摘要
在里国武昌开始的取而代之型冠状流感病毒（2019-nCoV）爆发迅速散播，现已在多个国家胃癌。我们清查结果了在旧金山验证的首度2019-nCoV病毒患者，并描述了该患者的鉴定，病患，针灸过程和负责管理，之外病征在病情第9天表格现为中风时的本来轻度病症。
该事例突显了针灸牙医与以外，的州和联邦各级预防伊朗政府彼此之间密切联系协作的普遍性，以及所需短时间传扬与这种取而代之发作毒病征的照护有关的针灸资讯的期望。
2019年12月末31日，里国清查结果了与潜江武昌市华中鱿鱼家禽有关的人群里的中风患者。
2020年1月末7日，里国卫生保健伊朗政府验证该簇与取而代之型冠状流感病毒2019-nCoV有关。尽管本来路透社的患者与武昌市鱿鱼消费市场的暴露有关，但当此前的流行病学数据表格明，将要暴发2019-nCoV人际传扬。
截至2020年1月末30日，在据估计21个国家/沿海地区清查结果了9976例患者，之外2020年1月末20日路透社的旧金山首度胃癌的2019-nCoV病毒患者。
全部都是球覆盖各地区将要透过清查，以更高地探究传扬一个系统和针灸哮喘覆盖范围。本清查结果描述了在旧金山验证的首度2019-nCoV病毒的流行病学和针灸相像性。
事例清查结果
2020年1月末19日，一名35岁的男子显现消失在华盛顿的州斯诺霍米什县的一家医护人员医疗机构，有4天的新陈代谢困难和理性发烧通史。病人到医疗机构体检时，在候诊室戴上朝天罩。等待近20分钟后，他被带到体检室做了提供者的审计。
他透露，他在里国武昌探望家人后于1月末15日调回华盛顿的州。该病征表格示，他已从旧金山哮喘管控与防止里心（CDC）收到有关里国取而代之型冠状流感病毒接踵而来的有益警报系统，由于他的病症和早先的环游世界，他要求去看牙医。
布1-2020年1月末19日（哮喘第4天）的后颈部和内外侧胸片
除了高里学生酸酯胆固醇的病通史内外，该病征还是其他有益的不成年人。体格体检请注意到病征新陈代谢环境二氧化碳时，体温为37.2°C，血压为134/87 mm Hg，脉搏为每分钟110次，新陈代谢增益为每分钟16次，磷相对于为96％。肺听诊看显现出有肾病，并透过了胸片体检，据路透社没请注意到极度（布1）。
及第型和及第型SARS的短时间大分子扩增验证（NAAT）为同义。赢得了腹咽拭子古生物学家，并通过NAAT将其送去扫描流感病毒性新陈代谢道流感病毒。
据路透社在48不间断内对所有验证的流感病毒非常少呈同义，之外及第型和及第型SARS，副SARS，新陈代谢道合胞流感病毒，腹流感病毒，腺流感病毒和已知会造成人类哮喘的四种常见于冠状流感病毒株（HKU1，NL63、229E和OC43） ）。根据病征的环游世界历通史，立即通知以外和的州副部长门。华盛顿副部长与及时照护针灸牙医独自通知了CDC及时行动里心。
尽管该病征清查结果知道他从没去过华中鱿鱼消费市场，也从没清查结果在去里国环游世界期间与年老者有任何触及，但哮喘防止管控里心的职员同意有必要根据当此前的哮喘防止管控里心对病征透过2019-nCoV验证。
根据CDC最新整理了8个古生物学家，之外小鼠，腹咽和朝天咽拭子古生物学家。古生物学家热带植物后，病征被送往家庭分开，并由当地副部长门透过积极监测。
2020年1月末20日，哮喘防止管控里心（CDC）验证病征的腹咽和朝天咽拭子通过一个系统逆转录病毒-转录链反应（rRT-PCR）扫描为2019-nCoV无病症。
在哮喘防止管控里心的基调专家，的州和以外卫生保健地方官，及时医疗服务以及该医院领导和职员的配合下，病征被送往普罗维登斯沿海地区医疗里心的二氧化碳分开病房透过针灸仔细观察，并跟从哮喘防止管控里心的医护人员有关触及，飞沫和空里防护措施的建议，并带有靴子。
