简述
在西方武昌开始的新型流感病毒性（2019-nCoV）爆推促使蔓延，曾一度在多个国家肺癌。我们统计数据了在旧金山断定的元月2019-nCoV感染者病病症，并描述了该病病症的鉴定，确诊，医学过程和经营管理，包括病病症在病情第9天展现出为肺结核时的在此之后轻度病症状。
该案例突显了医学心理医生与之之外，和州和美国联邦各级医疗保健当局彼此之间深厚协作的关键性性，以及必须更快传播者与这种新推感染者病病症的保健有关的医学反馈的需求。
2019年12年初31日，西方统计数据了与常德市武昌市珠江三角洲菜式批推有关的人群此此前的肺结核病病症。
2020年1年初7日，西方卫生保健当局断定该簇与新型流感病毒性2019-nCoV有关。尽管在此之后美联社的病病症与武昌市菜式市场的暴露有关，但当此前的流行病学数据此说明了，正在推生2019-nCoV彼此间传播者。
截至2020年1年初30日，在至少21个国家/周边地区统计数据了9976例病病症，包括2020年1年初20日美联社的旧金山元月肺癌的2019-nCoV感染者病病症。
全世界适用以之外正在顺利完成调查，以更好地了解传播者动态和医学病因适用范围。本统计数据描述了在旧金山断定的元月2019-nCoV感染者的流行病学和医学特征。
案例统计数据
2020年1年初19日，一名35岁的男子显现出在华盛顿和州华莱士霍米基达的的公司急诊诊所，有4天的气喘和主观推烧史。病人到诊所安全检查时，在候诊室戴上头罩。等待左右20分钟后，他被带到安全检查室放弃了终端用户的评估。
他透露，他在西方武昌接回母亲时为1年初15日返回华盛顿和州。该病病症此问到，他已从旧金山病因控制与预防措施此此前心（CDC）收到有关西方新型流感病毒性暴推的健康警报，由于他的病症状和已经有的之旅，他最终去看心理医生。
绘出1-2020年1年初19日（病因第4天）的后此胸部和之外侧胸片
除了高三酸酯血病症的病病症之外，该病病症还是其他健康的不吸烟者。体格安全检查推掘出病病症吞咽环境空气时，代谢率为37.2°C，血压为134/87 mm Hg，头痛为每分钟110次，吞咽频率为每分钟16次，氨相对于为96％。心脏听诊推断有弥漫性，并顺利完成了胸片安全检查，据美联社未推掘出反常（绘出1）。
当季型和乙型流感的更快多肽扩增检验（NAAT）为比如真是。给与了腹咽拭子化石，并通过NAAT将其放去安全检查流感病毒性吞咽道寄生虫。
据美联社在48天内内对所有检验的寄生虫以之外排列成比如真是，包括当季型和乙型流感，副流感，吞咽道合胞流感病毒，腹流感病毒，腺流感病毒和已知会导致人类病因的四种常见流感病毒性株（HKU1，NL63、229E和OC43） ）。根据病病症的之旅历史，马上通知之之外和和州防疫。华盛顿卫生保健部与先行保健医学心理医生一起通知了CDC先行行动此此前心。
尽管该病病症统计数据真是他不能去过珠江三角洲菜式市场，也不能统计数据在去西方之旅之前与生病者有任何碰触，但病因预防措施控制此此前心的人员同意有必要根据当此前的病因预防措施控制此此前心对病病症顺利完成2019-nCoV检验。
根据CDC手册抽取了8个化石，包括肝脏，腹咽和头咽拭子化石。化石收集后，病病症被放往家庭分开，并由当地防疫顺利完成积极监测。
2020年1年初20日，病因预防措施控制此此前心（CDC）断定病病症的腹咽和头咽拭子通过实时反转录-聚合酶不可逆（rRT-PCR）安全检查为2019-nCoV白血病。
在病因预防措施控制此此前心的隐喻专家，和州和之之外卫生保健官员，先行医疗服务以及医务人员领导和人员的配合下，病病症被放往奥尔巴尼周边地区医疗此此前心的空气分开病房顺利完成医学仔细观察，并跟著病因预防措施控制此此前心的医护人员有关碰触，飞沫和空此此前护甲措施的建议，并带有护目镜。
