摘要
在华北南部南昌开始的取而代之型亚型接种(2019-nCoV)一触即发很快更为轻微,时才在多个国家胃癌。我们调查报告了在英美两国话说明的尚能属2019-nCoV接种患病,并描述了该患病的鉴别,临床,以外科更进一步和管理机构,之以外患儿在病况第9天备注现为败血症时的最初轻度癫痫状。
该案同上务实了以外科眼科医生与人西南侧众多,一个州和合众国各级公共医疗政府之间密切协作的举足轻重性,以及须要较慢传递与这种取而代之发接种患儿的医疗有关的以外科个人信息的需求。
2019年12月末31日,华北南部调查报告了与湖北省南昌市珠江三角洲鲍鱼批发市场有关的人群中的的败血症患病。
2020年1月末7日,华北南部医疗政府话说明该簇与取而代之型亚型接种2019-nCoV有关。尽管最初媒体报道的患病与南昌市鲍鱼市场的暴露有关,但意味着的统计学数据资料备注明,打算再次发生2019-nCoV人际传递。
截至2020年1月末30日,在至少21个国家/南部调查报告了9976同上患病,之以外2020年1月末20日媒体报道的英美两国尚能属胃癌的2019-nCoV接种患病。
全都球区域内打算展开调查,以很好地认识传递一个系统和以外科哮喘范围。本调查报告描述了在英美两国话说明的尚能属2019-nCoV接种的统计学和以外科外观上。
案同上调查报告
2020年1月末19日,一名35岁的男子注意到在犹他一个州斯诺霍米什县的杂货店急诊诊所,有4天的咳嗽和认知头痛日本史。病人到诊所核查时,在候诊室戴上西南侧罩。等待大约20分钟后,他被带到核查室接纳了提供者的评估。
他透露,他在华北南部南昌返家父母后于1月末15日回到犹他一个州。该患儿备注示,他已从英美两国哮喘依靠与防治中的心(CDC)收到有关华北南部取而代之型亚型接种更为轻微的健康警报,由于他的癫痫状和除此以外的之旅,他尽快去看眼科医生。
由此可知1-2020年1月末19日(哮喘第4天)的后前胸和以侧边胸片
除了高三酸酯血癫痫的躁郁症以外,该患儿还是其他健康的不吸烟者。体格核查发现患儿气管环境二硫化碳时,心率为37.2°C,血压为134/87 mm Hg,脉搏为每分钟110次,气管频率为每分钟16次,硫相对于为96%。肺部听诊辨识有支气管炎,并展开了胸片核查,据媒体报道已经发现异常(由此可知1)。
乙型和乙型疾病的较慢核酸扩增试验(NAAT)为形容词。得不到了喉咽拭子取而代之种,并通过NAAT将其送来去测定病毒接种性气管道寄生虫。
据媒体报道在48足足内对所有试验的寄生虫仅有红褐色形容词,之以外乙型和乙型疾病,副疾病,气管道合胞病毒接种,喉病毒接种,腺病毒接种和已知会导致人类哮喘的四种常见亚型接种株(HKU1,NL63、229E和OC43) )。根据患儿的之旅文化日本史,立即接到人西南侧众多和一个州当地政府。华盛顿医疗部与及时医疗以外科眼科医生一同接到了CDC及时行动中的心。
尽管该患儿调查报告话说他没有人去过珠江三角洲鲍鱼市场,也没有人调查报告在去华北南部之旅之前与生病者有任何认识,但哮喘防治机房的工作技术人员同意有必要根据意味着的哮喘防治机房对患儿展开2019-nCoV试验。
根据CDC范本采集了8个取而代之种,之以外毒素,喉咽和西南侧咽拭子取而代之种。取而代之种采集后,患儿被送来往家庭强制,并由当地当地政府展开全力监测。
2020年1月末20日,哮喘防治机房(CDC)话说明患儿的喉咽和西南侧咽拭子通过实时抗病毒-酵素脉动(rRT-PCR)测定为2019-nCoV乙型肝炎。
在哮喘防治机房的主题医学专家,一个州和人西南侧众多医疗官员,及时医疗服务以及病房全力支持和工作技术人员的配合下,患儿被送来往奥尔巴尼南部医疗中的心的二硫化碳强制病房展开以外科观察,并一同哮喘防治机房的医护技术人员有关认识,飞沫和直升飞机的防盗措施的建言,并类似于护目镜。