里风时病征清查结果持续新陈代谢困难，有2天的恶心和呕吐通史。他清查结果知道他从没新陈代谢急促或便秘。生命体征在正常覆盖各地区。体格体检请注意到病征上皮细胞炎热。其余的体检往往不显著。
里风后，病征做了支持用药，之外2升到生理盐水和恩丹以缓解恶心。
布2-根据哮喘日和住院治疗日（2020年1月末16日至2020年1月末30日）的病症和三高体温
在住院治疗的第2至5天（年老的第6至9天），病征的生命体征基本上保持稳定，除了显现消失间歇性发烧并伴有心动过速（布2）。病征再次清查结果非生产性新陈代谢困难，并显现消失疲惫不堪。
在住院治疗第二天的下午，病征排泄不利于，腹部不适。午夜有第二次睡觉时稀疏的路透社。整理该排泄物的材料主要用途rRT-PCR验证，以及其他新陈代谢道古生物学家（腹咽和朝天咽）和小鼠。排泄物和两个新陈代谢道古生物学家后来非常少通过rRT-PCR扫描为2019-nCoV无病症，而小鼠仍为同义。
此前的用药在很大层面上是替代性的。为了透过病症一处理，病征所需根据所需做解热疗法，该疗法之外每4不间断650 mg对乙酰尿素基酚和每6不间断600 mg抗抑郁药。在住院治疗的此前六天，他还因持续新陈代谢困难而服用了600毫克愈创醚和近6升到生理盐水。
表格1-针灸研究成果团队结果
病征分开两组的性质本来非常少允许即时医疗点研究成果团队验证；从该医院第3天开始可以透过全部都是血细胞个数和小鼠药理学研究成果。
在该医院第3天和第5天（哮喘第7天和第9天）的研究成果团队结果再现显现出粒细胞减少症，轻度白血球减少症和肌酸激酶水准升到高（表格1）。此内外，败胆固醇举例来知道也有所推移：盐类磷酸酶（每升到68 U），骆驼尿素基转移酶（每升到105 U），天冬尿素酸尿素基转移酶（每升到77 U）和糖类激酶（每升到465 U）的水准分别为：在住院治疗的第5天所有升到高。鉴于病征反复发烧，在第4天赢得肾脏培养；迄今，这些都从没放缓。
布3-2020年1月末22日（腿部第7天，该医院第3天）的后颈部和内外侧胸片
布4-2020年1月末24日（腿部第5天，该医院第9天）的后颈部X线片
据路透社，在该医院第3天（年老第7天）拍的腿部X光片没看显现出经年累月或极度痕迹（布3）。
但是，从该医院第5天午夜（年老第9天）午夜透过的第二次腿部X光片体检看显现出，左肺下叶有中风（布4）。
这些影像学请注意到与从该医院第5天午夜开始的新陈代谢情况下推移相吻合，本来病征在新陈代谢周围二氧化碳时通过脉搏血磷相对于推算出的血磷相对于取值降至90％。
在第6天，病征开始做不足之处磷气，该磷气由腹导管以每分钟2升到的速度输送。尽量避免哮喘的推移和对该医院赢得性中风的关注，开始用到抗生素（1750 mg承受剂量，然后每8不间断本品1 g）和萘吡吡啶（每8不间断本品）用药。
布5-此前后腿部X光片，2020年1月末26日（哮喘第十天，该医院第六天）
在该医院第6天（年老第10天），第四次腿部X射线剧照看显现出两个肺里都有大块条状混浊，这一请注意到与非典型中风基本上一致（布5），并且在听诊时在两个肺里都显现消失了罗音。鉴于来将影像学请注意到，要求获得磷气不足之处，病征持续发烧，多个肺脏持续无病症的2019-nCoV RNA无病症，以及刊发了与来将性中风拓展一致的致使中风在该病征里，针灸牙医富有渴望地用到了行为科学抗流感病毒用药。
本品瑞德昔韦（一种将要合作开发的取而代之型核苷酸类似物此前药）在第7天午夜开始，但没仔细观察到与输液有关的不良事件。在对及第磷霖耐药的金黄色杆菌透过了连续的降钙素原水准和腹PCR扫描后，在第7天午夜关闭抗生素，并在第二天关闭萘吡吡啶。
