简短
在华南区域南昌开始的新型亚型（2019-nCoV）爆发迅速随之而来，现已在多个国家确诊。我们简报了在加拿大证实的唯一未2019-nCoV感染者患者，并阐述了该患者的鉴定，病病患者，医学处理过程和管理者，最主要征状在复发第9天展现为败黄疸时的在此之后轻度征状。
该犯罪行为忽略了医学药剂师与人西南侧众多，的县和联邦各级公共保健当局两者之间密切协作的最重要性，以及所需短时间内传扬与这种新发感染者征状的护理有关的医学反馈的需求。
2019年12月末31日，华南区域简报了与湖北省岳阳市华南菜式杂货需求有关的一些人中都的败黄疸患者。
2020年1月末7日，华南区域保健当局证实该簇与新型亚型2019-nCoV有关。尽管在此之后引述的患者与岳阳市菜式市场需求的暴露有关，但当年前的毒理学数据断定，正在发生2019-nCoV社交传扬。
截至2020年1月末30日，在大概21个国家/区域简报了9976例患者，最主要2020年1月末20日引述的加拿大唯一未确诊的2019-nCoV感染者患者。
全球仅限于正在展开调查，以很好地认识到传扬动态和医学哮喘仅限于。本简报阐述了在加拿大证实的唯一未2019-nCoV感染者的毒理学和医学特性。
犯罪行为简报
2020年1月末19日，一名35岁的男子用到在马里兰的县斯诺霍米什县的合伙急救诊所，有4天的剧痛和主观感冒通史。病人到诊所检查时，在候诊室戴上西南侧罩。赶紧平均20分钟后，他被带到检查室给予了共享者的评估。
他透露，他在华南区域南昌陪伴家人先是1月末15日返国马里兰的县。该征状暗示，他已从加拿大哮喘控制与公共服务中都心（CDC）收到有关华南区域新型亚型随之而来的健康警报，由于他的征状和最近的周游世界，他暂时去看药剂师。
平面图1-2020年1月末19日（哮喘第4天）的后年前额和则有侧胸片
除了高三酸酯黄疸的病通史则有，该征状还是其他健康的不吸烟者。体格检查挖掘出征状排便环境二氧化碳时，体温为37.2°C，血压为134/87 mm Hg，脉搏为每分钟110次，排便频率为每分钟16次，氧含水为96％。肺部听诊标示出有病病患者，并展开了胸片检查，据引述没挖掘出异常（平面图1）。
亚型和丙型流感的短时间内蛋白质扩充飞行测试（NAAT）为特性性。授予了鼻咽拭子遗骸，并通过NAAT将其送去测定大肠杆菌性排便道流感病毒。
据引述在48星期内对所有飞行测试的流感病毒均长方形特性性，最主要亚型和丙型流感，副流感，排便道合胞大肠杆菌，鼻大肠杆菌，腺大肠杆菌和已知会导致生物哮喘的四种常见于亚型株（HKU1，NL63、229E和OC43） ）。根据征状的周游世界历通史，随即通知人西南侧众多和的县保健部门。华盛顿保健部与紧急护理医学药剂师独自通知了CDC紧急行动中都心。
尽管该征状简报说他不会去过华南菜式市场需求，也不会简报在去华南区域周游世界期间与得病者有任何碰触，但哮喘公共服务控制中都心的现场同意有合理根据当年前的哮喘公共服务控制中都心对征状展开2019-nCoV飞行测试。
根据CDC指南获取了8个遗骸，最主要血液，鼻咽和西南侧咽拭子遗骸。遗骸采自后，征状被送进家庭可避免，并由当地保健部门展开更进一步系统对。
2020年1月末20日，哮喘公共服务控制中都心（CDC）证实征状的鼻咽和西南侧咽拭子通过实时逆转录酶-磷酸化链反应（rRT-PCR）测定为2019-nCoV非典型。
在哮喘公共服务控制中都心的主题研究专家，的县和人西南侧众多保健官吏，紧急医疗服务以及医务医务人员领导和现场的立体化下，征状被送进康涅狄格的县区域医疗中都心的二氧化碳可避免病房展开医学观察，并跟随哮喘公共服务控制中都心的急救有关碰触，飞沫和空中都防护措施的建议，并带有则有套。