病况恶化时患儿调查报告持续性咳嗽,有2天的白痴和呕吐日本史。他调查报告话说他没有人气管急促或咳嗽。心灵以外科备注现在也就是话说区域内。体格核查发现患儿毛细血管干燥。其余的核查通常不明显。
病况恶化后,患儿接纳了支持治疗,之以外2擢为生理盐水和恩丹以缓和白痴。
由此可知2-根据哮喘日和中的风日(2020年1月末16日至2020年1月末30日)的癫痫状和高达心率
在中的风的第2至5天(生病的第6至9天),患儿的心灵以外科备注现也就是话说维持稳定,除了注意到注意到异常头痛并常为心动过速(由此可知2)。患儿暂时调查报告非生产性咳嗽,并注意到虚弱。
在中的风第二天的下午,患儿吞咽顺畅,腹部不适。凌晨有第二次大便稀疏的媒体报道。采集该粪便的采样用于rRT-PCR试验,以及其他气管道取而代之种(喉咽和西南侧咽)和毒素。粪便和两个气管道取而代之种后来仅有通过rRT-PCR测定为2019-nCoV乙型肝炎,而毒素仍为形容词。
在此之前的治疗在很大往往上是支持性的。为了展开癫痫状管控,患儿须要根据须要接纳解热化学疗法,该化学疗法之以外每4足足650 mg对乙酰尿素基酚和每6足足600 mg布洛芬。在中的风的前六天,他还因持续性咳嗽而服用了600毫克稍创醚和大约6擢为生理盐水。
备注1-以外科实验室结果
患儿强制单元的性质最初非常少允许即时医疗点实验室试验;从病房第3天开始可以展开全都皮下计数和毒素化学研究者。
在病房第3天和第5天(哮喘第7天和第9天)的实验室结果反映出白细胞减少癫痫,轻度血小板减少癫痫和肌酸激酶高度擢为高(备注1)。此以外,冠心病量化也太大叠加:碱性脂质(每擢为68 U),甘尿素酸尿素基转移酶(每擢为105 U),天冬尿素酸尿素基转移酶(每擢为77 U)和甘油羟化酶(每擢为465 U)的高度大致相同:在中的风的第5天所有擢为高。鉴于患儿有规律头痛,在第4天得不到血浆培养;纵观,这些都没有人增长。
由此可知3-2020年1月末22日(腰部第7天,病房第3天)的后前胸和以侧边胸片
由此可知4-2020年1月末24日(腰部第5天,病房第9天)的后前胸X线片
据媒体报道,在病房第3天(生病第7天)拍摄的腰部X光片已经辨识常为或异常有可能(由此可知3)。
但是,从病房第5天凌晨(生病第9天)凌晨展开的第二次腰部X光片核查辨识,左肺下叶有败血症(由此可知4)。
这些影像学发现与从病房第5天凌晨开始的气管精神状态叠加密切相关,当时患儿在气管周围二硫化碳时通过脉搏血硫相对于测定的血硫相对于最大值降至90%。
在第6天,患儿开始接纳多余硫气,该硫气由喉导管以每分钟2擢为的速度运输来。毕竟以外科备注现的叠加和对病房得不到性败血症的关注,开始用作抗生素(1750 mg负荷剂量,然后每8足足麻醉1 g)和头孢锦标苯酚(每8足足麻醉)治疗。
由此可知5-前后腰部X光片,2020年1月末26日(哮喘第十天,病房第六天)
在病房第6天(生病第10天),第四次腰部X射线剧照辨识两个肺中的都有基底条状混浊,这一发现与非众所周知败血症相符(由此可知5),并且在听诊时在两个肺中的都注意到了罗音。鉴于辐射影像学发现,尽快给予硫气多余,患儿持续性头痛,多个部位持续性乙型肝炎的2019-nCoV RNA乙型肝炎,以及发备注了与辐射性败血症的发展赞同的轻微败血症在该患儿中的,以外科眼科医生富有责任感地用作了研究者性抗病毒接种治疗。
麻醉瑞德昔韦(一种打算开发的取而代之型核苷酸酰胺前药)在第7天凌晨开始,但已经观察到与十二指肠有关的不良事件。在对乙硫周明耐药的金黄色葡萄球菌展开了年中的降钙素原高度和喉PCR测定后,在第7天凌晨改用抗生素,并在第二天改用头孢锦标苯酚。
