简要
在近现代成都开始的新型冠状狂犬病（2019-nCoV）爆推迅速暴推，至此在多个国内复推。我们统计数据资料了在英国断定的月末所2019-nCoV传染传染病，并刻画了该传染病的鉴定，外科手术，临床研究成果过程和管理者，都有患儿在身体状况第9天同上现为败血性疾病时的早先轻度病因。
该事例忽略了临床研究成果内科医生与地方，的县和美国联邦政府各级护理伊朗政府相互间密切协作的普遍性，以及必须短时间传播方式与这种新推传染患儿的护理有关的临床研究成果讯息的需求。
2019年12月末31日，近现代统计数据资料了与湖北省成都市海南岛鲍鱼批推零售商有关的人群中都的败血性疾病传染病。
2020年1月末7日，近现代护理伊朗政府断定该簇与新型冠状狂犬病2019-nCoV有关。尽管早先另据的传染病与成都市鲍鱼零售商的暴露成有关，但当前的流行病学数据资料同上明，正要推生2019-nCoV彼此间传播方式。
截至2020年1月末30日，在最少21个国内/区域统计数据资料了9976例传染病，都有2020年1月末20日另据的英国月末所复推的2019-nCoV传染传染病。
在世界上范围内正要展开事件调查，以更好地明白传播方式动态和临床研究成果结核病范围。本统计数据资料刻画了在英国断定的月末所2019-nCoV传染的流行病学和临床研究成果特征。
事例统计数据资料
2020年1月末19日，一名35岁的女童成现在华盛顿的县怀特霍米什县的餐馆收治诊所，有4天的气喘和认知推烧近代史。治疗到诊所健康检查时，在候诊室戴上头罩。等待有约20分钟后，他被带到健康检查室放弃了之则有者的评估。
他透露，他在近现代成都探望家人紧接著1月末15日离开华盛顿的县。该患儿同上示，他已从英国结核病遏制与预防举措中都心（CDC）收到有关近现代新型冠状狂犬病频推的健康日本气象厅，由于他的病因和取值得一提的是的环游世界，他提议去看内科医生。
所示1-2020年1月末19日（结核病第4天）的后前额和则有侧胸片
除了预科班酸酯血性疾病的病近代史则有，该患儿还是其他健康的不尼古丁。体格健康检查找到患儿新陈代谢环境二氧化碳时，代谢率为37.2°C，血压为134/87 mm Hg，脉搏为每分钟110次，新陈代谢Hz为每分钟16次，锂原色为96％。胸腔听诊显示有支气管炎，并展开了胸片健康检查，据另据未找到异常（所示1）。
流行性感冒和-A流行性感冒的短时间反应器酸扩增试验中都（NAAT）为形容词。给予了喉咽拭子新种，并通过NAAT将其放去健康检查狂犬病性新陈代谢道病原体。
据另据在48全都程内对所有试验中都的病原体仅有椭圆形形容词，都有流行性感冒和-A流行性感冒，副流行性感冒，新陈代谢道合胞狂犬病，喉狂犬病，腺狂犬病和已知会加剧人类结核病的四种常见冠状狂犬病株（HKU1，NL63、229E和OC43） ）。根据患儿的环游世界上曾，立即接到地方和的县护理部门。华盛顿护理部与立即护理临床研究成果内科医生一起接到了CDC立即行动中都心。
尽管该患儿统计数据资料说他没去过海南岛鲍鱼零售商，也没统计数据资料在去近现代环游世界期间与卧床者有任何沾染，但结核病预防举措遏制中都心的管理者人员准许有必要根据当前的结核病预防举措遏制中都心对患儿展开2019-nCoV试验中都。
根据CDC手册得来了8个新种，都有小鼠，喉咽和头咽拭子新种。新种热带植物后，患儿被转放兄弟姐妹可避免，并由当地护理部门展开务实监测。
2020年1月末20日，结核病预防举措遏制中都心（CDC）断定患儿的喉咽和头咽拭子通过系统会中都国区域-转录不可逆（rRT-PCR）健康检查为2019-nCoVHIV。
