摘要
在欧美武昌开始的新型冠状病原（2019-nCoV）爆所发短时间内散播，现已在多个发达国家患病。我们研究报告了在英美两国获知的尚能从未有2019-nCoV染病患病，并描述了该患病的鉴定，治疗，针灸更进一步和行政，之之外病患在病情第9天展示出为结核病时的原先轻度疼痛。
该与此就其忽略了针灸心理医生与区域内，一个州和联邦议会各级医疗卫生当地政府彼此之间密切关系协作的重要性，以及能够短时间内散播与这种新所发染病病患的护理有关的针灸接收者的需求。
2019年12同月31日，欧美研究报告了与湖北省武昌市广东鱿鱼批所发高于价有关的老年人中就会的结核病患病。
2020年1同月7日，欧美医疗卫生当地政府获知该簇与新型冠状病原2019-nCoV有关。尽管原先另据的患病与武昌市鱿鱼高于价的暴露有关，但意味着的流行病学原始数据列于明，正在所发生2019-nCoV人际散播。
截至2020年1同月30日，在极为少21个发达国家/地区研究报告了9976例患病，之之外2020年1同月20日另据的英美两国尚能从未有患病的2019-nCoV染病患病。
当今世界适用仅限于正在同步进行调查，以好处地认识到散播自适应和针灸结核病适用范围。本研究报告描述了在英美两国获知的尚能从未有2019-nCoV染病的流行病学和针灸基本特征。
与此就其研究报告
2020年1同月19日，一名35岁的蹦床显现用到在纽约市一个州斯诺霍米什县的餐馆收治养老院，有4天的呕吐和主观所哮喘史。病童到养老院检验时，在候诊室戴上侧罩。等待共约20分钟后，他被放回检验室遵从了包括者的评估。
他透露，他在欧美武昌探望家人都于1同月15日留在纽约市一个州。该病患列于示，他已从英美两国结核病压制与防治中就会心（CDC）所发显现出有关欧美新型冠状病原暴所发的健康警报，由于他的疼痛和仍然有的旅程，他提议去看心理医生。
示意图1-2020年1同月19日（结核病第4天）的后前胸和之外侧胸片
除了高一酸酯血病症的躁郁病症之外，该病患还是其他健康的不吸烟者。体格检验所找到病患吞咽环境液体时，代谢率为37.2°C，血压为134/87 mm Hg，脉搏为每分钟110次，吞咽高频率为每分钟16次，氮明度为96％。肺部听诊推断有支气管炎，并同步进行了胸片检验，据另据从未所找到反常（示意图1）。
流行性感冒和甲类SARS的短时间内大分子扩增测试者（NAAT）为中性。拿到了背咽拭子遗骸，并通过NAAT将其放去检验病原性吞咽道病原。
据另据在48不间断内对所有测试者的病原外呈中性，之之外流行性感冒和甲类SARS，副SARS，吞咽道合胞病原，背病原，腺病原和已知就会致使人类所结核病的四种常用冠状病原株（HKU1，NL63、229E和OC43） ）。根据病患的旅程上曾，立即通知区域内和一个州医疗卫生部门。纽约市医疗卫生部与先行护理针灸心理医生一起通知了CDC先行行动中就会心。
尽管该病患研究报告说他从从未去过广东鱿鱼高于价，也从从未研究报告在去欧美旅程在此之前与病患有任何触及，但结核病防治压制中就会心的工作工作人员同意有必要根据意味着的结核病防治压制中就会心对病患同步进行2019-nCoV测试者。
根据CDC须知获取了8个遗骸，之之外小鼠，背咽和侧咽拭子遗骸。遗骸搜集后，病患被带往普通家庭受控，并由当地医疗卫生部门同步进行积极系统对。
2020年1同月20日，结核病防治压制中就会心（CDC）获知病患的背咽和侧咽拭子通过实时表型物质-大分子链反应（rRT-PCR）检验为2019-nCoV白血病。
在结核病防治压制中就会心的趣味专家，一个州和区域内医疗卫生官员，先行医疗服务以及公立医院领袖和工作工作人员的配合下，病患被带往普罗维登斯地区医疗中就会心的液体受控病房同步进行针灸辨别，并跟随结核病防治压制中就会心的医护工作人员有关触及，飞沫和空中就会护甲保护措施的提议，并带有护目镜。
