参考资料
在之前华人民共和国武昌开始的新的型亚型（2019-nCoV）爆唯短时间蔓延，现已在多个唯达国家确诊。我们研究者报告了在American核实的月所2019-nCoV病菌传染病，并时说明了了该传染病的鉴定，病人，针灸过程和负责管理，有数病因在之前风第9天表格现为心肌梗塞时的本来轻度病因。
该案例合理化了针灸精神科与；也，的州和联邦各级预防政策当局密切关系密切协作的重要性，以及并不需要迅速扩散与这种新的唯病菌病因的看护有关的针灸信息的需要。
2019年12年底31日，之前华人民共和国研究者报告了与湖北省武昌市华东紫菜批唯消费市场有关的老年人之前的心肌梗塞传染病。
2020年1年底7日，之前华人民共和国医疗保健卫生当局核实该簇与新的型亚型2019-nCoV有关。尽管本来报导的传染病与武昌市紫菜消费市场的渗透到有关，但当前的医学研究者数据声称，将要唯生2019-nCoV彼此间扩散。
截至2020年1年底30日，在有数21个唯达国家/海地区研究者报告了9976例传染病，有数2020年1年底20日报导的American月所确诊的2019-nCoV病菌传染病。
仅有球覆盖以外将要透过调查，以更好地明白扩散实时和针灸结核病覆盖范围。本研究者报告时说明了了在American核实的月所2019-nCoV病菌的医学研究者和针灸构造。
案例研究者报告
2020年1年底19日，一名35岁的男子显现出新在纽约的州斯诺霍米达县的服装店门诊门诊，有4天的肿胀和表格象腹泻简史。病人到门诊生活品质检查时，在候诊室戴上眼镜。等待约20分钟后，他被带到生活品质检查室不感兴趣了终端用户的检验。
他透漏，他在之前华人民共和国武昌探望母亲时为1年底15日返回纽约的州。该病因表格示，他已从American结核病控制与预防政策之前心（CDC）送出有关之前华人民共和国新的型亚型暴唯的生活品质警报，由于他的病因和在在的旅程，他尽快去看精神科。
示意图1-2020年1年底19日（结核病第4天）的后腹部和以外侧胸片
除了高二酸酯胱氨酸的病简史以外，该病因还是其他生活品质的不酒精。体格生活品质检查推测病因换气环境气体时，含氧量为37.2°C，心血管为134/87 mm Hg，不止为每分钟110次，换气增益为每分钟16次，锂原色为96％。肺部听诊揭示有支气管炎，并透过了胸片生活品质检查，据报导未推测异常（示意图1）。
丙型和-B禽流感的迅速大分子缩减试验（NAAT）为单数。赢得了颊咽拭子骨骸，并通过NAAT将其送去验证狂犬病性换气道微生物。
据报导在48每隔内对所有试验的微生物原则上长方形单数，有数丙型和-B禽流感，副禽流感，换气道合胞狂犬病，颊狂犬病，腺狂犬病和已知则会所致人类结核病的四种常用亚型株（HKU1，NL63、229E和OC43） ）。根据病因的旅程历简史，随即接到；也和的州不作为。纽约市医疗保健卫生部与紧急看护针灸精神科一起接到了CDC紧急行动之前心。
尽管该病因研究者报告时说他从未去过华东紫菜消费市场，也从未研究者报告在去之前华人民共和国旅程此后与卧床者有任何请注意到，但结核病预防政策控制之前心的第一时间同意有必要性根据当前的结核病预防政策控制之前心对病因透过2019-nCoV试验。
根据CDC最新的搜罗了8个骨骸，有数血液，颊咽和口外咽拭子骨骸。骨骸野外后，病因被送到家庭监护，并由当地不作为透过鼓励监测。
2020年1年底20日，结核病预防政策控制之前心（CDC）核实病因的颊咽和口外咽拭子通过数据执行核苷-聚合酶裂解（rRT-PCR）验证为2019-nCoV病菌性。
在结核病预防政策控制之前心的主轴专家，的州和；也医疗保健卫生；也官吏，紧急医疗保健服务以及该医院主导和第一时间的因应下，病因被送到阿拉巴马海地区医疗保健之前心的气体监护病房透过针灸通过观察，并跟从结核病预防政策控制之前心的伤者有关心意到，飞沫和陆上防弹政策的促请，并带有护目镜。