在病房第8天(生病第12天),患儿的以外科情形得不到降低。取消多余硫气,他在气管周围二硫化碳时的硫相对于最大值降低到94%至96%。先前的双侧下叶罗音不再存在。他的血清素得不到降低,除了注意到异常干咳和喉漏以外,他没有人癫痫状。
截至2020年1月末30日,患儿仍中的风。他有发光,除咳嗽以外,所有癫痫状仅有已缓和,咳嗽的往往打算减缓。
步骤
取而代之种采集
根据CDC范本得不到用于2019-nCoV临床试验的以外科取而代之种。用合成纤维拭子采集了12个喉咽和西南侧咽拭子取而代之种。
将每个拭子弹出包含2至3 ml病毒接种转运真空的也就是话说上无菌循环系统的。将血集在毒素分离出来循环系统的,然后根据CDC范本展开离心。尿液和粪便取而代之种分别采集在无菌取而代之种容器中的。采样在2°C至8°C之间储藏,直到准备好运送来至CDC。
在哮喘的第7、11和12天采集了重复展开的2019-nCoV试验的取而代之种,之以外喉咽和西南侧咽拭子,毒素以及尿液和粪便采样。
2019-NCOV的临床试验
用作从披露面世的病毒接种脱硫核糖核酸的发展而来的rRT-PCR量化试验了以外科取而代之种。与先前针对重癫痫急性气管综合症亚型接种(SARS-CoV)和南亚气管综合症亚型接种(MERS-CoV)的临床步骤类似,它具三个核衣壳DNA靶标和一个乙型肝炎相比较靶标。该测定的描述为RRT-PCR面板引物和探针和脱硫核糖核酸个人信息中的一般来话说的CDC实验室个人信息网站2019-nCoV上。
基因基因组
2020年1月末7日,华北南部研究者技术人员通过英美两国国立医疗研究者院GenBank数据资料库和全都球相关联所有疾病数据资料发起者(GISAID)数据资料库相关联了2019-nCoV的比较简单DNA脱硫核糖核酸;随后面世了有关强制2019-nCoV的调查报告。
从rRT-PCR乙型肝炎取而代之种(西南侧咽和喉咽)中的所含核酸,并在Sanger和下一代基因组平台(Illumina和MinIon)上用于全都DNA组基因组。用作5.4.6海外版的Sequencher软体(Sanger)完成了脱硫核糖核酸组装。minimap软体,海外版本2.17(MinIon);和freebayes软体1.3.1海外版(MiSeq)。将比较简单DNA组与一般来话说的2019-nCoV参考脱硫核糖核酸(GenBank登录号NC_045512.2)展开比较。
结果
2019-NCOV的取而代之种试验
备注2-2019年取而代之型亚型接种(2019-nCoV)的实时抗病毒-酵素-脉动试验结果
该患儿在生病第4天时得不到的初始气管道采样(喉咽拭子和西南侧咽拭子)在2019-nCoV红褐色乙型肝炎(备注2)。
尽管患儿最初备注现为轻度癫痫状,但在哮喘第4天的低循环系统阈最大值(Ct)最大值(喉咽取而代之种中的为18至20,西南侧咽取而代之种中的为21至22)备注明这些取而代之种中的病毒接种高度低。
在哮喘第7天得不到的两个上气管道取而代之种在2019-nCoV仍维持乙型肝炎,之以外喉咽拭子取而代之种中的持续性高高度(Ct最大值23至24)。在哮喘第7天得不到的粪便在2019-nCoV中的也红褐色乙型肝炎(Ct最大值为36至38)。两种采集月份的毒素采样在2019-nCoV仅有为形容词。
在哮喘第11天和第12天得不到的喉咽和西南侧咽取而代之种辨识出病毒接种高度下降的渐进。
西南侧咽取而代之种在生病第12天的2019-nCoV试验红褐色形容词。在这些月份得不到的毒素的rRT-PCR结果仍显然一致。
基因基因组
西南侧咽和喉咽取而代之种的比较简单DNA组脱硫核糖核酸彼此相同,并且与其他一般来话说的2019-nCoV脱硫核糖核酸几乎相同。
该患儿的病毒接种与2019-nCoV参考脱硫核糖核酸(NC_045512.2)在新开阅读框8处全部都是3个核苷酸和1个不同。该脱硫核糖核酸可通过GenBank得不到(登录号MN985325)。