入院时病患研究报告小规模呕吐，有2天的麻木和呕吐史。他研究报告说他从从未吞咽急促或心悸。永生恶性肿瘤在正常人适用仅限于。体格检验所找到病患粘膜湿。其余的检验通常不引人注意。
入院后，病患遵从了支持放射治疗，之之外2再降生理盐水和恩丹以减缓麻木。
示意图2-根据结核病日和住院日（2020年1同月16日至2020年1同月30日）的疼痛和三高代谢率
在住院的第2至5天（患的第6至9天），病患的永生恶性肿瘤基本比较稳定，除了显现用到间歇性所哮喘并诱发心动过速（示意图2）。病患之后研究报告非生产性呕吐，并显现用到虚弱。
在住院第二天的下午，病患排便通畅，腹部不适。凌晨有第二次饱稀疏的另据。获取该老鼠的试样用于rRT-PCR测试者，以及其他吞咽道遗骸（背咽和侧咽）和小鼠。老鼠和两个吞咽道遗骸在此之后外通过rRT-PCR检验为2019-nCoV白血病，而小鼠仍为中性。
从那时起的放射治疗在较大程度上是支持性的。为了同步进行疼痛附近理，病患能够根据能够遵从解热药物，该药物之之外每4不间断650 mg对乙酰氮基酚和每6不间断600 mg布洛芬。在住院的前六天，他还因小规模呕吐而施打了600毫克愈创醚和共约6再降生理盐水。
列于1-针灸研究室结果
病患受控单元的性质原先仅受限制短时间内医疗点研究室测试者；从公立医院第3天开始可以同步进行以外血细胞计数和小鼠化学研究课题。
在公立医院第3天和第5天（结核病第7天和第9天）的研究室结果反映显现出炎病症缩减病症，轻度血小板缩减病症和肌酸激酶程度增高（列于1）。此之外，肝功能量化也大大变异：碱性糖类（每再降68 U），丙氮酸氮基转移酶（每再降105 U），苹果酸氮基转移酶（每再降77 U）和乳酸脱氢酶（每再降465 U）的程度分别为：在住院的第5天所有增高。鉴于病患连续不断所哮喘，在第4天拿到血液培养；迄今为止，这些都从从未增长速度快。
示意图3-2020年1同月22日（腿部第7天，公立医院第3天）的后前胸和之外侧胸片
示意图4-2020年1同月24日（腿部第5天，公立医院第9天）的后前胸X线片
据另据，在公立医院第3天（患第7天）拍摄的腿部X光片从未推断浸润或反常或许（示意图3）。
但是，从公立医院第5天凌晨（患第9天）凌晨同步进行的第二次腿部X光片检验推断，左肺下叶有结核病（示意图4）。
这些CT所找到与从公立医院第5天凌晨开始的吞咽状态变异相吻合，当时病患在吞咽四周液体时通过脉搏血压明度精确测量的血压明度最大值降至90％。
在第6天，病患开始遵从必需氮气，该氮气由背尿道以每分钟2再降的速度快输放。难以实现针灸展示出的变异和对公立医院拿到结核病的关注，开始用到MRSA（1750 mg负荷口服，然后每8不间断施打1 g）和萘吡肟（每8不间断施打）放射治疗。
示意图5-前后腿部X光片，2020年1同月26日（结核病第十天，公立医院第六天）
在公立医院第6天（患第10天），第四次腿部X射线照片推断两个肺中就会都有基底条状浅色，这一所找到与非的现代结核病相符（示意图5），并且在听诊时在两个肺中就会都显现用到了罗音。鉴于放射线CT所找到，提议拒绝接受氮气必需，病患小规模所哮喘，多个口腔小规模白血病的2019-nCoV RNA白血病，以及刊出了与放射线结核病所转型恰当的情况严重结核病在该病患中就会，针灸心理医生高贵同情心地用到了研究课题性抗病原放射治疗。
施打怀特昔韦（一种正在开所发的新型氨基酸类似物前药）在第7天凌晨开始，但从未辨别到与用药有关的经常性事件。在对甲氮丁耐药的金黄色细菌性同步进行了连续的降钙素原程度和背PCR检验后，在第7天凌晨停运MRSA，并在第二天停运萘吡肟。