入院时病因研究者报告持续性肿胀，有2天的眩晕和呕吐简史。他研究者报告时说他从未换气急促或肿胀。生命征象在也就是时说覆盖以外。体格生活品质检查推测病因上皮干燥。其余的生活品质检查上会不明显。
入院后，病因不感兴趣了默许疗程，有数2擢为生理盐水和恩丹以缓解眩晕。
示意图2-根据结核病日和就医日（2020年1年底16日至2020年1年底30日）的病因和最高含氧量
在就医的第2至5天（卧床的第6至9天），病因的生命征象整体保持稳定，除了显现出新断续腹泻并伴有心动过速（示意图2）。病因继续研究者报告非生产性肿胀，并显现出新疲倦。
在就医第二天的下午，病因排便利于，腹部不适。早上有第二次大便稀疏的报导。搜罗该排泄物的样品用于rRT-PCR试验，以及其他换气道骨骸（颊咽和口外咽）和血液。排泄物和两个换气道骨骸后来原则上通过rRT-PCR验证为2019-nCoV病菌性，而血液仍为单数。
在此此后的疗程在很大持续性性上是默许性的。为了透过病因执行，病因并不需要根据并不需要不感兴趣止痛麻醉药，该麻醉药有数每4每隔650 mg无毒和每6每隔600 mg布洛芬。在就医的前六天，他还因持续性肿胀而服用了600毫克愈创醚密约6擢为生理盐水。
表格1-针灸麻省理工学院结果
病因监护三组的特性本来仅允许定时医疗保健点麻省理工学院试验；从该医院第3天开始可以透过仅有血细胞计数和血液化学研究者。
在该医院第3天和第5天（结核病第7天和第9天）的麻省理工学院结果反映出新血小板下降病患者，轻度血小板下降病患者和肌酸激酶持续性性擢为高（表格1）。此以外，肺功能指标也相当程度唯生变化：碱性蛋白酶（每擢为68 U），丙氨酸氨基转移酶（每擢为105 U），胺基酸氨基转移酶（每擢为77 U）和甘油羟化酶（每擢为465 U）的持续性性共有：在就医的第5天所有擢为高。鉴于病因反复腹泻，在第4天赢得血液培养；迄今为止，这些都从未增长。
示意图3-2020年1年底22日（腰部第7天，该医院第3天）的后腹部和以外侧胸片
示意图4-2020年1年底24日（腰部第5天，该医院第9天）的后腹部X线片
据报导，在该医院第3天（卧床第7天）拍摄的腰部X光片未揭示灌注或异常先兆（示意图3）。
但是，从该医院第5天早上（卧床第9天）早上透过的第二次腰部X光片生活品质检查揭示，左肺下叶有心肌梗塞（示意图4）。
这些影像学推测与从该医院第5天早上开始的换气完全唯生变化相赞同，当时病因在换气以外围气体时通过不止血锂原色测出新的血锂原色参数下调90％。
在第6天，病因开始不感兴趣足量一锂化碳，该一锂化碳由颊腹腔以每分钟2擢为的运动速度输送。顾及针灸表格现的唯生变化和对该医院赢得心律不整的关心，开始常用万古霉素（1750 mg负荷施打，然后每8每隔制剂1 g）和嗪夺标肟（每8每隔制剂）疗程。
示意图5-前后腰部X光片，2020年1年底26日（结核病第十天，该医院第六天）
在该医院第6天（卧床第10天），第四次腰部X射线照片揭示两个肺之前都有一组大块水色，这一推测与非典型心肌梗塞吻合（示意图5），并且在听诊时在两个肺之前都显现出新了罗音。鉴于人口为120人影像学推测，尽快给予一锂化碳足量，病因持续性腹泻，多个部位持续性病菌性的2019-nCoV RNA病菌性，以及唯表格了与人口为120人心律不整唯展赞同的来得严重心肌梗塞在该病因之前，针灸精神科富有冷漠地常用了人文学科类固醇疗程。
制剂凯西昔韦（一种将要整合的新的型核酸化学合成前药）在第7天早上开始，但未通过观察到与输注有关的所致事件。在对的大锂西林致病的金黄色葡萄球菌透过了连续的降钙素原持续性性和颊PCR验证后，在第7天早上关闭万古霉素，并在第二天关闭嗪夺标肟。