讨论区
我们关于英美两国尚能属2019-nCoV胃癌患病的调查报告话说明了这一取而代之兴哮喘的几个方面尚能已经显然都认识,之以外传递一个系统和以外科哮喘的全都部范围。
我们的患病患儿曾去过华北南部南昌,但调查报告话说他在南昌之前没有人去过鲍鱼批发市场或医疗机构,也没有人生病的认识。尽管他的2019-nCoV接种的来源尚能不确实,但已披露了人对人传递的证据。
到2020年1月末30日,尚能已经发现与此患病之以外的2019-nCoV继发患病,但仍在密切监视下。
在哮喘的第4天和第7天从上气管道取而代之种中的测定到具低Ct最大值的2019-nCoV RNA,备注明病毒接种总重量高且具传递实用价值。
最大值得提醒的是,我们还在患儿生病第7天采集的粪便采样中的测定到了2019-nCoV RNA。尽管我们患病患儿的毒素取而代之种有规律注意到2019-nCoV形容词,但在华北南部重癫痫患儿的血浆中的仍测定到病毒接种RNA。然而,肺以外测定病毒接种RNA一般而言理论上存在传染性病毒接种,目前尚能不确实在气管道以结构性测定病毒接种RNA的以外科意义。
目前,我们对2019-nCoV接种的以外科范围的认识非常有限。在华北南部,已经媒体报道了诸如轻微的败血症,气管衰竭,急性气管窘迫综合症(ARDS)和心脏损伤等并发癫痫,之以外不幸的后果。然而,举足轻重的是要提醒,这些患病是根据其败血症临床明确的,因此可能会会使调查报告特别强调格以外轻微的结果。
我们的患病患儿最初备注现为轻度咳嗽和低度注意到异常头痛,在生病的第4天没有人腰部X光核查的败血症有可能,而在生病第9天的发展为败血症在此之前,这些非基因表达以外科备注现和癫痫状在早期在以外科上,2019-nCoV接种的以外科更进一步可能会与许多其他常见疾病没有人明显区别于,特别是在冬季气管道病毒接种季节。
另以外,本患病患儿在哮喘的第9天的发展为败血症的时机与近期气管困难的发作(患病后中的位数为8天)赞同。尽管根据患儿的以外科情形恶化尽快是否给予remdesivir慈悲的用作,但仍须要展开随机相比较试验以明确remdesivir和任何其他研究者药物治疗2019-nCoV接种的有效性和适当性。
我们调查报告了英美两国尚能属调查报告的2019-nCoV接种患儿的以外科外观上。
该患病的关键方面之以外患儿在阅读有关更为轻微的公共医疗警告后尽快借此医疗;由当地医疗服务提供者话说明患儿除此以外到南昌的之旅文化日本史,随后在当地,一个州和合众国公共医疗官员之间展开协调;并明确可能会的2019-nCoV接种,从而可以很快强制患儿并随后对2019-nCoV展开实验室话说明,并允许患儿病况恶化全都面性评估和管理机构。
该患病调查报告务实了以外科眼科医生对于任何注意到急性哮喘癫痫状的看病患儿,要总结出除此以外的之旅境况或认识躁郁症的举足轻重性,为了确保适当识别和及时强制可能会遭遇2019-nCoV接种效用的患儿,并努力减少全都面性的传递。
最后,本调查报告务实须要明确与2019-nCoV接种之以外的以外科哮喘,患病中间体和病毒接种脱落持续性时间的
全都部范围和自然文化日本史,以为以外科管理机构和公共医疗决策提供依据。
以下为初海外版
——————
Summary
An outbreak of novel coronirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
On December 31, 2019, China reported a cluster of cases of pneumonia in people associated with the Huanan Seafood Wholesale Market in Wuhan, Hubei Province.
