20日，传染病防范指挥之在此之前心（CDC）证实病症的颊咽和；大咽拭子通过实时抗病毒-聚合酶不可逆（rRT-PCR）电子束为2019-nCoVHIV。
在传染病防范指挥之在此之前心的主题科学家，特拉华和人；大众多环境卫生高官，紧急公共卫生服务以及该医院领导和职员的因应下，病症被送进普罗维登斯南部公共卫生之在此之前心的气体永久性病房顺利完成药理学观察，并跟随传染病防范指挥之在此之前心的医护人员有关注意到，飞沫和直升飞机防护措施的建议，并隐含护目镜。
出院时病症调查结果停滞腹痛，有2天的头痛和呕吐史。他调查结果说是他不似乎会痉挛急促或便秘。灵魂征象在正常覆盖以外。体格定期检查辨认出病症上皮细胞干旱。其余的定期检查通常不相比。
出院后，病症给予了支持者治疗，还包括2升到生理盐水和恩丹以更为严重影响头痛。
所示2-根据传染病日和不止院日（2020年1年底16日至2020年1年底30日）的病症和最高血流量
在不止院的第2至5天（病重的第6至9天），病症的灵魂征象理论上保证稳定，除了不止现暂时性发烧并；还有心动过速（所示2）。病症一直调查结果非生产性腹痛，并不止现疲劳。
在不止院第二天的下午，病症排便保证了，腹部不适。早晨有第二次大便浓密的美联社。采集该排泄物的电子束用于rRT-PCR试验，以及其他溃疡骨骼（颊咽和；大咽）和肝脏。排泄物和两个溃疡骨骼此后皆通过rRT-PCR电子束为2019-nCoVHIV，而肝脏仍为复数。
在此其间的治疗在很大程度上是支持者性的。为了顺利完成病症管控，病症需根据需给予解热临床，该临床还包括每4同一时间650 mg对乙酰甲醇基酚和每6同一时间600 mg布洛芬。在不止院的在此之前六天，他还因停滞腹痛而服用了600毫克愈创醚和分之一6升到生理盐水。
列于1-药理学分析小组结果
病症永久性模组的物理性质起初仅受限制即刻公共卫生点分析小组试验；从该医院第3天开始可以顺利完成全部都是血细胞计数和肝脏化学分析。
在该医院第3天和第5天（传染病第7天和第9天）的分析小组结果反映不止粒细胞提高症，轻度肝细胞提高症和肌酸激酶总体急剧下降（列于1）。此内外，肝功能指标也有所巨大变化：水溶性激酶（每升到68 U），丙甲醇酸甲醇基转移酶（每升到105 U），天冬甲醇酸甲醇基转移酶（每升到77 U）和乳酸半乳糖（每升到465 U）的总体分别为：在不止院的第5天所有急剧下降。鉴于病症反复发烧，在第4天取得血液养成；迄今为止，这些都不似乎会激增。
所示3-2020年1年底22日（臀部第7天，该医院第3天）的后在此之前胸和侧面胸片
所示4-2020年1年底24日（臀部第5天，该医院第9天）的后在此之前胸X线片
据美联社，在该医院第3天（病重第7天）拍摄的臀部X光片未标示出灌注或异常有可能（所示3）。
但是，从该医院第5天早晨（病重第9天）早晨顺利完成的第二次臀部X光片定期检查标示出，左肺下叶有肾脏病（所示4）。
这些CT辨认出与从该医院第5天早晨开始的痉挛状况巨大变化相吻合，当时病症在痉挛四周气体时通过不止血钾酸度推算出的血钾酸度数值降至90％。
在第6天，病症开始给予不足之处钾气，该钾气由颊尿道以每分钟2升到的平均速度输送。受限于药理学展现出的巨大变化和对该医院取得肺水肿的关注，开始运用于万古霉素（1750 mg承受剂量，然后每8同一时间本品1 g）和红霉素联赛杯苯酚（每8同一时间本品）治疗。
所示5-在此之前后臀部X光片，2020年1年底26日（传染病第十天，该医院第六天）
在该医院第6天（病重第10天），第四次臀部X射线合照标示出两个肺之在此之前都有基底条状浑浊，这一辨认出与非典型肾脏病实际上部都是符合（所示5），并且在听诊时在两个肺之在此之前都不止现了罗音。鉴于辐射CT辨认出，决定给予钾气不足之处，病症停滞发烧，多个肺脏停滞HIV的2019-nCoV RNAHIV，以及发列于了与辐射肺水肿转变一致的严重影响肾脏病在该病症之在此之前，药理学医生极富同情心地运用于了分析性抗病原治疗。
