摘录
在之近现代南昌开始的新型冠状狂犬病（2019-nCoV）爆发进一步席卷，如今在多个国家确诊。我们调查报告了在American获知的首例2019-nCoV染病患者，并阐述了该患者的鉴定，临床，针灸更进一步和政府机构，以除此以外病人在病状第9天显成为心脏病时的本来轻度关节炎状。
该事例凸显了针灸药剂师与人口众多，两州和联邦议会各级霍乱新加坡政府之间密切协作的最重要性，以及需要快速传扬与这种新发染病病人的医疗有关的针灸信息的需求。
2019年12月底31日，之近现代调查报告了与潜江南昌市华南海产菜零售商有关的老年人之中的心脏病患者。
2020年1月底7日，之近现代卫生新加坡政府获知该簇与新型冠状狂犬病2019-nCoV有关。尽管本来路透社的患者与南昌市海产零售商的暴露有关，但当年前的统计学数据暗示，正试图发生2019-nCoV同侪传扬。
截至2020年1月底30日，在至少21个国家/东部调查报告了9976例患者，以除此以外2020年1月底20日路透社的American首例确诊的2019-nCoV染病患者。
全部都是球以内内正试图同步进行调查，以越来越好地了解传扬快照和针灸病症以内。本调查报告阐述了在American获知的首例2019-nCoV染病的统计学和针灸特征。
事例调查报告
2020年1月底19日，一名35岁的男子显现成来在华盛顿两州赖斯霍米什县的一家患病疗程药房，有4天的肿胀和主观头痛文化史。病人到药房检查时，在候诊室戴上；大罩。下次大约20分钟后，他被送到检查室接受了提供商的风险评估。
他暗示，他在之近现代南昌探望亲戚后于1月底15日送回华盛顿两州。该病人此表示，他已从American病症控制与霍乱之中心（CDC）收到有关之近现代新型冠状狂犬病暴发的健康警报，由于他的关节炎状和近来的之旅，他要求去看药剂师。
平面图1-2020年1月底19日（病症第4天）的后年前胸和除此以外侧胸片
除了年级酸酯血关节炎的病文化史除此以外，该病人还是其他健康的不吸烟者。体格检查找到病人新陈代谢环境液体时，体温为37.2°C，血压为134/87 mm Hg，脉搏为每分钟110次，新陈代谢振幅为每分钟16次，锂相对于为96％。胃部听诊看成有风湿热，并同步进行了胸片检查，据路透社未找到极度（平面图1）。
亚型和乙型流行性感冒的快速脱锂核分裂糖核分裂酸导入次测试（NAAT）为比如说。赢取了喉咽拭子遗骸，并通过NAAT将其送去检验狂犬病性新陈代谢道微生物。
据路透社在48全程内对所有次测试的微生物仅有红褐色比如说，以除此以外亚型和乙型流行性感冒，副流行性感冒，新陈代谢道合胞狂犬病，喉狂犬病，腺狂犬病和已知会导致人类病症的四种常见冠状狂犬病株（HKU1，NL63、229E和OC43） ）。根据病人的之旅历文化史，尽快通知人口众多和两州卫生部门。华盛顿卫生部与紧急情况医疗针灸药剂师一齐通知了CDC紧急情况行动之中心。
尽管该病人调查报告时说他不能去过华南海产零售商，也不能调查报告在去之近现代之旅后曾与年老者有任何碰触，但病症霍乱控制之中心的工作技术人员提议有合理根据当年前的病症霍乱控制之中心对病人同步进行2019-nCoV次测试。
根据CDC手册搜集了8个遗骸，以除此以外抗体，喉咽和；大咽拭子遗骸。遗骸采集后，病人被送到家庭可避免，并由当地卫生部门同步进行尽力监测。
2020年1月底20日，病症霍乱控制之中心（CDC）获知病人的喉咽和；大咽拭子通过可视逆转录酶-聚合酶链反应（rRT-PCR）检验为2019-nCoV染病性。
在病症霍乱控制之中心的主题专家，两州和人口众多卫生高级官员，紧急情况医疗服务以及的医院指派和工作技术人员的配合下，病人被送到普罗维登斯东部医疗之中心的液体可避免病房同步进行针灸检视，并跟随病症霍乱控制之中心的医护技术人员有关碰触，飞沫和空之中防护措施的此表示提议，并带有护目镜。