On January 7, 2020, Chinese health authorities confirmed that this cluster was associated with a novel coronirus, 2019-nCoV.
Although cases were originally reported to be associated with exposure to the seafood market in Wuhan, current epidemiologic data indicate that person-to-person transmission of 2019-nCoV is occurring.
As of January 30, 2020, a total of 9976 cases had been reported in at least 21 countries,including the first confirmed case of 2019-nCoV infection in the United States, reported on January 20, 2020.
Investigations are under way worldwide to better understand transmission dynamics and the spectrum of clinical illness.
This report describes the epidemiologic and clinical features of the first case of 2019-nCoV infection confirmed in the United States.
Case Report
On January 19, 2020, a 35-year-old man presented to an urgent care clinic in Snohomish County, Washington, with a 4-day history of cough and subjective fever.
On checking into the clinic, the patient put on a mask in the waiting room. After waiting approximately 20 minutes, he was taken into an examination room and underwent evaluation by a provider. He disclosed that he had returned to Washington State on January 15 after treling to visit family in Wuhan, China.
The patient stated that he had seen a health alert from the U.S. Centers for Disease Control and Prevention (CDC) about the novel coronirus outbreak in China and, because of his symptoms and recent trel, decided to see a health care provider.
Figure 1.Posteroanterior and Lateral Chest Radiographs, January 19, 2020 (Illness Day 4).
Apart from a history of hypertriglyceridemia, the patient was an otherwise healthy nonsmoker. The physical examination revealed a body temperature of 37.2°C, blood pressure of 134/87 mm Hg, pulse of 110 beats per minute, respiratory rate of 16 breaths per minute, and oxygen saturation of 96% while the patient was breathing ambient air. Lung auscultation revealed rhonchi, and chest radiography was performed, which was reported as showing no abnormalities (Figure 1).
A rapid nucleic acid amplification test (NAAT) for influenza A and B was negative. A nasopharyngeal swab specimen was obtained and sent for detection of viral respiratory pathogens by NAAT; this was reported back within 48 hours as negative for all pathogens tested, including influenza A and B, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, and four common coronirus strains known to cause illness in humans (HKU1, NL63, 229E, and OC43).
Given the patient’s trel history, the local and state health departments were immediately notified. Together with the urgent care clinician, the Washington Department of Health notified the CDC Emergency Operations Center.
Although the patient reported that he had not spent time at the Huanan seafood market and reported no known contact with ill persons during his trel to China, CDC staff concurred with the need to test the patient for 2019-nCoV on the basis of current CDC “persons under investigation” case definitions.
Specimens were collected in accordance with CDC guidance and included serum and nasopharyngeal and oropharyngeal swab specimens. After specimen collection, the patient was discharged to home isolation with active monitoring by the local health department.
On January 20, 2020, the CDC confirmed that the patient’s nasopharyngeal and oropharyngeal swabs tested positive for 2019-nCoV by real-time reverse-transcriptase–polymerase-chain-reaction (rRT-PCR) assay.
In coordination with CDC subject-matter experts, state and local health officials, emergency medical services, and hospital leadership and staff, the patient was admitted to an airborne-isolation unit at Providence Regional Medical Center for clinical observation, with health care workers following CDC recommendations for contact, droplet, and airborne precautions with eye protection.
