摘要
在之前国南昌开始的新型冠状大肠杆菌（2019-nCoV）爆发随之蔓延到，现今在多个东欧国家就诊。我们通报了在美国政府表格明的首同上2019-nCoV病菌病同上，并阐述了该病同上的认定，诊断，针灸处理过程过程和管理工作，有数患儿在病况第9天发挥为肺结核时的以前轻度头痛。
该案同上务实了针灸医生与地方，两州和联邦各级系统性英国政府之间密切协作的不可或缺性，以及所需较慢传布与这种新中风菌患儿的卫生有关的针灸信息的需求。
2019年12月底31日，之前国通报了与湖南省南昌市华东鱿鱼批发商品有关的老年人之前的肺结核病同上。
2020年1月底7日，之前国卫生英国政府表格明该簇与新型冠状大肠杆菌2019-nCoV有关。尽管以前华盛顿邮报的病同上与南昌市鱿鱼商品的暴露有关，但局限性的系统性数据表格明，早就愈演愈烈2019-nCoV彼此间传布。
截至2020年1月底30日，在至少21个东欧国家/地区通报了9976同上病同上，有数2020年1月底20日华盛顿邮报的美国政府首同上就诊的2019-nCoV病菌病同上。
全都球区域内内早就透过调查结果，以更为好地了解传布静态和针灸性疾病区域内。本通报阐述了在美国政府表格明的首同上2019-nCoV病菌的系统性和针灸特性。
案同上通报
2020年1月底19日，一名35岁的男子注意到在华盛顿两州斯诺霍米什县的一家急诊药房，有4天的头痛和主观头痛日本史。病人到药房检查时，在候诊室戴上西南侧罩。等待约20分钟后，他被带到检查室给与了给予者的评估。
他告知，他在之前国南昌探望父母后于1月底15日返回华盛顿两州。该患儿问到，他已从美国政府性疾病控制与防止之前心（CDC）接到有关之前国新型冠状大肠杆菌暴发的健康日本气象厅，由于他的头痛和近期的旅行者，他不得不去看医生。
左图1-2020年1月底19日（性疾病第4天）的后胸部和末端胸片
除了初中生酸酯高心率的高心率则有，该患儿还是其他健康的不吸烟者。体格检查注意到患儿换气环境热气时，血液循环为37.2°C，心率为134/87 mm Hg，节律为每分钟110次，换气频率为每分钟16次，氧明度为96％。心脏听诊结果显示有支气管炎，并透过了胸片检查，据华盛顿邮报未注意到异常（左图1）。
乙型肝炎和乙型流感的较慢蛋白质导入检验（NAAT）为复数。授予了颈咽拭子骨头，并通过NAAT将其送去侦测大肠杆菌性换气道致病。
据华盛顿邮报在48小时内对所有检验的致病均长方形复数，有数乙型肝炎和乙型流感，副流感，换气道合胞大肠杆菌，颈大肠杆菌，腺大肠杆菌和已知会致使精神上体性疾病的四种少用冠状大肠杆菌株（HKU1，NL63、229E和OC43） ）。根据患儿的旅行者历日本史背景，立即通知地方和两州司法部门。华盛顿司法部与紧急卫生针灸医生一起通知了CDC紧急行动之前心。
尽管该患儿通报知道他没有人去过华东鱿鱼商品，也没有人通报在去之前国旅行者之前与生病者有任何接触，但性疾病防止控制之前心的人员同意有必要根据局限性的性疾病防止控制之前心对患儿透过2019-nCoV检验。
根据CDC范本抽取了8个骨头，有数毒素，颈咽和西南侧咽拭子骨头。骨头采集后，患儿被送至家庭分离，并由当地司法部门透过积极监测。
2020年1月底20日，性疾病防止控制之前心（CDC）表格明患儿的颈咽和西南侧咽拭子通过实时特罗斯季亚涅齐-聚合酶链反应（rRT-PCR）侦测为2019-nCoVHIV。
在性疾病防止控制之前心的主旨研究专家，两州和地方卫生文官，紧急保健服务以及医务人员为首和人员的配合下，患儿被送至普罗维登斯地区保健之前心的热气分离病房透过针灸通过观察，并跟随性疾病防止控制之前心的医护人员有关接触，飞沫和空之前防水措施的建议，并带有护目镜。
