简介
在中也许会国武汉开始的上新型亚型（2019-nCoV）一触即发更快死灰复燃，现已在多个国内胃癌。我们通报了在旧金山证实的尚属2019-nCoV细菌感染传染病，并所述了该传染病的氢对，病患，医学流程和负责管理，最主要病人在病情恶化第9天展现为胃癌时的在此之前轻度病因。
该系统性强调了医学护士与大都，俄克拉荷马州和美利坚合众国各级公共保健当局两者之间的关系协作的极其效用，以及无需更快传递与这种上新发细菌感染病人的护理有关的医学文档的所需。
2019年12月初31日，中也许会国通报了与湖北省武汉市华南鱼肉家禽有关的群体中也许会的胃癌传染病。
2020年1月初7日，中也许会国保健当局证实该簇与上新型亚型2019-nCoV有关。尽管在此之前报导的传染病与武汉市鱼肉零售商的受伤害有关，但也就是知道的医学统计数据指出有，悄悄牵涉到2019-nCoV人际传递。
截至2020年1月初30日，在大概21个国内/内陆地区通报了9976则有传染病，最主要2020年1月初20日报导的旧金山尚属胃癌的2019-nCoV细菌感染传染病。
仅有球之内悄悄开展调查，以更好地洞察传递特性和医学营养不良范围内。本通报所述了在旧金山证实的尚属2019-nCoV细菌感染的医学和医学形态。
系统性通报
2020年1月初19日，一名35岁的蹦床出有现在哥伦比亚特区俄克拉荷马州里德霍米什县的一家急诊诊所，有4天的气喘和客观性咳嗽世界史。病人到诊所定期检查时，在候诊室戴上沟罩。等待约20分钟后，他被送给到定期检查室拒绝接受了提供者的指标。
他问及，他在中也许会国武汉探望家人先于1月初15日返回哥伦比亚特区俄克拉荷马州。该病人注记示，他已从旧金山营养不良依靠与预防中也许会心（CDC）接获有关中也许会国上新型亚型愈演愈烈的身体健康日本气象厅，由于他的病因和不太也许的旅途，他决定去看护士。
由此可知1-2020年1月初19日（营养不良第4天）的后前额和除此以侧面胸片
除了高三酸酯黄疸的家族世界史除此以外，该病人还是其他身体健康的不吸烟。体格定期检查见到病人痉挛环境湿气时，上新陈代谢为37.2°C，血压为134/87 mm Hg，节律为每分钟110次，痉挛频率为每分钟16次，氢原色为96％。肺部听诊标示出有支气管炎，并开展了胸片定期检查，据报导没见到异常（由此可知1）。
HIV性和九一霍乱的更快大分子扩增检验（NAAT）为有性。获了背咽拭子见到地，并通过NAAT将其送给去检测HIV性肺部寄生虫。
据报导在48星期内对所有检验的寄生虫除此以外圆形有性，最主要HIV性和九一霍乱，副霍乱，肺部合胞HIV，背HIV，腺HIV和已知也许会所致人类营养不良的四种少用亚型株（HKU1，NL63、229E和OC43） ）。根据病人的旅途上曾，立即通知大都和俄克拉荷马州保健部门。哥伦比亚特区保健部与即刻护理医学护士一起通知了CDC即刻行动中也许会心。
尽管该病人通报知道他从未去过华南鱼肉零售商，也从未通报在去中也许会国旅途之后与年老者有任何认识，但营养不良预防依靠中也许会心的保安职员同意有必要根据也就是知道的营养不良预防依靠中也许会心对病人开展2019-nCoV检验。
根据CDC概要整理了8个见到地，最主要肾脏，背咽和沟咽拭子见到地。见到地挖掘后，病人被带往普通家庭隔离，并由当地保健部门开展积极检测。
2020年1月初20日，营养不良预防依靠中也许会心（CDC）证实病人的背咽和沟咽拭子通过同步逆转录酶-酵素的单（rRT-PCR）检测为2019-nCoV白血病。
