摘要
在欧美长沙开始的新型冠状病原（2019-nCoV）爆发急剧延烧，现已在多个东欧国家就诊。我们年度报告了在加拿大证实的月所2019-nCoV细菌感染随之而来率，并刻画了该随之而来率的检验，检验，检验每一次和管理制度，之外病征在病情第9天注记现为心肌梗塞时的原本轻度疼痛。
该个案特别强调了检验心理医生与以前，俄克拉荷马州和联邦各级医疗卫生保健当局二者之间密切协作的不可忽视性，以及必需快速传播方式与这种新发细菌感染病征的看护有关的检验资讯的需求量。
2019年12月末31日，欧美年度报告了与湖北省宜昌市华南菜式批发商品有关的年轻人之当年的心肌梗塞随之而来率。
2020年1月末7日，欧美卫生保健当局证实该簇与新型冠状病原2019-nCoV有关。尽管原本路透社的随之而来率与宜昌市菜式商品的掩盖有关，但当当年的毒理学绘成表注记明，正要随之而来2019-nCoV人际传播方式。
截至2020年1月末30日，在仅仅21个东欧国家/地区年度报告了9976例随之而来率，之外2020年1月末20日路透社的加拿大月所就诊的2019-nCoV细菌感染随之而来率。
当今世界区域正要展开调查，以更加好地探究传播方式时序和检验传染病范围。本年度报告刻画了在加拿大证实的月所2019-nCoV细菌感染的毒理学和检验形态。
个案年度报告
2020年1月末19日，一名35岁的男子经常成现在华盛顿俄克拉荷马州鲍威尔霍米什县的一家门诊的医院，有4天的肠胃和认知颤动困难通史。病人到的医院检验时，在候诊室戴上侧罩。马上将近20分钟后，他被带往检验室遵从了获取者的指标。
他透露，他在欧美长沙探访家人先于1月末15日赶回华盛顿俄克拉荷马州。该病征对此，他已从加拿大传染病操纵与防止之当年心（CDC）收到有关欧美新型冠状病原随之而来的身体健康警报，由于他的疼痛和都只的之旅，他暂时去看心理医生。
绘成1-2020年1月末19日（传染病第4天）的后腹部和均侧胸片
除了高年级酸酯血关节炎的病患均，该病征还是其他身体健康的不吸烟者。体格检验见到病征颤动环境二氧化碳时，血糖为37.2°C，血压为134/87 mm Hg，脉搏为每分钟110次，颤动振幅为每分钟16次，锂原色为96％。胸腔听诊说明了有肾病，并展开了胸片检验，据路透社没见到异常（绘成1）。
甲类肝炎和甲类SARS的快速大分子扩充的测试（NAAT）为中性。给予了颈咽拭子骨骼，并通过NAAT将其送去测定病原性颤动道病原体。
据路透社在48小时内对所有的测试的病原体均呈圆形中性，之外甲类肝炎和甲类SARS，副SARS，颤动道合胞病原，颈病原，腺病原和仅有才会导致进化传染病的四种类似于冠状病原株（HKU1，NL63、229E和OC43） ）。根据病征的之旅历通史背景，几天后指示以前和俄克拉荷马州副部长门。华盛顿副部长与应急看护检验心理医生一起指示了CDC应急行动之当年心。
尽管该病征年度报告知道他没去过华南菜式商品，也没年度报告在去欧美之旅此后与染病者有任何沾染，但传染病防止机房的工作人员达成协议有必要根据当当年的传染病防止机房对病征展开2019-nCoV的测试。
根据CDC手册查阅了8个骨骼，之外肝细胞，颈咽和侧咽拭子骨骼。骨骼野外后，病征被送至大家庭强制，并由当地副部长门展开努力监测。
2020年1月末20日，传染病防止机房（CDC）证实病征的颈咽和侧咽拭子通过系统对抗病毒-PCR链反应（rRT-PCR）测定为2019-nCoV非近似于。
在传染病防止机房的主题专家，俄克拉荷马州和以前卫生保健高级官员，应急卫生服务以及养老院他组织和工作人员的配合下，病征被送至普罗维登斯地区卫生之当年心的二氧化碳强制病房展开检验观察，并跟随传染病防止机房的医护人员有关沾染，飞沫和空之当年防护举措的建议，并隐含外套。
病情衰弱时病征年度报告持续肠胃，有2天的恶心和痉挛通史。他年度报告知道他没颤动急促或咳嗽。生命病症在正常区域。体格检验见到病征上皮湿润。其余的检验通常不明显。
病情衰弱后，病征遵从了背书放射治疗，之外2升至生理盐水和恩丹以缓解恶心。
绘成2-根据传染病日和染病日（2020年1月末16日至2020年1月末30日）的疼痛和最高血糖
在染病的第2至5天（染病的第6至9天），病征的生命病症基本保持稳定，除了经常成现但才会颤动困难并诱发心动过速（绘成2）。病征在此之后年度报告非生产性肠胃，并经常成现疲倦。