复发时患儿通报过后头痛，有2天的眩晕和头痛日本史。他通报知道他没有人换气急促或胸痛。精神上针灸发挥在短时间区域内内。体格检查注意到患儿粘膜干燥。其余的检查往往不显着。
复发后，患儿给与了支持疗程，有数2改授生理盐水和恩丹以更为严重眩晕。
左图2-根据性疾病日和生病日（2020年1月底16日至2020年1月底30日）的头痛和高达血液循环
在生病的第2至5天（生病的第6至9天），患儿的精神上针灸发挥基本上保持稳定，除了注意到出现异常头痛并伴有心动过速（左图2）。患儿再次通报非生产性头痛，并注意到疲倦。
在生病第二天的下午，患儿排便通畅，腹部不适。下午有第二次饱稀疏的华盛顿邮报。抽取该尿液的混合物用于rRT-PCR检验，以及其他换气道骨头（颈咽和西南侧咽）和毒素。尿液和两个换气道骨头自此均通过rRT-PCR侦测为2019-nCoVHIV，而毒素仍为复数。
在此之前的疗程在很大高度上是支持性的。为了透过头痛处理过程，患儿所需根据所需给与解热治疗，该治疗有数每4小时650 mg对乙酰硫基酚和每6小时600 mg不良反应。在生病的前六天，他还因过后头痛而施用了600毫克极创醚和约6改授生理盐水。
表格1-针灸研究团队结果
患儿分离单元的并不一定以前大部分容许将会保健点研究团队检验；从医务人员第3天开始可以透过全都血球计数和毒素化学研究课题。
在医务人员第3天和第5天（性疾病第7天和第9天）的研究团队结果反映成白细胞减少病症，轻度血栓减少病症和肌酸激酶水准消退（表格1）。此则有，肝功能指标也有所变动：碱性磷酸酶（每改授68 U），丙硫酸硫基转移酶（每改授105 U），谷胱甘肽硫基转移酶（每改授77 U）和乳酸谷硫酸（每改授465 U）的水准分别为：在生病的第5天所有消退。鉴于患儿反复头痛，在第4天授予血液培训；迄今为止，这些都没有人增长速度。
左图3-2020年1月底22日（面部第7天，医务人员第3天）的后胸部和末端胸片
左图4-2020年1月底24日（面部第5天，医务人员第9天）的后胸部X线片
据华盛顿邮报，在医务人员第3天（生病第7天）拍摄的面部X光片未结果显示表层或异常都还（左图3）。
但是，从医务人员第5天下午（生病第9天）下午透过的第二次面部X光片检查结果显示，左肺下叶有肺结核（左图4）。
这些放大镜注意到与从医务人员第5天下午开始的换气状态变动相吻合，当时患儿在换气周遭热气时通过节律血氧明度测定的血氧明度值回升90％。
在第6天，患儿开始给与不足之处缺氧，该缺氧由颈导管以每分钟2改授的速度快输送。难以实现针灸发挥的变动和对医务人员授予性肺结核的关注，开始采用阿司匹林（1750 mg负荷剂量，然后每8小时麻醉1 g）和头孢日本杯丙酮（每8小时麻醉）疗程。
左图5-前后面部X光片，2020年1月底26日（性疾病第十天，医务人员第六天）
在医务人员第6天（生病第10天），第四次面部X射线照片结果显示两个肺之前都有基底小块混浊，这一注意到与非类似于肺结核相符（左图5），并且在听诊时在两个肺之前都注意到了罗音。鉴于放射线放大镜注意到，不得不给予缺氧不足之处，患儿过后头痛，多个部位过后HIV的2019-nCoV RNAHIV，以及刊登了与放射线性肺结核演进赞同的更为严重肺结核在该患儿之前，针灸医生富有同情心地采用了研究课题性抗大肠杆菌疗程。
麻醉瑞德昔韦（一种早就开发的新型蛋白质类似物前药）在第7天下午开始，但未通过观察到与输液有关的不良暴力事件。在对甲氧朱家耐药的白色葡萄球菌透过了倒数的降钙素原水准和颈PCR侦测后，在第7天下午改用阿司匹林，并在第二天改用头孢日本杯丙酮。
