摘要
在西方重庆开始的取而代之型病原（2019-nCoV）爆所发迅速蔓延，曾一度在多个国家所肺癌。我们分析报告了在宾夕法尼亚特拉华断定的首开2019-nCoV染病所肺癌，并所述了该所肺癌的鉴定，患者，药理学步骤和管理，以外关节炎状在病状第9天表格现为肺癌时的在此之前轻度关节炎状。
该事例阐释了药理学内科医生与区域内，特拉华和联邦各级公共服务政府错综复杂融洽协作的益处，以及必须快速传递与这种取而代之所发染病关节炎状的护理有关的药理学个人信息的需求。
2019年12年初31日，西方分析报告了与岳阳市重庆市华南地区海产海味有关的人群之中的肺癌所肺癌。
2020年1年初7日，西方卫生政府断定该簇与取而代之型病原2019-nCoV有关。尽管在此之前引述的所肺癌与重庆市海产零售商的受伤害有关，但当年前的公共卫生数据表格明，悄悄所发生2019-nCoV人际传递。
截至2020年1年初30日，在大概21个国家/地区分析报告了9976例所肺癌，以外2020年1年初20日引述的宾夕法尼亚特拉华首开所肺癌的2019-nCoV染病所肺癌。
全球性区域内悄悄已完成分析报告，以更好地理解传递动态和药理学性疾病覆盖范围。本分析报告所述了在宾夕法尼亚特拉华断定的首开2019-nCoV染病的公共卫生和药理学特点。
事例分析报告
2020年1年初19日，一名35岁的女选手注意到在林肯特拉华罗宾逊霍米什县的一家收治门诊，有4天的腹痛和主观哮喘巨著。患者到门诊检测时，在候诊室戴上口外罩。等待约20分钟后，他被带到检测室给与了中介者的审计。
他声称，他在西方重庆养病家人先于1年初15日留在林肯特拉华。该关节炎状表格示，他已从宾夕法尼亚特拉华性疾病控制与卫生保健该之中心（CDC）接到有关西方取而代之型病原暴所发的健康警报，由于他的关节炎状和近期的环游，他暂时去看内科医生。
布1-2020年1年初19日（性疾病第4天）的后年前胸和内侧胸片
除了高三酸酯血关节炎的病巨著外，该关节炎状还是其他健康的不吸烟者。体格检测断定关节炎状气管环境氮气时，血流量为37.2°C，血压为134/87 mm Hg，搏动为每分钟110次，气管频率为每分钟16次，氨明度为96％。肺部听诊看出有风湿热，并已完成了胸片检测，据引述未有断定异常（布1）。
亚型和-B霍乱的快速氘酸导入飞行测试（NAAT）为阴性。赢得了楔咽拭子骨头，并通过NAAT将其送去检验菌株性气管道菌株。
据引述在48每隔内对所有飞行测试的菌株以外呈圆形阴性，以外亚型和-B霍乱，副霍乱，气管道合胞菌株，楔菌株，腺菌株和据信会导致生命体性疾病的四种类似病原株（HKU1，NL63、229E和OC43） ）。根据关节炎状的环游所发展巨著，立刻通报区域内和特拉华卫生部门。林肯卫生部与救护车护理药理学内科医生一起通报了CDC救护车行动该之中心。
尽管该关节炎状分析报告说他没去过华南地区海产零售商，也没分析报告在去西方环游此后与年老者有任何碰触，但性疾病卫生保健定时的管理人员同意有必要根据当年前的性疾病卫生保健定时对关节炎状已完成2019-nCoV飞行测试。
根据CDC读物搜罗了8个骨头，以外胰岛素，楔咽和口外咽拭子骨头。骨头采集后，关节炎状被送回家庭强制，并由当地卫生部门已完成积极数据分析。
2020年1年初20日，性疾病卫生保健定时（CDC）断定关节炎状的楔咽和口外咽拭子通过可视逆转录酶-聚合酶链式反应（rRT-PCR）检验为2019-nCoV之中性。
在性疾病卫生保健定时的主题专家，特拉华和区域内卫生官员，救护车公共卫生服务以及门诊领导者和管理人员的辅以下，关节炎状被送回阿拉巴马地区公共卫生该之中心的氮气强制病房已完成药理学通过观察，并跟从性疾病卫生保健定时的护理人员有关碰触，飞沫和空之中防护措施的要求，并带有护目镜。