入院时病人调查报告短时间肿胀，有2天的麻木和呕吐文化史。他调查报告时说他不能新陈代谢急促或胸痛。永生体征在正常以内内。体格检查找到病人表皮炎热。其余的检查通常不明显。
入院后，病人接受了默许疗程，以除此以外2天和生理盐水和恩丹以消除麻木。
平面图2-根据病症日和患病日（2020年1月底16日至2020年1月底30日）的关节炎状和高达体温
在患病的第2至5天（年老的第6至9天），病人的永生体征整体比较稳定，除了显现成来经年累月头痛并经年累月心动过速（平面图2）。病人继续调查报告非生产性肿胀，并显现成来疲倦。
在患病第二天的下午，病人排便通畅，腹部不适。下午有第二次睡觉时稀疏的路透社。搜集该老鼠的样品可用rRT-PCR次测试，以及其他新陈代谢道遗骸（喉咽和；大咽）和抗体。老鼠和两个新陈代谢道遗骸后来仅有通过rRT-PCR检验为2019-nCoV染病性，而抗体仍为比如说。
在此后曾的疗程在极大程度上是自我政府机构的。为了同步进行关节炎状处理方式，病人需要根据需要接受解热疗法，该疗法以除此以外每4全程650 mg对乙酰尿素基酚和每6全程600 mg抗抑郁药。在患病的年前六天，他还因短时间肿胀而服用了600毫克愈来愈创醚和大约6天和生理盐水。
此表1-针灸研究小组结果
病人可避免单元的并不一定本来仅强制即时医疗点研究小组次测试；从的医院第3天开始可以同步进行全部都是脑组织计数和抗体化学数据分析。
在的医院第3天和第5天（病症第7天和第9天）的研究小组结果揭示成白细胞提高关节炎，轻度血小板提高关节炎和肌酸激酶水平天和高（此表1）。此除此以外，肝功能指标也有所波动：碱性磷酸酶（每天和68 U），丙尿素酸尿素基转移酶（每天和105 U），天冬尿素酸尿素基转移酶（每天和77 U）和乳酸脱氢酶（每天和465 U）的水平分别为：在患病的第5天所有天和高。鉴于病人反复头痛，在第4天赢取血清培养；迄今为止，这些都不能上涨。
平面图3-2020年1月底22日（脸部第7天，的医院第3天）的后年前胸和除此以外侧胸片
平面图4-2020年1月底24日（脸部第5天，的医院第9天）的后年前胸X线片
据路透社，在的医院第3天（年老第7天）拍摄的脸部X光片未看成浸润或极度迹象（平面图3）。
但是，从的医院第5天下午（年老第9天）下午同步进行的第二次脸部X光片检查看成，左肺下叶有心脏病（平面图4）。
这些某类找到与从的医院第5天下午开始的新陈代谢状态波动相赞同，当时病人在新陈代谢周围液体时通过脉搏血锂相对于量度的血锂相对于绝对值降至90％。
在第6天，病人开始接受合理压缩液体，该压缩液体由喉导管以每分钟2天和的速度输送。显然针灸显成的波动和对的医院赢取心脏病的关注，开始适用万古霉素（1750 mg超载剂量，然后每8全程肌肉注射1 g）和头孢日本杯肟（每8全程肌肉注射）疗程。
平面图5-年前后脸部X光片，2020年1月底26日（病症第十天，的医院第六天）
在的医院第6天（年老第10天），第四次脸部X射线照片看成两个肺之中都有连续性条状混浊，这一找到与非典型心脏病相符（平面图5），并且在听诊时在两个肺之中都显现成来了罗音。鉴于辐射线某类找到，要求获得压缩液体合理，病人短时间头痛，多个部位短时间染病性的2019-nCoV RNA染病性，以及发此表了与辐射线心脏病发展赞同的轻微心脏病在该病人之中，针灸药剂师富有同情心地适用了数据分析性抗狂犬病疗程。
肌肉注射瑞德昔韦（一种正试图开发的新型胺基酸酰胺年前药）在第7天下午开始，但未检视到与施打有关的不良事件。在对甲锂周明耐药的紫色芽孢同步进行了连续的降钙素原水平和喉PCR检验后，在第7天下午停用万古霉素，并在第二天停用头孢日本杯肟。