在营养不良预防依靠中也许会心的题材专家，俄克拉荷马州和大都保健地方官，即刻公共保健服务以及该医院领导和保安职员的配合下，病人被带往阿拉巴马内陆地区公共保健中也许会心的湿气隔离病房开展医学观察，并追随营养不良预防依靠中也许会心的医护职员有关认识，飞沫和空中也许会防护措施的同意，并带有丝袜。
入院时病人通报长时间气喘，有2天的眩晕和呕吐世界史。他通报知道他从未痉挛急促或胸痛。灵魂病因在正常之内。体格定期检查见到病人消化道湿气。其余的定期检查通常不微小。
入院后，病人拒绝接受了支持疗法，最主要2再降生理盐水和恩丹以缓解眩晕。
由此可知2-根据营养不良日和休养日（2020年1月初16日至2020年1月初30日）的病因和最高上新陈代谢
在休养的第2至5天（年老的第6至9天），病人的灵魂病因基本上保持良好稳定，除了出有现间歇性咳嗽并眩晕心动过速（由此可知2）。病人继续通报非生产性气喘，并出有现虚弱。
在休养第二天的下午，病人大便在行，腹部不适。傍晚有第二次水泡稀疏的报导。整理该粪的材料应用于rRT-PCR检验，以及其他肺部见到地（背咽和沟咽）和肾脏。粪和两个肺部见到地便除此以外通过rRT-PCR检测为2019-nCoV白血病，而肾脏仍为有性。
在此之后的疗法在很小总体上是支持性的。为了开展病因一处置，病人无需根据无需拒绝接受解热疗法，该疗法最主要每4星期650 mg对乙酰氯基酚和每6星期600 mg抗炎药。在休养的前六天，他还因长时间气喘而用药了600毫克愈创醚和约6再降生理盐水。
注记1-医学麻省理工学院结果
病人隔离两组的性质在此之前仅意味着须要公共保健点麻省理工学院检验；从该医院第3天开始可以开展仅有血细胞枚举和肾脏化学深入研究。
在该医院第3天和第5天（营养不良第7天和第9天）的麻省理工学院结果反映出有白细胞减缓症，轻度血小板减缓症和肌酸激酶素质再降高（注记1）。此除此以外，肝脏当前也有所改变：盐类甘氨酸（每再降68 U），丙氯酸氯基转移酶（每再降105 U），天冬氯酸氯基转移酶（每再降77 U）和甘油半乳糖（每再降465 U）的素质分别为：在休养的第5天所有再降高。鉴于病人重复咳嗽，在第4天获肾脏培养；迄今为止，这些都从未更快增长。
由此可知3-2020年1月初22日（腰部第7天，该医院第3天）的后前额和除此以侧面胸片
由此可知4-2020年1月初24日（腰部第5天，该医院第9天）的后前额X线片
据报导，在该医院第3天（年老第7天）拍摄的腰部X光片没标示出浸润或异常确实（由此可知3）。
但是，从该医院第5天傍晚（年老第9天）傍晚开展的第二次腰部X光片定期检查标示出，左肺下叶有胃癌（由此可知4）。
这些影像学见到与从该医院第5天傍晚开始的痉挛状态改变相吻合，当时病人在痉挛附近湿气时通过节律血氢原色精确测量的血氢原色倍数回升90％。
在第6天，病人开始拒绝接受补足氢气，该氢气由背腹腔以每分钟2再降的运动速度输送给。考虑到医学展现的改变和对该医院获性胃癌的注意，开始常用本品（1750 mg负荷血糖，然后每8星期低剂量1 g）和类抗生素两场肟（每8星期低剂量）疗法。
由此可知5-前后腰部X光片，2020年1月初26日（营养不良第十天，该医院第六天）
在该医院第6天（年老第10天），第四次腰部X射线照片标示出两个肺中也许会都有大块小块混浊，这一见到与非典型胃癌相符（由此可知5），并且在听诊时在两个肺中也许会都出有现了罗音。鉴于人沟为120人影像学见到，决定给予氢气补足，病人长时间咳嗽，多个部位长时间白血病的2019-nCoV RNA白血病，以及发注记了与人沟为120人性胃癌工业发展一致的不堪重负胃癌在该病人中也许会，医学护士富于同情心地常用了深入研究性抗HIV疗法。
