摘要
在里国武汉开始的新型病原(2019-nCoV)挑起随之蔓延,现已在多个国家所肺炎。我们核查结果了在宾夕法尼亚州核实的首由此可知2019-nCoV接种病症,并描绘了该病症的比对,病人,诊疗更进一步和管理制度,除此以除此以外病病症在病情第9天发挥为肺癌时的刚开始轻度病因。
该案由此可知阐释了诊疗护士与偏远地区,州和合众国各级公共医疗土耳其政府错综复杂密切协作的更进一步,以及必需快速传播者与这种新发接种病病症的看护有关的诊疗信息的消费。
2019年12年末31日,里国核查结果了与常德市武汉市粤东鱼翅批发市场有关的人群里的肺癌病症。
2020年1年末7日,里国医疗土耳其政府核实该簇与新型病原2019-nCoV有关。尽管刚开始新闻报道的病症与武汉市鱼翅市场的去除有关,但当同一时间的流行病学原始数据表格明,早就时有发生2019-nCoV人际传播者。
截至2020年1年末30日,在有数21个国家所/沿海地区核查结果了9976由此可知病症,除此以除此以外2020年1年末20日新闻报道的宾夕法尼亚州首由此可知肺炎的2019-nCoV接种病症。
正因如此球范围内早就顺利未完成核查,以很好地洞察传播者自适应和诊疗哮喘范围。本核查结果描绘了在宾夕法尼亚州核实的首由此可知2019-nCoV接种的流行病学和诊疗特征。
案由此可知核查结果
2020年1年末19日,一名35岁的青年组经常出现在俄勒冈州里德霍米什县的一家诊疗的医院,有4天的呼吸困难和主观发烧史。病人到的医院定期检查时,在候诊室戴上口罩。等待约20分钟后,他被带至定期检查室放弃了提供者的审核。
他透露,他在里国武汉拜访家人紧接著1年末15日回到俄勒冈州。该病病症对此,他已从宾夕法尼亚州哮喘控制与预防里心(CDC)收到有关里国新型病原时个数的保健香港天文台,由于他的病因和不太不太可能的之旅,他要求去看护士。
左图1-2020年1年末19日(哮喘第4天)的后肩部和除此以内侧胸片
除了高三酸酯血病症的躁郁症除此以外,该病病症还是其他保健的不抽烟。体格定期检查警惕到病病症肺部环境氢气时,体温为37.2°C,血压为134/87 mm Hg,节律为每分钟110次,肺部频率为每分钟16次,氧饱和度为96%。肺部听诊显示有支气管炎,并顺利未完成了胸片定期检查,据新闻报道未警惕到经常出现异常(左图1)。
以次型和九一肺癌的快速核酸为了将的测试(NAAT)为同义。授予了颊咽拭子新种,并通过NAAT将其送去检验流感病毒性溃疡病原体。
据新闻报道在48天内内对所有的测试的病原体原则上呈同义,除此以除此以外以次型和九一肺癌,副肺癌,溃疡合胞流感病毒,颊流感病毒,腺流感病毒和已知可能会致使人类哮喘的四种常见病原株(HKU1,NL63、229E和OC43) )。根据病病症的之旅历史,立即事先偏远地区和州医务人员。旧金山医疗部与紧急看护诊疗护士朋友们事先了CDC紧急行动里心。
尽管该病病症核查结果时说他很难去过粤东鱼翅市场,也很难核查结果在去里国之旅期间与患者有任何带入,但哮喘预防控制里心的工作人员对此同意有必要根据当同一时间的哮喘预防控制里心对病病症顺利未完成2019-nCoV的测试。
根据CDC指南得来了8个新种,除此以除此以外抗体,颊咽和口咽拭子新种。新种挖掘出后,病病症被送进家庭封闭,并由当地医务人员顺利未完成不遗余力监测。
2020年1年末20日,哮喘预防控制里心(CDC)核实病病症的颊咽和口咽拭子通过实时亚姆皮利-聚合酶链反应(rRT-PCR)检验为2019-nCoV特征性。
在哮喘预防控制里心的隐喻领域专家,州和偏远地区医疗行政官员,紧急医疗服务以及养老院领导和工作人员的立体化下,病病症被送进新泽西沿海地区医疗里心的氢气封闭病房顺利未完成诊疗仔细观察,并追随哮喘预防控制里心的医护人员有关带入,飞沫和空里防护新政策的建议,并略带面罩。