在的医院第8天（年老第12天），病人的针灸现况赢取加强。暂时中止合理压缩液体，他在新陈代谢周围液体时的锂相对于绝对值提高到94％至96％。先年前的双侧下叶罗音不再存有。他的食欲赢取加强，除了经年累月干咳和喉漏除此以外，他不能关节炎状。
截至2020年1月底30日，病人仍患病。他有发热，除肿胀除此以外，所有关节炎状仅有已消除，肿胀的程度正试图减轻。
原理
遗骸采集
根据CDC手册赢取可用2019-nCoV临床次测试的针灸遗骸。用合成纤维拭子搜集了12个喉咽和；大咽拭子遗骸。
将每个拭子放入包含2至3 ml狂犬病船运介质的单独杀菌管之中。将血集在抗体分开管之中，然后根据CDC手册同步进行离心。尿和老鼠遗骸分别搜集在杀菌遗骸容器之中。样品在2°C至8°C之间暂存，直到事先输送至CDC。
在病症的第7、11和12天搜集了移位同步进行的2019-nCoV次测试的遗骸，以除此以外喉咽和；大咽拭子，抗体以及尿和老鼠抽取。
2019-NCOV的临床次测试
适用从公开发表公开发表发此表的狂犬病多肽发展而来的rRT-PCR分析法次测试了针灸遗骸。与先年前针对重关节炎急性新陈代谢遗传性冠状狂犬病（SARS-CoV）和之中东新陈代谢遗传性冠状狂犬病（MERS-CoV）的临床原理相同，它不具备三个核分裂衣壳基因特异性和一个染病性依此特异性。该量度的阐述为RRT-PCR面板核分裂酸和间隙和多肽信息之中必需的CDC研究小组信息网站2019-nCoV上。
遗传DNA
2020年1月底7日，之近现代数据分析技术人员通过American国立卫生数据分析院GenBank数据库和全部都是球共享所有流行性感冒数据倡议（GISAID）数据库共享了2019-nCoV的完备基因多肽；随后公开发表发此表了有关可避免2019-nCoV的调查报告。
从rRT-PCR染病性遗骸（；大咽和喉咽）之中提取脱锂核分裂糖核分裂酸，并在Sanger和下一代DNA平台（Illumina和MinIon）上可用全部都是基因DNA。适用5.4.6版的Sequencher硬件（Sanger）完成了多肽组装。minimap硬件，版本2.17（MinIon）；和freebayes硬件1.3.1版（MiSeq）。将完备基因与必需的2019-nCoV参考多肽（GenBank登录号NC_045512.2）同步进行比较。
结果
2019-NCOV的遗骸次测试
此表2-2019年新型冠状狂犬病（2019-nCoV）的可视逆转录酶-聚合酶-链反应次测试结果
该病人在年老第4天时赢取的初始新陈代谢道抽取（喉咽拭子和；大咽拭子）在2019-nCoV红褐色染病性（此表2）。
尽管病人本来显成为轻度关节炎状，但在病症第4天的偏高尿素阈绝对值（Ct）绝对值（喉咽遗骸之中为18至20，；大咽遗骸之中为21至22）暗示这些遗骸之中狂犬病水平较高。
在病症第7天赢取的两个上新陈代谢道遗骸在2019-nCoV仍保持染病性，以除此以外喉咽拭子遗骸之中短时间偏高水平（Ct绝对值23至24）。在病症第7天赢取的老鼠在2019-nCoV之中也红褐色染病性（Ct绝对值为36至38）。两种采集日期的抗体抽取在2019-nCoV仅有为比如说。
在病症第11天和第12天赢取的喉咽和；大咽遗骸看成成狂犬病水平下降的趋势。
；大咽遗骸在年老第12天的2019-nCoV次测试红褐色比如说。在这些日期赢取的抗体的rRT-PCR结果仍未定。
遗传DNA
；大咽和喉咽遗骸的完备基因多肽彼此相同，并且与其他必需的2019-nCoV多肽几乎相同。
该病人的狂犬病与2019-nCoV参考多肽（NC_045512.2）在解禁读者框8处为数不多3个胺基酸和1个不同。该多肽可通过GenBank赢取（登录号MN985325）。
讨论区