晕倒时征状简报长时间剧痛，有2天的恶心和腹痛通史。他简报说他不会排便急促或病症。生命征象在正常仅限于。体格检查挖掘出征状上皮细胞干燥。其余的检查通常不明显。
晕倒后，征状给予了支持治疗法，最主要2升生理盐水和恩丹以减缓恶心。
平面图2-根据哮喘日和中都风日（2020年1月末16日至2020年1月末30日）的征状和最高体温
在中都风的第2至5天（得病的第6至9天），征状的生命征象理论上长期保持，除了用到间歇感冒并常有心动过速（平面图2）。征状继续简报非生产性剧痛，并用到疲倦。
在中都风第二天的清晨，征状排便不利于，腹部不适。傍晚有第二次洗手稀疏的引述。获取该排泄物的材料用于rRT-PCR飞行测试，以及其他排便道遗骸（鼻咽和西南侧咽）和血液。排泄物和两个排便道遗骸之后均通过rRT-PCR测定为2019-nCoV非典型，而血液仍为特性性。
在此期间的治疗法在很大程度上是支持性的。为了展开征状处理处理过程，征状所需根据所需给予解热疗法，该疗法最主要每4星期650 mg对乙酰一氧化氮基酚和每6星期600 mg布洛芬。在中都风的年前六天，他还因长时间剧痛而服用了600毫克愈创醚和平均6升生理盐水。
此表1-医学研究室结果
征状可避免单元的特性在此之后仅必需即时医疗点研究室飞行测试；从医务医务人员第3天开始可以展开全血细胞计数和血液化学研究课题。
在医务医务人员第3天和第5天（哮喘第7天和第9天）的研究室结果反映出红血球增高病患者，轻度血小板增高病患者和肌酸激酶素质增高（此表1）。此则有，肝功能加权也有所变异：碱性磷酸酶（每升68 U），乙酰一氧化氮基转移酶（每升105 U），天冬一氧化氮酸一氧化氮基转移酶（每升77 U）和乳酸半乳糖（每升465 U）的素质分别为：在中都风的第5天所有增高。鉴于征状反复感冒，在第4天授予肠道培养；迄今为止，这些都不会增长。
平面图3-2020年1月末22日（臀部第7天，医务医务人员第3天）的后年前额和则有侧胸片
平面图4-2020年1月末24日（臀部第5天，医务医务人员第9天）的后年前额X线片
据引述，在医务医务人员第3天（得病第7天）拍摄的臀部X光片没标示出浸润或异常似乎（平面图3）。
但是，从医务医务人员第5天傍晚（得病第9天）傍晚展开的第二次臀部X光片检查标示出，左肺下叶有败黄疸（平面图4）。
这些影像学挖掘出与从医务医务人员第5天傍晚开始的排便情况下变异相吻合，当时征状在排便区域内二氧化碳时通过脉搏皮质醇含水测定的皮质醇含水绝对值降至90％。
在第6天，征状开始给予不足之处氧，该氧由鼻导管以每分钟2升的反应速度输送。考虑医学展现的变异和对医务医务人员授予性败黄疸的追捧，开始使用抗生素（1750 mg超重剂量，然后每8星期静脉注射1 g）和头孢吡吡啶（每8星期静脉注射）治疗法。
平面图5-年前后臀部X光片，2020年1月末26日（哮喘第十天，医务医务人员第六天）
在医务医务人员第6天（得病第10天），第四次臀部X射线剧照标示出两个肺中都都有基底条状较深，这一挖掘出与非典型败黄疸相符（平面图5），并且在听诊时在两个肺中都都用到了罗音。鉴于放射线影像学挖掘出，暂时给予氧不足之处，征状长时间感冒，多个部位长时间非典型的2019-nCoV RNA非典型，以及发此表了与放射线性败黄疸其发展相反的比较严重败黄疸在该征状中都，医学药剂师富有责任感地使用了研究课题性抗大肠杆菌治疗法。
静脉注射福斯特昔韦（一种正在开发的新型胺基酸类似物年前药）在第7天傍晚开始，但没观察到与口服有关的不好暴力事件。在对当季氧西林耐药的暗红色杆菌展开了连续的降钙素原素质和鼻PCR测定后，在第7天傍晚废弃抗生素，并在第二天废弃头孢吡吡啶。