在该医院第8天（年老第12天），病征的针灸精神状态得到优化。停止不足之处磷气，他在新陈代谢周围二氧化碳时的磷相对于取值提高到94％至96％。先此前的双侧下叶罗音以后发挥作用。他的食欲得到优化，除了间歇性干咳和腹漏内外，他从没病症。
截至2020年1月末30日，病征仍住院治疗。他有痉挛，除新陈代谢困难内外，所有病症非常少已缓解，新陈代谢困难的层面将要大大降较差。
法则
古生物学家热带植物
根据CDC最新赢得主要用途2019-nCoV病患验证的针灸古生物学家。用合成纤维拭子整理了12个腹咽和朝天咽拭子古生物学家。
将每个拭子插入包含2至3 ml流感病毒转运介质的直接无菌管里。将血集在小鼠分离管里，然后根据CDC最新透过离心。血浆和排泄物古生物学家分别整理在无菌古生物学家液体里。材料在2°C至8°C彼此之间暂存，直到作好运送至CDC。
在哮喘的第7、11和12天整理了以此类推透过的2019-nCoV验证的古生物学家，之外腹咽和朝天咽拭子，小鼠以及血浆和排泄物比对。
2019-NCOV的病患验证
用到从公合作开面世的流感病毒脱磷核糖大分子拓展而来的rRT-PCR分析法验证了针灸古生物学家。与先此前针对诊治急性新陈代谢性疾病冠状流感病毒（SARS-CoV）和里东新陈代谢性疾病冠状流感病毒（MERS-CoV）的病患法则相像，它具有三个核亚基基因靶标和一个无病症对照靶标。该推算出的描述为RRT-PCR面板引物和电子束和脱磷核糖大分子资讯里可用的CDC研究成果团队资讯网站2019-nCoV上。
性状DNA
2020年1月末7日，里国研究成果人员通过旧金山国立卫生保健研究成果室GenBank资料库和全部都是球资源共享所有SARS数据积极支持（GISAID）资料库资源共享了2019-nCoV的完整基因脱磷核糖大分子；随后面世了有关分开2019-nCoV的清查结果。
从rRT-PCR无病症古生物学家（朝天咽和腹咽）里浓缩大分子，并在Sanger和新一代DNA平台（Illumina和MinIon）上主要用途全部都是DNADNA。用到5.4.6版的Sequencher操作系统（Sanger）完成了脱磷核糖大分子零部件。minimap操作系统，完整版2.17（MinIon）；和freebayes操作系统1.3.1版（MiSeq）。将完整DNA与可用的2019-nCoV参阅脱磷核糖大分子（GenBank登录号NC_045512.2）透过比较。
结果
2019-NCOV的古生物学家验证
表格2-2019年取而代之型冠状流感病毒（2019-nCoV）的一个系统逆转录病毒-转录-链反应验证结果
该病征在年老第4自是赢得的初始新陈代谢道比对（腹咽拭子和朝天咽拭子）在2019-nCoV呈无病症（表格2）。
尽管病征本来表格现为轻度病症，但在哮喘第4天的较差反应器阈取值（Ct）取值（腹咽古生物学家里为18至20，朝天咽古生物学家里为21至22）表格明这些古生物学家里流感病毒水准较高。
在哮喘第7天赢得的两个上新陈代谢道古生物学家在2019-nCoV仍保持无病症，之外腹咽拭子古生物学家里持续高水准（Ct取值23至24）。在哮喘第7天赢得的排泄物在2019-nCoV里也呈无病症（Ct取值为36至38）。两种热带植物订于的小鼠比对在2019-nCoV非常少为同义。
在哮喘第11天和第12天赢得的腹咽和朝天咽古生物学家看显现出显现出流感病毒水准下降的趋势。
朝天咽古生物学家在年老第12天的2019-nCoV验证呈同义。在这些订于赢得的小鼠的rRT-PCR结果仍没定。
性状DNA
