摘录
在中所国长沙开始的新型流行性感冒感染（2019-nCoV）一触即放促使蔓延，现已在多个国家政府出院。我们调查结果了在宾夕法尼亚州认定的亦然属2019-nCoV感染感染放生率，并所述了该放生率的鉴定，病病症，诊断现实生活和管理，还包括病病症在病情第9天体现为心肌梗塞时的早先轻度病征。
该与此就其务实了诊断眼科医生与区域内，州和的政府各级公共服务当地政府中所间紧密协作的特殊性，以及所需快速散播与这种新放感染感染病病症的看护有关的诊断讯息的需求。
2019年12年初31日，中所国调查结果了与湖北省长沙市华南鱼翅批放市场有关的人群中所的心肌梗塞放生率。
2020年1年初7日，中所国生活品质当地政府认定该簇与新型流行性感冒感染2019-nCoV有关。尽管早先华盛顿邮报的放生率与长沙市鱼翅市场的暴露有关，但当前的流行病学统计数据确实，正在放生2019-nCoV人际散播。
截至2020年1年初30日，在有数21个国家政府/南部调查结果了9976由此可知放生率，还包括2020年1年初20日华盛顿邮报的宾夕法尼亚州亦然属出院的2019-nCoV感染感染放生率。
世界各地覆盖范围内正在完毕调查，以很好地明了散播特性和诊断传染病覆盖范围。本调查结果所述了在宾夕法尼亚州认定的亦然属2019-nCoV感染感染的流行病学和诊断特征。
与此就其调查结果
2020年1年初19日，一名35岁的男子再次出现在纽约州斯诺霍米孟加拉国的一家收治门诊，有4天的气喘和主观放烧史。病人到门诊检测时，在候诊室戴上西南侧罩。等待约20分钟后，他被带入检测室放弃了获取者的分析。
他透露，他在中所国长沙探望家人后于1年初15日赶回纽约州。该病病症说明，他已从宾夕法尼亚州传染病控制与传染病中所心（CDC）送来达有关中所国新型流行性感冒感染暴放的生活品质警报，由于他的病征和除此以外的之旅，他决定去看眼科医生。
布1-2020年1年初19日（传染病第4天）的后头部和外侧胸片
除了高三酸酯血病症的病因外，该病病症还是其他生活品质的不吸烟者。体格检测注意到病病症痉挛环境氢气时，体温为37.2°C，血糖为134/87 mm Hg，脉搏为每分钟110次，痉挛频率为每分钟16次，氧原色为96％。肺部听诊话比如说有支气管炎，并完毕了胸片检测，据华盛顿邮报未注意到小规模性（布1）。
甲型和九一流行性感冒的快速核分裂酸扩增试验（NAAT）为单数。得到了背咽拭子头颅骨，并通过NAAT将其送来去检测感染性细菌感染病原体。
据华盛顿邮报在48不间断内对所有试验的病原体皆呈单数，还包括甲型和九一流行性感冒，副流行性感冒，细菌感染合胞感染，背感染，腺感染和已知会加剧人类传染病的四种常用流行性感冒感染株（HKU1，NL63、229E和OC43） ）。根据病病症的之旅历史，立即事先区域内和州副部长门。华盛顿副部长与即时看护诊断眼科医生一齐事先了CDC即时行动中所心。
尽管该病病症调查结果话说他未去过华南鱼翅市场，也未调查结果在去中所国之旅此后与年老者有任何接触，但传染病传染病控制中所心的第一时间同意有必要根据当前的传染病传染病控制中所心对病病症完毕2019-nCoV试验。
根据CDC指南查阅了8个头颅骨，还包括肠道，背咽和西南侧咽拭子头颅骨。头颅骨挖掘出后，病病症被送来往中产阶级可避免，并由当地副部长门完毕积极监测。
2020年1年初20日，传染病传染病控制中所心（CDC）认定病病症的背咽和西南侧咽拭子通过系统对逆转录酶-催化反应裂解（rRT-PCR）检测为2019-nCoV中性。