在该医院第8天（卧床第12天），病因的针灸状况受益增加。停止足量一锂化碳，他在换气以外围气体时的锂原色参数降较低到94％至96％。早先的侧下叶罗音不再长期存在。他的食欲受益增加，除了断续干咳和颊漏以外，他从未病因。
截至2020年1年底30日，病因仍就医。他有肿胀，除肿胀以外，所有病因原则上已缓解，肿胀的持续性性将要减轻。
方法有
骨骸野外
根据CDC最新的赢得用于2019-nCoV病人试验的针灸骨骸。用橡胶拭子搜罗了12个颊咽和口外咽拭子骨骸。
将每个拭子抽出新参数得注意2至3 ml狂犬病唯运微粒的单独乳胶缓步。将血集在血液分立缓步，然后根据CDC最新的透过离心。尿和排泄物骨骸分别搜罗在乳胶骨骸密封之前。样品在2°C至8°C密切关系储存，直到准备好运送至CDC。
在结核病的第7、11和12天搜罗了减法透过的2019-nCoV试验的骨骸，有数颊咽和口外咽拭子，血液以及尿和排泄物样本。
2019-NCOV的病人试验
常用从公开场合刊唯的狂犬病氨基酸唯展而来的rRT-PCR新方法试验了针灸骨骸。与早先针对诊治急性换气病患者亚型（SARS-CoV）和之前东换气病患者亚型（MERS-CoV）的病人方法有相像，它较强三个核衣壳等位基因遗传物质和一个病菌性比对遗传物质。该测出新的时说明了为RRT-PCRLCD模板和磁性和氨基酸信息之前只用的CDC麻省理工学院信息该网站2019-nCoV上。
遗传高通量
2020年1年底7日，之前华人民共和国研究者人员通过American国立医疗保健卫生社会科学院GenBank元数据和仅有球共享所有禽流感数据倡议（GISAID）元数据共享了2019-nCoV的相当简单等位基因氨基酸；随后刊唯了有关监护2019-nCoV的研究者报告。
从rRT-PCR病菌性骨骸（口外咽和颊咽）之前提取大分子，并在Sanger和下一代高通量平台（Illumina和MinIon）上用于仅有等位基因组高通量。常用5.4.6旧版的Sequencher应用软件（Sanger）未完成了氨基酸组装。minimap应用软件，旧版本2.17（MinIon）；和freebayes应用软件1.3.1旧版（MiSeq）。将相当简单等位基因组与只用的2019-nCoV参考资料氨基酸（GenBank登录号NC_045512.2）透过来得。
结果
2019-NCOV的骨骸试验
表格2-2019年新的型亚型（2019-nCoV）的数据执行核苷-聚合酶-裂解试验结果
该病因在卧床第4天时赢得的初始换气道样本（颊咽拭子和口外咽拭子）在2019-nCoV长方形病菌性（表格2）。
尽管病因本来表格现为轻度病因，但在结核病第4天的较低循环阈参数（Ct）参数（颊咽骨骸之前为18至20，口外咽骨骸之前为21至22）声称这些骨骸之前狂犬病持续性性较低。
在结核病第7天赢得的两个上换气道骨骸在2019-nCoV仍保持病菌性，有数颊咽拭子骨骸之前持续性高持续性性（Ct参数23至24）。在结核病第7天赢得的排泄物在2019-nCoV之前也长方形病菌性（Ct参数为36至38）。两种野外日期的血液样本在2019-nCoV原则上为单数。
在结核病第11天和第12天赢得的颊咽和口外咽骨骸揭示出新狂犬病持续性性下降的趋势。
口外咽骨骸在卧床第12天的2019-nCoV试验长方形单数。在这些日期赢得的血液的rRT-PCR结果仍定。
遗传高通量
口外咽和颊咽骨骸的相当简单等位基因组氨基酸彼此各有不同，并且与其他只用的2019-nCoV氨基酸近乎各有不同。
该病因的狂犬病与2019-nCoV参考资料氨基酸（NC_045512.2）在封闭阅读框8处仅有3个核酸和1个各有不同。该氨基酸可通过GenBank赢得（登录号MN985325）。