康复时病病症统计数据接下来气喘，有2天的恶心和呕吐史。他统计数据真是他不能吞咽急促或胸痛。心灵先兆在正常适用以之外。体格安全检查推掘出病病症小肠干燥。其余的安全检查通常不明显。
康复后，病病症放弃了支持化疗，包括2再降生理盐水和恩丹以减轻恶心。
绘出2-根据病因日和康复日（2020年1年初16日至2020年1年初30日）的病症状和最高代谢率
在康复的第2至5天（生病的第6至9天），病病症的心灵先兆基本保持稳定，除了显现出间歇性推烧并伴有心动过速（绘出2）。病病症独自统计数据非生产性气喘，并显现出舒服。
在康复第二天的下午，病病症排便通畅，腹部不适。午夜有第二次洗手稀疏的美联社。抽取该粪便的仪器用作rRT-PCR检验，以及其他吞咽道化石（腹咽和头咽）和肝脏。粪便和两个吞咽道化石之后以之外通过rRT-PCR安全检查为2019-nCoV白血病，而肝脏仍为比如真是。
在此之前的化疗在不大相对上是替代性的。为了顺利完成病症状处理，病病症必须根据必须放弃解热临床，该临床包括每4天内650 mg对乙酰硫基酚和每6天内600 mg布洛芬。在康复的此前六天，他还因接下来气喘而服用了600毫克愈创醚和左右6再降生理盐水。
此表1-医学科学实验结果
病病症分开单元的年中性在此之后仅准许即时医疗点科学实验检验；从医务人员第3天开始可以顺利完成全血细胞计数和肝脏有机化学研究。
在医务人员第3天和第5天（病因第7天和第9天）的科学实验结果真是明了出白细胞缩减病症，轻度红血球缩减病症和肌酸激酶准确度再降高（此表1）。此之外，高血压指标也不大变化：碱性丝氨酸（每再降68 U），丙硫酸硫基转移酶（每再降105 U），天冬硫酸硫基转移酶（每再降77 U）和乳酸NAD（每再降465 U）的准确度分别为：在康复的第5天所有再降高。鉴于病病症反复推烧，在第4天给与血液培养；迄今为止，这些都不能更快增长。
绘出3-2020年1年初22日（背部第7天，医务人员第3天）的后此胸部和之外侧胸片
绘出4-2020年1年初24日（背部第5天，医务人员第9天）的后此胸部X线片
据美联社，在医务人员第3天（生病第7天）拍的背部X光片未推断浸润或反常可能（绘出3）。
但是，从医务人员第5天午夜（生病第9天）午夜顺利完成的第二次背部X光片安全检查推断，左肺下叶有肺结核（绘出4）。
这些之外科推掘出与从医务人员第5天午夜开始的吞咽状态变化相吻合，以前病病症在吞咽周围空气时通过头痛血氨相对于校准的血氨相对于数值降至90％。
在第6天，病病症开始放弃缺少氨气，该氨气由腹小孔以每分钟2再降的速率输放。毕竟医学展现出的变化和对医务人员给与性肺结核的关注，开始运用作抗流感病毒（1750 mg承受剂量，然后每8天内静脉注射1 g）和头孢夺标甲苯（每8天内静脉注射）化疗。
绘出5-此前后背部X光片，2020年1年初26日（病因第十天，医务人员第六天）
在医务人员第6天（生病第10天），第四次背部X射线照片推断两个肺此此前都有一组面会混浊，这一推掘出与非典型肺结核相符（绘出5），并且在听诊时在两个肺此此前都显现出了罗音。鉴于来将之外科推掘出，最终给与氨气缺少，病病症接下来推烧，多个部位接下来白血病的2019-nCoV RNA白血病，以及推此表了与来将性肺结核推展一致的情况严重肺结核在该病病症此此前，医学心理医生富有同情心地运用作了研究性抗流感病毒化疗。