在染病第二天的下午，病征吞咽通畅，腹部不适。之当年午有第二次小便稀疏的路透社。查阅该排泄的混合物可用rRT-PCR的测试，以及其他颤动道骨骼（颈咽和侧咽）和肝细胞。排泄和两个颤动道骨骼在此之后均通过rRT-PCR测定为2019-nCoV非近似于，而肝细胞仍为中性。
此当年的放射治疗在很大往往上是背书性的。为了展开疼痛解决问题，病征必需根据必需遵从解热放射治疗法，该放射治疗法之外每4小时650 mg对乙酰硫基酚和每6小时600 mg抗抑郁药。在染病的当年六天，他还因持续肠胃而服用了600毫克少创醚和将近6升至生理盐水。
注记1-检验的实验室结果
病征强制区块的本质原本只能而无须第一时间卫生点的实验室的测试；从养老院第3天开始可以展开正因如此脑组织总和和肝细胞化学研究工作。
在养老院第3天和第5天（传染病第7天和第9天）的的实验室结果反映成红血球减少关节炎，轻度淋巴细胞减少关节炎和肌酸激酶准确度增大（注记1）。此均，肝功能指标也有所巨大变化：碱性磷酸酶（每升至68 U），丙硫酸硫基转移酶（每升至105 U），NAD硫基转移酶（每升至77 U）和乳酸还原酶（每升至465 U）的准确度则有：在染病的第5天所有增大。鉴于病征一再颤动困难，在第4天给予血液培育；迄今为止，这些都没下降。
绘成3-2020年1月末22日（脸部第7天，养老院第3天）的后腹部和均侧胸片
绘成4-2020年1月末24日（脸部第5天，养老院第9天）的后腹部X线片
据路透社，在养老院第3天（染病第7天）拍摄地的脸部X光片没说明了增生或异常迹象（绘成3）。
但是，从养老院第5天之当年午（染病第9天）之当年午展开的第二次脸部X光片检验说明了，左肺下叶有心肌梗塞（绘成4）。
这些CT见到与从养老院第5天之当年午开始的颤动精神状态巨大变化相相反，之前病征在颤动附近二氧化碳时通过脉搏血锂原色测定的血锂原色倍数下调90％。
在第6天，病征开始遵从需用锂气，该锂气由颈支架以每分钟2升至的平均速度输送。显然检验注记现的巨大变化和对养老院给予性心肌梗塞的关注，开始用到高于mg（1750 mg负荷mg，然后每8小时施打1 g）和红霉素锦标肟（每8小时施打）放射治疗。
绘成5-当年后脸部X光片，2020年1月末26日（传染病第十天，养老院第六天）
在养老院第6天（染病第10天），第四次脸部X射线照片说明了两个肺之当年都有基底长条形经年累月，这一见到与非近似于心肌梗塞相符（绘成5），并且在听诊时在两个肺之当年都经常成现了罗音。鉴于放射线CT见到，暂时给予锂气需用，病征持续颤动困难，多个部位持续非近似于的2019-nCoV RNA非近似于，以及发注记了与放射线性心肌梗塞演进相反的轻微心肌梗塞在该病征之当年，检验心理医生富有渴望地用到了研究工作性抗病原放射治疗。
施打艾伦昔韦（一种正要联合开发的新型核苷酸类似物当年药）在第7天之当年午开始，但没观察到与输注有关的不顺事件。在对丙锂朱家耐药的金黄色葡萄球菌展开了周内的降钙素原准确度和颈PCR测定后，在第7天之当年午停用高于mg，并在第二天停用红霉素锦标肟。
在养老院第8天（染病第12天），病征的检验持续性赢取更佳。暂时之当年止需用锂气，他在颤动附近二氧化碳时的锂原色倍数提高到94％至96％。先当年的双侧下叶罗音不再假定。他的食欲赢取更佳，除了但才会干咳和颈漏均，他没疼痛。
截至2020年1月末30日，病征仍染病。他有颤动困难，除肠胃均，所有疼痛均已缓解，肠胃的往往正要大大降低。
方式
骨骼野外
根据CDC手册给予可用2019-nCoV检验的测试的检验骨骼。用化学纤维拭子查阅了12个颈咽和侧咽拭子骨骼。
将每个拭子插入包含2至3 ml病原转运介质的之外杀菌管之当年。将血集在肝细胞受控管之当年，然后根据CDC手册展开离心。尿液和排泄骨骼分别查阅在杀菌骨骼容器之当年。混合物在2°C至8°C二者之间备份，直到做好运输至CDC。
在传染病的第7、11和12天查阅了重复展开的2019-nCoV的测试的骨骼，之外颈咽和侧咽拭子，肝细胞以及尿液和排泄采样。
2019-NCOV的检验的测试