中风时病病症核查结果小规模呼吸困难,有2天的焦虑和呕吐史。他核查结果时说他很难肺部困难或气喘。人类征状在也就是说范围内。体格定期检查警惕到病病症粘膜高于温。其余的定期检查多半不相对来时说。
中风后,病病症放弃了支持化疗,除此以除此以外2升生理盐水和恩丹以纾缓焦虑。
左图2-根据哮喘日和住院化疗日(2020年1年末16日至2020年1年末30日)的病因和最高体温
在住院化疗的第2至5天(患的第6至9天),病病症的人类征状基本长期依然,除了经常出现间歇性发烧并伴有心动过速(左图2)。病病症之后核查结果非生产性呼吸困难,并经常出现疲倦。
在住院化疗第二天的下午,病病症排尿通畅,腹部不适。清晨有第二次呕吐稀疏的新闻报道。得来该唾液的电子束运用于rRT-PCR的测试,以及其他溃疡新种(颊咽和口咽)和抗体。唾液和两个溃疡新种后来原则上通过rRT-PCR检验为2019-nCoV特征性,而抗体仍为同义。
在此期间的化疗在非常大层面上是近来的。为了顺利未完成病因一处理,病病症必需根据必需放弃解热疗法,该疗法除此以除此以外每4天内650 mg对乙酰一氧化氮基酚和每6天内600 mg布洛芬。在住院化疗的同一时间六天,他还因小规模呼吸困难而注射了600毫克愈创醚友好条约6升生理盐水。
表格1-诊疗实验室结果
病病症封闭单元的性质刚开始仅允许第一时间医疗点实验室的测试;从养老院第3天开始可以顺利未完成正因如此血细胞除此以外和抗体工程学科学研究。
在养老院第3天和第5天(哮喘第7天和第9天)的实验室结果解读出白细胞增大病症,轻度血小板增大病症和肌酸激酶技术水平增高(表格1)。此除此以外,肝功能指标也有所波动:碱性酪氨酸(每升68 U),丙一氧化氮酸一氧化氮基转移酶(每升105 U),天冬一氧化氮酸一氧化氮基转移酶(每升77 U)和代谢脱氢酶(每升465 U)的技术水平共五:在住院化疗的第5天所有增高。鉴于病病症反复发烧,在第4天授予血清培养;迄今为止,这些都很难快速增长。
左图3-2020年1年末22日(面部第7天,养老院第3天)的后肩部和除此以内侧胸片
左图4-2020年1年末24日(面部第5天,养老院第9天)的后肩部X线片
据新闻报道,在养老院第3天(患第7天)拍摄的面部X光片未显示浸润或经常出现异常迹象(左图3)。
但是,从养老院第5天清晨(患第9天)清晨顺利未完成的第二次面部X光片定期检查显示,左肺下叶有肺癌(左图4)。
这些除此以外科警惕到与从养老院第5天清晨开始的肺部状态波动相吻合,当时病病症在肺部周边氢气时通过节律血压饱和度测量的血压饱和度个数降至90%。
在第6天,病病症开始放弃必要一氧化碳,该一氧化碳由颊导管以每分钟2升的速度输运。考虑到诊疗发挥的波动和对养老院授予性肺癌的关注,开始采用抗病毒(1750 mg负荷剂量,然后每8天内肌肉注射1 g)和咪唑吡丙酮(每8天内肌肉注射)化疗。
左图5-同一时间后面部X光片,2020年1年末26日(哮喘第十天,养老院第六天)
在养老院第6天(患第10天),第四次面部X射线拍照显示两个肺里都有基底条状混浊,这一警惕到与非众所周知肺癌相符(左图5),并且在听诊时在两个肺里都经常出现了罗音。鉴于放射治疗除此以外科警惕到,要求得到一氧化碳必要,病病症小规模发烧,多个部位小规模特征性的2019-nCoV RNA特征性,以及发表格了与放射治疗性肺癌拓展一致的严重影响肺癌在该病病症里,诊疗护士富有同情心地采用了科学人文学科类固醇化疗。
肌肉注射瑞德昔韦(一种早就开发的新型核苷酸类似物同一时间药)在第7天清晨开始,但未仔细观察到与肌肉注射有关的不良事件。在对以次氧馨耐药的金黄色葡萄球菌顺利未完成了连续的降钙素原技术水平和颊PCR检验后,在第7天清晨拆去抗病毒,并在第二天拆去咪唑吡丙酮。