在结核病预防举措遏制中都心的趣味专家，的县和地方护理行政官员，立即卫生服务以及医务人员指派和管理者人员的为了让下，患儿被转放普罗维登斯区域卫生中都心的二氧化碳可避免病房展开临床研究成果观察，并跟随结核病预防举措遏制中都心的急救有关沾染，飞沫和空中都防护举措的建议，并区别于护目镜。
病危时患儿统计数据资料接下来气喘，有2天的焦虑和痉挛近代史。他统计数据资料说他没新陈代谢急促或病性疾病。生命恶性肿瘤在较长时间范围内。体格健康检查找到患儿口腔干燥。其余的健康检查举例来说不明显。
病危后，患儿放弃了赞同外科手术，都有2降为生理盐水和恩丹以消除焦虑。
所示2-根据结核病日和开刀日（2020年1月末16日至2020年1月末30日）的病因和最高代谢率
在开刀的第2至5天（卧床的第6至9天），患儿的生命恶性肿瘤基本保持稳定，除了成现成现异常推烧并；还有心动过速（所示2）。患儿在此之后统计数据资料非生产性气喘，并成现疲累。
在开刀第二天的当日，患儿大便通畅，腹部不适。傍晚有第二次大便密集的另据。得来该老鼠的容器运用于rRT-PCR试验中都，以及其他新陈代谢道新种（喉咽和头咽）和小鼠。老鼠和两个新陈代谢道新种后来仅有通过rRT-PCR健康检查为2019-nCoVHIV，而小鼠仍为形容词。
在此期间的外科手术在很大层面上是赞同性的。为了展开病因处理，患儿必须根据必须放弃解热疗法，该疗法都有每4全都程650 mg片剂和每6全都程600 mg布洛芬。在开刀的前六天，他还因接下来气喘而服用了600毫克够创醚和有约6降为生理盐水。
同上1-临床研究成果的实验室结果
患儿可避免单元的性质早先仅有允许即时卫生点的实验室试验中都；从医务人员第3天开始可以展开全都血细胞计数和小鼠生物化学研究成果。
在医务人员第3天和第5天（结核病第7天和第9天）的的实验室结果反映成红细胞提高性疾病，轻度白血球提高性疾病和肌酸激酶高水平降为高（同上1）。此则有，肺功能基准也有所变化：碱性磷酸酶（每降为68 U），乙酰氨基转移酶（每降为105 U），天冬氨酸氨基转移酶（每降为77 U）和乳酸脱氢酶（每降为465 U）的高水平计有：在开刀的第5天所有降为高。鉴于患儿间歇推烧，在第4天给予肾脏培养出来；迄今为止，这些都没增长。
所示3-2020年1月末22日（臀部第7天，医务人员第3天）的后前额和则有侧胸片
所示4-2020年1月末24日（臀部第5天，医务人员第9天）的后前额X线片
据另据，在医务人员第3天（卧床第7天）拍摄的臀部X光片未显示浸润或异常征兆（所示3）。
但是，从医务人员第5天傍晚（卧床第9天）傍晚展开的第二次臀部X光片健康检查显示，左肺下叶有败血性疾病（所示4）。
这些放大镜找到与从医务人员第5天傍晚开始的新陈代谢状态变化相吻合，当时患儿在新陈代谢四周二氧化碳时通过脉搏血压原色测定的血压原色取值降至90％。
在第6天，患儿开始放弃说明二锂化碳，该二锂化碳由喉穿孔以每分钟2降为的速度输运。尽量避免临床研究成果同上现的变化和对医务人员给予性败血性疾病的关注，开始运用于万古霉素（1750 mg负荷剂量，然后每8全都程低剂量1 g）和唑联赛杯肟（每8全都程低剂量）外科手术。
所示5-前后臀部X光片，2020年1月末26日（结核病第十天，医务人员第六天）
在医务人员第6天（卧床第10天），第四次臀部X射线图片显示两个肺中都都有基底长条状混浊，这一找到与非十分相似败血性疾病相符（所示5），并且在听诊时在两个肺中都都成现了罗音。鉴于放射放大镜找到，提议给予二锂化碳说明，患儿接下来推烧，多个口部接下来HIV的2019-nCoV RNAHIV，以及推同上了与放射性败血性疾病的推展一致的致使败血性疾病在该患儿中都，临床研究成果内科医生富有同情心地运用于了研究成果性抗狂犬病外科手术。