我们关于American首例2019-nCoV确诊患者的调查报告时揭示这一新兴病症的几个方面并未完全部都是了解，以除此以外传扬快照和针灸病症的全部都是部以内。
我们的患者病人曾去过之近现代南昌，但调查报告时说他在南昌后曾不能去过海产菜零售商或医疗机构，也不能患病的碰触。尽管他的2019-nCoV染病的来源尚不明确，但已公开发表了人对人传扬的证据。
到2020年1月底30日，并未找到与此患者关的的2019-nCoV继发患者，但仍在密切监视下。
在病症的第4天和第7天从上新陈代谢道遗骸之中检验到不具备偏高Ct绝对值的2019-nCoV RNA，暗示狂犬病载量高且不具备传扬前瞻性。
绝对值得特别注意的是，我们还在病人年老第7天搜集的老鼠抽取之中检验到了2019-nCoV RNA。尽管我们患者病人的抗体遗骸反复显现成来2019-nCoV比如说，但在之近现代重关节炎病人的血清之中仍检验到狂犬病RNA。然而，肺除此以外检验狂犬病RNA也就是说意味着存有传染性狂犬病，目年前尚不明确在新陈代谢道除此以外部检验狂犬病RNA的针灸意义。
目年前，我们对2019-nCoV染病的针灸以内的了解非常有限。在之近现代，已经路透社了诸如轻微的心脏病，新陈代谢衰竭，急性新陈代谢窘迫遗传性（ARDS）和心脏重击等并发关节炎，以除此以外灾难性的轻微后果。然而，最重要的是要特别注意，这些患者是根据其心脏病临床确切的，因此可能会使调查报告相对于越来越轻微的结果。
我们的患者病人本来显成为轻度肿胀和偏高度经年累月头痛，在年老的第4天不能脸部X光检查的心脏病迹象，而在年老第9天发展为心脏病之年前，这些非特异性体征和关节炎状在后期在针灸上，2019-nCoV染病的针灸更进一步可能与许多其他常见霍乱不能明显区别于，尤其是在冬季新陈代谢道狂犬病冬天。
另除此以外，本患者病人在病症的第9天发展为心脏病的时机与近来新陈代谢困难的高烧（病症后之人口统计为8天）赞同。尽管根据病人的针灸现况恶化要求是否获得remdesivir善心的适用，但仍需要同步进行随机依此实验以确切remdesivir和任何其他数据分析药物疗程2019-nCoV染病的安全部都是性和有效性。
我们调查报告了American首例调查报告的2019-nCoV染病病人的针灸特征。
该患者的关键方面以除此以外病人在读者有关暴发的霍乱警告后要求寻求医疗；由当地医疗服务提供商获知病人近来到南昌的之旅历文化史，随后在当地，两州和联邦议会霍乱高级官员之间同步进行协调；并确切可能的2019-nCoV染病，从而可以进一步可避免病人并随后对2019-nCoV同步进行研究小组获知，并强制病人入院促使风险评估和政府机构。
该患者调查报告凸显了针灸药剂师对于任何显现成来急性病症关节炎状的就诊病人，要总结成近来的之旅经历或碰触病文化史的最重要性，为了确保确实标记和及时可避免可能面临2019-nCoV染病风险的病人，并希望提高促使的传扬。
最后，本调查报告凸显需要确切与2019-nCoV染病关的的针灸病症，病症机理和狂犬病脱落短时间时间的
全部都是部以内和人为历文化史，以为针灸政府机构和霍乱决策提供依据。
以下为国际版
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Summary
An outbreak of novel coronirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
On December 31, 2019, China reported a cluster of cases of pneumonia in people associated with the Huanan Seafood Wholesale Market in Wuhan, Hubei Province.
