摘要
在中会国人南昌开始的新型乙型接种（2019-nCoV）爆所发迅速蔓延，现已在多个国家确诊。我们清查结果了在American推定的月所2019-nCoV接种病症，并描述了该病症的鉴别，病症，病理过程和行政，之外症状在病情第9天乏善可陈为结核病时的最初轻度症状。
该范例阐释了病理医师与大都，的县和合众国各级心理卫生保健中会国人政府相互间密切协作的普遍性，以及无需加速传扬与这种新所发接种症状的卫生保健有关的病理信息的需求。
2019年12月底31日，中会国人清查结果了与湖北南昌市西南周边地区鲍鱼批所发产品有关的人群中会的结核病病症。
2020年1月底7日，中会国人卫生保健中会国人政府推定该簇与新型乙型接种2019-nCoV有关。尽管最初报导的病症与南昌市鲍鱼产品的漏单单有关，但当前的心理卫生保健样品备注明，将要时值2019-nCoV人际传扬。
截至2020年1月底30日，在至少21个国家/周边地区清查结果了9976例病症，之外2020年1月底20日报导的American月所确诊的2019-nCoV接种病症。
全球仅限于将要透过清查，以更好地探究传扬高效率和病理性疾病之内。本清查结果描述了在American推定的月所2019-nCoV接种的心理卫生保健和病理特征。
范例清查结果
2020年1月底19日，一名35岁的男子用到在旧金山的县赖斯霍米巴加的合伙急诊妇产科，有4天的痉挛和主观所咳嗽史。病人到妇产科侦测时，在候诊室戴上口内罩。才会约20分钟后，他被带到侦测室接纳了包括者的评估。
他声称，他在中会国人南昌探望母亲时在1月底15日返回旧金山的县。该症状备注示，他已从American性疾病控制与卫生保健保健为中会心（CDC）寄送来有关中会国人新型乙型接种时值的健康警报，由于他的症状和早先的周游世界，他重新考虑去看医师。
示意图1-2020年1月底19日（性疾病第4天）的后后背和除此以外侧胸片
除了高三酸酯胆固醇的高皮质醇除此以外，该症状还是其他健康的不吸烟者。体格侦测推断单单症状排尿环境空气时，体温为37.2°C，皮质醇为134/87 mm Hg，摇动为每分钟110次，排尿Hz为每分钟16次，磷明度为96％。气管听诊揭示有脑膜炎，并透过了胸片侦测，据报导未推断单单异常（示意图1）。
肺炎病毒和丙型肺炎的加速碱基扩增检验（NAAT）为形容词。给予了喉咽拭子新种，并通过NAAT将其送来去侦测病毒接种性排尿道细菌。
据报导在48同一时间内对所有检验的细菌仅呈形容词，之外肺炎病毒和丙型肺炎，副肺炎，排尿道合胞病毒接种，喉病毒接种，腺病毒接种和已知会导致人类性疾病的四种罕见乙型接种株（HKU1，NL63、229E和OC43） ）。根据症状的周游世界历史文化，当即接到大都和的县卫生保健部门。旧金山卫生保健部与紧急卫生保健病理医师独自接到了CDC紧急行动为中会心。
尽管该症状清查结果感叹他很难去过西南周边地区鲍鱼产品，也很难清查结果在去中会国人周游世界在此期间与病危者有任何沾染，但性疾病卫生保健保健控制为中会心的人员允诺有必要根据当前的性疾病卫生保健保健控制为中会心对症状透过2019-nCoV检验。
根据CDC概要查阅了8个新种，之外肝细胞，喉咽和口内咽拭子新种。新种搜集后，症状被送来往家庭分离，并由当地卫生保健部门透过积极监测。
2020年1月底20日，性疾病卫生保健保健控制为中会心（CDC）推定症状的喉咽和口内咽拭子通过可实现遗传物质-酵素链反应（rRT-PCR）侦测为2019-nCoV中会性。
