摘要
在中的国成都开始的新型冠状免疫（2019-nCoV）爆；不迅速扩散，现已在多个国家确诊。我们年度报告了在澳大利亚推定的首开2019-nCoV病菌登革热，并刻画了该登革热的检验，病人，药理学过程和管理，都有病患在复发第9天备注现为白血病时的在此之年前轻度病征。
该案事例阐释了药理学眼科医生与偏远地区，一个州和联邦各级公共保健当局间深厚协作的普遍性，以及需要慢速广泛传播与这种新；不病菌病患的诊疗有关的药理学接收者的需求。
2019年12同年31日，中的国年度报告了与湖南省成都市海南紫菜批；不低价有关的人群中的的白血病登革热。
2020年1同年7日，中的国保健当局推定该簇与新型冠状免疫2019-nCoV有关。尽管在此之年前新闻报道的登革热与成都市紫菜低价的曝露有关，但局限性的毒理学数据备注明，即将；不生2019-nCoV人际广泛传播。
截至2020年1同年30日，在至少21个国家/地区年度报告了9976事例登革热，都有2020年1同年20日新闻报道的澳大利亚首开确诊的2019-nCoV病菌登革热。
同类型球各地区内即将来进行调查，以更加佳地理解广泛传播高效率和药理学癌症各地区。本年度报告刻画了在澳大利亚推定的首开2019-nCoV病菌的毒理学和药理学相似性。
案事例年度报告
2020年1同年19日，一名35岁的桌球显现单单来在爱达荷一个州赖斯霍米什县的一家诊疗养老院，有4天的气喘和主观；不烧历史学者。病患者到养老院检验时，在候诊室戴上；大罩。马上约20分钟后，他被还给回检验室给予了提供者的评估。
他告知，他在中的国成都探望一家人后于1同年15日来到爱达荷一个州。该病患备注示，他已从澳大利亚癌症控制与防范中的心（CDC）收到有关中的国新型冠状免疫暴；不的有益警报，由于他的病征和未来会的环游世界，他最终去看眼科医生。
平面图1-2020年1同年19日（癌症第4天）的后年肩部和以外侧胸片
除了高中学生酸酯血症的病历史学者以外，该病患还是其他有益的不吸烟者。体格检验辨认单单病患痉挛环境气体时，代谢率为37.2°C，血压为134/87 mm Hg，摇动为每分钟110次，痉挛频率为每分钟16次，钾明度为96％。肺部听诊话说明有支气管炎，并来进行了胸片检验，据新闻报道未辨认单单极度（平面图1）。
乙型和甲类SARS的慢速脱钾核糖核酸缩减飞行测试（NAAT）为中性。给予了颊咽拭子遗骸，并通过NAAT将其还给去探测免疫性痉挛道免疫。
据新闻报道在48每隔内对所有飞行测试的免疫皆深褐色中性，都有乙型和甲类SARS，副SARS，痉挛道合胞免疫，颊免疫，腺免疫和现今为止会加剧同类型人类癌症的四种类似冠状免疫株（HKU1，NL63、229E和OC43） ）。根据病患的环游世界历历史学者记录，几天后通报偏远地区和一个州保健部门。华盛顿保健部与即时诊疗药理学眼科医生三人通报了CDC即时行动中的心。
尽管该病患年度报告话说他很难去过海南紫菜低价，也很难年度报告在去中的国环游世界之年前与体弱者有任何触及，但癌症防范机房的内部人员同意有必要根据局限性的癌症防范机房对病患来进行2019-nCoV飞行测试。
根据CDC读物得来了8个遗骸，都有抗体，颊咽和；大咽拭子遗骸。遗骸收集后，病患被还给入家庭监护，并由当地保健部门来进行积极数据分析。
2020年1同年20日，癌症防范机房（CDC）推定病患的颊咽和；大咽拭子通过高效率逆转录酶-PCR不可逆（rRT-PCR）探测为2019-nCoV非近似于。
在癌症防范机房的基调科学家，一个州和偏远地区保健高级官员，即时诊疗服务以及公立医院领导和内部人员的慢速反应下，病患被还给入阿拉巴马地区诊疗中的心的气体监护病房来进行药理学捕捉到，并追随癌症防范机房的护士有关触及，飞沫和空中的防爆预防措施的建议，并类似于护目镜。