静脉注射威尔森昔韦（一种正在开推的新型蛋白质N-此前药）在第7天午夜开始，但未仔细观察到与透析有关的不良事件。在对当季氨西林耐药的淡黄色葡萄球菌顺利完成了年中的降钙素原准确度和腹PCR安全检查后，在第7天午夜停运抗流感病毒，并在第二天停运头孢夺标甲苯。
在医务人员第8天（生病第12天），病病症的医学状况获得提再降。停止缺少氨气，他在吞咽周围空气时的氨相对于数值更高到94％至96％。先此前的铰下叶罗音不必存在。他的食欲获得提再降，除了间歇性干咳和腹漏之外，他不能病症状。
截至2020年1年初30日，病病症仍康复。他有推热，除气喘之外，所有病症状以之外已减轻，气喘的相对正在减轻。
方法
化石收集
根据CDC手册给与用作2019-nCoV确诊检验的医学化石。用人造纤维拭子抽取了12个腹咽和头咽拭子化石。
将每个拭子填入包括2至3 ml流感病毒水路介质的实质上无菌管此此前。将血集在肝脏分离管此此前，然后根据CDC手册顺利完成离心。粪便和粪便化石分别抽取在无菌化石容器此此前。仪器在2°C至8°C彼此之间储存，直到准备好运放至CDC。
在病因的第7、11和12天抽取了移位顺利完成的2019-nCoV检验的化石，包括腹咽和头咽拭子，肝脏以及粪便和粪便比对。
2019-NCOV的确诊检验
运用作从公开披露的流感病毒基因组推展而来的rRT-PCR分析法检验了医学化石。与先此前针对门诊急性吞咽综合征流感病毒性（SARS-CoV）和此此前东吞咽综合征流感病毒性（MERS-CoV）的确诊方法相似，它具三个核衣壳基因靶标和一个白血病对照靶标。该校准的描述为RRT-PCR面板引物和核酸和基因组反馈此此前可用的CDC科学实验反馈网页2019-nCoV上。
遗传有机化学合成
2020年1年初7日，西方研究人员通过旧金山国立卫生保健研究院GenBank数据库和全世界构建所有流感数据倡议（GISAID）数据库构建了2019-nCoV的清晰基因基因组；随后披露了有关分开2019-nCoV的统计数据。
从rRT-PCR白血病化石（头咽和腹咽）此此前浓缩多肽，并在Sanger和下一代有机化学合成平台（Illumina和MinIon）上用作全遗传物质有机化学合成。运用作5.4.6版的Sequencher应用软件（Sanger）完成了基因组装配。minimap应用软件，发行版2.17（MinIon）；和freebayes应用软件1.3.1版（MiSeq）。将清晰遗传物质与可用的2019-nCoV参考基因组（GenBank登录号NC_045512.2）顺利完成比起。
结果
2019-NCOV的化石检验
此表2-2019年新型流感病毒性（2019-nCoV）的实时反转录-聚合酶-不可逆检验结果
该病病症在生病第4天时给与的初始吞咽道比对（腹咽拭子和头咽拭子）在2019-nCoV排列成白血病（此表2）。
尽管病病症在此之后展现出为轻度病症状，但在病因第4天的低循环阈数值（Ct）数值（腹咽化石此此前为18至20，头咽化石此此前为21至22）此说明了这些化石此此前流感病毒准确度极高。
在病因第7天给与的两个上吞咽道化石在2019-nCoV仍保持白血病，包括腹咽拭子化石此此前接下来高准确度（Ct数值23至24）。在病因第7天给与的粪便在2019-nCoV此此前也排列成白血病（Ct数值为36至38）。两种收集时间此表的肝脏比对在2019-nCoV以之外为比如真是。
在病因第11天和第12天给与的腹咽和头咽化石推断出流感病毒准确度下降的近来。
头咽化石在生病第12天的2019-nCoV检验排列成比如真是。在这些时间此表给与的肝脏的rRT-PCR结果仍未定。
遗传有机化学合成
头咽和腹咽化石的清晰遗传物质基因组彼此相同，并且与其他可用的2019-nCoV基因组依然相同。
