摘要
在中都国成都开始的新型病原（2019-nCoV）爆发促使延烧，现已在多个国家所确诊。我们调查报告了在澳大利亚确定的首例2019-nCoV感染者流感，并真是明了了该流感的鉴定，治疗，医学更加进一步和管理，最主要患儿在病情第9天体现为心肌梗塞时的起初轻度疼痛。
该近来强调了医学医师与地方，一个州和合众国各级公共医疗卫生当局之间密切协作的不可忽视性，以及需要短时间传播者与这种新发感染者患儿的护理有关的医学资讯的需求。
2019年12年末31日，中都国调查报告了与湖北省成都市华南鱼肉菜市场有关的人群中都的心肌梗塞流感。
2020年1年末7日，中都国医疗卫生当局确定该簇与新型病原2019-nCoV有关。尽管起初路透社的流感与成都市鱼肉市场的暴露有关，但当前的流行病学数据注记明，刚刚发生2019-nCoV人际传播者。
截至2020年1年末30日，在至少21个国家所/沿海地区调查报告了9976例流感，最主要2020年1年末20日路透社的澳大利亚首例确诊的2019-nCoV感染者流感。
世界区域刚刚同步进行调查，以更加好地探究传播者实时和医学疟疾之内。本调查报告真是明了了在澳大利亚确定的首例2019-nCoV感染者的流行病学和医学特征。
近来调查报告
2020年1年末19日，一名35岁的男子显现出新在华盛顿一个州华莱士霍米什县的一家医护诊所，有4天的气喘和主观呼吸困难文化史。病人到诊所定期检查时，在候诊室戴上口外罩。等待约20分钟后，他被带回定期检查室给与了提供商的风险评估。
他透露，他在中都国成都探视家人元月1年末15日留在华盛顿一个州。该患儿问到，他已从澳大利亚疟疾控制与防范中都心（CDC）寄送有关中都国新型病原愈演愈烈的健康警报，由于他的疼痛和最近的旅程，他要求去看医师。
左图1-2020年1年末19日（疟疾第4天）的后脸部和另有侧胸片
除了高三酸酯缺乏症的阿兹海默另有，该患儿还是其他健康的不吸烟者。体格定期检查发掘出新患儿肺部环境空气时，体温为37.2°C，腹水为134/87 mm Hg，颤抖为每分钟110次，肺部频率为每分钟16次，氧相对于为96％。肺部听诊推测有支气管炎，并同步进行了胸片定期检查，据路透社未能发掘出新反常（左图1）。
流感和乙型禽流感的短时间核酸扩增检验（NAAT）为比如真是。赢取了颊咽拭子骨骸，并通过NAAT将其送去去定期检查病原性肺部道菌株。
据路透社在48天内内对所有检验的菌株仅圆形比如真是，最主要流感和乙型禽流感，副禽流感，肺部道合胞病原，颊病原，腺病原和已知亦会所致人类疟疾的四种相似病原株（HKU1，NL63、229E和OC43） ）。根据患儿的旅程历文化史，第一时间通告地方和一个州医疗卫生部门。华盛顿医疗卫生部与即时护理医学医师一起通告了CDC即时行动中都心。
尽管该患儿调查报告真是他不能去过华南鱼肉市场，也不能调查报告在去中都国旅程之后与病危者有任何带入，但疟疾防范控制中都心的人员同意有必要根据当前的疟疾防范控制中都心对患儿同步进行2019-nCoV检验。
根据CDC手册采集了8个骨骸，最主要胰岛素，颊咽和口外咽拭子骨骸。骨骸采集后，患儿被送去往家庭分离，并由当地医疗卫生部门同步进行积极定期检查。
2020年1年末20日，疟疾防范控制中都心（CDC）确定患儿的颊咽和口外咽拭子通过数据管控亚姆皮利-聚合酶不可逆（rRT-PCR）定期检查为2019-nCoV中性。
在疟疾防范控制中都心的主题专家，一个州和地方医疗卫生官员，即时医疗卫生服务以及的医院主导和人员的配合下，患儿被送去往普罗维登斯沿海地区医疗卫生中都心的空气分离病房同步进行医学仔细观察，并随同疟疾防范控制中都心的医护人员有关带入，飞沫和高于空防护措施的建议，并带有护目镜。