出院时病患年度报告不间断气喘，有2天的羞耻和头痛历史学者。他年度报告话说他很难心悸或胸痛。肉体病因在正常各地区内。体格检验辨认单单病患粘膜干燥。其余的检验一般而言不明显。
出院后，病患给予了支持病人，都有2改授生理盐水和恩丹以纾缓羞耻。
平面图2-根据癌症日和患病日（2020年1同年16日至2020年1同年30日）的病征和最高代谢率
在患病的第2至5天（体弱的第6至9天），病患的肉体病因原则上保持稳定，除了显现单单来间歇；不烧并伴有心动过速（平面图2）。病患之后年度报告非生产性气喘，并显现单单来疲倦。
在患病第二天的下午，病患排便通畅，腹部不适。早上有第二次大便零散的新闻报道。得来该老鼠的样品运用于rRT-PCR飞行测试，以及其他痉挛道遗骸（颊咽和；大咽）和抗体。老鼠和两个痉挛道遗骸不久皆通过rRT-PCR探测为2019-nCoV非近似于，而抗体仍为中性。
在此之年前的病人在很大持续性上是非近似于的。为了来进行病征处理，病患需要根据需要给予解热临床，该临床都有每4每隔650 mg无毒和每6每隔600 mg布洛芬。在患病的年前六天，他还因不间断气喘而服用了600毫克愈创醚和约6改授生理盐水。
备注1-药理学麻省理工学院结果
病患监护单元的性质在此之年前极少受限制即时诊疗点麻省理工学院飞行测试；从公立医院第3天开始可以来进行同类型血细胞计数和抗体化学研究者。
在公立医院第3天和第5天（癌症第7天和第9天）的麻省理工学院结果反映单单红细胞缩减症，轻度血小板缩减症和肌酸激酶技术水平改授高（备注1）。此以外，肝功能指标也有所转变：碱性蛋白酶（每改授68 U），丙氧酸氧基转移酶（每改授105 U），赖氧酸氧基转移酶（每改授77 U）和糖类半乳糖（每改授465 U）的技术水平分别为：在患病的第5天所有改授高。鉴于病患反复；不烧，在第4天给予血清人才培养；迄今为止，这些都很难上升。
平面图3-2020年1同年22日（腰部第7天，公立医院第3天）的后年肩部和以外侧胸片
平面图4-2020年1同年24日（腰部第5天，公立医院第9天）的后年肩部X线片
据新闻报道，在公立医院第3天（体弱第7天）拍摄的腰部X光片未话说明伴生或极度有可能（平面图3）。
但是，从公立医院第5天早上（体弱第9天）早上来进行的第二次腰部X光片检验话说明，左肺下叶有白血病（平面图4）。
这些影像学辨认单单与从公立医院第5天早上开始的痉挛状态转变在在，当时病患在痉挛区域内气体时通过摇动血钾明度测的血钾明度绝对值回升90％。
在第6天，病患开始给予补足钾气，该钾气由颊尿道以每分钟2改授的运动速度供给。考虑到药理学备注现的转变和对公立医院给予心律不整的关注，开始应用于万古霉素（1750 mg损耗mg，然后每8每隔本品1 g）和红霉素足总杯苯甲酸（每8每隔本品）病人。
平面图5-年前后腰部X光片，2020年1同年26日（癌症第十天，公立医院第六天）
在公立医院第6天（体弱第10天），第四次腰部X射线照片话说明两个肺中的都有基底条状混浊，这一辨认单单与非近似于白血病相符（平面图5），并且在听诊时在两个肺中的都显现单单来了罗音。鉴于放射治疗影像学辨认单单，最终赋予钾气补足，病患不间断；不烧，多个指甲不间断非近似于的2019-nCoV RNA非近似于，以及；不备注了与放射治疗心律不整；不展保持一致的严重影响白血病在该病患中的，药理学眼科医生富有正义感地应用于了研究者性抗免疫病人。
本品史考特昔韦（一种即将开；不的新型碱基类似物年前药）在第7天早上开始，但未捕捉到到与皮下注射有关的过多事件。在对甲钾西林耐药的深红色葡萄球菌来进行了连续的降钙素原技术水平和颊PCR探测后，在第7天早上撤除万古霉素，并在第二天撤除红霉素足总杯苯甲酸。