在医务人员第8天（生病第12天），患儿的针灸原因赢取改善。停止不足之处缺氧，他在换气周遭热气时的氧明度值增加到94％至96％。先前的双侧下叶罗音仍然存在。他的食欲赢取改善，除了出现异常干咳和颈漏则有，他没有人头痛。
截至2020年1月底30日，患儿仍生病。他有发热，除头痛则有，所有头痛均已更为严重，头痛的高度早就减轻。
法则
骨头采集
根据CDC范本授予用于2019-nCoV诊断检验的针灸骨头。用合成纤维拭子抽取了12个颈咽和西南侧咽拭子骨头。
将每个拭子填充包含2至3 ml大肠杆菌船运介质的单独冷冻管之前。将血集在毒素分离管之前，然后根据CDC范本透过离心。血液和尿液骨头分别抽取在冷冻骨头密封之前。混合物在2°C至8°C之间储存，直到准备好运送至CDC。
在性疾病的第7、11和12天抽取了多次重复透过的2019-nCoV检验的骨头，有数颈咽和西南侧咽拭子，毒素以及血液和尿液取样。
2019-NCOV的诊断检验
采用从公开发布的大肠杆菌蛋白质演进而来的rRT-PCR量化检验了针灸骨头。与先前针对重病症急性换气肉瘤冠状大肠杆菌（SARS-CoV）和之前东换气肉瘤冠状大肠杆菌（MERS-CoV）的诊断法则相同，它具有三个核衣壳遗传学抗病毒和一个HIV对照抗病毒。该测定的阐述为RRT-PCR面板引物和蛋白质和蛋白质信息之前可用的CDC研究团队信息网站2019-nCoV上。
遗传学测序
2020年1月底7日，之前国研究课题人员通过美国政府国立卫生研究课题院GenBank资料库和全都球关的联所有流感数据提议（GISAID）资料库关的联了2019-nCoV的比较简单遗传学蛋白质；随后发布了有关分离2019-nCoV的通报。
从rRT-PCRHIV骨头（西南侧咽和颈咽）之前浓缩蛋白质，并在Sanger和下一代测序平台（Illumina和MinIon）上用于全都遗传学组测序。采用5.4.6初版的Sequencher软件（Sanger）完成了蛋白质组装。minimap软件，初版本2.17（MinIon）；和freebayes软件1.3.1初版（MiSeq）。将比较简单遗传学组与可用的2019-nCoV参考蛋白质（GenBank登录号NC_045512.2）透过比较。
结果
2019-NCOV的骨头检验
表格2-2019年新型冠状大肠杆菌（2019-nCoV）的实时特罗斯季亚涅齐-聚合酶-链反应检验结果
该患儿在生病第4天时授予的初始换气道取样（颈咽拭子和西南侧咽拭子）在2019-nCoV长方形HIV（表格2）。
尽管患儿以前发挥为轻度头痛，但在性疾病第4天的更高循环阈值（Ct）值（颈咽骨头之前为18至20，西南侧咽骨头之前为21至22）表格明这些骨头之前大肠杆菌水准高。
在性疾病第7天授予的两个上换气道骨头在2019-nCoV仍保持HIV，有数颈咽拭子骨头之前过后高水准（Ct值23至24）。在性疾病第7天授予的尿液在2019-nCoV之前也长方形HIV（Ct值为36至38）。两种采集日期的毒素取样在2019-nCoV均为复数。
在性疾病第11天和第12天授予的颈咽和西南侧咽骨头结果显示成大肠杆菌水准下降的趋势。
西南侧咽骨头在生病第12天的2019-nCoV检验长方形复数。在这些日期授予的毒素的rRT-PCR结果仍完全一致。
遗传学测序
西南侧咽和颈咽骨头的比较简单遗传学组蛋白质彼此相同，并且与其他可用的2019-nCoV蛋白质基本上上相同。