On admission, the patient reported persistent dry cough and a 2-day history of nausea and vomiting; he reported that he had no shortness of breath or chest pain. Vital signs were within normal ranges. On physical examination, the patient was found to he dry mucous membranes. The remainder of the examination was generally unremarkable. After admission, the patient received supportive care, including 2 liters of normal saline and ondansetron for nausea.
Figure 2.Symptoms and Maximum Body Temperatures According to Day of Illness and Day of Hospitalization, January 16 to January 30, 2020.
On days 2 through 5 of hospitalization (days 6 through 9 of illness), the patient’s vital signs remained largely stable, apart from the development of intermittent fevers accompanied by periods of tachycardia (Figure 2).
The patient continued to report a nonproductive cough and appeared fatigued. On the afternoon of hospital day 2, the patient passed a loose bowel movement and reported abdominal discomfort. A second episode of loose stool was reported overnight; a sample of this stool was collected for rRT-PCR testing, along with additional respiratory specimens (nasopharyngeal and oropharyngeal) and serum.
The stool and both respiratory specimens later tested positive by rRT-PCR for 2019-nCoV, whereas the serum remained negative.
Treatment during this time was largely supportive. For symptom management, the patient received, as needed, antipyretic therapy consisting of 650 mg of acetaminophen every 4 hours and 600 mg of ibuprofen every 6 hours. He also received 600 mg of guaifenesin for his continued cough and approximately 6 liters of normal saline over the first 6 days of hospitalization.
Table 1.Clinical Laboratory Results.
The nature of the patient isolation unit permitted only point-of-care laboratory testing initially; complete blood counts and serum chemical studies were ailable starting on hospital day 3.
Laboratory results on hospital days 3 and 5 (illness days 7 and 9) reflected leukopenia, mild thrombocytopenia, and elevated levels of creatine kinase (Table 1).
In addition, there were alterations in hepatic function measures: levels of alkaline phosphatase (68 U per liter), alanine aminotransferase (105 U per liter), aspartate aminotransferase (77 U per liter), and lactate dehydrogenase (465 U per liter) were all elevated on day 5 of hospitalization.
Given the patient’s recurrent fevers, blood cultures were obtained on day 4; these he shown no growth to date.
Figure 3.Posteroanterior and Lateral Chest Radiographs, January 22, 2020 (Illness Day 7, Hospital Day 3).
Figure 4.Posteroanterior Chest Radiograph, January 24, 2020 (Illness Day 9, Hospital Day 5).
A chest radiograph taken on hospital day 3 (illness day 7) was reported as showing no evidence of infiltrates or abnormalities (Figure 3).
However, a second chest radiograph from the night of hospital day 5 (illness day 9) showed evidence of pneumonia in the lower lobe of the left lung (Figure 4).
These radiographic findings coincided with a change in respiratory status starting on the evening of hospital day 5, when the patient’s oxygen saturation values as measured by pulse oximetry dropped to as low as 90% while he was breathing ambient air.
On day 6, the patient was started on supplemental oxygen, delivered by nasal cannula at 2 liters per minute.
Given the changing clinical presentation and concern about hospital-acquired pneumonia, treatment with vancomycin (a 1750-mg loading dose followed by 1 g administered intrenously every 8 hours) and cefepime (administered intrenously every 8 hours) was initiated.
Figure 5.Anteroposterior and Lateral Chest Radiographs, January 26, 2020 (Illness Day 10, Hospital Day 6).
On hospital day 6 (illness day 10), a fourth chest radiograph showed basilar streaky opacities in both lungs, a finding consistent with atypical pneumonia (Figure 5), and rales were noted in both lungs on auscultation.
Given the radiographic findings, the decision to administer oxygen supplementation, the patient’s ongoing fevers, the persistent positive 2019-nCoV RNA at multiple sites, and published reports of the development of severe pneumonia at a period consistent with the development of radiographic pneumonia in this patient, clinicians pursued compassionate use of an investigational antiviral therapy.