在公立医院第8天（患第12天），病患的针灸状况赢取改善。中断必需氮气，他在吞咽四周液体时的氮明度最大值提高到94％至96％。此前的双侧下叶罗音便不存在。他的食欲赢取改善，除了间歇性干咳和背漏之外，他从从未疼痛。
截至2020年1同月30日，病患仍住院。他大大发热，除呕吐之外，所有疼痛外已减缓，呕吐的程度正在减低。
方法有
遗骸搜集
根据CDC须知拿到用于2019-nCoV治疗测试者的针灸遗骸。用合成纤维拭子获取了12个背咽和侧咽拭子遗骸。
将每个拭子插入包含2至3 ml病原转运等离子体的直接无菌气管就会。将血集在小鼠转化气管就会，然后根据CDC须知同步进行离心。尿和老鼠遗骸分别获取在无菌遗骸装入中就会。试样在2°C至8°C彼此之间储存，直到事先运往至CDC。
在结核病的第7、11和12天获取了重复同步进行的2019-nCoV测试者的遗骸，之之外背咽和侧咽拭子，小鼠以及尿和老鼠采样。
2019-NCOV的治疗测试者
用到从披露所公开发表的病原氨基酸所转型而来的rRT-PCR分析法测试者了针灸遗骸。与此前针对加护急性吞咽性疾病冠状病原（SARS-CoV）和中就会东吞咽性疾病冠状病原（MERS-CoV）的治疗方法有相似，它不具备三个核衣壳基因靶标和一个白血病印证靶标。该精确测量的描述为RRT-PCR面板核苷酸和探针和氨基酸接收者中就会必需的CDC研究室接收者网上2019-nCoV上。
表型分子生物学
2020年1同月7日，欧美研究课题工作人员通过英美两国国立医疗卫生研究课题院GenBank资料库和当今世界共享所有SARS原始数据倡议（GISAID）资料库共享了2019-nCoV的值得注意基因氨基酸；随后所公开发表了有关受控2019-nCoV的研究报告。
从rRT-PCR白血病遗骸（侧咽和背咽）中就会提取大分子，并在Sanger和下一代分子生物学SDK（Illumina和MinIon）上用于以外基因组分子生物学。用到5.4.6版的Sequencher软件（Sanger）顺利完成了氨基酸被装。minimap软件，版本2.17（MinIon）；和freebayes软件1.3.1版（MiSeq）。将值得注意基因组与必需的2019-nCoV参考氨基酸（GenBank登录号NC_045512.2）同步进行比较。
结果
2019-NCOV的遗骸测试者
列于2-2019年新型冠状病原（2019-nCoV）的实时表型物质-大分子-链反应测试者结果
该病患在患第4天时拿到的初始吞咽道采样（背咽拭子和侧咽拭子）在2019-nCoV呈白血病（列于2）。
尽管病患原先展示出为轻度疼痛，但在结核病第4天的高于尿素阈最大值（Ct）最大值（背咽遗骸中就会为18至20，侧咽遗骸中就会为21至22）列于明这些遗骸中就会病原程度较高于。
在结核病第7天拿到的两个上吞咽道遗骸在2019-nCoV仍保持白血病，之之外背咽拭子遗骸中就会小规模上佳（Ct最大值23至24）。在结核病第7天拿到的老鼠在2019-nCoV中就会也呈白血病（Ct最大值为36至38）。两种搜集时间表的小鼠采样在2019-nCoV外为中性。
在结核病第11天和第12天拿到的背咽和侧咽遗骸推断显现出病原程度下降的近来。
侧咽遗骸在患第12天的2019-nCoV测试者呈中性。在这些时间表拿到的小鼠的rRT-PCR结果仍从未定。
表型分子生物学
侧咽和背咽遗骸的值得注意基因组氨基酸彼此不同，并且与其他必需的2019-nCoV氨基酸几乎不同。
该病患的病原与2019-nCoV参考氨基酸（NC_045512.2）在以外站读者侧边8附近差不多3个氨基酸和1个并不不同。该氨基酸可通过GenBank拿到（登录号MN985325）。
讨论区
我们关于英美两国尚能从未有2019-nCoV患病患病的研究报告说明这一新兴结核病的几个方面尚能从未实质上认识到，之之外散播自适应和针灸结核病的以外部适用范围。