On January 7, 2020, Chinese health authorities confirmed that this cluster was associated with a novel coronirus, 2019-nCoV.
Although cases were originally reported to be associated with exposure to the seafood market in Wuhan, current epidemiologic data indicate that person-to-person transmission of 2019-nCoV is occurring.
As of January 30, 2020, a total of 9976 cases had been reported in at least 21 countries,including the first confirmed case of 2019-nCoV infection in the United States, reported on January 20, 2020.
Investigations are under way worldwide to better understand transmission dynamics and the spectrum of clinical illness.
This report describes the epidemiologic and clinical features of the first case of 2019-nCoV infection confirmed in the United States.
Case Report
On January 19, 2020, a 35-year-old man presented to an urgent care clinic in Snohomish County, Washington, with a 4-day history of cough and subjective fever.
On checking into the clinic, the patient put on a mask in the waiting room. After waiting approximately 20 minutes, he was taken into an examination room and underwent evaluation by a provider. He disclosed that he had returned to Washington State on January 15 after treling to visit family in Wuhan, China.
The patient stated that he had seen a health alert from the U.S. Centers for Disease Control and Prevention (CDC) about the novel coronirus outbreak in China and, because of his symptoms and recent trel, decided to see a health care provider.
Figure 1.Posteroanterior and Lateral Chest Radiographs, January 19, 2020 (Illness Day 4).
Apart from a history of hypertriglyceridemia, the patient was an otherwise healthy nonsmoker. The physical examination revealed a body temperature of 37.2°C, blood pressure of 134/87 mm Hg, pulse of 110 beats per minute, respiratory rate of 16 breaths per minute, and oxygen saturation of 96% while the patient was breathing ambient air. Lung auscultation revealed rhonchi, and chest radiography was performed, which was reported as showing no abnormalities (Figure 1).
A rapid nucleic acid amplification test (NAAT) for influenza A and B was negative. A nasopharyngeal swab specimen was obtained and sent for detection of viral respiratory pathogens by NAAT; this was reported back within 48 hours as negative for all pathogens tested, including influenza A and B, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, and four common coronirus strains known to cause illness in humans (HKU1, NL63, 229E, and OC43).
Given the patient’s trel history, the local and state health departments were immediately notified. Together with the urgent care clinician, the Washington Department of Health notified the CDC Emergency Operations Center.
Although the patient reported that he had not spent time at the Huanan seafood market and reported no known contact with ill persons during his trel to China, CDC staff concurred with the need to test the patient for 2019-nCoV on the basis of current CDC “persons under investigation” case definitions.
Specimens were collected in accordance with CDC guidance and included serum and nasopharyngeal and oropharyngeal swab specimens. After specimen collection, the patient was discharged to home isolation with active monitoring by the local health department.
On January 20, 2020, the CDC confirmed that the patient’s nasopharyngeal and oropharyngeal swabs tested positive for 2019-nCoV by real-time reverse-transcriptase–polymerase-chain-reaction (rRT-PCR) assay.
In coordination with CDC subject-matter experts, state and local health officials, emergency medical services, and hospital leadership and staff, the patient was admitted to an airborne-isolation unit at Providence Regional Medical Center for clinical observation, with health care workers following CDC recommendations for contact, droplet, and airborne precautions with eye protection.