Treatment with intrenous remdesivir (a novel nucleotide ogue prodrug in development) was initiated on the evening of day 7, and no adverse events were observed in association with the infusion.
Vancomycin was discontinued on the evening of day 7, and cefepime was discontinued on the following day, after serial negative procalcitonin levels and negative nasal PCR testing for methicillin-resistant Staphylococcus aureus.
On hospital day 8 (illness day 12), the patient’s clinical condition improved. Supplemental oxygen was discontinued, and his oxygen saturation values improved to 94 to 96% while he was breathing ambient air.
The previous bilateral lower-lobe rales were no longer present. His appetite improved, and he was asymptomatic aside from intermittent dry cough and rhinorrhea.
As of January 30, 2020, the patient remains hospitalized. He is afebrile, and all symptoms he resolved with the exception of his cough, which is decreasing in severity.
Methods
SPECIMEN COLLECTIONClinical specimens for 2019-nCoV diagnostic testing were obtained in accordance with CDC guidelines. Nasopharyngeal and oropharyngeal swab specimens were collected with synthetic fiber swabs; each swab was inserted into a separate sterile tube containing 2 to 3 ml of viral transport medium. Serum was collected in a serum separator tube and then centrifuged in accordance with CDC guidelines. The urine and stool specimens were each collected in sterile specimen containers. Specimens were stored between 2°C and 8°C until ready for shipment to the CDC. Specimens for repeat 2019-nCoV testing were collected on illness days 7, 11, and 12 and included nasopharyngeal and oropharyngeal swabs, serum, and urine and stool samples.
DIAGNOSTIC TESTING FOR 2019-NCOV
Clinical specimens were tested with an rRT-PCR assay that was developed from the publicly released virus sequence. Similar to previous diagnostic assays for severe acute respiratory syndrome coronirus (SARS-CoV) and Middle East respiratory syndrome coronirus (MERS-CoV), it has three nucleocapsid gene targets and a positive control target.
A description of this assay and sequence information for the rRT-PCR panel primers and probes are ailable on the CDC Laboratory Information website for 2019-nCoV.
GENETIC SEQUENCING
On January 7, 2020, Chinese researchers shared the full genetic sequence of 2019-nCoV through the National Institutes of Health GenBank database and the Global Initiative on Sharing All Influenza Data (GISAID) database; a report about the isolation of 2019-nCoV was later published.
Nucleic acid was extracted from rRT-PCR–positive specimens (oropharyngeal and nasopharyngeal) and used for whole-genome sequencing on both Sanger and next-generation sequencing platforms (Illumina and MinIon).
Sequence assembly was completed with the use of Sequencher software, version 5.4.6 (Sanger); minimap software, version 2.17 (MinIon); and freebayes software, version 1.3.1 (MiSeq). Complete genomes were compared with the ailable 2019-nCoV reference sequence (GenBank accession number NC_045512.2).
Results
SPECIMEN TESTING FOR 2019-NCOV
Table 2.Results of Real-Time Reverse-Transcriptase–Polymerase-Chain-Reaction Testing for the 2019 Novel Coronirus (2019-nCoV).
The initial respiratory specimens (nasopharyngeal and oropharyngeal swabs) obtained from this patient on day 4 of his illness were positive for 2019-nCoV (Table 2).
The low cycle threshold (Ct) values (18 to 20 in nasopharyngeal specimens and 21 to 22 in oropharyngeal specimens) on illness day 4 suggest high levels of virus in these specimens, despite the patient’s initial mild symptom presentation.
Both upper respiratory specimens obtained on illness day 7 remained positive for 2019-nCoV, including persistent high levels in a nasopharyngeal swab specimen (Ct values, 23 to 24). Stool obtained on illness day 7 was also positive for 2019-nCoV (Ct values, 36 to 38).
Serum specimens for both collection dates were negative for 2019-nCoV. Nasopharyngeal and oropharyngeal specimens obtained on illness days 11 and 12 showed a trend toward decreasing levels of virus. The oropharyngeal specimen tested negative for 2019-nCoV on illness day 12. The rRT-PCR results for serum obtained on these dates are still pending.