低剂量怀特昔韦（一种悄悄开发的上新型氢苷酸N-前药）在第7天傍晚开始，但没观察到与输注有关的不良惨案。在对中三氢周明耐药的紫红色葡萄球菌开展了年终的降钙素原素质和背PCR检测后，在第7天傍晚废弃本品，并在第二天废弃类抗生素两场肟。
在该医院第8天（年老第12天），病人的医学状况获得增加。停止补足氢气，他在痉挛附近湿气时的氢原色倍数提高到94％至96％。之前的侧下叶罗音暂时存有。他的食欲获得增加，除了间歇性干咳和背漏除此以外，他从未病因。
截至2020年1月初30日，病人仍休养。他有发烧，除气喘除此以外，所有病因除此以外已缓解，气喘的总体悄悄减轻。
分析方法
见到地挖掘
根据CDC概要获应用于2019-nCoV病患检验的医学见到地。用橡胶拭子整理了12个背咽和沟咽拭子见到地。
将每个拭子插入包含2至3 mlHIV转运介质的单独冷藏的水也许会。将血集在肾脏分离的水也许会，然后根据CDC概要开展离心。尿液和粪见到地分别整理在冷藏见到地盖子中也许会。材料在2°C至8°C两者之间储存，直到准备好运出至CDC。
在营养不良的第7、11和12天整理了重复开展的2019-nCoV检验的见到地，最主要背咽和沟咽拭子，肾脏以及尿液和粪比对。
2019-NCOV的病患检验
常用从公开发注记发行的HIV大分子工业发展而来的rRT-PCR量化检验了医学见到地。与之前针对病患急性痉挛病症亚型（SARS-CoV）和中也许会东痉挛病症亚型（MERS-CoV）的病患分析方法相似，它有着三个氢双链基因索科利夫卡和一个白血病对照索科利夫卡。该精确测量的所述为RRT-PCR面板多肽和剪切和大分子文档中也许会可用的CDC麻省理工学院文档网站2019-nCoV上。
性状人类基因序列计划
2020年1月初7日，中也许会国深入研究职员通过旧金山国立保健深入研究院GenBank元统计数据和仅有球特别联所有霍乱统计数据积极支持（GISAID）元统计数据特别联了2019-nCoV的基本上基因大分子；随后发行了有关隔离2019-nCoV的通报。
从rRT-PCR白血病见到地（沟咽和背咽）中也许会提取大分子，并在Sanger和下一代人类基因序列计划该平台（Illumina和MinIon）上应用于仅有基因序列人类基因序列计划。常用5.4.6特别版的Sequencher该软件（Sanger）完成了大分子零部件。minimap该软件，特别正式版2.17（MinIon）；和freebayes该软件1.3.1特别版（MiSeq）。将基本上基因序列与可用的2019-nCoV详见大分子（GenBank登录号NC_045512.2）开展比较。
结果
2019-NCOV的见到地检验
注记2-2019年上新型亚型（2019-nCoV）的同步逆转录酶-酵素-的单检验结果
该病人在年老第4点将获的初始肺部比对（背咽拭子和沟咽拭子）在2019-nCoV圆形白血病（注记2）。
尽管病人在此之前展现为轻度病因，但在营养不良第4天的高于循环电位（Ct）倍数（背咽见到地中也许会为18至20，沟咽见到地中也许会为21至22）指出有这些见到地中也许会HIV素质很高。
在营养不良第7天获的两个上肺部见到地在2019-nCoV仍保持良好白血病，最主要背咽拭子见到地中也许会长时间高素质（Ct倍数23至24）。在营养不良第7天获的粪在2019-nCoV中也许会也圆形白血病（Ct倍数为36至38）。两种挖掘年份的肾脏比对在2019-nCoV除此以外为有性。
在营养不良第11天和第12天获的背咽和沟咽见到地标示出出有HIV素质下降的趋势。
沟咽见到地在年老第12天的2019-nCoV检验圆形有性。在这些年份获的肾脏的rRT-PCR结果仍没定。
性状人类基因序列计划