我们的患病病患曾去过欧美武昌，但研究报告说他在武昌在此之前从从未去过鱿鱼批所发高于价或医疗机构，也从从未病危的触及。尽管他的2019-nCoV染病的来源尚能不明了，但已披露了人对人散播的证据。
到2020年1同月30日，尚能从未所找到与此患病就其的2019-nCoV继所发患病，但仍在密切关系监视下。
在结核病的第4天和第7天从上吞咽道遗骸中就会检验到不具备高于Ct最大值的2019-nCoV RNA，列于明病原载量高且不具备散播转型前景。
最大值得注意的是，我们还在病患患第7天获取的老鼠采样中就会检验到了2019-nCoV RNA。尽管我们患病病患的小鼠遗骸连续不断显现用到2019-nCoV中性，但在欧美加护病患的血液中就会仍检验到病原RNA。然而，肺之外检验病原RNA并不一定意味着不存在传染性病原，现有尚能不明了在吞咽道之受控检验病原RNA的针灸意义。
现有，我们对2019-nCoV染病的针灸适用范围的认识到极为有限。在欧美，仍然另据了诸如情况严重的结核病，吞咽衰竭，急性吞咽窘迫性疾病（ARDS）和瓣膜损伤等并所发病症，之之外关键时刻的后果。然而，重要的是要注意，这些患病是根据其结核病治疗确切的，因此或许就会使研究报告偏向更情况严重的结果。
我们的患病病患原先展示出为轻度呕吐和高于度间歇性所哮喘，在患的第4天从从未腿部X光检验的结核病或许，而在患第9天所转型为结核病在此之前，这些非特异性恶性肿瘤和疼痛在早期在针灸上，2019-nCoV染病的针灸更进一步或许与许多其他常用结核病从从未引人注意不同点，尤其是在冬季吞咽道病原季节。
另之外，本患病病患在结核病的第9天所转型为结核病的时机与近期吞咽困难的所高烧（所发病后中就会位数为8天）恰当。尽管根据病患的针灸状况好转提议到底拒绝接受remdesivir愿的用到，但仍能够同步进行随机印证试验车以确切remdesivir和任何其他研究课题本品放射治疗2019-nCoV染病的必需性和系统性。
我们研究报告了英美两国尚能从未有研究报告的2019-nCoV染病病患的针灸基本特征。
该患病的极为重要方面之之外病患在读者有关暴所发的医疗卫生警告后提议寻求医疗；由当地医疗服务包括者获知病患仍然有到武昌的旅程上曾，随后在当地，一个州和联邦议会医疗卫生官员彼此之间同步进行协调；并确切或许的2019-nCoV染病，从而可以短时间内受控病患并随后对2019-nCoV同步进行研究室获知，并受限制病患入院进一步评估和行政。
该患病研究报告忽略了针灸心理医生对于任何显现用到急性结核病疼痛的看病病患，要总结显现出仍然有的旅程经历或触及躁郁病症的重要性，为了确保正确识别和及时受控或许面临2019-nCoV染病风险的病患，并帮助缩减进一步的散播。
此前，本研究报告忽略能够确切与2019-nCoV染病就其的针灸结核病，所发病机理和病原脱落周期的
以外部适用范围和自然上曾，以为针灸行政和医疗卫生决策包括依据。
此列于为中文版
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Summary
An outbreak of novel coronirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
On December 31, 2019, China reported a cluster of cases of pneumonia in people associated with the Huanan Seafood Wholesale Market in Wuhan, Hubei Province.