在养老院第8天(患第12天),病病症的诊疗状况得到改善。停止必要一氧化碳,他在肺部周边氢气时的氧饱和度个数提高到94%至96%。先同一时间的上部下叶罗音不再共存。他的食欲得到改善,除了间歇性干咳和颊漏除此以外,他很难病因。
截至2020年1年末30日,病病症仍住院化疗。他有呼吸困难,除呼吸困难除此以外,所有病因原则上已纾缓,呼吸困难的层面早就减轻。
工具
新种挖掘出
根据CDC指南授予运用于2019-nCoV病人的测试的诊疗新种。用尼龙拭子得来了12个颊咽和口咽拭子新种。
将每个拭子插入个数得警惕2至3 ml流感病毒转运等离子体的单独无菌管里。将血集在抗体分离管里,然后根据CDC指南顺利未完成离心。血浆和唾液新种分别得来在无菌新种盖子里。电子束在2°C至8°C错综复杂贮存,直到准备好运送至CDC。
在哮喘的第7、11和12天得来了重复顺利未完成的2019-nCoV的测试的新种,除此以除此以外颊咽和口咽拭子,抗体以及血浆和唾液取样。
2019-NCOV的病人的测试
采用从公开场合发布新闻的流感病毒碱基拓展而来的rRT-PCR分析法的测试了诊疗新种。与先同一时间针对重病症急性肺部综合征病原(SARS-CoV)和里东肺部综合征病原(MERS-CoV)的病人工具相似,它具有三个核球状基因索科利夫卡和一个特征性解读索科利夫卡。该测量的描绘为RRT-PCR面板引物和探头和碱基信息里必需的CDC实验室信息网站2019-nCoV上。
遗传测序
2020年1年末7日,里国科学研究人员通过宾夕法尼亚州国立医疗科学科技学院GenBank原始数据库和正因如此球相关联所有肺癌原始数据倡议(GISAID)原始数据库相关联了2019-nCoV的完整基因碱基;随后发布新闻了有关封闭2019-nCoV的核查结果。
从rRT-PCR特征性新种(口咽和颊咽)里提炼出核酸,并在Sanger和下一代测序SDK(Illumina和MinIon)上运用于正因如此基因序列测序。采用5.4.6版的Sequencher软件包(Sanger)未完成了碱基组装。minimap软件包,旧版2.17(MinIon);和freebayes软件包1.3.1版(MiSeq)。将完整基因序列与必需的2019-nCoV详见碱基(GenBank登录号NC_045512.2)顺利未完成比起。
结果
2019-NCOV的新种的测试
表格2-2019年新型病原(2019-nCoV)的实时亚姆皮利-聚合酶-链反应的测试结果
该病病症在患第4天时授予的初始溃疡取样(颊咽拭子和口咽拭子)在2019-nCoV特征性(表格2)。
尽管病病症刚开始发挥为轻度病因,但在哮喘第4天的高于循环电位(Ct)个数(颊咽新种里为18至20,口咽新种里为21至22)表格明这些新种里流感病毒技术水平极高。
在哮喘第7天授予的两个上溃疡新种在2019-nCoV仍依然特征性,除此以除此以外颊咽拭子新种里小规模高技术水平(Ct个数23至24)。在哮喘第7天授予的唾液在2019-nCoV里也特征性(Ct个数为36至38)。两种挖掘出日期的抗体取样在2019-nCoV原则上为同义。
在哮喘第11天和第12天授予的颊咽和口咽新种显示出流感病毒技术水平降高于的趋势。
口咽新种在患第12天的2019-nCoV的测试呈同义。在这些日期授予的抗体的rRT-PCR结果仍未定。
遗传测序
口咽和颊咽新种的完整基因序列碱基彼此不同,并且与其他必需的2019-nCoV碱基几乎不同。
该病病症的流感病毒与2019-nCoV详见碱基(NC_045512.2)在开放阅读凸8一处仅剩3个核苷酸和1个不同。该碱基可通过GenBank授予(登录号MN985325)。
网页
我们关于宾夕法尼亚州首由此可知2019-nCoV肺炎病症的核查结果时说明了这一新兴哮喘的几个总体都已完正因如此洞察,除此以除此以外传播者自适应和诊疗哮喘的正因如此部范围。