该病病症的流感病毒与2019-nCoV参考基因组（NC_045512.2）在开放学习者框8处仅有3个蛋白质和1个不同。该基因组可通过GenBank给与（登录号MN985325）。
讨论区
我们关于旧金山元月2019-nCoV肺癌病病症的统计数据真是明了这一新兴病因的几个多方面仍未无论如何了解，包括传播者动态和医学病因的全部适用范围。
我们的病病症病病症曾去过西方武昌，但统计数据真是他在武昌之前不能去过菜式批推或医疗机构，也不能生病的碰触。尽管他的2019-nCoV感染者的来源尚不吻合，但已公开了人对人传播者的事实。
到2020年1年初30日，仍未推掘出与此病病症之之外的2019-nCoV继推病病症，但仍在深厚监视下。
在病因的第4天和第7天从上吞咽道化石此此前安全检查到具低Ct数值的2019-nCoV RNA，此说明了流感病毒量高且具传播者潜力。
数值得注意的是，我们还在病病症生病第7天抽取的粪便比对此此前安全检查到了2019-nCoV RNA。尽管我们病病症病病症的肝脏化石反复显现出2019-nCoV比如真是，但在西方门诊病病症的血液此此前仍安全检查到流感病毒RNA。然而，肺之外安全检查流感病毒RNA并不一定意味着存在传染性流感病毒，目此前尚不吻合在吞咽道之外部安全检查流感病毒RNA的医学意义。
目此前，我们对2019-nCoV感染者的医学适用范围的了解相当有限。在西方，不太可能美联社了诸如情况严重的肺结核，吞咽衰竭，急性吞咽窘迫综合征（ARDS）和心脏损伤等并推病症，包括致命的严重后果。然而，关键性的是要注意，这些病病症是根据其肺结核确诊断定的，因此可能会使统计数据偏向更情况严重的结果。
我们的病病症病病症在此之后展现出为轻度气喘和低度间歇性推烧，在生病的第4天不能背部X光安全检查的肺结核可能，而在生病第9天推展为肺结核此此前，这些非酪氨酸先兆和病症状在早期在医学上，2019-nCoV感染者的医学过程可能与许多其他常见霍乱不能明显区别，偏爱是在夏季则吞咽道流感病毒季节。
另之外，本病病症病病症在病因的第9天推展为肺结核的及早与近期吞咽困难的推作（推病后此此前位数为8天）一致。尽管根据病病症的医学状况加剧最终是否给与remdesivir慈悲的运用作，但仍必须顺利完成随机对照试验车以断定remdesivir和任何其他研究药物化疗2019-nCoV感染者的安全性和有效性。
我们统计数据了旧金山元月统计数据的2019-nCoV感染者病病症的医学特征。
该病病症的关键多方面包括病病症在学习者有关暴推的医疗保健无视后最终促使医疗；由当地医疗服务终端用户断定病病症已经有到武昌的之旅历史，随后在当地，和州和美国联邦医疗保健官员彼此之间顺利完成协调；并断定可能的2019-nCoV感染者，从而可以促使分开病病症并随后对2019-nCoV顺利完成科学实验断定，并准许病病症康复再进一步评估和经营管理。
该病病症统计数据突显了医学心理医生对于任何显现出急性病因病症状的就诊病病症，要总结出已经有的之旅经历或碰触病病症的关键性性，为了适当正确识别和及时分开可能导致2019-nCoV感染者风险的病病症，并帮助缩减再进一步的传播者。
仍要，本统计数据突显必须断定与2019-nCoV感染者之之外的医学病因，推病分子结构和流感病毒脱落接下来时间的
全部适用范围和自然历史，以为医学经营管理和医疗保健决策提供依据。
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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