On January 7, 2020, Chinese health authorities confirmed that this cluster was associated with a novel coronirus, 2019-nCoV.
Although cases were originally reported to be associated with exposure to the seafood market in Wuhan, current epidemiologic data indicate that person-to-person transmission of 2019-nCoV is occurring.
As of January 30, 2020, a total of 9976 cases had been reported in at least 21 countries,including the first confirmed case of 2019-nCoV infection in the United States, reported on January 20, 2020.
Investigations are under way worldwide to better understand transmission dynamics and the spectrum of clinical illness.
This report describes the epidemiologic and clinical features of the first case of 2019-nCoV infection confirmed in the United States.
Case Report
On January 19, 2020, a 35-year-old man presented to an urgent care clinic in Snohomish County, Washington, with a 4-day history of cough and subjective fever.
On checking into the clinic, the patient put on a mask in the waiting room. After waiting approximately 20 minutes, he was taken into an examination room and underwent evaluation by a provider. He disclosed that he had returned to Washington State on January 15 after treling to visit family in Wuhan, China.
The patient stated that he had seen a health alert from the U.S. Centers for Disease Control and Prevention (CDC) about the novel coronirus outbreak in China and, because of his symptoms and recent trel, decided to see a health care provider.
Figure 1.Posteroanterior and Lateral Chest Radiographs, January 19, 2020 (Illness Day 4).
Apart from a history of hypertriglyceridemia, the patient was an otherwise healthy nonsmoker. The physical examination revealed a body temperature of 37.2°C, blood pressure of 134/87 mm Hg, pulse of 110 beats per minute, respiratory rate of 16 breaths per minute, and oxygen saturation of 96% while the patient was breathing ambient air. Lung auscultation revealed rhonchi, and chest radiography was performed, which was reported as showing no abnormalities (Figure 1).
A rapid nucleic acid amplification test (NAAT) for influenza A and B was negative. A nasopharyngeal swab specimen was obtained and sent for detection of viral respiratory pathogens by NAAT; this was reported back within 48 hours as negative for all pathogens tested, including influenza A and B, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, and four common coronirus strains known to cause illness in humans (HKU1, NL63, 229E, and OC43).
Given the patient’s trel history, the local and state health departments were immediately notified. Together with the urgent care clinician, the Washington Department of Health notified the CDC Emergency Operations Center.
Although the patient reported that he had not spent time at the Huanan seafood market and reported no known contact with ill persons during his trel to China, CDC staff concurred with the need to test the patient for 2019-nCoV on the basis of current CDC “persons under investigation” case definitions.
Specimens were collected in accordance with CDC guidance and included serum and nasopharyngeal and oropharyngeal swab specimens. After specimen collection, the patient was discharged to home isolation with active monitoring by the local health department.
On January 20, 2020, the CDC confirmed that the patient’s nasopharyngeal and oropharyngeal swabs tested positive for 2019-nCoV by real-time reverse-transcriptase–polymerase-chain-reaction (rRT-PCR) assay.
In coordination with CDC subject-matter experts, state and local health officials, emergency medical services, and hospital leadership and staff, the patient was admitted to an airborne-isolation unit at Providence Regional Medical Center for clinical observation, with health care workers following CDC recommendations for contact, droplet, and airborne precautions with eye protection.