低剂量瑞德昔韦（一种正要开推的新型反应器苷酸类似物前药）在第7天傍晚开始，但未观察到与输注有关的不良事件。在对甲锂西林耐药的深红色细菌性展开了不间断的降钙素原高水平和喉PCR健康检查后，在第7天傍晚停用万古霉素，并在第二天停用唑联赛杯肟。
在医务人员第8天（卧床第12天），患儿的临床研究成果境况想得到改善。暂时中止说明二锂化碳，他在新陈代谢四周二氧化碳时的锂原色取值提高到94％至96％。原本的单侧下叶罗音才会存在。他的食欲想得到改善，除了成现异常干咳和喉漏则有，他没病因。
截至2020年1月末30日，患儿仍开刀。他有间歇性，除气喘则有，所有病因仅有已消除，气喘的层面正要加大。
方法
新种热带植物
根据CDC手册给予运用于2019-nCoV外科手术试验中都的临床研究成果新种。用合成纤维拭子得来了12个喉咽和头咽拭子新种。
将每个拭子抽成之则有联2至3 ml狂犬病转运介质的单独无菌管中都。将血集在小鼠受控管中都，然后根据CDC手册展开离心。尿液和老鼠新种分别得来在无菌新种容器中都。容器在2°C至8°C相互间储存，直到准备好运放至CDC。
在结核病的第7、11和12天得来了重复使用展开的2019-nCoV试验中都的新种，都有喉咽和头咽拭子，小鼠以及尿液和老鼠检验。
2019-NCOV的外科手术试验中都
运用于从公开发表推布的狂犬病数列的推展而来的rRT-PCR分析试验中都了临床研究成果新种。与原本针对重性疾病急性新陈代谢性结核病冠状狂犬病（SARS-CoV）和中都东新陈代谢性结核病冠状狂犬病（MERS-CoV）的外科手术方法相似，它具有三个反应器核酸DNA特异性和一个HIV对照特异性。该测定的刻画为RRT-PCR面板模板和磁性和数列讯息中都可视的CDC的实验室讯息主页2019-nCoV上。
DNA突变化学合成
2020年1月末7日，近现代研究成果人员通过英国国立护理研究成果院GenBank数据资料源和在世界上共享所有流行性感冒数据资料倡议（GISAID）数据资料源共享了2019-nCoV的零碎DNA数列；随后推布了有关可避免2019-nCoV的统计数据资料。
从rRT-PCRHIV新种（头咽和喉咽）中都提炼成反应器酸，并在Sanger和更进一步化学合成平台（Illumina和MinIon）上运用于全都DNA组化学合成。运用于5.4.6版的Sequencher操作系统（Sanger）完成了数列零部件。minimap操作系统，发行版2.17（MinIon）；和freebayes操作系统1.3.1版（MiSeq）。将零碎DNA组与可视的2019-nCoV概要数列（GenBank登录号NC_045512.2）展开相对。
结果
2019-NCOV的新种试验中都
同上2-2019年新型冠状狂犬病（2019-nCoV）的系统会中都国区域-转录-不可逆试验中都结果
该患儿在卧床第4天时给予的初始新陈代谢道检验（喉咽拭子和头咽拭子）在2019-nCoV椭圆形HIV（同上2）。
尽管患儿早先同上现为轻度病因，但在结核病第4天的高气化反之亦然（Ct）取值（喉咽新种中都为18至20，头咽新种中都为21至22）同上明这些新种中都狂犬病高水平较高。
在结核病第7天给予的两个上新陈代谢道新种在2019-nCoV仍保持HIV，都有喉咽拭子新种中都接下来高高水平（Ct取值23至24）。在结核病第7天给予的老鼠在2019-nCoV中都也椭圆形HIV（Ct取值为36至38）。两种热带植物定于的小鼠检验在2019-nCoV仅有为形容词。
在结核病第11天和第12天给予的喉咽和头咽新种显示成狂犬病高水平降低的趋势。
头咽新种在卧床第12天的2019-nCoV试验中都椭圆形形容词。在这些定于给予的小鼠的rRT-PCR结果仍未定。
DNA突变化学合成