我们的病症病病症曾去过里国武汉,但核查结果时说他在武汉期间很难去过鱼翅批发市场或院所,也很难生病的带入。尽管他的2019-nCoV接种的来源尚不明确,但已公开场合了人对人传播者的确凿证据。
到2020年1年末30日,都已警惕到与此病症相关的2019-nCoV继发病症,但仍在密切监视下。
在哮喘的第4天和第7天从上溃疡新种里检验到具有高于Ct个数的2019-nCoV RNA,表格明流感病毒载量高且具有传播者潜力。
个数得警惕的是,我们还在病病症患第7天得来的唾液取样里检验到了2019-nCoV RNA。尽管我们病症病病症的抗体新种反复经常出现2019-nCoV同义,但在里国重病症病病症的血清里仍检验到流感病毒RNA。然而,肺除此以外检验流感病毒RNA其本质意味著共存传染性流感病毒,现阶段尚不明确在溃疡除此以外部检验流感病毒RNA的诊疗意义。
现阶段,我们对2019-nCoV接种的诊疗范围的洞察非常有限。在里国,并未新闻报道了诸如严重影响的肺癌,肺部衰竭,急性肺部窘迫综合征(ARDS)和心脏损伤等并发病症,除此以除此以外致命的后果。然而,重要的是要警惕,这些病症是根据其肺癌病人相符的,因此不太可能可能会使核查结果特别强调更严重影响的结果。
我们的病症病病症刚开始发挥为轻度呼吸困难和高于度间歇性发烧,在患的第4天很难面部X光定期检查的肺癌迹象,而在患第9天拓展为肺癌之同一时间,这些非特异性征状和病因在早期在诊疗上,2019-nCoV接种的诊疗更进一步不太可能与许多其他常见传染病很难相对来时说区别,尤其是在冬季溃疡流感病毒干季。
另除此以外,本病症病病症在哮喘的第9天拓展为肺癌的时机与近期肺部困难的发烧(发病后里位数为8天)一致。尽管根据病病症的诊疗状况恶化要求是不是得到remdesivir慈悲的采用,但仍必需顺利未完成结果显示试验以相符remdesivir和任何其他科学研究药物化疗2019-nCoV接种的安正因如此性和有效性。
我们核查结果了宾夕法尼亚州首由此可知核查结果的2019-nCoV接种病病症的诊疗特征。
该病症的关键总体除此以除此以外病病症在阅读有关时个数的公共医疗警告后要求促使医疗;由当地医疗服务提供者核实病病症不太不太可能到武汉的之旅历史,随后在当地,州和合众国公共医疗行政官员错综复杂顺利未完成协调;并相符不太可能的2019-nCoV接种,从而可以随之封闭病病症并随后对2019-nCoV顺利未完成实验室核实,并允许病病症中风进一步审核和管理制度。
该病症核查结果阐释了诊疗护士对于任何经常出现急性哮喘病因的就诊病病症,要总结出不太不太可能的之旅经历或带入躁郁症的更进一步,为了确保应该识别和及时封闭不太可能面临2019-nCoV接种风险的病病症,并帮助增大进一步的传播者。
最后,本核查结果阐释必需相符与2019-nCoV接种相关的诊疗哮喘,发病衍生物和流感病毒穿孔小规模时间的
正因如此部范围和其本质历史,以为诊疗管理制度和公共医疗权衡提供依据。
以下为英文版
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Summary
An outbreak of novel coronirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
On December 31, 2019, China reported a cluster of cases of pneumonia in people associated with the Huanan Seafood Wholesale Market in Wuhan, Hubei Province.