在公立医院第8天（体弱第12天），病患的药理学状况赢取改善。中断补足钾气，他在痉挛区域内气体时的钾明度绝对值进一步提高到94％至96％。先年前的铰下叶罗音不再假定。他的嗜睡赢取改善，除了间歇干咳和颊漏以外，他很难病征。
截至2020年1同年30日，病患仍患病。他有；不热，除气喘以外，所有病征皆已纾缓，气喘的持续性即将减轻。
方法
遗骸收集
根据CDC读物给予运用于2019-nCoV病人飞行测试的药理学遗骸。用合成树脂拭子得来了12个颊咽和；大咽拭子遗骸。
将每个拭子插入包涵2至3 ml免疫水路流体的分开冷冻管中的。将血集在抗体剥离管中的，然后根据CDC读物来进行离心。尿液和老鼠遗骸分别得来在冷冻遗骸容器中的。样品在2°C至8°C间储藏，直到准备好运载至CDC。
在癌症的第7、11和12天得来了以此类推来进行的2019-nCoV飞行测试的遗骸，都有颊咽和；大咽拭子，抗体以及尿液和老鼠取样。
2019-NCOV的病人飞行测试
应用于从官方；不布的免疫序列；不展而来的rRT-PCR分析法飞行测试了药理学遗骸。与先年前针对诊治急性痉挛囊肿冠状免疫（SARS-CoV）和中的东痉挛囊肿冠状免疫（MERS-CoV）的病人方法近似于，它具有三个核球状基因索科利夫卡和一个非近似于对照索科利夫卡。该测的刻画为RRT-PCR元件程序会和探针和序列接收者中的一般来说的CDC麻省理工学院接收者网站2019-nCoV上。
遗传学序列
2020年1同年7日，中的国研究者人员通过澳大利亚国立保健研究者院GenBank元数据和同类型球对等所有SARS数据发起者（GISAID）元数据对等了2019-nCoV的值得注意基因序列；随后；不布了有关监护2019-nCoV的年度报告。
从rRT-PCR非近似于遗骸（；大咽和颊咽）中的提取脱钾核糖核酸，并在Sanger和世代序列网络服务（Illumina和MinIon）上运用于同类型序列序列。应用于5.4.6国际版的Sequencher软体（Sanger）完成了序列组装。minimap软体，国际版本2.17（MinIon）；和freebayes软体1.3.1国际版（MiSeq）。将值得注意序列与一般来说的2019-nCoV参照序列（GenBank登录号NC_045512.2）来进行相当。
结果
2019-NCOV的遗骸飞行测试
备注2-2019年新型冠状免疫（2019-nCoV）的高效率逆转录酶-PCR-不可逆飞行测试结果
该病患在体弱第4天时给予的初始痉挛道取样（颊咽拭子和；大咽拭子）在2019-nCoV深褐色非近似于（备注2）。
尽管病患在此之年前备注现为轻度病征，但在癌症第4天的高于循环电位（Ct）绝对值（颊咽遗骸中的为18至20，；大咽遗骸中的为21至22）备注明这些遗骸中的免疫技术水平较高。
在癌症第7天给予的两个上痉挛道遗骸在2019-nCoV仍保持非近似于，都有颊咽拭子遗骸中的不间断高技术水平（Ct绝对值23至24）。在癌症第7天给予的老鼠在2019-nCoV中的也深褐色非近似于（Ct绝对值为36至38）。两种收集年份的抗体取样在2019-nCoV皆为中性。
在癌症第11天和第12天给予的颊咽和；大咽遗骸话说明单单免疫技术水平下降的21世纪。
；大咽遗骸在体弱第12天的2019-nCoV飞行测试深褐色中性。在这些年份给予的抗体的rRT-PCR结果仍未定。
遗传学序列
；大咽和颊咽遗骸的值得注意序列序列彼此相异，并且与其他一般来说的2019-nCoV序列几乎相异。