本品史密斯昔韦（一种正在开发的新型胺基酸类似物在此之前药）在第7天早晨开始，但未观察到与输注有关的不良事件。在对甲钾丁耐药的淡黄色葡萄球菌顺利完成了连续的降钙素原总体和颊PCR电子束后，在第7天早晨改用万古霉素，并在第二天改用红霉素联赛杯苯酚。
在该医院第8天（病重第12天），病症的药理学状况得到改善。停止不足之处钾气，他在痉挛四周气体时的钾酸度数值提高到94％至96％。先在此之前的双侧下叶罗音不再存在。他的食欲得到改善，除了暂时性干咳和颊漏内外，他不似乎会病症。
截至2020年1年底30日，病症仍不止院。他有发烧，除腹痛内外，所有病症皆已更为严重影响，腹痛的程度正在加重。
工具
骨骼采自
根据CDC简要取得用于2019-nCoV病症试验的药理学骨骼。用化学纤维拭子采集了12个颊咽和；大咽拭子骨骼。
将每个拭子抽出包含2至3 ml病原转运真空的单独冷藏水银。将血集在肝脏除去水银，然后根据CDC简要顺利完成离心。分泌物和排泄物骨骼分别采集在冷藏骨骼装入之在此之前。电子束在2°C至8°C密切关系贮存，直到准备好运送至CDC。
在传染病的第7、11和12天采集了重复顺利完成的2019-nCoV试验的骨骼，还包括颊咽和；大咽拭子，肝脏以及分泌物和排泄物采样。
2019-NCOV的病症试验
运用于从公开公布的病原基因组转变而来的rRT-PCR分析法试验了药理学骨骼。与先在此之前针对心绞痛急性痉挛遗传性冠状病原（SARS-CoV）和之在此之前东痉挛遗传性冠状病原（MERS-CoV）的病症工具十分相似，它具有三个核单链基因靶标和一个HIV依此靶标。该推算出的描绘为RRT-PCR扬声器亚硫酸盐和电子束和基因组资讯之在此之前最简单的CDC分析小组资讯网站2019-nCoV上。
遗传基因组
2020年1年底7日，之在此之前国分析人员通过新泽西特拉华国立环境卫生分析院GenBank数据库和亚洲南部协作所有流感数据倡议（GISAID）数据库协作了2019-nCoV的非常简单基因基因组；随后公布了有关永久性2019-nCoV的调查结果。
从rRT-PCRHIV骨骼（；大咽和颊咽）之在此之前合成核酸，并在Sanger和；也基因组和平台（Illumina和MinIon）上用于全部都是真核生物基因组。运用于5.4.6国际版的Sequencher应用软件（Sanger）完成了基因组组装。minimap应用软件，旧国际版2.17（MinIon）；和freebayes应用软件1.3.1国际版（MiSeq）。将非常简单真核生物与最简单的2019-nCoV概述基因组（GenBank登录号NC_045512.2）顺利完成比较。
结果
2019-NCOV的骨骼试验
列于2-2019年新型冠状病原（2019-nCoV）的实时抗病毒-聚合酶-不可逆试验结果
该病症在病重第4天时取得的初始溃疡采样（颊咽拭子和；大咽拭子）在2019-nCoV椭圆形HIV（列于2）。
尽管病症起初展现出为轻度病症，但在传染病第4天的低可逆阈数值（Ct）数值（颊咽骨骼之在此之前为18至20，；大咽骨骼之在此之前为21至22）指出这些骨骼之在此之前病原总体较高。
在传染病第7天取得的两个上溃疡骨骼在2019-nCoV仍保证HIV，还包括颊咽拭子骨骼之在此之前停滞高层次（Ct数值23至24）。在传染病第7天取得的排泄物在2019-nCoV之在此之前也椭圆形HIV（Ct数值为36至38）。两种采自年份的肝脏采样在2019-nCoV皆为复数。
在传染病第11天和第12天取得的颊咽和；大咽骨骼标示出不止病原总体下降的急遽。
；大咽骨骼在病重第12天的2019-nCoV试验椭圆形复数。在这些年份取得的肝脏的rRT-PCR结果仍未定。
遗传基因组
；大咽和颊咽骨骼的非常简单真核生物基因组彼此并不相同，并且与其他最简单的2019-nCoV基因组几乎并不相同。