On January 7, 2020, Chinese health authorities confirmed that this cluster was associated with a novel coronirus, 2019-nCoV.
Although cases were originally reported to be associated with exposure to the seafood market in Wuhan, current epidemiologic data indicate that person-to-person transmission of 2019-nCoV is occurring.
As of January 30, 2020, a total of 9976 cases had been reported in at least 21 countries,including the first confirmed case of 2019-nCoV infection in the United States, reported on January 20, 2020.
Investigations are under way worldwide to better understand transmission dynamics and the spectrum of clinical illness.
This report describes the epidemiologic and clinical features of the first case of 2019-nCoV infection confirmed in the United States.
Case Report
On January 19, 2020, a 35-year-old man presented to an urgent care clinic in Snohomish County, Washington, with a 4-day history of cough and subjective fever.
On checking into the clinic, the patient put on a mask in the waiting room. After waiting approximately 20 minutes, he was taken into an examination room and underwent evaluation by a provider. He disclosed that he had returned to Washington State on January 15 after treling to visit family in Wuhan, China.
The patient stated that he had seen a health alert from the U.S. Centers for Disease Control and Prevention (CDC) about the novel coronirus outbreak in China and, because of his symptoms and recent trel, decided to see a health care provider.
Figure 1.Posteroanterior and Lateral Chest Radiographs, January 19, 2020 (Illness Day 4).
Apart from a history of hypertriglyceridemia, the patient was an otherwise healthy nonsmoker. The physical examination revealed a body temperature of 37.2°C, blood pressure of 134/87 mm Hg, pulse of 110 beats per minute, respiratory rate of 16 breaths per minute, and oxygen saturation of 96% while the patient was breathing ambient air. Lung auscultation revealed rhonchi, and chest radiography was performed, which was reported as showing no abnormalities (Figure 1).
A rapid nucleic acid amplification test (NAAT) for influenza A and B was negative. A nasopharyngeal swab specimen was obtained and sent for detection of viral respiratory pathogens by NAAT; this was reported back within 48 hours as negative for all pathogens tested, including influenza A and B, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, and four common coronirus strains known to cause illness in humans (HKU1, NL63, 229E, and OC43).
Given the patient’s trel history, the local and state health departments were immediately notified. Together with the urgent care clinician, the Washington Department of Health notified the CDC Emergency Operations Center.
Although the patient reported that he had not spent time at the Huanan seafood market and reported no known contact with ill persons during his trel to China, CDC staff concurred with the need to test the patient for 2019-nCoV on the basis of current CDC “persons under investigation” case definitions.
Specimens were collected in accordance with CDC guidance and included serum and nasopharyngeal and oropharyngeal swab specimens. After specimen collection, the patient was discharged to home isolation with active monitoring by the local health department.
On January 20, 2020, the CDC confirmed that the patient’s nasopharyngeal and oropharyngeal swabs tested positive for 2019-nCoV by real-time reverse-transcriptase–polymerase-chain-reaction (rRT-PCR) assay.
In coordination with CDC subject-matter experts, state and local health officials, emergency medical services, and hospital leadership and staff, the patient was admitted to an airborne-isolation unit at Providence Regional Medical Center for clinical observation, with health care workers following CDC recommendations for contact, droplet, and airborne precautions with eye protection.