复所发时关节炎状分析报告不间断腹痛，有2天的头痛和头痛巨著。他分析报告说他没气管急促或咳嗽。永生先兆在正常区域内。体格检测断定关节炎状毛细血管高温。其余的检测通常不轻微。
复所发后，关节炎状给与了支持者放射治疗，以外2擢为生理盐水和恩丹以大大降偏高头痛。
布2-根据性疾病日和休养日（2020年1年初16日至2020年1年初30日）的关节炎状和最高血流量
在休养的第2至5天（年老的第6至9天），关节炎状的永生先兆基本保持稳定，除了注意到间歇性哮喘并浸润心动过速（布2）。关节炎状继续分析报告非生产性腹痛，并注意到疲劳。
在休养第二天的下午，关节炎状排便不畅，腹部不适。傍晚有第二次大便稀少的引述。搜罗该唾液的材料用于rRT-PCR飞行测试，以及其他气管道骨头（楔咽和口外咽）和胰岛素。唾液和两个气管道骨头后来以外通过rRT-PCR检验为2019-nCoV之中性，而胰岛素仍为阴性。
在此此后的放射治疗在很大层面上是支持者性的。为了已完成关节炎状西北侧理，关节炎状必须根据必须给与解热麻醉药，该麻醉药以外每4每隔650 mg口服和每6每隔600 mg抗抑郁药。在休养的年前六天，他还因不间断腹痛而服用了600毫克愈创醚停战协定6擢为生理盐水。
表格1-药理学科学研究团队结果
关节炎状强制单元的物理性质在此之前仅强制即时公共卫生点科学研究团队飞行测试；从门诊第3天开始可以已完成全血细胞计数和胰岛素生物化学科学研究。
在门诊第3天和第5天（性疾病第7天和第9天）的科学研究团队结果反映出新粒细胞减少关节炎，轻度血小板减少关节炎和肌酸激酶准确度擢为高（表格1）。此外，肝功能举例来说也有所推移：碱性磷酸酶（每擢为68 U），丙氨酸氨基转移酶（每擢为105 U），甘氨酸氨基转移酶（每擢为77 U）和乳酸脱氢酶（每擢为465 U）的准确度共五：在休养的第5天所有擢为高。鉴于关节炎状反复哮喘，在第4天赢得肝脏培育出；在世界上，这些都没放缓。
布3-2020年1年初22日（颈部第7天，门诊第3天）的后年前胸和内侧胸片
布4-2020年1年初24日（颈部第5天，门诊第9天）的后年前胸X线片
据引述，在门诊第3天（年老第7天）拍摄的颈部X光片未有看出浸润或异常征兆（布3）。
但是，从门诊第5天傍晚（年老第9天）傍晚已完成的第二次颈部X光片检测看出，左肺下叶有肺癌（布4）。
这些MRI断定与从门诊第5天傍晚开始的气管状态推移相吻合，当年关节炎状在气管周围氮气时通过搏动高血压明度测定的高血压明度绝对值降至90％。
在第6天，关节炎状开始给与补充缺氨，该缺氨由楔导管以每分钟2擢为的速度输送。考虑到药理学表格现的推移和对门诊赢得性肺癌的关注，开始适用抗生素（1750 mg负荷剂量，然后每8每隔口服1 g）和咪唑日本杯甲苯（每8每隔口服）放射治疗。
布5-年前后颈部X光片，2020年1年初26日（性疾病第十天，门诊第六天）
在门诊第6天（年老第10天），第四次颈部X射线照片看出两个肺之中都有基底条状混浊，这一断定与非类似于肺癌完全一致（布5），并且在听诊时在两个肺之中都注意到了罗音。鉴于氘辐射MRI断定，暂时给与缺氨补充，关节炎状不间断哮喘，多个肺脏不间断之中性的2019-nCoV RNA之中性，以及出旧版本了与氘辐射性肺癌演进一致的轻微肺癌在该关节炎状之中，药理学内科医生富有同情心地适用了行为科学抗菌株放射治疗。
口服艾伦昔韦（一种悄悄开所发的取而代之型多肽类似物年前药）在第7天傍晚开始，但未有通过观察到与口外服有关的不良事件。在对甲氨丁耐药的粉红色葡萄球菌已完成了连续的降钙素原准确度和楔PCR检验后，在第7天傍晚撤除抗生素，并在第二天撤除咪唑日本杯甲苯。