GENETIC SEQUENCING
The full genome sequences from oropharyngeal and nasopharyngeal specimens were identical to one another and were nearly identical to other ailable 2019-nCoV sequences.
There were only 3 nucleotides and 1 amino acid that differed at open reading frame 8 between this patient’s virus and the 2019-nCoV reference sequence (NC_045512.2). The sequence is ailable through GenBank (accession number MN985325).
DISCUSSION
Our report of the first confirmed case of 2019-nCoV in the United States illustrates several aspects of this emerging outbreak that are not yet fully understood, including transmission dynamics and the full spectrum of clinical illness.
Our case patient had treled to Wuhan, China, but reported that he had not visited the wholesale seafood market or health care facilities or had any sick contacts during his stay in Wuhan. Although the source of his 2019-nCoV infection is unknown, evidence of person-to-person transmission has been published.
Through January 30, 2020, no secondary cases of 2019-nCoV related to this case he been identified, but monitoring of close contacts continues.
Detection of 2019-nCoV RNA in specimens from the upper respiratory tract with low Ct values on day 4 and day 7 of illness is suggestive of high viral loads and potential for transmissibility.
It is notable that we also detected 2019-nCoV RNA in a stool specimen collected on day 7 of the patient’s illness. Although serum specimens from our case patient were repeatedly negative for 2019-nCoV, viral RNA has been detected in blood in severely ill patients in China.
However, extrapulmonary detection of viral RNA does not necessarily mean that infectious virus is present, and the clinical significance of the detection of viral RNA outside the respiratory tract is unknown at this time.
Currently, our understanding of the clinical spectrum of 2019-nCoV infection is very limited. Complications such as severe pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), and cardiac injury, including fatal outcomes, he been reported in China.
However, it is important to note that these cases were identified on the basis of their pneumonia diagnosis and thus may bias reporting toward more severe outcomes.
Our case patient initially presented with mild cough and low-grade intermittent fevers, without evidence of pneumonia on chest radiography on day 4 of his illness, before hing progression to pneumonia by illness day 9.
These nonspecific signs and symptoms of mild illness early in the clinical course of 2019-nCoV infection may be indistinguishable clinically from many other common infectious diseases, particularly during the winter respiratory virus season. In addition, the timing of our case patient’s progression to pneumonia on day 9 of illness is consistent with later onset of dyspnea (at a median of 8 days from onset) reported in a recent publication.
Although a decision to administer remdesivir for compassionate use was based on the case patient’s worsening clinical status, randomized controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection.
We report the clinical features of the first reported patient with 2019-nCoV infection in the United States.
Key aspects of this case included the decision made by the patient to seek medical attention after reading public health warnings about the outbreak; recognition of the patient’s recent trel history to Wuhan by local providers, with subsequent coordination among local, state, and federal public health officials; and identification of possible 2019-nCoV infection, which allowed for prompt isolation of the patient and subsequent laboratory confirmation of 2019-nCoV, as well as for admission of the patient for further evaluation and management.
This case report highlights the importance of clinicians eliciting a recent history of trel or exposure to sick contacts in any patient presenting for medical care with acute illness symptoms, in order to ensure appropriate identification and prompt isolation of patients who may be at risk for 2019-nCoV infection and to help reduce further transmission.
Finally, this report highlights the need to determine the full spectrum and natural history of clinical disease, pathogenesis, and duration of viral shedding associated with 2019-nCoV infection to inform clinical management and public health decision making.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
This article was published on January 31, 2020, at NEJM.org.
We thank the patient; the nurses and clinical staff who are providing care for the patient; staff at the local and state health departments; staff at the Washington State Department of Health Public Health Laboratories and at the Centers for Disease Control and Prevention (CDC) Division of Viral Disease Laboratory; CDC staff at the Emergency Operations Center; and members of the 2019-nCoV response teams at the local, state, and national levels.
相关新闻
上一页:阑尾炎也是经痛的原因之一
下一页:腹部双热量CT定量技术(下)
相关问答