专页
我们关于American月所2019-nCoV确诊传染病的研究者报告时说明了这一新的兴结核病的几个上都已为未完仅有明白，有数扩散实时和针灸结核病的仅有部覆盖范围。
我们的传染病病因曾去过之前华人民共和国武昌，但研究者报告时说他在武昌此后从未去过紫菜批唯消费市场或医疗保健机构，也从未生病的请注意到。尽管他的2019-nCoV病菌的比如说已为不确切，但已公开场合了人对人扩散的论据。
到2020年1年底30日，已为未推测与此传染病系统性的2019-nCoV继唯传染病，但仍在密切监视下。
在结核病的第4天和第7天从上换气道骨骸之前验证到较强较低Ct参数的2019-nCoV RNA，声称狂犬病载量高且较强扩散潜力。
参数得请注意的是，我们还在病因卧床第7天搜罗的排泄物样本之前验证到了2019-nCoV RNA。尽管我们传染病病因的血液骨骸反复显现出新2019-nCoV单数，但在之前华人民共和国诊治病因的血液之前仍验证到狂犬病RNA。然而，肺以外验证狂犬病RNA也就是时说意味着长期存在传染性狂犬病，以外已为不确切在换气道以直接验证狂犬病RNA的针灸意义。
以外，我们对2019-nCoV病菌的针灸覆盖范围的明白相当受限。在之前华人民共和国，从未报导了诸如来得严重的心肌梗塞，换气衰竭，急性换气困窘病患者（ARDS）和肺部损伤等并唯病患者，有数骇人的后果。然而，重要的是要请注意，这些传染病是根据其心肌梗塞病人未确定的，因此不会则会使研究者报告相对于更来得严重的结果。
我们的传染病病因本来表格现为轻度肿胀和较低度断续腹泻，在卧床的第4天从未腰部X光生活品质检查的心肌梗塞先兆，而在卧床第9天唯展为心肌梗塞之前，这些非特异性征象和病因在早期在针灸上，2019-nCoV病菌的针灸过程不会与许多其他常用传染病从未明显区别，特别是在是在严寒换气道狂犬病夏天。
另以外，本传染病病因在结核病的第9天唯展为心肌梗塞的才会与近期换气困难的唯作（唯病后之前位数为8天）赞同。尽管根据病因的针灸状况恶化尽快是否给予remdesivir慈悲的常用，但仍并不需要透过数据分析试验以未确定remdesivir和任何其他研究者药物疗程2019-nCoV病菌的安仅有性和有效性。
我们研究者报告了American月所研究者报告的2019-nCoV病菌病因的针灸构造。
该传染病的关键上都有数病因在阅读有关暴唯的预防政策警告后尽快寻求医疗保健；由当地医疗保健服务终端用户核实病因在在到武昌的旅程历简史，随后在当地，的州和联邦预防政策；也官吏密切关系透过协调；并未确定不会的2019-nCoV病菌，从而可以短时间监护病因并随后对2019-nCoV透过麻省理工学院核实，并允许病因入院再进一步检验和负责管理。
该传染病研究者报告合理化了针灸精神科对于任何显现出新急性结核病病因的看病病因，要总结出新在在的旅程随之而来或请注意到病简史的重要性，为了确保正确标记和及时监护不会陷入2019-nCoV病菌风险的病因，并协助下降再进一步的扩散。
再次，本研究者报告合理化并不需要未确定与2019-nCoV病菌系统性的针灸结核病，唯病机理和狂犬病裂开持续性时间的
仅有部覆盖范围和自然历简史，以为针灸负责管理和预防政策决策者提供依据。
请请注意为英文旧版
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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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