该病症的病原与2019-nCoV概述基因组（NC_045512.2）在免费写出支架8处差不多3个胺基酸和1个不同。该基因组可通过GenBank取得（登录号MN985325）。
专页
我们关于新泽西特拉华月所2019-nCoV确诊结核病的调查结果说是明了这一新兴传染病的几个不足之处已为未实际上部都是知晓，还包括传播动态和药理学传染病的全部都是部覆盖范围。
我们的结核病病症曾去过之在此之前国郑特拉华，但调查结果说是他在郑特拉华其间不似乎会去过鱼翅批发产品或教育机构，也不似乎会得病的注意到。尽管他的2019-nCoV接种的举例来说已为不确切，但已公开了人对人传播的证据。
到2020年1年底30日，已为未辨认出与此结核病就其的2019-nCoV继发结核病，但仍在密切警卫下。
在传染病的第4天和第7天从上溃疡骨骼之在此之前电子束到具有低Ct数值的2019-nCoV RNA，指出病原载量高且具有传播创造力。
数值得注意的是，我们还在病症病重第7天采集的排泄物采样之在此之前电子束到了2019-nCoV RNA。尽管我们结核病病症的肝脏骨骼反复不止现2019-nCoV复数，但在之在此之前国心绞痛病症的血液之在此之前仍电子束到病原RNA。然而，肺内外电子束病原RNA不一定也就是说存在传染性病原，迄今为止已为不确切在溃疡举例来说是电子束病原RNA的药理学意义。
迄今为止，我们对2019-nCoV接种的药理学覆盖范围的知晓非常实际。在之在此之前国，并未美联社了诸如严重影响的肾脏病，痉挛衰竭，急性痉挛岌岌可危遗传性（ARDS）和肾脏损伤等之在此之前风，还包括致命的后果。然而，最重要的是要注意，这些结核病是根据其肾脏病病症未确定的，因此不必要使调查结果相对于更严重影响的结果。
我们的结核病病症起初展现出为轻度腹痛和低度暂时性发烧，在病重的第4天不似乎会臀部X光定期检查的肾脏病有可能，而在病重第9天转变为肾脏病此在此之前，这些非专一性征象和病症在早期在药理学上，2019-nCoV接种的药理学管控过程似乎与许多其他类似于结核病不似乎会相比分野，尤其是在夏天溃疡病原秋夏天。
另内外，本结核病病症在传染病的第9天转变为肾脏病的必定似乎会与近期痉挛困难的癫痫（发病后之在此之前位数为8天）一致。尽管根据病症的药理学状况缓和决定是否给予remdesivir喜乐的运用于，但仍需顺利完成随机依此试验以未确定remdesivir和任何其他分析药剂治疗2019-nCoV接种的安全部都是性和合理性。
我们调查结果了新泽西特拉华月所调查结果的2019-nCoV接种病症的药理学特征。
该结核病的更为重要不足之处还包括病症在写出有关死灰复燃的公共环境卫生通告后决定寻求公共卫生；由当地公共卫生服务之在此之前介证实病症近来到郑特拉华的周游世界历史文化，随后在当地，特拉华和联邦公共环境卫生高官密切关系顺利完成协调；并未确定似乎的2019-nCoV接种，从而可以很快永久性病症并随后对2019-nCoV顺利完成分析小组证实，并受限制病症出院促使检验和管理者。
该结核病调查结果合理化了药理学医生对于任何不止现急性传染病病症的住院病症，要总结不止近来的周游世界随之而来或注意到阿兹海默的最层面，为了确保正确识别和及时永久性似乎面临2019-nCoV接种风险的病症，并借助提高促使的传播。
最后，本调查结果合理化需未确定与2019-nCoV接种就其的药理学传染病，发病专一性和病原破损时期内的
全部都是部覆盖范围和自然历史文化，以为药理学管理者和公共环境卫生决策提供依据。
以下为英文国际版
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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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