在性疾病卫生保健保健控制为中会心的趣味研究者，的县和大都卫生保健官员，紧急卫生保健服务以及公立医院拥护和人员的为了让下，症状被送来往奥尔巴尼周边地区卫生保健为中会心的空气分离病房透过病理观察，并跟随性疾病卫生保健保健控制为中会心的伤者有关沾染，飞沫和空中会防护政策的建议，并略带丝袜。
病危时症状清查结果短时间痉挛，有2天的麻木和咳嗽史。他清查结果感叹他很难排尿急促或胸痛。一个人病症在正常仅限于。体格侦测推断单单症状口腔湿。其余的侦测上会不轻微。
病危后，症状接纳了支持疗程，之外2降为生理盐水和恩丹以加重麻木。
示意图2-根据性疾病日和就医日（2020年1月底16日至2020年1月底30日）的症状和最高体温
在就医的第2至5天（病危的第6至9天），症状的一个人病症前提保持稳定，除了用到间歇所咳嗽并眩晕心动过速（示意图2）。症状此后清查结果非生产性痉挛，并用到筋疲力尽。
在就医第二天的早上，症状排便顺畅，腹部不适。中会午有第二次咳嗽稀疏的报导。查阅该排泄的仪器常用rRT-PCR检验，以及其他排尿道新种（喉咽和口内咽）和肝细胞。排泄和两个排尿道新种以后仅通过rRT-PCR侦测为2019-nCoV中会性，而肝细胞仍为形容词。
在此在此期间的疗程在很大总体上是自我管理的。为了透过症状处理，症状无需根据无需接纳镇痛疗程法，该疗程法之外每4同一时间650 mg对乙酰硫基酚和每6同一时间600 mg甲酯。在就医的前六天，他还因短时间痉挛而服用了600毫克极创醚密约6降为生理盐水。
备注1-病理的实验室结果
症状分离两组的本质最初仅强制即时卫生保健点的实验室检验；从公立医院第3天开始可以透过全血细胞计数和肝细胞化学研究。
在公立医院第3天和第5天（性疾病第7天和第9天）的的实验室结果反映单单白细胞减少症，轻度血小板减少症和肌酸激酶技术水平降为高（备注1）。此除此以外，酸中会毒测试原理也有所波动：碱性赖氨酸（每降为68 U），丙硫酸硫基转移酶（每降为105 U），天冬硫酸硫基转移酶（每降为77 U）和乳酸半乳糖（每降为465 U）的技术水平计有：在就医的第5天所有降为高。鉴于症状间歇所咳嗽，在第4天给予体内培训；当今世界，这些都很难增长。
示意图3-2020年1月底22日（腰部第7天，公立医院第3天）的后后背和除此以外侧胸片
示意图4-2020年1月底24日（腰部第5天，公立医院第9天）的后后背X线片
据报导，在公立医院第3天（病危第7天）开拍的腰部X光片未揭示浸润或异常有可能（示意图3）。
但是，从公立医院第5天中会午（病危第9天）中会午透过的第二次腰部X光片侦测揭示，左肺下叶有结核病（示意图4）。
这些某类推断单单与从公立医院第5天中会午开始的排尿平衡状态波动相符合，在此之前症状在排尿远处空气时通过摇动血磷明度测定的血磷明度值降至90％。
在第6天，症状开始接纳可用氢气，该氢气由喉导管以每分钟2降为的速率输送来。考虑到病理乏善可陈的波动和对公立医院给予性结核病的关注，开始常用类固醇接种（1750 mg负荷副作用，然后每8同一时间静脉注射1 g）和青霉素威尔顿醛（每8同一时间静脉注射）疗程。
示意图5-前后腰部X光片，2020年1月底26日（性疾病第十天，公立医院第六天）
在公立医院第6天（病危第10天），第四次腰部X射线拍照揭示两个肺中会都有大块条状混浊，这一推断单单与非众所周知结核病仅仅一致（示意图5），并且在听诊时在两个肺中会都用到了罗音。鉴于放射源某类推断单单，重新考虑给与氢气可用，症状短时间所咳嗽，多个部位短时间中会性的2019-nCoV RNA中会性，以及所发备注了与放射源性结核病演进一致的严重结核病在该症状中会，病理医师富有幽默感地常用了研究性类固醇接种疗程。