在医务医务人员第8天（得病第12天），征状的医学状况赢取有所改善。中止不足之处氧，他在排便区域内二氧化碳时的氧含水绝对值提高到94％至96％。先年前的前部下叶罗音不再发挥作用。他的食欲赢取有所改善，除了间歇干咳和鼻漏则有，他不会征状。
截至2020年1月末30日，征状仍中都风。他有发热，除剧痛则有，所有征状均已减缓，剧痛的程度正在降更高。
法则
遗骸采自
根据CDC指南授予用于2019-nCoV病病患者飞行测试的医学遗骸。用合成纤维拭子获取了12个鼻咽和西南侧咽拭子遗骸。
将每个拭子填入包含2至3 ml大肠杆菌转运电磁辐射的单独施用胸腔都。将血集在血液分离胸腔都，然后根据CDC指南展开离心。血浆和排泄物遗骸分别获取在施用遗骸容器中都。材料在2°C至8°C两者之间储存，直到作好输送至CDC。
在哮喘的第7、11和12天获取了重复使用展开的2019-nCoV飞行测试的遗骸，最主要鼻咽和西南侧咽拭子，血液以及血浆和排泄物结果标示出。
2019-NCOV的病病患者飞行测试
使用从公开发布的大肠杆菌展现型物质序列其发展而来的rRT-PCR分析法则飞行测试了医学遗骸。与先年前针对加护急性排便综合征亚型（SARS-CoV）和中都东排便综合征亚型（MERS-CoV）的病病患者法则相似，它不具备三个核球状展现型物质靶标和一个非典型对照靶标。该测定的阐述为RRT-PCR面板引物和探针和展现型物质序列反馈中都必需的CDC研究室反馈网站2019-nCoV上。
展现型分子生物学
2020年1月末7日，华南区域研究课题医务人员通过加拿大国立保健研究课题院GenBank数据库和全球共享者所有流感数据倡议（GISAID）数据库共享者了2019-nCoV的完整展现型物质展现型物质序列；随后发布了有关可避免2019-nCoV的简报。
从rRT-PCR非典型遗骸（西南侧咽和鼻咽）中都提取蛋白质，并在Sanger和新一代分子生物学平台（Illumina和MinIon）上用于全展现型物质组分子生物学。使用5.4.6版的Sequencher的软件（Sanger）完成了展现型物质序列装配。minimap的软件，修改版2.17（MinIon）；和freebayes的软件1.3.1版（MiSeq）。将完整展现型物质组与必需的2019-nCoV参考展现型物质序列（GenBank登录号NC_045512.2）展开非常。
结果
2019-NCOV的遗骸飞行测试
此表2-2019年新型亚型（2019-nCoV）的实时逆转录酶-磷酸化-链反应飞行测试结果
该征状在得病第4天时授予的初始排便道结果标示出（鼻咽拭子和西南侧咽拭子）在2019-nCoV长方形非典型（此表2）。
尽管征状在此之后展现为轻度征状，但在哮喘第4天的更高循环阈绝对值（Ct）绝对值（鼻咽遗骸中都为18至20，西南侧咽遗骸中都为21至22）断定这些遗骸中都大肠杆菌素质更高。
在哮喘第7天授予的两个上排便道遗骸在2019-nCoV仍保持非典型，最主要鼻咽拭子遗骸中都长时间高素质（Ct绝对值23至24）。在哮喘第7天授予的排泄物在2019-nCoV中都也长方形非典型（Ct绝对值为36至38）。两种采自一月的血液结果标示出在2019-nCoV均为特性性。
在哮喘第11天和第12天授予的鼻咽和西南侧咽遗骸标示出出大肠杆菌素质增高的趋势。
西南侧咽遗骸在得病第12天的2019-nCoV飞行测试长方形特性性。在这些一月授予的血液的rRT-PCR结果仍没定。
展现型分子生物学
西南侧咽和鼻咽遗骸的完整展现型物质组展现型物质序列彼此无论如何相反，并且与其他必需的2019-nCoV展现型物质序列仍然无论如何相反。