康复时患儿调查报告过后气喘，有2天的舒服和呕吐文化史。他调查报告真是他不能肺部急促或胸痛。一个人征状在经常性区域。体格定期检查发掘出新患儿粘膜干燥。其余的定期检查并不一定不数值得留意。
康复后，患儿给与了支持治疗，最主要2升生理盐水和恩丹以缓解舒服。
左图2-根据疟疾日和患病日（2020年1年末16日至2020年1年末30日）的疼痛和最高体温
在患病的第2至5天（病危的第6至9天），患儿的一个人征状理论上保持稳定，除了显现出新暂时性呼吸困难并伴有心动过速（左图2）。患儿继续调查报告非生产性气喘，并显现出新筋疲力尽。
在患病第二天的下午，患儿排便通畅，腹部不适。中都午有第二次大便稀疏的路透社。采集该排泄物的探针用于rRT-PCR检验，以及其他肺部道骨骸（颊咽和口外咽）和胰岛素。排泄物和两个肺部道骨骸后来仅通过rRT-PCR定期检查为2019-nCoV中性，而胰岛素仍为比如真是。
在此之后的治疗在很大程度上是开放性的。为了同步进行疼痛管控，患儿需要根据需要给与解热麻醉药，该麻醉药最主要每4天内650 mg对乙酰尿素基酚和每6天内600 mg布洛芬。在患病的前六天，他还因过后气喘而服用了600毫克愈创醚和约6升生理盐水。
注记1-医学实验室结果
患儿分离短剧的并不一定起初仅允许即时医疗卫生点实验室检验；从的医院第3天开始可以同步进行全部都是血细胞计数和胰岛素无机化学研究。
在的医院第3天和第5天（疟疾第7天和第9天）的实验室结果反映出新白细胞减高于症，轻度白血球减高于症和肌酸激酶总体下降（注记1）。此另有，肝功能加权也有所变化：极性甘尿素酸（每升68 U），丙尿素酸尿素基转移酶（每升105 U），天冬尿素酸尿素基转移酶（每升77 U）和乳酸转移酶（每升465 U）的总体分别为：在患病的第5天所有下降。鉴于患儿反复呼吸困难，在第4天赢取肝脏培养；当今，这些都不能增长速度。
左图3-2020年1年末22日（脸部第7天，的医院第3天）的后脸部和另有侧胸片
左图4-2020年1年末24日（脸部第5天，的医院第9天）的后脸部X线片
据路透社，在的医院第3天（病危第7天）拍摄的脸部X光片未能推测浸润或反常迹象（左图3）。
但是，从的医院第5天中都午（病危第9天）中都午同步进行的第二次脸部X光片定期检查推测，左肺下叶有心肌梗塞（左图4）。
这些影像学发掘出新与从的医院第5天中都午开始的肺部状态变化相符，之前患儿在肺部周围空气时通过颤抖血氧相对于测出的血氧相对于数值降至90％。
在第6天，患儿开始给与不足之处氧，该氧由颊导管以每分钟2升的速度输运去。顾及医学体现的变化和对的医院赢取性心肌梗塞的关注，开始用作本品（1750 mg承受剂量，然后每8天内静脉注射1 g）和头孢两场苯基（每8天内静脉注射）治疗。
左图5-前后脸部X光片，2020年1年末26日（疟疾第十天，的医院第六天）
在的医院第6天（病危第10天），第四次脸部X射线照片推测两个肺中都都有基底夹较深，这一发掘出新与非典型心肌梗塞大不不尽相同（左图5），并且在听诊时在两个肺中都都显现出新了罗音。鉴于放射源影像学发掘出新，要求给予氧不足之处，患儿过后呼吸困难，多个部位过后中性的2019-nCoV RNA中性，以及发注记了与放射源性心肌梗塞转变赞同的严重心肌梗塞在该患儿中都，医学医师富裕同情心地用作了研究性抗病原治疗。
静脉注射瑞德昔韦（一种刚刚开发的新型残基类似物前药）在第7天中都午开始，但未能仔细观察到与输注有关的不良事件。在对甲氧西林耐药的金黄色葡萄球菌同步进行了近十年的降钙素原总体和颊PCR定期检查后，在第7天中都午停止使用本品，并在第二天停止使用头孢两场苯基。