On admission, the patient reported persistent dry cough and a 2-day history of nausea and vomiting; he reported that he had no shortness of breath or chest pain. Vital signs were within normal ranges. On physical examination, the patient was found to he dry mucous membranes. The remainder of the examination was generally unremarkable. After admission, the patient received supportive care, including 2 liters of normal saline and ondansetron for nausea.
Figure 2.Symptoms and Maximum Body Temperatures According to Day of Illness and Day of Hospitalization, January 16 to January 30, 2020.
On days 2 through 5 of hospitalization (days 6 through 9 of illness), the patient’s vital signs remained largely stable, apart from the development of intermittent fevers accompanied by periods of tachycardia (Figure 2).
The patient continued to report a nonproductive cough and appeared fatigued. On the afternoon of hospital day 2, the patient passed a loose bowel movement and reported abdominal discomfort. A second episode of loose stool was reported overnight; a sample of this stool was collected for rRT-PCR testing, along with additional respiratory specimens (nasopharyngeal and oropharyngeal) and serum.
The stool and both respiratory specimens later tested positive by rRT-PCR for 2019-nCoV, whereas the serum remained negative.
Treatment during this time was largely supportive. For symptom management, the patient received, as needed, antipyretic therapy consisting of 650 mg of acetaminophen every 4 hours and 600 mg of ibuprofen every 6 hours. He also received 600 mg of guaifenesin for his continued cough and approximately 6 liters of normal saline over the first 6 days of hospitalization.
Table 1.Clinical Laboratory Results.
The nature of the patient isolation unit permitted only point-of-care laboratory testing initially; complete blood counts and serum chemical studies were ailable starting on hospital day 3.
Laboratory results on hospital days 3 and 5 (illness days 7 and 9) reflected leukopenia, mild thrombocytopenia, and elevated levels of creatine kinase (Table 1).
In addition, there were alterations in hepatic function measures: levels of alkaline phosphatase (68 U per liter), alanine aminotransferase (105 U per liter), aspartate aminotransferase (77 U per liter), and lactate dehydrogenase (465 U per liter) were all elevated on day 5 of hospitalization.
Given the patient’s recurrent fevers, blood cultures were obtained on day 4; these he shown no growth to date.
Figure 3.Posteroanterior and Lateral Chest Radiographs, January 22, 2020 (Illness Day 7, Hospital Day 3).
Figure 4.Posteroanterior Chest Radiograph, January 24, 2020 (Illness Day 9, Hospital Day 5).
A chest radiograph taken on hospital day 3 (illness day 7) was reported as showing no evidence of infiltrates or abnormalities (Figure 3).
However, a second chest radiograph from the night of hospital day 5 (illness day 9) showed evidence of pneumonia in the lower lobe of the left lung (Figure 4).
These radiographic findings coincided with a change in respiratory status starting on the evening of hospital day 5, when the patient’s oxygen saturation values as measured by pulse oximetry dropped to as low as 90% while he was breathing ambient air.
On day 6, the patient was started on supplemental oxygen, delivered by nasal cannula at 2 liters per minute.
Given the changing clinical presentation and concern about hospital-acquired pneumonia, treatment with vancomycin (a 1750-mg loading dose followed by 1 g administered intrenously every 8 hours) and cefepime (administered intrenously every 8 hours) was initiated.
Figure 5.Anteroposterior and Lateral Chest Radiographs, January 26, 2020 (Illness Day 10, Hospital Day 6).
On hospital day 6 (illness day 10), a fourth chest radiograph showed basilar streaky opacities in both lungs, a finding consistent with atypical pneumonia (Figure 5), and rales were noted in both lungs on auscultation.
Given the radiographic findings, the decision to administer oxygen supplementation, the patient’s ongoing fevers, the persistent positive 2019-nCoV RNA at multiple sites, and published reports of the development of severe pneumonia at a period consistent with the development of radiographic pneumonia in this patient, clinicians pursued compassionate use of an investigational antiviral therapy.
Treatment with intrenous remdesivir (a novel nucleotide ogue prodrug in development) was initiated on the evening of day 7, and no adverse events were observed in association with the infusion.