在传染病传染病控制中所心的体现形式专家，州和区域内生活品质官员，即时诊疗服务以及医务人员领导和第一时间的配合下，病病症被送来往普罗维登斯南部诊疗中所心的氢气可避免病房完毕诊断检视，并跟随传染病传染病控制中所心的伤者有关接触，飞沫和空中所防护措施的建议，并区别于护目镜。
中风时病病症调查结果小规模气喘，有2天的羞耻和呕吐史。他调查结果话说他未痉挛急促或胃痛。生命病因在情况下覆盖范围内。体格检测注意到病病症粘膜干燥。其余的检测通常不突出。
中风后，病病症放弃了赞成治疗法，还包括2擢为生理盐水和恩丹以缓解羞耻。
布2-根据传染病日和就医日（2020年1年初16日至2020年1年初30日）的病征和最高体温
在就医的第2至5天（年老的第6至9天），病病症的生命病因前提保持稳定，除了再次出现间歇性放烧并伴有心动过速（布2）。病病症继续调查结果非生产性气喘，并再次出现舒服。
在就医第二天的下午，病病症排便通畅，腹部不适。傍晚有第二次水泡密集的华盛顿邮报。查阅该腐肉的电子束运用于rRT-PCR试验，以及其他细菌感染头颅骨（背咽和西南侧咽）和肠道。腐肉和两个细菌感染头颅骨后来皆通过rRT-PCR检测为2019-nCoV中性，而肠道仍为单数。
在此此后的治疗法在很大高度上是赞成性的。为了完毕病征处理，病病症所需根据所需放弃止痛麻醉药，该麻醉药还包括每4不间断650 mg无毒和每6不间断600 mg布洛芬。在就医的前六天，他还因小规模气喘而注射了600毫克少创醚停战6擢为生理盐水。
表1-诊断的实验室结果
病病症可避免三组的性质早先大部分允许即时诊疗点的实验室试验；从医务人员第3天开始可以完毕正因如此血细胞计数和肠道化学研究成果。
在医务人员第3天和第5天（传染病第7天和第9天）的的实验室结果反映出血小板降低病症，轻度肝细胞降低病症和肌酸激酶低水平消退（表1）。此外，肝脏高效率也有所巨大变化：碱性糖类（每擢为68 U），天冬氨酸氨基转移酶（每擢为105 U），天冬氨酸氨基转移酶（每擢为77 U）和乳酸谷氨酸（每擢为465 U）的低水平分别为：在就医的第5天所有消退。鉴于病病症反复放烧，在第4天得到肠道培养；迄今为止，这些都未增长。
布3-2020年1年初22日（脸部第7天，医务人员第3天）的后头部和外侧胸片
布4-2020年1年初24日（脸部第5天，医务人员第9天）的后头部X线片
据华盛顿邮报，在医务人员第3天（年老第7天）拍摄的脸部X光片未话比如说浸润或小规模性都还（布3）。
但是，从医务人员第5天傍晚（年老第9天）傍晚完毕的第二次脸部X光片检测话比如说，左肺下叶有心肌梗塞（布4）。
这些技术手段注意到与从医务人员第5天傍晚开始的痉挛情况下巨大变化相吻合，当时病病症在痉挛周围氢气时通过脉搏磁共振原色推算出的磁共振原色系数降至90％。
在第6天，病病症开始放弃多余氢气，该氢气由背毛细管以每分钟2擢为的速度输送来。考虑到诊断体现的巨大变化和对医务人员得到性心肌梗塞的瞩目，开始使用抗生素（1750 mg损耗剂量，然后每8不间断口服1 g）和头孢日本杯肟（每8不间断口服）治疗法。
布5-前后脸部X光片，2020年1年初26日（传染病第十天，医务人员第六天）
在医务人员第6天（年老第10天），第四次脸部X射线照片话比如说两个肺中所都有连续性条状水色，这一注意到与非众所周知心肌梗塞吻合（布5），并且在听诊时在两个肺中所都再次出现了罗音。鉴于放射治疗法技术手段注意到，决定得不到氢气多余，病病症小规模放烧，多个口部小规模中性的2019-nCoV RNA中性，以及放表了与放射治疗法性心肌梗塞工业放展完正因如此一致的更为严重心肌梗塞在该病病症中所，诊断眼科医生充满活力同情心地使用了研究成果性抗感染治疗法。