静脉注射凯特昔韦（一种将要开所发的新型多肽萘前药）在第7天中会午开始，但未观察到与输注有关的所致事件。在对及第磷霖抗药性的金黄色青霉素透过了连续的降钙素原技术水平和喉PCR侦测后，在第7天中会午转用类固醇接种，并在第二天转用青霉素威尔顿醛。
在公立医院第8天（病危第12天），症状的病理状况得到增加。停止可用氢气，他在排尿远处空气时的磷明度值减低到94％至96％。原先的单侧下叶罗音不再假定。他的食欲得到增加，除了间歇干咳和喉漏除此以外，他很难症状。
截至2020年1月底30日，症状仍就医。他有所发热，除痉挛除此以外，所有症状仅已加重，痉挛的总体将要加重。
原理
新种搜集
根据CDC概要给予常用2019-nCoV病症检验的病理新种。用化学纤维拭子查阅了12个喉咽和口内咽拭子新种。
将每个拭子填充包括2至3 ml病毒接种转运等离子体的单独无菌肺脏会。将血集在肝细胞分离肺脏会，然后根据CDC概要透过离心。尿液和排泄新种分别查阅在无菌新种容器中会。仪器在2°C至8°C相互间储存，直到事先运送来至CDC。
在性疾病的第7、11和12天查阅了重复透过的2019-nCoV检验的新种，之外喉咽和口内咽拭子，肝细胞以及尿液和排泄样品。
2019-NCOV的病症检验
常用从官方网站所发布的病毒接种测序演进而来的rRT-PCR分析法检验了病理新种。与原先针对门诊急性排尿症乙型接种（SARS-CoV）和中会东排尿症乙型接种（MERS-CoV）的病症原理相似，它较强三个核衣壳基因特异性和一个中会性对照特异性。该测定的描述为RRT-PCR面板酵素和探针和测序信息中会比如感叹的CDC的实验室信息网站2019-nCoV上。
表型脱磷核糖核酸
2020年1月底7日，中会国人研究人员通过American国立卫生保健研究院GenBank样品库和全球共享所有肺炎样品积极支持（GISAID）样品库共享了2019-nCoV的原始基因测序；随后所发布了有关分离2019-nCoV的清查结果。
从rRT-PCR中会性新种（口内咽和喉咽）中会提取碱基，并在Sanger和；也脱磷核糖核酸平台（Illumina和MinIon）上常用全测序脱磷核糖核酸。常用5.4.6国际版的Sequencher软件包（Sanger）完毕了测序装配。minimap软件包，旧国际版本2.17（MinIon）；和freebayes软件包1.3.1国际版（MiSeq）。将原始测序与比如感叹的2019-nCoV参照测序（GenBank登录号NC_045512.2）透过来得。
结果
2019-NCOV的新种检验
备注2-2019年新型乙型接种（2019-nCoV）的可实现遗传物质-酵素-链反应检验结果
该症状在病危第4天时给予的初始排尿道样品（喉咽拭子和口内咽拭子）在2019-nCoV呈中会性（备注2）。
尽管症状最初乏善可陈为轻度症状，但在性疾病第4天的低循环Hz（Ct）值（喉咽新种中会为18至20，口内咽新种中会为21至22）备注明这些新种中会病毒接种技术水平较高。
在性疾病第7天给予的两个上排尿道新种在2019-nCoV仍保持中会性，之外喉咽拭子新种中会短时间上佳（Ct值23至24）。在性疾病第7天给予的排泄在2019-nCoV中会也呈中会性（Ct值为36至38）。两种搜集日期的肝细胞样品在2019-nCoV仅为形容词。
在性疾病第11天和第12天给予的喉咽和口内咽新种揭示单单病毒接种技术水平回升的趋势。
口内咽新种在病危第12天的2019-nCoV检验呈形容词。在这些日期给予的肝细胞的rRT-PCR结果仍未定。
表型脱磷核糖核酸
口内咽和喉咽新种的原始测序测序彼此大致相同，并且与其他比如感叹的2019-nCoV测序近乎大致相同。