Vancomycin was discontinued on the evening of day 7, and cefepime was discontinued on the following day, after serial negative procalcitonin levels and negative nasal PCR testing for methicillin-resistant Staphylococcus aureus.
On hospital day 8 (illness day 12), the patient’s clinical condition improved. Supplemental oxygen was discontinued, and his oxygen saturation values improved to 94 to 96% while he was breathing ambient air.
The previous bilateral lower-lobe rales were no longer present. His appetite improved, and he was asymptomatic aside from intermittent dry cough and rhinorrhea.
As of January 30, 2020, the patient remains hospitalized. He is afebrile, and all symptoms he resolved with the exception of his cough, which is decreasing in severity.
Methods
SPECIMEN COLLECTIONClinical specimens for 2019-nCoV diagnostic testing were obtained in accordance with CDC guidelines. Nasopharyngeal and oropharyngeal swab specimens were collected with synthetic fiber swabs; each swab was inserted into a separate sterile tube containing 2 to 3 ml of viral transport medium. Serum was collected in a serum separator tube and then centrifuged in accordance with CDC guidelines. The urine and stool specimens were each collected in sterile specimen containers. Specimens were stored between 2°C and 8°C until ready for shipment to the CDC. Specimens for repeat 2019-nCoV testing were collected on illness days 7, 11, and 12 and included nasopharyngeal and oropharyngeal swabs, serum, and urine and stool samples.
DIAGNOSTIC TESTING FOR 2019-NCOV
Clinical specimens were tested with an rRT-PCR assay that was developed from the publicly released virus sequence. Similar to previous diagnostic assays for severe acute respiratory syndrome coronirus (SARS-CoV) and Middle East respiratory syndrome coronirus (MERS-CoV), it has three nucleocapsid gene targets and a positive control target.
A description of this assay and sequence information for the rRT-PCR panel primers and probes are ailable on the CDC Laboratory Information website for 2019-nCoV.
GENETIC SEQUENCING
On January 7, 2020, Chinese researchers shared the full genetic sequence of 2019-nCoV through the National Institutes of Health GenBank database and the Global Initiative on Sharing All Influenza Data (GISAID) database; a report about the isolation of 2019-nCoV was later published.
Nucleic acid was extracted from rRT-PCR–positive specimens (oropharyngeal and nasopharyngeal) and used for whole-genome sequencing on both Sanger and next-generation sequencing platforms (Illumina and MinIon).
Sequence assembly was completed with the use of Sequencher software, version 5.4.6 (Sanger); minimap software, version 2.17 (MinIon); and freebayes software, version 1.3.1 (MiSeq). Complete genomes were compared with the ailable 2019-nCoV reference sequence (GenBank accession number NC_045512.2).
Results
SPECIMEN TESTING FOR 2019-NCOV
Table 2.Results of Real-Time Reverse-Transcriptase–Polymerase-Chain-Reaction Testing for the 2019 Novel Coronirus (2019-nCoV).
The initial respiratory specimens (nasopharyngeal and oropharyngeal swabs) obtained from this patient on day 4 of his illness were positive for 2019-nCoV (Table 2).
The low cycle threshold (Ct) values (18 to 20 in nasopharyngeal specimens and 21 to 22 in oropharyngeal specimens) on illness day 4 suggest high levels of virus in these specimens, despite the patient’s initial mild symptom presentation.
Both upper respiratory specimens obtained on illness day 7 remained positive for 2019-nCoV, including persistent high levels in a nasopharyngeal swab specimen (Ct values, 23 to 24). Stool obtained on illness day 7 was also positive for 2019-nCoV (Ct values, 36 to 38).
Serum specimens for both collection dates were negative for 2019-nCoV. Nasopharyngeal and oropharyngeal specimens obtained on illness days 11 and 12 showed a trend toward decreasing levels of virus. The oropharyngeal specimen tested negative for 2019-nCoV on illness day 12. The rRT-PCR results for serum obtained on these dates are still pending.