沟咽和背咽见到地的基本上基因序列大分子彼此相异，并且与其他可用的2019-nCoV大分子依然相异。
该病人的HIV与2019-nCoV详见大分子（NC_045512.2）在免费写出框8一处仅有3个氢苷酸和1个各有不同。该大分子可通过GenBank获（登录号MN985325）。
专页
我们关于旧金山尚属2019-nCoV胃癌传染病的通报知道明了这一上新兴营养不良的几个各个方面尚没实际上洞察，最主要传递特性和医学营养不良的仅有部范围内。
我们的传染病病人曾去过中也许会国武汉，但通报知道他在武汉之后从未去过鱼肉家禽或公共保健机构，也从未生病的认识。尽管他的2019-nCoV细菌感染的是从尚不确切，但已公开发注记了人对人传递的结论。
到2020年1月初30日，尚没见到与此传染病特别的2019-nCoV继中风则有，但仍在的关系看管下。
在营养不良的第4天和第7天从上肺部见到地中也许会检测到有着高于Ct倍数的2019-nCoV RNA，指出有HIV载重高且有着传递潜力。
倍数得注意到的是，我们还在病人年老第7天整理的粪比对中也许会检测到了2019-nCoV RNA。尽管我们传染病病人的肾脏见到地重复出有现2019-nCoV有性，但在中也许会国病患病人的肾脏中也许会仍检测到HIVRNA。然而，肺除此以外检测HIVRNA并不一定也就是说存有传染性HIV，目前尚不确切在肺部除此以外部检测HIVRNA的医学意义。
目前，我们对2019-nCoV细菌感染的医学范围内的洞察比较受限。在中也许会国，仍然报导了诸如不堪重负的胃癌，痉挛衰竭，急性痉挛困窘病症（ARDS）和心脏损伤等并发症，最主要关键因素时刻的灾难性。然而，极其重要的是要注意到，这些传染病是根据其胃癌病患确切的，因此也许也许会使通报偏向更不堪重负的结果。
我们的传染病病人在此之前展现为轻度气喘和高于度间歇性咳嗽，在年老的第4天从未腰部X光定期检查的胃癌确实，而在年老第9天工业发展为胃癌之前，这些非特异性病因和病因在早期在医学上，2019-nCoV细菌感染的医学流程也许与许多其他少用病原从未微小不同点，尤其是在春季肺部HIV干季。
另除此以外，本传染病病人在营养不良的第9天工业发展为胃癌的时机与不太也许痉挛困难的复发（中风后中也许会位数为8天）一致。尽管根据病人的医学状况好转决定是否给予remdesivir慈悲的常用，但仍无需开展随机对照检验以确切remdesivir和任何其他深入研究类固醇疗法2019-nCoV细菌感染的实用性和必要性。
我们通报了旧金山尚属通报的2019-nCoV细菌感染病人的医学形态。
该传染病的关键因素各个方面最主要病人在写出有关愈演愈烈的公共保健指示后决定寻求公共保健；由当地公共保健服务提供者证实病人不太也许到武汉的旅途上曾，随后在当地，俄克拉荷马州和美利坚合众国公共保健地方官两者之间开展协调；并确切也许的2019-nCoV细菌感染，从而可以更快隔离病人并随后对2019-nCoV开展麻省理工学院证实，并意味着病人入院全面指标和负责管理。
该传染病通报强调了医学护士对于任何出有现急性营养不良病因的休养病人，要总结出有不太也许的旅途经历或认识家族世界史的极其效用，为了确保正确识别和立即隔离也许面临2019-nCoV细菌感染危险性的病人，并帮助减缓全面的传递。
终于，本通报强调无需确切与2019-nCoV细菌感染特别的医学营养不良，中风机理和HIV脱落长时间时间的
仅有部范围内和大自然上曾，以为医学负责管理和公共保健决策提供依据。
一般而言为英文特别版
——————
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