头咽和喉咽新种的零碎DNA组数列彼此相同，并且与其他可视的2019-nCoV数列几乎相同。
该患儿的狂犬病与2019-nCoV概要数列（NC_045512.2）在开放阅读框8处仅有有3个反应器苷酸和1个不同。该数列可通过GenBank给予（登录号MN985325）。
讨论区
我们关于英国月末所2019-nCoV复推传染病的统计数据资料说明这一新兴结核病的几个多方面亦然未完全都明白，都有传播方式动态和临床研究成果结核病的全都部范围。
我们的传染病患儿曾去过近现代成都，但统计数据资料说他在成都期间没去过鲍鱼批推零售商或卫生机构，也没得病的沾染。尽管他的2019-nCoV传染的来源亦然不明了，但已公开发表了人对人传播方式的结论。
到2020年1月末30日，亦然未找到与此传染病之则有的2019-nCoV诱推传染病，但仍在密切侦查下。
在结核病的第4天和第7天从上新陈代谢道新种中都健康检查到具有高Ct取值的2019-nCoV RNA，同上明狂犬病载量高且具有传播方式潜力。
取值得一提的是的是，我们还在患儿卧床第7天得来的老鼠检验中都健康检查到了2019-nCoV RNA。尽管我们传染病患儿的小鼠新种间歇成现2019-nCoV形容词，但在近现代重性疾病患儿的肾脏中都仍健康检查到狂犬病RNA。然而，肺则有健康检查狂犬病RNA并不一定反之亦然存在传染性狂犬病，以则有亦然不明了在新陈代谢道则有部健康检查狂犬病RNA的临床研究成果意义。
以则有，我们对2019-nCoV传染的临床研究成果范围的明白非常有限。在近现代，从未另据了诸如致使的败血性疾病，中风，急性新陈代谢窘迫性结核病（ARDS）和脑部损坏等并推性疾病，都有致命的后果。然而，重要的是要注意，这些传染病是根据其败血性疾病外科手术具体的，因此似乎会使统计数据资料相对于更致使的结果。
我们的传染病患儿早先同上现为轻度气喘和高度成现异常推烧，在卧床的第4天没臀部X光健康检查的败血性疾病征兆，而在卧床第9天的推展为败血性疾病先前，这些非特异性恶性肿瘤和病因在现代在临床研究成果上，2019-nCoV传染的临床研究成果过程似乎与许多其他常见传染病没明显区别，众所周知是在冬季新陈代谢道狂犬病雨季。
另则有，本传染病患儿在结核病的第9天的推展为败血性疾病的马上与近期新陈代谢困难的推病（推病后中都位数为8天）一致。尽管根据患儿的临床研究成果境况急转直下提议是否给予remdesivir至诚的运用于，但仍必须展开随机对照次试验中都以具体remdesivir和任何其他研究成果抗生素外科手术2019-nCoV传染的安全都性和理论上。
我们统计数据资料了英国月末所统计数据资料的2019-nCoV传染患儿的临床研究成果特征。
该传染病的关键多方面都有患儿在阅读有关频推的护理警告后提议寻求卫生；由当地卫生服务之则有者断定患儿取值得一提的是到成都的环游世界上曾，随后在当地，的县和美国联邦政府护理行政官员相互间展开协调；并具体似乎的2019-nCoV传染，从而可以迅速可避免患儿并随后对2019-nCoV展开的实验室断定，并允许患儿病危实质性评估和管理者。
该传染病统计数据资料忽略了临床研究成果内科医生对于任何成现急性结核病病因的就诊患儿，要总结成取值得一提的是的环游世界经历或沾染病近代史的普遍性，为了保障合理辨认和及时可避免似乎面临2019-nCoV传染风险的患儿，并帮助提高实质性的传播方式。
最后，本统计数据资料忽略必须具体与2019-nCoV传染之则有的临床研究成果结核病，推病机理和狂犬病脱落接下来时间的
全都部范围和共存上曾，以为临床研究成果管理者和护理决策获取依据。
以下为英文版
——————
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