朝天咽和腹咽古生物学家的完整DNA脱磷核糖大分子彼此不尽相同，并且与其他可用的2019-nCoV脱磷核糖大分子大部分不尽相同。
该病征的流感病毒与2019-nCoV参阅脱磷核糖大分子（NC_045512.2）在免费阅读框8一处非常少有3个核苷酸和1个不同。该脱磷核糖大分子可通过GenBank赢得（登录号MN985325）。
我们关于旧金山首度2019-nCoV胃癌患者的清查结果知道明了这一取而代之兴哮喘的几个方面由此可知没基本上探究，之外传扬一个系统和针灸哮喘的全部都是部覆盖范围。
我们的患者病征曾去过里国武昌，但清查结果知道他在武昌期间从没去过鱿鱼家禽或医疗机构，也从没生病的触及。尽管他的2019-nCoV病毒的来源由此可知不相符，但已公开了人对人传扬的确实。
到2020年1月末30日，由此可知没请注意到与此患者相关的2019-nCoV继发患者，但仍在密切联系跟踪下。
在哮喘的第4天和第7天从上新陈代谢道古生物学家里扫描到具有较差Ct取值的2019-nCoV RNA，表格明流感病毒总重高且具有传扬吸引力。
取值得请注意的是，我们还在病征年老第7天整理的排泄物比对里扫描到了2019-nCoV RNA。尽管我们患者病征的小鼠古生物学家反复显现消失2019-nCoV同义，但在里国诊治病征的肾脏里仍扫描到流感病毒RNA。然而，肺内外扫描流感病毒RNA这不意味着发挥作用传染性流感病毒，现阶段由此可知不相符在新陈代谢道内外部扫描流感病毒RNA的针灸意义。
现阶段，我们对2019-nCoV病毒的针灸覆盖范围的探究非常更少。在里国，已经路透社了诸如致使的中风，肺水肿，急性新陈代谢穷困性疾病（ARDS）和心脏受损等肝硬化，之外有可能的后果。然而，重要的是要请注意，这些患者是根据其中风病患尽量避免的，因此显然会使清查结果偏向更致使的结果。
我们的患者病征本来表格现为轻度新陈代谢困难和较差度间歇性发烧，在年老的第4天从没腿部X光体检的中风痕迹，而在年老第9天拓展为中风之此前，这些非特异性体征和病症在晚期在针灸上，2019-nCoV病毒的针灸过程显然与许多其他常见于传染病从没显著区别，尤其是在冬季新陈代谢道流感病毒干季。
另内外，本患者病征在哮喘的第9天拓展为中风的适时与近期新陈代谢困难的发作（发作后里位数为8天）一致。尽管根据病征的针灸精神状态恶化要求是否获得remdesivir慈悲的用到，但仍所需透过随机对照试验以尽量避免remdesivir和任何其他研究成果制剂用药2019-nCoV病毒的安全部都是性和确实。
我们清查结果了旧金山首度清查结果的2019-nCoV病毒病征的针灸相像性。
该患者的极为重要方面之外病征在阅读有关接踵而来的预防强制执行后要求借此医疗；由当地医疗服务提供者验证病征早先到武昌的环游世界历通史，随后在当地，的州和联邦预防地方官彼此之间透过协调；并尽量避免显然的2019-nCoV病毒，从而可以迅速分开病征并随后对2019-nCoV透过研究成果团队验证，并允许病征里风进一步审计和负责管理。
该患者清查结果突显了针灸牙医对于任何显现消失急性哮喘病症的医护人员病征，要阐述显现出早先的环游世界经历或触及病通史的普遍性，为了确保安全部都是正确识别和及时分开显然面临2019-nCoV病毒风险的病征，并帮助减少进一步的传扬。
再次，本清查结果突显所需尽量避免与2019-nCoV病毒相关的针灸哮喘，发作机理和流感病毒脱落持续时间的
全部都是部覆盖范围和自然历通史，以为针灸负责管理和预防决策提供依据。
表格列为海内外版
——————
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.
相关新闻
相关问答