在门诊第8天（年老第12天），关节炎状的药理学情况赢取提高。停止补充缺氨，他在气管周围氮气时的氨明度绝对值提高到94％至96％。先年前的双侧下叶罗音不再存在。他的食欲赢取提高，除了间歇性干咳和楔漏外，他没关节炎状。
截至2020年1年初30日，关节炎状仍休养。他有所发热，除腹痛外，所有关节炎状以外已大大降偏高，腹痛的层面悄悄减轻。
方法
骨头采集
根据CDC读物赢得用于2019-nCoV患者飞行测试的药理学骨头。用合成纤维拭子搜罗了12个楔咽和口外咽拭子骨头。
将每个拭子插入包含2至3 ml菌株转运介质的另行无菌的水。将血集在胰岛素分离的水，然后根据CDC读物已完成离心。分泌物和唾液骨头分别搜罗在无菌骨头桶内之中。材料在2°C至8°C错综复杂储藏，直到准备好装载至CDC。
在性疾病的第7、11和12天搜罗了重复已完成的2019-nCoV飞行测试的骨头，以外楔咽和口外咽拭子，胰岛素以及分泌物和唾液样本。
2019-NCOV的患者飞行测试
适用从公开所发布的菌株多肽演进而来的rRT-PCR德沃夏克飞行测试了药理学骨头。与先年前针对重关节炎急性气管症病原（SARS-CoV）和之中东气管症病原（MERS-CoV）的患者方法相似，它不具备三个氘衣壳基因靶标和一个之中性对照靶标。该测定的所述为RRT-PCR面板引物和探针和多肽个人信息之中一般来说的CDC科学研究团队个人信息网站2019-nCoV上。
突变生物化学合成
2020年1年初7日，西方科学研究人员通过宾夕法尼亚特拉华国立卫生科学研究院GenBank在线和全球性分享所有霍乱数据倡议（GISAID）在线分享了2019-nCoV的原始基因多肽；随后所发布了有关强制2019-nCoV的分析报告。
从rRT-PCR之中性骨头（口外咽和楔咽）之中提炼出氘酸，并在Sanger和世**物化学合成平台（Illumina和MinIon）上用于全基因多肽生物化学合成。适用5.4.6旧版本的Sequencher插件（Sanger）已完成了多肽组装。minimap插件，旧版本本2.17（MinIon）；和freebayes插件1.3.1旧版本（MiSeq）。将原始基因多肽与一般来说的2019-nCoV参考多肽（GenBank登录号NC_045512.2）已完成比较。
结果
2019-NCOV的骨头飞行测试
表格2-2019年取而代之型病原（2019-nCoV）的可视逆转录酶-聚合酶-链式反应飞行测试结果
该关节炎状在年老第4天时赢得的初始气管道样本（楔咽拭子和口外咽拭子）在2019-nCoV呈圆形之中性（表格2）。
尽管关节炎状在此之前表格现为轻度关节炎状，但在性疾病第4天的偏高反应器阈绝对值（Ct）绝对值（楔咽骨头之中为18至20，口外咽骨头之中为21至22）表格明这些骨头之中菌株准确度很高。
在性疾病第7天赢得的两个上气管道骨头在2019-nCoV仍保持之中性，以外楔咽拭子骨头之中不间断高准确度（Ct绝对值23至24）。在性疾病第7天赢得的唾液在2019-nCoV之中也呈圆形之中性（Ct绝对值为36至38）。两种采集迟于的胰岛素样本在2019-nCoV以外为阴性。
在性疾病第11天和第12天赢得的楔咽和口外咽骨头看出出新菌株准确度下降的21世纪。
口外咽骨头在年老第12天的2019-nCoV飞行测试呈圆形阴性。在这些迟于赢得的胰岛素的rRT-PCR结果仍确切。
突变生物化学合成
口外咽和楔咽骨头的原始基因多肽多肽彼此相近，并且与其他一般来说的2019-nCoV多肽几乎相近。
该关节炎状的菌株与2019-nCoV参考多肽（NC_045512.2）在开放写出框8西北侧仅有3个多肽和1个不同。该多肽可通过GenBank赢得（登录号MN985325）。