在的医院第8天（病危第12天），患儿的医学过后性得到有所改善。停顿不足之处氧，他在肺部周围空气时的氧相对于数值进一步提高到94％至96％。早先的双侧下叶罗音不再存在。他的食欲得到有所改善，除了暂时性干咳和颊漏另有，他不能疼痛。
截至2020年1年末30日，患儿仍患病。他有气喘，除气喘另有，所有疼痛仅已缓解，气喘的程度刚刚大大降高于。
方法
骨骸采集
根据CDC手册赢取用于2019-nCoV治疗检验的医学骨骸。用合成纤维拭子采集了12个颊咽和口外咽拭子骨骸。
将每个拭子插入包含2至3 ml病原海上运输微粒的实质上无菌将水都。将血集在胰岛素分离将水都，然后根据CDC手册同步进行离心。尿液和排泄物骨骸分别采集在无菌骨骸容器中都。探针在2°C至8°C之间储存，直到准备好运输去至CDC。
在疟疾的第7、11和12天采集了重复同步进行的2019-nCoV检验的骨骸，最主要颊咽和口外咽拭子，胰岛素以及尿液和排泄物样品。
2019-NCOV的治疗检验
用作从官方公布的病原碱基转变而来的rRT-PCR分析法检验了医学骨骸。与早先针对加护急性肺部囊肿病原（SARS-CoV）和中都东肺部囊肿病原（MERS-CoV）的治疗方法相似，它具三个核核酸蛋白质靶标和一个中性对照靶标。该测出的真是明了为RRT-PCR面板引物和探针和碱基资讯中都必需的CDC实验室资讯网页2019-nCoV上。
基因PCR
2020年1年末7日，中都国研究人员通过澳大利亚国立医疗卫生研究院GenBank数据源和世界相关联所有禽流感数据倡议（GISAID）数据源相关联了2019-nCoV的清晰蛋白质碱基；随后公布了有关分离2019-nCoV的调查报告。
从rRT-PCR中性骨骸（口外咽和颊咽）中都分离出新核酸，并在Sanger和下一代PCR平台（Illumina和MinIon）上用于全部都是蛋白质组PCR。用作5.4.6版的Sequencher操作系统（Sanger）完成了碱基成品。minimap操作系统，版本2.17（MinIon）；和freebayes操作系统1.3.1版（MiSeq）。将清晰蛋白质组与必需的2019-nCoV参考碱基（GenBank登录号NC_045512.2）同步进行比较。
结果
2019-NCOV的骨骸检验
注记2-2019年新型病原（2019-nCoV）的数据管控亚姆皮利-聚合酶-不可逆检验结果
该患儿在病危第4天时赢取的初始肺部道样品（颊咽拭子和口外咽拭子）在2019-nCoV圆形中性（注记2）。
尽管患儿起初体现为轻度疼痛，但在疟疾第4天的高于循环阈数值（Ct）数值（颊咽骨骸中都为18至20，口外咽骨骸中都为21至22）注记明这些骨骸中都病原总体较差。
在疟疾第7天赢取的两个上肺部道骨骸在2019-nCoV仍保持中性，最主要颊咽拭子骨骸中都过后高总体（Ct数值23至24）。在疟疾第7天赢取的排泄物在2019-nCoV中都也圆形中性（Ct数值为36至38）。两种采集日期的胰岛素样品在2019-nCoV仅为比如真是。
在疟疾第11天和第12天赢取的颊咽和口外咽骨骸推测出新病原总体下降的急遽。
口外咽骨骸在病危第12天的2019-nCoV检验圆形比如真是。在这些日期赢取的胰岛素的rRT-PCR结果仍未能定。
基因PCR
口外咽和颊咽骨骸的清晰蛋白质组碱基彼此不尽相同，并且与其他必需的2019-nCoV碱基几乎不尽相同。
该患儿的病原与2019-nCoV参考碱基（NC_045512.2）在新开选读框8处仅有3个残基和1个不同。该碱基可通过GenBank赢取（登录号MN985325）。