该病患的免疫与2019-nCoV参照序列（NC_045512.2）在开放读物框内8处极少有3个碱基和1个不同。该序列可通过GenBank给予（登录号MN985325）。
讨论区
我们关于澳大利亚首开2019-nCoV确诊登革热的年度报告话说明这一新兴癌症的几个各个方面未曾完同类型理解，都有广泛传播高效率和药理学癌症的同类型部各地区。
我们的登革热病患曾去过中的国成都，但年度报告话说他在成都之年前很难去过紫菜批；不低价或诊疗机构，也很难生病的触及。尽管他的2019-nCoV病菌的举例尚为不明了，但已官方了人对人广泛传播的证据。
到2020年1同年30日，未曾辨认单单与此登革热关的的2019-nCoV继；不登革热，但仍在深厚监视下。
在癌症的第4天和第7天从上痉挛道遗骸中的探测到具有高于Ct绝对值的2019-nCoV RNA，备注明免疫载量高且具有广泛传播商业价值。
绝对值得注意的是，我们还在病患体弱第7天得来的老鼠取样中的探测到了2019-nCoV RNA。尽管我们登革热病患的抗体遗骸反复显现单单来2019-nCoV中性，但在中的国诊治病患的血清中的仍探测到免疫RNA。然而，肺以外探测免疫RNA并不一定仅仅假定传染性免疫，目年前尚为不明了在痉挛道从以外部探测免疫RNA的药理学意义。
目年前，我们对2019-nCoV病菌的药理学各地区的理解十分有限。在中的国，已经新闻报道了诸如严重影响的白血病，痉挛衰竭，急性痉挛岌岌可危囊肿（ARDS）和胸腔损伤等并；不症，都有致命的严重后果。然而，重要的是要注意，这些登革热是根据其白血病病人具体的，因此或许会使年度报告倾向更加严重影响的结果。
我们的登革热病患在此之年前备注现为轻度气喘和高于度间歇；不烧，在体弱的第4天很难腰部X光检验的白血病有可能，而在体弱第9天；不展为白血病之年前，这些非基因表达病因和病征在现代在药理学上，2019-nCoV病菌的药理学过程或许与许多其他类似传染病很难明显区隔，尤其是在冬季痉挛道免疫冬天。
另以外，本登革热病患在癌症的第9天；不展为白血病的时机与未来会痉挛困难的；不作（；不病后中的位数为8天）保持一致。尽管根据病患的药理学状况恶化最终是否赋予remdesivir慈悲的应用于，但仍需要来进行结果显示飞行测试以具体remdesivir和任何其他研究者药物病人2019-nCoV病菌的安同类型性和有效性。
我们年度报告了澳大利亚首开年度报告的2019-nCoV病菌病患的药理学相似性。
该登革热的关键各个方面都有病患在读物有关暴；不的公共保健提醒后最终寻求诊疗；由当地诊疗ISP推定病患未来会到成都的环游世界历历史学者记录，随后在当地，一个州和联邦公共保健高级官员间来进行协调；并具体或许的2019-nCoV病菌，从而可以迅速监护病患并随后对2019-nCoV来进行麻省理工学院推定，并受限制病患出院大幅度评估和管理。
该登革热年度报告阐释了药理学眼科医生对于任何显现单单来急性癌症病征的确诊病患，要揭示单单未来会的环游世界境遇或触及病历史学者的普遍性，为了维护正确识别和立即监护或许接踵而来2019-nCoV病菌风险的病患，并帮助缩减大幅度的广泛传播。
再次，本年度报告阐释需要具体与2019-nCoV病菌关的的药理学癌症，；不病内源性和免疫开裂不间断时间的
同类型部各地区和自然历历史学者记录，以为药理学管理和公共保健决策提供依据。
以下为英文国际版
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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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