On admission, the patient reported persistent dry cough and a 2-day history of nausea and vomiting; he reported that he had no shortness of breath or chest pain. Vital signs were within normal ranges. On physical examination, the patient was found to he dry mucous membranes. The remainder of the examination was generally unremarkable. After admission, the patient received supportive care, including 2 liters of normal saline and ondansetron for nausea.
Figure 2.Symptoms and Maximum Body Temperatures According to Day of Illness and Day of Hospitalization, January 16 to January 30, 2020.
On days 2 through 5 of hospitalization (days 6 through 9 of illness), the patient’s vital signs remained largely stable, apart from the development of intermittent fevers accompanied by periods of tachycardia (Figure 2).
The patient continued to report a nonproductive cough and appeared fatigued. On the afternoon of hospital day 2, the patient passed a loose bowel movement and reported abdominal discomfort. A second episode of loose stool was reported overnight; a sample of this stool was collected for rRT-PCR testing, along with additional respiratory specimens (nasopharyngeal and oropharyngeal) and serum.
The stool and both respiratory specimens later tested positive by rRT-PCR for 2019-nCoV, whereas the serum remained negative.
Treatment during this time was largely supportive. For symptom management, the patient received, as needed, antipyretic therapy consisting of 650 mg of acetaminophen every 4 hours and 600 mg of ibuprofen every 6 hours. He also received 600 mg of guaifenesin for his continued cough and approximately 6 liters of normal saline over the first 6 days of hospitalization.
Table 1.Clinical Laboratory Results.
The nature of the patient isolation unit permitted only point-of-care laboratory testing initially; complete blood counts and serum chemical studies were ailable starting on hospital day 3.
Laboratory results on hospital days 3 and 5 (illness days 7 and 9) reflected leukopenia, mild thrombocytopenia, and elevated levels of creatine kinase (Table 1).
In addition, there were alterations in hepatic function measures: levels of alkaline phosphatase (68 U per liter), alanine aminotransferase (105 U per liter), aspartate aminotransferase (77 U per liter), and lactate dehydrogenase (465 U per liter) were all elevated on day 5 of hospitalization.
Given the patient’s recurrent fevers, blood cultures were obtained on day 4; these he shown no growth to date.
Figure 3.Posteroanterior and Lateral Chest Radiographs, January 22, 2020 (Illness Day 7, Hospital Day 3).
Figure 4.Posteroanterior Chest Radiograph, January 24, 2020 (Illness Day 9, Hospital Day 5).
A chest radiograph taken on hospital day 3 (illness day 7) was reported as showing no evidence of infiltrates or abnormalities (Figure 3).
However, a second chest radiograph from the night of hospital day 5 (illness day 9) showed evidence of pneumonia in the lower lobe of the left lung (Figure 4).
These radiographic findings coincided with a change in respiratory status starting on the evening of hospital day 5, when the patient’s oxygen saturation values as measured by pulse oximetry dropped to as low as 90% while he was breathing ambient air.
On day 6, the patient was started on supplemental oxygen, delivered by nasal cannula at 2 liters per minute.
Given the changing clinical presentation and concern about hospital-acquired pneumonia, treatment with vancomycin (a 1750-mg loading dose followed by 1 g administered intrenously every 8 hours) and cefepime (administered intrenously every 8 hours) was initiated.
Figure 5.Anteroposterior and Lateral Chest Radiographs, January 26, 2020 (Illness Day 10, Hospital Day 6).
On hospital day 6 (illness day 10), a fourth chest radiograph showed basilar streaky opacities in both lungs, a finding consistent with atypical pneumonia (Figure 5), and rales were noted in both lungs on auscultation.
Given the radiographic findings, the decision to administer oxygen supplementation, the patient’s ongoing fevers, the persistent positive 2019-nCoV RNA at multiple sites, and published reports of the development of severe pneumonia at a period consistent with the development of radiographic pneumonia in this patient, clinicians pursued compassionate use of an investigational antiviral therapy.