On admission, the patient reported persistent dry cough and a 2-day history of nausea and vomiting; he reported that he had no shortness of breath or chest pain. Vital signs were within normal ranges. On physical examination, the patient was found to he dry mucous membranes. The remainder of the examination was generally unremarkable. After admission, the patient received supportive care, including 2 liters of normal saline and ondansetron for nausea.
Figure 2.Symptoms and Maximum Body Temperatures According to Day of Illness and Day of Hospitalization, January 16 to January 30, 2020.
On days 2 through 5 of hospitalization (days 6 through 9 of illness), the patient’s vital signs remained largely stable, apart from the development of intermittent fevers accompanied by periods of tachycardia (Figure 2).
The patient continued to report a nonproductive cough and appeared fatigued. On the afternoon of hospital day 2, the patient passed a loose bowel movement and reported abdominal discomfort. A second episode of loose stool was reported overnight; a sample of this stool was collected for rRT-PCR testing, along with additional respiratory specimens (nasopharyngeal and oropharyngeal) and serum.
The stool and both respiratory specimens later tested positive by rRT-PCR for 2019-nCoV, whereas the serum remained negative.
Treatment during this time was largely supportive. For symptom management, the patient received, as needed, antipyretic therapy consisting of 650 mg of acetaminophen every 4 hours and 600 mg of ibuprofen every 6 hours. He also received 600 mg of guaifenesin for his continued cough and approximately 6 liters of normal saline over the first 6 days of hospitalization.
Table 1.Clinical Laboratory Results.
The nature of the patient isolation unit permitted only point-of-care laboratory testing initially; complete blood counts and serum chemical studies were ailable starting on hospital day 3.
Laboratory results on hospital days 3 and 5 (illness days 7 and 9) reflected leukopenia, mild thrombocytopenia, and elevated levels of creatine kinase (Table 1).
In addition, there were alterations in hepatic function measures: levels of alkaline phosphatase (68 U per liter), alanine aminotransferase (105 U per liter), aspartate aminotransferase (77 U per liter), and lactate dehydrogenase (465 U per liter) were all elevated on day 5 of hospitalization.
Given the patient’s recurrent fevers, blood cultures were obtained on day 4; these he shown no growth to date.
Figure 3.Posteroanterior and Lateral Chest Radiographs, January 22, 2020 (Illness Day 7, Hospital Day 3).
Figure 4.Posteroanterior Chest Radiograph, January 24, 2020 (Illness Day 9, Hospital Day 5).
A chest radiograph taken on hospital day 3 (illness day 7) was reported as showing no evidence of infiltrates or abnormalities (Figure 3).
However, a second chest radiograph from the night of hospital day 5 (illness day 9) showed evidence of pneumonia in the lower lobe of the left lung (Figure 4).
These radiographic findings coincided with a change in respiratory status starting on the evening of hospital day 5, when the patient’s oxygen saturation values as measured by pulse oximetry dropped to as low as 90% while he was breathing ambient air.
On day 6, the patient was started on supplemental oxygen, delivered by nasal cannula at 2 liters per minute.
Given the changing clinical presentation and concern about hospital-acquired pneumonia, treatment with vancomycin (a 1750-mg loading dose followed by 1 g administered intrenously every 8 hours) and cefepime (administered intrenously every 8 hours) was initiated.
Figure 5.Anteroposterior and Lateral Chest Radiographs, January 26, 2020 (Illness Day 10, Hospital Day 6).
On hospital day 6 (illness day 10), a fourth chest radiograph showed basilar streaky opacities in both lungs, a finding consistent with atypical pneumonia (Figure 5), and rales were noted in both lungs on auscultation.
Given the radiographic findings, the decision to administer oxygen supplementation, the patient’s ongoing fevers, the persistent positive 2019-nCoV RNA at multiple sites, and published reports of the development of severe pneumonia at a period consistent with the development of radiographic pneumonia in this patient, clinicians pursued compassionate use of an investigational antiviral therapy.