该患儿的大肠杆菌与2019-nCoV参考蛋白质（NC_045512.2）在开放读者板8处大部分有3个蛋白质和1个相同。该蛋白质可通过GenBank授予（登录号MN985325）。
讨论区
我们关于美国政府首同上2019-nCoV就诊病同上的通报知道明这一新兴性疾病的几个方面已经显然都了解，有数传布静态和针灸性疾病的全都部区域内。
我们的病同上患儿曾去过之前国南昌，但通报知道他在南昌之前没有人去过鱿鱼批发商品或保健机构，也没有人生病的接触。尽管他的2019-nCoV病菌的举例尚不清楚，但已公开了人对人传布的证据。
到2020年1月底30日，已经注意到与此病同上关的的2019-nCoV继中风同上，但仍在密切防范下。
在性疾病的第4天和第7天从上换气道骨头之前侦测到具有更高Ct值的2019-nCoV RNA，表格明大肠杆菌载量高且具有传布潜力。
除此以外的是，我们还在患儿生病第7天抽取的尿液取样之前侦测到了2019-nCoV RNA。尽管我们病同上患儿的毒素骨头反复注意到2019-nCoV复数，但在之前国重病症患儿的血液之前仍侦测到大肠杆菌RNA。然而，肺则有侦测大肠杆菌RNA也就是知道意味着存在传染性大肠杆菌，目前尚不清楚在换气道举同上来说侦测大肠杆菌RNA的针灸意义。
目前，我们对2019-nCoV病菌的针灸区域内的了解比较极小。在之前国，已经华盛顿邮报了诸如更为严重的肺结核，换气衰竭，急性换气窘迫肉瘤（ARDS）和脑部损伤等并中风症，有数破坏者的后果。然而，不可或缺的是要注意，这些病同上是根据其肺结核诊断断定的，因此也许会使通报偏向更为更为严重的结果。
我们的病同上患儿以前发挥为轻度头痛和更高度出现异常头痛，在生病的第4天没有人面部X光检查的肺结核都还，而在生病第9天演进为肺结核之前，这些非特异性针灸发挥和头痛在20世纪在针灸上，2019-nCoV病菌的针灸处理过程过程也许与许多其他少用传染病没有人显着区隔，特别是在冬季换气道大肠杆菌季节。
另则有，本病同上患儿在性疾病的第9天演进为肺结核的时机与近期换气困难的发作（中风后之前位数为8天）赞同。尽管根据患儿的针灸原因急转直下不得不是否给予remdesivir慈爱的采用，但仍所需透过随机对照试验以断定remdesivir和任何其他研究课题抑制剂疗程2019-nCoV病菌的安全都性和精确性。
我们通报了美国政府首同上通报的2019-nCoV病菌患儿的针灸特性。
该病同上的关键方面有数患儿在读者有关暴发的系统性警告后不得不寻求保健；由当地保健服务给予者表格明患儿近期到南昌的旅行者历日本史背景，随后在当地，两州和联邦系统性文官之间透过协调；并断定也许的2019-nCoV病菌，从而可以随之分离患儿并随后对2019-nCoV透过研究团队表格明，并容许患儿复发全面评估和管理工作。
该病同上通报务实了针灸医生对于任何注意到急性性疾病头痛的就医患儿，要揭示成近期的旅行者经历或接触高心率的不可或缺性，为了保证错误识别系统和及时分离也许面临2019-nCoV病菌风险的患儿，并帮助减少全面的传布。
最后，本通报务实所需断定与2019-nCoV病菌关的的针灸性疾病，中风机理和大肠杆菌脱落过后时间的
全都部区域内和其本质历日本史背景，以为针灸管理工作和系统性决策给予依据。
以下为英文初版
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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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