Treatment with intrenous remdesivir (a novel nucleotide ogue prodrug in development) was initiated on the evening of day 7, and no adverse events were observed in association with the infusion.
Vancomycin was discontinued on the evening of day 7, and cefepime was discontinued on the following day, after serial negative procalcitonin levels and negative nasal PCR testing for methicillin-resistant Staphylococcus aureus.
On hospital day 8 (illness day 12), the patient’s clinical condition improved. Supplemental oxygen was discontinued, and his oxygen saturation values improved to 94 to 96% while he was breathing ambient air.
The previous bilateral lower-lobe rales were no longer present. His appetite improved, and he was asymptomatic aside from intermittent dry cough and rhinorrhea.
As of January 30, 2020, the patient remains hospitalized. He is afebrile, and all symptoms he resolved with the exception of his cough, which is decreasing in severity.
Methods
SPECIMEN COLLECTIONClinical specimens for 2019-nCoV diagnostic testing were obtained in accordance with CDC guidelines. Nasopharyngeal and oropharyngeal swab specimens were collected with synthetic fiber swabs; each swab was inserted into a separate sterile tube containing 2 to 3 ml of viral transport medium. Serum was collected in a serum separator tube and then centrifuged in accordance with CDC guidelines. The urine and stool specimens were each collected in sterile specimen containers. Specimens were stored between 2°C and 8°C until ready for shipment to the CDC. Specimens for repeat 2019-nCoV testing were collected on illness days 7, 11, and 12 and included nasopharyngeal and oropharyngeal swabs, serum, and urine and stool samples.
DIAGNOSTIC TESTING FOR 2019-NCOV
Clinical specimens were tested with an rRT-PCR assay that was developed from the publicly released virus sequence. Similar to previous diagnostic assays for severe acute respiratory syndrome coronirus (SARS-CoV) and Middle East respiratory syndrome coronirus (MERS-CoV), it has three nucleocapsid gene targets and a positive control target.
A description of this assay and sequence information for the rRT-PCR panel primers and probes are ailable on the CDC Laboratory Information website for 2019-nCoV.
GENETIC SEQUENCING
On January 7, 2020, Chinese researchers shared the full genetic sequence of 2019-nCoV through the National Institutes of Health GenBank database and the Global Initiative on Sharing All Influenza Data (GISAID) database; a report about the isolation of 2019-nCoV was later published.
Nucleic acid was extracted from rRT-PCR–positive specimens (oropharyngeal and nasopharyngeal) and used for whole-genome sequencing on both Sanger and next-generation sequencing platforms (Illumina and MinIon).
Sequence assembly was completed with the use of Sequencher software, version 5.4.6 (Sanger); minimap software, version 2.17 (MinIon); and freebayes software, version 1.3.1 (MiSeq). Complete genomes were compared with the ailable 2019-nCoV reference sequence (GenBank accession number NC_045512.2).
Results
SPECIMEN TESTING FOR 2019-NCOV
Table 2.Results of Real-Time Reverse-Transcriptase–Polymerase-Chain-Reaction Testing for the 2019 Novel Coronirus (2019-nCoV).
The initial respiratory specimens (nasopharyngeal and oropharyngeal swabs) obtained from this patient on day 4 of his illness were positive for 2019-nCoV (Table 2).
The low cycle threshold (Ct) values (18 to 20 in nasopharyngeal specimens and 21 to 22 in oropharyngeal specimens) on illness day 4 suggest high levels of virus in these specimens, despite the patient’s initial mild symptom presentation.
Both upper respiratory specimens obtained on illness day 7 remained positive for 2019-nCoV, including persistent high levels in a nasopharyngeal swab specimen (Ct values, 23 to 24). Stool obtained on illness day 7 was also positive for 2019-nCoV (Ct values, 36 to 38).
Serum specimens for both collection dates were negative for 2019-nCoV. Nasopharyngeal and oropharyngeal specimens obtained on illness days 11 and 12 showed a trend toward decreasing levels of virus. The oropharyngeal specimen tested negative for 2019-nCoV on illness day 12. The rRT-PCR results for serum obtained on these dates are still pending.