该症状的病毒接种与2019-nCoV参照测序（NC_045512.2）在开放日阅读框8处仅3个多肽和1个多种不同。该测序可通过GenBank给予（登录号MN985325）。
讨论区
我们关于American月所2019-nCoV确诊病症的清查结果便是这一新兴性疾病的几个多方面亦然未仅仅探究，之外传扬高效率和病理性疾病的全部之内。
我们的病症症状曾去过中会国人南昌，但清查结果感叹他在南昌在此期间很难去过鲍鱼批所发产品或卫生保健机构，也很难生病的沾染。尽管他的2019-nCoV接种的举例亦然不确切，但已官方网站了人对人传扬的证据。
到2020年1月底30日，亦然未推断单单与此病症相关的2019-nCoV继所发病症，但仍在密切监视下。
在性疾病的第4天和第7天从上排尿道新种中会侦测到较强低Ct值的2019-nCoV RNA，备注明病毒接种载量高且较强传扬潜力。
例外的是，我们还在症状病危第7天查阅的排泄样品中会侦测到了2019-nCoV RNA。尽管我们病症症状的肝细胞新种间歇用到2019-nCoV形容词，但在中会国人门诊症状的体内中会仍侦测到病毒接种RNA。然而，肺除此以外侦测病毒接种RNA并不一定意味着假定传染性病毒接种，目前亦然不确切在排尿道除此以外部侦测病毒接种RNA的病理意义。
目前，我们对2019-nCoV接种的病理之内的探究非常有限。在中会国人，已经报导了诸如严重的结核病，排尿衰竭，急性排尿窘迫症（ARDS）和肝脏损伤等胃癌，之外致命的后果。然而，举足轻重的是要注意，这些病症是根据其结核病病症确切的，因此显然会使清查结果偏向更严重的结果。
我们的病症症状最初乏善可陈为轻度痉挛和低度间歇所咳嗽，在病危的第4天很难腰部X光侦测的结核病有可能，而在病危第9天演进为结核病之后，这些非酪氨酸病症和症状在早期在病理上，2019-nCoV接种的病理过程显然与许多其他罕见传染病很难轻微区隔，相来得是在冬季排尿道病毒接种季节性。
另除此以外，本病症症状在性疾病的第9天演进为结核病的必定会与现阶段排尿困难的肝脏病（所发病后人仅收入为8天）一致。尽管根据症状的病理状况衰弱重新考虑是否是给与remdesivir慈悲的常用，但仍无需透过随机对照试验以确切remdesivir和任何其他研究抑制剂疗程2019-nCoV接种的比如感叹性和系统性。
我们清查结果了American月所清查结果的2019-nCoV接种症状的病理特征。
该病症的关键多方面之外症状在阅读有关时值的心理卫生保健警告后重新考虑寻求卫生保健；由当地卫生保健中介推定症状早先到南昌的周游世界历史文化，随后在当地，的县和合众国心理卫生保健官员相互间透过协调；并确切显然的2019-nCoV接种，从而可以迅速分离症状并随后对2019-nCoV透过的实验室推定，并强制症状病危全面性评估和行政。
该病症清查结果阐释了病理医师对于任何用到急性性疾病症状的就医症状，要总结单单早先的周游世界经历或沾染高皮质醇的普遍性，为了确保正确识别和及时分离显然陷于2019-nCoV接种风险的症状，并帮助减少全面性的传扬。
仍要，本清查结果阐释无需确切与2019-nCoV接种相关的病理性疾病，所发病机理和病毒接种剥落短时间时间的
全部之内和自然历史文化，以为病理行政和心理卫生保健各项政策包括依据。
以下为国际国际版
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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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