Treatment with intrenous remdesivir (a novel nucleotide ogue prodrug in development) was initiated on the evening of day 7, and no adverse events were observed in association with the infusion.
Vancomycin was discontinued on the evening of day 7, and cefepime was discontinued on the following day, after serial negative procalcitonin levels and negative nasal PCR testing for methicillin-resistant Staphylococcus aureus.
On hospital day 8 (illness day 12), the patient’s clinical condition improved. Supplemental oxygen was discontinued, and his oxygen saturation values improved to 94 to 96% while he was breathing ambient air.
The previous bilateral lower-lobe rales were no longer present. His appetite improved, and he was asymptomatic aside from intermittent dry cough and rhinorrhea.
As of January 30, 2020, the patient remains hospitalized. He is afebrile, and all symptoms he resolved with the exception of his cough, which is decreasing in severity.
Methods
SPECIMEN COLLECTIONClinical specimens for 2019-nCoV diagnostic testing were obtained in accordance with CDC guidelines. Nasopharyngeal and oropharyngeal swab specimens were collected with synthetic fiber swabs; each swab was inserted into a separate sterile tube containing 2 to 3 ml of viral transport medium. Serum was collected in a serum separator tube and then centrifuged in accordance with CDC guidelines. The urine and stool specimens were each collected in sterile specimen containers. Specimens were stored between 2°C and 8°C until ready for shipment to the CDC. Specimens for repeat 2019-nCoV testing were collected on illness days 7, 11, and 12 and included nasopharyngeal and oropharyngeal swabs, serum, and urine and stool samples.
DIAGNOSTIC TESTING FOR 2019-NCOV
Clinical specimens were tested with an rRT-PCR assay that was developed from the publicly released virus sequence. Similar to previous diagnostic assays for severe acute respiratory syndrome coronirus (SARS-CoV) and Middle East respiratory syndrome coronirus (MERS-CoV), it has three nucleocapsid gene targets and a positive control target.
A description of this assay and sequence information for the rRT-PCR panel primers and probes are ailable on the CDC Laboratory Information website for 2019-nCoV.
GENETIC SEQUENCING
On January 7, 2020, Chinese researchers shared the full genetic sequence of 2019-nCoV through the National Institutes of Health GenBank database and the Global Initiative on Sharing All Influenza Data (GISAID) database; a report about the isolation of 2019-nCoV was later published.
Nucleic acid was extracted from rRT-PCR–positive specimens (oropharyngeal and nasopharyngeal) and used for whole-genome sequencing on both Sanger and next-generation sequencing platforms (Illumina and MinIon).
Sequence assembly was completed with the use of Sequencher software, version 5.4.6 (Sanger); minimap software, version 2.17 (MinIon); and freebayes software, version 1.3.1 (MiSeq). Complete genomes were compared with the ailable 2019-nCoV reference sequence (GenBank accession number NC_045512.2).
Results
SPECIMEN TESTING FOR 2019-NCOV
Table 2.Results of Real-Time Reverse-Transcriptase–Polymerase-Chain-Reaction Testing for the 2019 Novel Coronirus (2019-nCoV).
The initial respiratory specimens (nasopharyngeal and oropharyngeal swabs) obtained from this patient on day 4 of his illness were positive for 2019-nCoV (Table 2).
The low cycle threshold (Ct) values (18 to 20 in nasopharyngeal specimens and 21 to 22 in oropharyngeal specimens) on illness day 4 suggest high levels of virus in these specimens, despite the patient’s initial mild symptom presentation.
Both upper respiratory specimens obtained on illness day 7 remained positive for 2019-nCoV, including persistent high levels in a nasopharyngeal swab specimen (Ct values, 23 to 24). Stool obtained on illness day 7 was also positive for 2019-nCoV (Ct values, 36 to 38).
Serum specimens for both collection dates were negative for 2019-nCoV. Nasopharyngeal and oropharyngeal specimens obtained on illness days 11 and 12 showed a trend toward decreasing levels of virus. The oropharyngeal specimen tested negative for 2019-nCoV on illness day 12. The rRT-PCR results for serum obtained on these dates are still pending.