GENETIC SEQUENCING
The full genome sequences from oropharyngeal and nasopharyngeal specimens were identical to one another and were nearly identical to other ailable 2019-nCoV sequences.
There were only 3 nucleotides and 1 amino acid that differed at open reading frame 8 between this patient’s virus and the 2019-nCoV reference sequence (NC_045512.2). The sequence is ailable through GenBank (accession number MN985325).
DISCUSSION
Our report of the first confirmed case of 2019-nCoV in the United States illustrates several aspects of this emerging outbreak that are not yet fully understood, including transmission dynamics and the full spectrum of clinical illness.
Our case patient had treled to Wuhan, China, but reported that he had not visited the wholesale seafood market or health care facilities or had any sick contacts during his stay in Wuhan. Although the source of his 2019-nCoV infection is unknown, evidence of person-to-person transmission has been published.
Through January 30, 2020, no secondary cases of 2019-nCoV related to this case he been identified, but monitoring of close contacts continues.
Detection of 2019-nCoV RNA in specimens from the upper respiratory tract with low Ct values on day 4 and day 7 of illness is suggestive of high viral loads and potential for transmissibility.
It is notable that we also detected 2019-nCoV RNA in a stool specimen collected on day 7 of the patient’s illness. Although serum specimens from our case patient were repeatedly negative for 2019-nCoV, viral RNA has been detected in blood in severely ill patients in China.
However, extrapulmonary detection of viral RNA does not necessarily mean that infectious virus is present, and the clinical significance of the detection of viral RNA outside the respiratory tract is unknown at this time.
Currently, our understanding of the clinical spectrum of 2019-nCoV infection is very limited. Complications such as severe pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), and cardiac injury, including fatal outcomes, he been reported in China.
However, it is important to note that these cases were identified on the basis of their pneumonia diagnosis and thus may bias reporting toward more severe outcomes.
Our case patient initially presented with mild cough and low-grade intermittent fevers, without evidence of pneumonia on chest radiography on day 4 of his illness, before hing progression to pneumonia by illness day 9.
These nonspecific signs and symptoms of mild illness early in the clinical course of 2019-nCoV infection may be indistinguishable clinically from many other common infectious diseases, particularly during the winter respiratory virus season. In addition, the timing of our case patient’s progression to pneumonia on day 9 of illness is consistent with later onset of dyspnea (at a median of 8 days from onset) reported in a recent publication.
Although a decision to administer remdesivir for compassionate use was based on the case patient’s worsening clinical status, randomized controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection.
We report the clinical features of the first reported patient with 2019-nCoV infection in the United States.
Key aspects of this case included the decision made by the patient to seek medical attention after reading public health warnings about the outbreak; recognition of the patient’s recent trel history to Wuhan by local providers, with subsequent coordination among local, state, and federal public health officials; and identification of possible 2019-nCoV infection, which allowed for prompt isolation of the patient and subsequent laboratory confirmation of 2019-nCoV, as well as for admission of the patient for further evaluation and management.
This case report highlights the importance of clinicians eliciting a recent history of trel or exposure to sick contacts in any patient presenting for medical care with acute illness symptoms, in order to ensure appropriate identification and prompt isolation of patients who may be at risk for 2019-nCoV infection and to help reduce further transmission.
Finally, this report highlights the need to determine the full spectrum and natural history of clinical disease, pathogenesis, and duration of viral shedding associated with 2019-nCoV infection to inform clinical management and public health decision making.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
This article was published on January 31, 2020, at NEJM.org.
We thank the patient; the nurses and clinical staff who are providing care for the patient; staff at the local and state health departments; staff at the Washington State Department of Health Public Health Laboratories and at the Centers for Disease Control and Prevention (CDC) Division of Viral Disease Laboratory; CDC staff at the Emergency Operations Center; and members of the 2019-nCoV response teams at the local, state, and national levels.
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