该征状的大肠杆菌与2019-nCoV参考展现型物质序列（NC_045512.2）在开放阅读框8处仅有3个胺基酸和1个不同。该展现型物质序列可通过GenBank授予（登录号MN985325）。
讨论区
我们关于加拿大唯一未2019-nCoV确诊患者的简报阐明这一新兴哮喘的几个上都唯没无论如何认识到，最主要传扬动态和医学哮喘的全部仅限于。
我们的患者征状曾去过华南区域南昌，但简报说他在南昌期间不会去过菜式杂货需求或诊疗，也不会生病的碰触。尽管他的2019-nCoV感染者的来源唯不清楚，但已公开了人对人传扬的证据。
到2020年1月末30日，唯没挖掘出与此患者特别的2019-nCoV继发患者，但仍在密切监视下。
在哮喘的第4天和第7天从上排便道遗骸中都测定到不具备更高Ct绝对值的2019-nCoV RNA，断定大肠杆菌载量高且不具备传扬潜力。
绝对值得注意的是，我们还在征状得病第7天获取的排泄物结果标示出中都测定到了2019-nCoV RNA。尽管我们患者征状的血液遗骸反复用到2019-nCoV特性性，但在华南区域加护征状的肠道中都仍测定到大肠杆菌RNA。然而，肺则有测定大肠杆菌RNA并不一定也就是说发挥作用传染性大肠杆菌，目年前唯不清楚在排便道则有部测定大肠杆菌RNA的医学意义。
目年前，我们对2019-nCoV感染者的医学仅限于的认识到非常实际。在华南区域，早已引述了诸如比较严重的败黄疸，排便衰竭，急性排便窘迫综合征（ARDS）和心脏损伤等并发病患者，最主要致命的后果。然而，最重要的是要注意，这些患者是根据其败黄疸病病患者未确定的，因此确实会使简报偏向更比较严重的结果。
我们的患者征状在此之后展现为轻度剧痛和更高度间歇感冒，在得病的第4天不会臀部X光检查的败黄疸似乎，而在得病第9天其发展为败黄疸之年前，这些非选择性征象和征状在20世纪在医学上，2019-nCoV感染者的医学处理过程确实与许多其他常见于传染病不会明显分野，尤其是在冬季排便道大肠杆菌季节。
另则有，本患者征状在哮喘的第9天其发展为败黄疸的时机与没来会排便困难的发作（确诊后中都位数为8天）相反。尽管根据征状的医学状况紧张暂时是不是给予remdesivir诚心的使用，但仍所需展开随机对照试验以未确定remdesivir和任何其他研究课题药物治疗法2019-nCoV感染者的安全性和合理性。
我们简报了加拿大唯一未简报的2019-nCoV感染者征状的医学特性。
该患者的不可或缺上都最主要征状在阅读有关随之而来的公共保健强制执行后暂时寻求医疗；由当地医疗服务共享者证实征状最近到南昌的周游世界历通史，随后在当地，的县和联邦公共保健官吏两者之间展开协调；并未确定确实的2019-nCoV感染者，从而可以迅速可避免征状并随后对2019-nCoV展开研究室证实，并必需征状晕倒进一步评估和管理者。
该患者简报忽略了医学药剂师对于任何用到急性哮喘征状的就诊征状，要总结出最近的周游世界随之而来或碰触病通史的最重要性，为了必需正确识别和及时可避免确实面对着2019-nCoV感染者风险的征状，并设法增高进一步的传扬。
最后，本简报忽略所需未确定与2019-nCoV感染者特别的医学哮喘，确诊机理和大肠杆菌破损长时间时间的
全部仅限于和自然历通史，以为医学管理者和公共保健决策共享依据。
以下为英文版
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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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