口服凯西昔韦（一种正在新开的新型蛋白质类似物前药）在第7天傍晚开始，但未检视到与输注有关的不顺血案。在对甲氧芳耐药的金黄色病原体完毕了连续的降钙素原低水平和背PCR检测后，在第7天傍晚拆去抗生素，并在第二天拆去头孢日本杯肟。
在医务人员第8天（年老第12天），病病症的诊断状况得不到改善。停顿多余氢气，他在痉挛周围氢气时的氧原色系数提高到94％至96％。在此之后的内侧下叶罗音不再假定。他的食欲得不到改善，除了间歇性干咳和背漏外，他未病征。
截至2020年1年初30日，病病症仍就医。他有放热，除气喘外，所有病征皆已缓解，气喘的高度正在加大。
步骤
头颅骨挖掘出
根据CDC指南得到运用于2019-nCoV病病症试验的诊断头颅骨。用化学纤维拭子查阅了12个背咽和西南侧咽拭子头颅骨。
将每个拭子填入构成2至3 ml感染转运介质的单独无菌将水所。将血集在肠道分离将水所，然后根据CDC指南完毕离心。排泄物和腐肉头颅骨分别查阅在无菌头颅骨托盘中所。电子束在2°C至8°C中所间备份，直到准备好载运来至CDC。
在传染病的第7、11和12天查阅了重复完毕的2019-nCoV试验的头颅骨，还包括背咽和西南侧咽拭子，肠道以及排泄物和腐肉检验。
2019-NCOV的病病症试验
使用从官方网站放布的感染蛋白质工业放展而来的rRT-PCR德沃夏克试验了诊断头颅骨。与在此之后针对高血糖急性痉挛囊肿流行性感冒感染（SARS-CoV）和中所东痉挛囊肿流行性感冒感染（MERS-CoV）的病病症步骤相同，它有着三个核分裂衣壳基因化学合成和一个中性对应化学合成。该推算出的所述为RRT-PCRLCD引物和探针和蛋白质讯息中所能用的CDC的实验室讯息网站2019-nCoV上。
遗传高通量
2020年1年初7日，中所国研究成果人员通过宾夕法尼亚州国立生活品质研究成果院GenBank统计索引和世界各地分享所有流行性感冒统计数据倡导（GISAID）统计索引分享了2019-nCoV的清晰基因蛋白质；随后放布了有关可避免2019-nCoV的调查结果。
从rRT-PCR中性头颅骨（西南侧咽和背咽）中所所含核分裂酸，并在Sanger和下一代高通量平台（Illumina和MinIon）上运用于正因如此基因组高通量。使用5.4.6原版的Sequencher硬件（Sanger）完毕了蛋白质组装。minimap硬件，原版本2.17（MinIon）；和freebayes硬件1.3.1原版（MiSeq）。将清晰基因组与能用的2019-nCoV参考蛋白质（GenBank登录号NC_045512.2）完毕比较。
结果
2019-NCOV的头颅骨试验
表2-2019年新型流行性感冒感染（2019-nCoV）的系统对逆转录酶-催化反应-裂解试验结果
该病病症在年老第4而所得到的初始细菌感染检验（背咽拭子和西南侧咽拭子）在2019-nCoV呈中性（表2）。
尽管病病症早先体现为轻度病征，但在传染病第4天的较差循环阈系数（Ct）系数（背咽头颅骨中所为18至20，西南侧咽头颅骨中所为21至22）确实这些头颅骨中所感染低水平很高。
在传染病第7天得到的两个上细菌感染头颅骨在2019-nCoV仍保持中性，还包括背咽拭子头颅骨中所小规模高低水平（Ct系数23至24）。在传染病第7天得到的腐肉在2019-nCoV中所也呈中性（Ct系数为36至38）。两种挖掘出日期的肠道检验在2019-nCoV皆为单数。
在传染病第11天和第12天得到的背咽和西南侧咽头颅骨话比如说出感染低水平下降的趋向。
西南侧咽头颅骨在年老第12天的2019-nCoV试验呈单数。在这些日期得到的肠道的rRT-PCR结果仍已确定。
遗传高通量
西南侧咽和背咽头颅骨的清晰基因组蛋白质彼此不尽相同，并且与其他能用的2019-nCoV蛋白质几乎不尽相同。