GENETIC SEQUENCING
The full genome sequences from oropharyngeal and nasopharyngeal specimens were identical to one another and were nearly identical to other ailable 2019-nCoV sequences.
There were only 3 nucleotides and 1 amino acid that differed at open reading frame 8 between this patient’s virus and the 2019-nCoV reference sequence (NC_045512.2). The sequence is ailable through GenBank (accession number MN985325).
DISCUSSION
Our report of the first confirmed case of 2019-nCoV in the United States illustrates several aspects of this emerging outbreak that are not yet fully understood, including transmission dynamics and the full spectrum of clinical illness.
Our case patient had treled to Wuhan, China, but reported that he had not visited the wholesale seafood market or health care facilities or had any sick contacts during his stay in Wuhan. Although the source of his 2019-nCoV infection is unknown, evidence of person-to-person transmission has been published.
Through January 30, 2020, no secondary cases of 2019-nCoV related to this case he been identified, but monitoring of close contacts continues.
Detection of 2019-nCoV RNA in specimens from the upper respiratory tract with low Ct values on day 4 and day 7 of illness is suggestive of high viral loads and potential for transmissibility.
It is notable that we also detected 2019-nCoV RNA in a stool specimen collected on day 7 of the patient’s illness. Although serum specimens from our case patient were repeatedly negative for 2019-nCoV, viral RNA has been detected in blood in severely ill patients in China.
However, extrapulmonary detection of viral RNA does not necessarily mean that infectious virus is present, and the clinical significance of the detection of viral RNA outside the respiratory tract is unknown at this time.
Currently, our understanding of the clinical spectrum of 2019-nCoV infection is very limited. Complications such as severe pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), and cardiac injury, including fatal outcomes, he been reported in China.
However, it is important to note that these cases were identified on the basis of their pneumonia diagnosis and thus may bias reporting toward more severe outcomes.
Our case patient initially presented with mild cough and low-grade intermittent fevers, without evidence of pneumonia on chest radiography on day 4 of his illness, before hing progression to pneumonia by illness day 9.
These nonspecific signs and symptoms of mild illness early in the clinical course of 2019-nCoV infection may be indistinguishable clinically from many other common infectious diseases, particularly during the winter respiratory virus season. In addition, the timing of our case patient’s progression to pneumonia on day 9 of illness is consistent with later onset of dyspnea (at a median of 8 days from onset) reported in a recent publication.
Although a decision to administer remdesivir for compassionate use was based on the case patient’s worsening clinical status, randomized controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection.
We report the clinical features of the first reported patient with 2019-nCoV infection in the United States.
Key aspects of this case included the decision made by the patient to seek medical attention after reading public health warnings about the outbreak; recognition of the patient’s recent trel history to Wuhan by local providers, with subsequent coordination among local, state, and federal public health officials; and identification of possible 2019-nCoV infection, which allowed for prompt isolation of the patient and subsequent laboratory confirmation of 2019-nCoV, as well as for admission of the patient for further evaluation and management.
This case report highlights the importance of clinicians eliciting a recent history of trel or exposure to sick contacts in any patient presenting for medical care with acute illness symptoms, in order to ensure appropriate identification and prompt isolation of patients who may be at risk for 2019-nCoV infection and to help reduce further transmission.
Finally, this report highlights the need to determine the full spectrum and natural history of clinical disease, pathogenesis, and duration of viral shedding associated with 2019-nCoV infection to inform clinical management and public health decision making.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
This article was published on January 31, 2020, at NEJM.org.
We thank the patient; the nurses and clinical staff who are providing care for the patient; staff at the local and state health departments; staff at the Washington State Department of Health Public Health Laboratories and at the Centers for Disease Control and Prevention (CDC) Division of Viral Disease Laboratory; CDC staff at the Emergency Operations Center; and members of the 2019-nCoV response teams at the local, state, and national levels.
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