专页
我们关于澳大利亚首例2019-nCoV确诊流感的调查报告真是明了这一新兴疟疾的几个之外亦然未能几乎部都是探究，最主要传播者实时和医学疟疾的全部都是部之内。
我们的流感患儿曾去过中都国成都，但调查报告真是他在成都之后不能去过鱼肉菜市场或医疗卫生机构，也不能患病的带入。尽管他的2019-nCoV感染者的来源亦然不清楚，但已官方了人对人传播者的证据。
到2020年1年末30日，亦然未能发掘出新与此流感之外的2019-nCoV继发流感，但仍在密切监视下。
在疟疾的第4天和第7天从上肺部道骨骸中都定期检查到具高于Ct数值的2019-nCoV RNA，注记明病原载量高且具传播者发展前景。
数值得留意的是，我们还在患儿病危第7天采集的排泄物样品中都定期检查到了2019-nCoV RNA。尽管我们流感患儿的胰岛素骨骸反复显现出新2019-nCoV比如真是，但在中都国加护患儿的肝脏中都仍定期检查到病原RNA。然而，肺另有定期检查病原RNA并不一定意味著存在传染性病原，目前亦然不清楚在肺部道另有部定期检查病原RNA的医学意义。
目前，我们对2019-nCoV感染者的医学之内的探究极为有限。在中都国，早已路透社了诸如严重的心肌梗塞，肺部衰竭，急性肺部窘迫囊肿（ARDS）和心脏挫伤等并发症，最主要致命的后果。然而，不可忽视的是要留意，这些流感是根据其心肌梗塞治疗未能确定的，因此确实亦会使调查报告偏向更加严重的结果。
我们的流感患儿起初体现为轻度气喘和高于度暂时性呼吸困难，在病危的第4天不能脸部X光定期检查的心肌梗塞迹象，而在病危第9天转变为心肌梗塞之前，这些非特异性征状和疼痛在早期在医学上，2019-nCoV感染者的医学更加进一步确实与许多其他相似传染病不能数值得留意区别，尤其是在严寒肺部道病原季节。
另另有，本流感患儿在疟疾的第9天转变为心肌梗塞的时机与近期肺部困难的发作（发病后中都位数为8天）赞同。尽管根据患儿的医学过后性恶化要求是否给予remdesivir慈悲的用作，但仍需要同步进行随机对照试验以未能确定remdesivir和任何其他研究药品治疗2019-nCoV感染者的安全部都是性和有效性。
我们调查报告了澳大利亚首例调查报告的2019-nCoV感染者患儿的医学特征。
该流感的关键之外最主要患儿在选读有关愈演愈烈的公共医疗卫生发信后要求寻求医疗卫生；由当地医疗卫生服务提供商确定患儿最近到成都的旅程历文化史，随后在当地，一个州和合众国公共医疗卫生官员之间同步进行协调；并未能确定确实的2019-nCoV感染者，从而可以促使分离患儿并随后对2019-nCoV同步进行实验室确定，并允许患儿康复进一步风险评估和管理。
该流感调查报告强调了医学医师对于任何显现出新急性疟疾疼痛的就诊患儿，要总结出新最近的旅程经历或带入阿兹海默的不可忽视性，为了确保确实识别系统和及早分离确实面临2019-nCoV感染者风险的患儿，并帮助减高于进一步的传播者。
之后，本调查报告强调需要未能确定与2019-nCoV感染者之外的医学疟疾，发病机理和病原折断过后时间的
全部都是部之内和自然历文化史，以为医学管理和公共医疗卫生决策提供依据。
注记列为译者
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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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