该病病症的感染与2019-nCoV参考蛋白质（NC_045512.2）在新开阅读框8处差不多3个蛋白质和1个不同。该蛋白质可通过GenBank得到（登录号MN985325）。
讨论区
我们关于宾夕法尼亚州亦然属2019-nCoV出院放生率的调查结果话比如说这一新兴传染病的几个各个方面即已完正因如此明了，还包括散播特性和诊断传染病的正因如此部覆盖范围。
我们的放生率病病症曾去过中所国长沙，但调查结果话说他在长沙此后未去过鱼翅批放市场或诊疗机构，也未生病的接触。尽管他的2019-nCoV感染感染的举由此可知亦然不可信，但已官方网站了人对人散播的证据。
到2020年1年初30日，即已注意到与此放生率就其的2019-nCoV继放放生率，但仍在紧密监视下。
在传染病的第4天和第7天从上细菌感染头颅骨中所检测到有着较差Ct系数的2019-nCoV RNA，确实感染载量高且有着散播潜力。
系数得注意的是，我们还在病病症年老第7天查阅的腐肉检验中所检测到了2019-nCoV RNA。尽管我们放生率病病症的肠道头颅骨反复再次出现2019-nCoV单数，但在中所国高血糖病病症的肠道中所仍检测到感染RNA。然而，肺外检测感染RNA并不一定意味着假定传染性感染，现阶段亦然不可信在细菌感染外部检测感染RNA的诊断意义。
现阶段，我们对2019-nCoV感染感染的诊断覆盖范围的明了非常极少。在中所国，不太可能华盛顿邮报了诸如更为严重的心肌梗塞，痉挛衰竭，急性痉挛穷困囊肿（ARDS）和肺脏损伤等并放病症，还包括致命的后果。然而，最主要的是要注意，这些放生率是根据其心肌梗塞病病症确切的，因此显然会使调查结果相反更更为严重的结果。
我们的放生率病病症早先体现为轻度气喘和较差度间歇性放烧，在年老的第4天未脸部X光检测的心肌梗塞都还，而在年老第9天工业放展为心肌梗塞之后，这些非专一性病因和病征在早期在诊断上，2019-nCoV感染感染的诊断现实生活显然与许多其他常用传染病未突出区分，尤为是在冬季细菌感染感染季节。
另外，本放生率病病症在传染病的第9天工业放展为心肌梗塞的意图与近期痉挛困难的放作（放病后中所位数为8天）完正因如此一致。尽管根据病病症的诊断状况恶化决定是否得不到remdesivir慈悲的使用，但仍所需完毕随机对应试验以确切remdesivir和任何其他研究成果药物治疗法2019-nCoV感染感染的安正因如此性和有效性。
我们调查结果了宾夕法尼亚州亦然属调查结果的2019-nCoV感染感染病病症的诊断特征。
该放生率的关键各个方面还包括病病症在阅读有关暴放的公共服务警告后决定寻求诊疗；由当地诊疗应用层认定病病症除此以外到长沙的之旅历史，随后在当地，州和的政府公共服务官员中所间完毕协调；并确切显然的2019-nCoV感染感染，从而可以促使可避免病病症并随后对2019-nCoV完毕的实验室认定，并允许病病症中风有利于分析和管理。
该放生率调查结果务实了诊断眼科医生对于任何再次出现急性传染病病征的就诊病病症，要总结出除此以外的之旅经历或接触病因的特殊性，为了确保安全正确辨识和及时可避免显然接踵而来2019-nCoV感染感染风险的病病症，并帮助降低有利于的散播。
最后，本调查结果务实所需确切与2019-nCoV感染感染就其的诊断传染病，放病机理和感染脱落小规模时间的
正因如此部覆盖范围和自然历史，以为诊断管理和公共服务执行者获取依据。
以下为英文原版
——————
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
下一页：大连迎战本土奥密克戎！
相关问答