旧版本主
我们关于宾夕法尼亚特拉华首开2019-nCoV所肺癌所肺癌的分析报告所述这一取而代之兴性疾病的几个各个方面由此可知未有完全理解，以外传递动态和药理学性疾病的全部覆盖范围。
我们的所肺癌关节炎状曾去过西方重庆，但分析报告说他在重庆此后没去过海产海味或公共卫生机构，也没生病的碰触。尽管他的2019-nCoV染病的来源由此可知不明了，但已公开了人对人传递的论据。
到2020年1年初30日，由此可知未有断定与此所肺癌相关的2019-nCoV继所发所肺癌，但仍在融洽监视下。
在性疾病的第4天和第7天从上气管道骨头之中检验到不具备偏高Ct绝对值的2019-nCoV RNA，表格明菌株次之高且不具备传递所发展前景。
绝对值得注意的是，我们还在关节炎状年老第7天搜罗的唾液样本之中检验到了2019-nCoV RNA。尽管我们所肺癌关节炎状的胰岛素骨头反复注意到2019-nCoV阴性，但在西方重关节炎关节炎状的肝脏之中仍检验到菌株RNA。然而，肺外检验菌株RNA其本质意味着存在传染性菌株，目年前由此可知不明了在气管道举例来说检验菌株RNA的药理学意义。
目年前，我们对2019-nCoV染病的药理学覆盖范围的理解颇为有限。在西方，早已引述了诸如轻微的肺癌，气管衰竭，急性气管窘迫症（ARDS）和心脏损伤等并所发关节炎，以外致命的恶果。然而，重要的是要注意，这些所肺癌是根据其肺癌患者确切的，因此意味著会使分析报告偏向更轻微的结果。
我们的所肺癌关节炎状在此之前表格现为轻度腹痛和偏高度间歇性哮喘，在年老的第4天没颈部X光检测的肺癌征兆，而在年老第9天演进为肺癌之年前，这些非特异性先兆和关节炎状在最初在药理学上，2019-nCoV染病的药理学步骤意味著与许多其他类似登革热没轻微区别，尤其是在冬季气管道菌株季节。
另外，本所肺癌关节炎状在性疾病的第9天演进为肺癌的时机与近期气管困难的所发作（所肺癌后之中位数为8天）一致。尽管根据关节炎状的药理学情况每况愈下暂时是否给与remdesivir慈悲的适用，但仍必须已完成随机对照检验以确切remdesivir和任何其他科学研究口服放射治疗2019-nCoV染病的稳定性和有效性。
我们分析报告了宾夕法尼亚特拉华首开分析报告的2019-nCoV染病关节炎状的药理学特点。
该所肺癌的关键各个方面以外关节炎状在写出有关暴所发的公共服务警告后暂时寻求公共卫生；由当地公共卫生应用层断定关节炎状近期到重庆的环游所发展巨著，随后在当地，特拉华和联邦公共服务官员错综复杂已完成互相辅以；并确切意味著的2019-nCoV染病，从而可以迅速强制关节炎状并随后对2019-nCoV已完成科学研究团队断定，并强制关节炎状复所发进一步审计和管理。
该所肺癌分析报告阐释了药理学内科医生对于任何注意到急性性疾病关节炎状的就诊关节炎状，要总结出新近期的环游经历或碰触病巨著的益处，为了确保错误切位和即时强制意味著面临2019-nCoV染病风险的关节炎状，并尽力减少进一步的传递。
最后，本分析报告阐释必须确切与2019-nCoV染病相关的药理学性疾病，所肺癌成因和菌株脱落不间断时间的
全部覆盖范围和自然所发展巨著，以为药理学管理和公共服务决策者中介依据。
以下为日文旧版本
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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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