GENETIC SEQUENCING
The full genome sequences from oropharyngeal and nasopharyngeal specimens were identical to one another and were nearly identical to other ailable 2019-nCoV sequences.
There were only 3 nucleotides and 1 amino acid that differed at open reading frame 8 between this patient’s virus and the 2019-nCoV reference sequence (NC_045512.2). The sequence is ailable through GenBank (accession number MN985325).
DISCUSSION
Our report of the first confirmed case of 2019-nCoV in the United States illustrates several aspects of this emerging outbreak that are not yet fully understood, including transmission dynamics and the full spectrum of clinical illness.
Our case patient had treled to Wuhan, China, but reported that he had not visited the wholesale seafood market or health care facilities or had any sick contacts during his stay in Wuhan. Although the source of his 2019-nCoV infection is unknown, evidence of person-to-person transmission has been published.
Through January 30, 2020, no secondary cases of 2019-nCoV related to this case he been identified, but monitoring of close contacts continues.
Detection of 2019-nCoV RNA in specimens from the upper respiratory tract with low Ct values on day 4 and day 7 of illness is suggestive of high viral loads and potential for transmissibility.
It is notable that we also detected 2019-nCoV RNA in a stool specimen collected on day 7 of the patient’s illness. Although serum specimens from our case patient were repeatedly negative for 2019-nCoV, viral RNA has been detected in blood in severely ill patients in China.
However, extrapulmonary detection of viral RNA does not necessarily mean that infectious virus is present, and the clinical significance of the detection of viral RNA outside the respiratory tract is unknown at this time.
Currently, our understanding of the clinical spectrum of 2019-nCoV infection is very limited. Complications such as severe pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), and cardiac injury, including fatal outcomes, he been reported in China.
However, it is important to note that these cases were identified on the basis of their pneumonia diagnosis and thus may bias reporting toward more severe outcomes.
Our case patient initially presented with mild cough and low-grade intermittent fevers, without evidence of pneumonia on chest radiography on day 4 of his illness, before hing progression to pneumonia by illness day 9.
These nonspecific signs and symptoms of mild illness early in the clinical course of 2019-nCoV infection may be indistinguishable clinically from many other common infectious diseases, particularly during the winter respiratory virus season. In addition, the timing of our case patient’s progression to pneumonia on day 9 of illness is consistent with later onset of dyspnea (at a median of 8 days from onset) reported in a recent publication.
Although a decision to administer remdesivir for compassionate use was based on the case patient’s worsening clinical status, randomized controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection.
We report the clinical features of the first reported patient with 2019-nCoV infection in the United States.
Key aspects of this case included the decision made by the patient to seek medical attention after reading public health warnings about the outbreak; recognition of the patient’s recent trel history to Wuhan by local providers, with subsequent coordination among local, state, and federal public health officials; and identification of possible 2019-nCoV infection, which allowed for prompt isolation of the patient and subsequent laboratory confirmation of 2019-nCoV, as well as for admission of the patient for further evaluation and management.
This case report highlights the importance of clinicians eliciting a recent history of trel or exposure to sick contacts in any patient presenting for medical care with acute illness symptoms, in order to ensure appropriate identification and prompt isolation of patients who may be at risk for 2019-nCoV infection and to help reduce further transmission.
Finally, this report highlights the need to determine the full spectrum and natural history of clinical disease, pathogenesis, and duration of viral shedding associated with 2019-nCoV infection to inform clinical management and public health decision making.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
This article was published on January 31, 2020, at NEJM.org.
We thank the patient; the nurses and clinical staff who are providing care for the patient; staff at the local and state health departments; staff at the Washington State Department of Health Public Health Laboratories and at the Centers for Disease Control and Prevention (CDC) Division of Viral Disease Laboratory; CDC staff at the Emergency Operations Center; and members of the 2019-nCoV response teams at the local, state, and national levels.
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