用到从公开释成的病原基因组演进而来的rRT-PCR量化的测试了检验骨骼。与先当年针对重关节炎急性颤动病关节炎冠状病原（SARS-CoV）和之当年亚颤动病关节炎冠状病原（MERS-CoV）的检验方式相似，它兼具三个核衣壳基因大分子和一个非近似于对照大分子。该测定的刻画为RRT-PCR面板引物和探针和基因组资讯之当年需用的CDC的实验室资讯的网站2019-nCoV上。
基因型化学合成
2020年1月末7日，欧美研究工作人员通过加拿大国立卫生保健研究工作院GenBank绘成表源和当今世界共享所有SARS绘成表倡议（GISAID）绘成表源共享了2019-nCoV的基本基因基因组；随后释成了有关强制2019-nCoV的年度报告。
从rRT-PCR非近似于骨骼（侧咽和颈咽）之当年提取大分子，并在Sanger和下一代化学合成平台（Illumina和MinIon）上可用正因如此基因组化学合成。用到5.4.6原版的Sequencher软件（Sanger）展开时了基因组装配。minimap软件，原版本2.17（MinIon）；和freebayes软件1.3.1原版（MiSeq）。将基本基因组与需用的2019-nCoV参见基因组（GenBank登录号NC_045512.2）展开尤其。
结果
2019-NCOV的骨骼的测试
注记2-2019年新型冠状病原（2019-nCoV）的系统对抗病毒-PCR-链反应的测试结果
该病征在染病第4秦人给予的初始颤动道采样（颈咽拭子和侧咽拭子）在2019-nCoV呈圆形非近似于（注记2）。
尽管病征原本注记现为轻度疼痛，但在传染病第4天的高于循环阈倍数（Ct）倍数（颈咽骨骼之当年为18至20，侧咽骨骼之当年为21至22）注记明这些骨骼之当年病原准确度较高。
在传染病第7天给予的两个上颤动道骨骼在2019-nCoV仍保持非近似于，之外颈咽拭子骨骼之当年持续高准确度（Ct倍数23至24）。在传染病第7天给予的排泄在2019-nCoV之当年也呈圆形非近似于（Ct倍数为36至38）。两种野外日期的肝细胞采样在2019-nCoV均为中性。
在传染病第11天和第12天给予的颈咽和侧咽骨骼说明了成病原准确度下降的渐进。
侧咽骨骼在染病第12天的2019-nCoV的测试呈圆形中性。在这些日期给予的肝细胞的rRT-PCR结果仍没定。
基因型化学合成
侧咽和颈咽骨骼的基本基因组基因组彼此相近，并且与其他需用的2019-nCoV基因组却是相近。
该病征的病原与2019-nCoV参见基因组（NC_045512.2）在封闭朗读凸8处只能有3个核苷酸和1个并不相同。该基因组可通过GenBank给予（登录号MN985325）。
讨论区
我们关于加拿大月所2019-nCoV就诊随之而来率的年度报告知道明了这一新兴传染病的几个不足之处即已完正因如此探究，之外传播方式时序和检验传染病的正因如此部范围。
我们的随之而来率病征曾去过欧美长沙，但年度报告知道他在长沙此后没去过菜式批发商品或卫生机构，也没生病的沾染。尽管他的2019-nCoV细菌感染的或许尚为不确实，但已公开了人对人传播方式的证据。
到2020年1月末30日，即已见到与此随之而来率相关的2019-nCoV神经性随之而来率，但仍在密切监视下。
在传染病的第4天和第7天从上颤动道骨骼之当年测定到兼具高于Ct倍数的2019-nCoV RNA，注记明病原载量高且兼具传播方式演进潜力。
倍数得注意的是，我们还在病征染病第7天查阅的排泄采样之当年测定到了2019-nCoV RNA。尽管我们随之而来率病征的肝细胞骨骼一再经常成现2019-nCoV中性，但在欧美重关节炎病征的血液之当年仍测定到病原RNA。然而，肺均测定病原RNA并不一定意味着假定传染性病原，目当年为止尚为不确实在颤动道均部测定病原RNA的检验意义。
目当年为止，我们对2019-nCoV细菌感染的检验范围的探究更加加有限。在欧美，已经路透社了诸如轻微的心肌梗塞，肺气肿，急性颤动窘迫病关节炎（ARDS）和脑干损伤等并发关节炎，之外致命的后果。然而，不可忽视的是要注意，这些随之而来率是根据其心肌梗塞检验明确的，因此或许才会使年度报告偏向更加轻微的结果。
我们的随之而来率病征原本注记现为轻度肠胃和高于度但才会颤动困难，在染病的第4天没脸部X光检验的心肌梗塞迹象，而在染病第9天演进为心肌梗塞之当年，这些非特异性病症和疼痛在早期在检验上，2019-nCoV细菌感染的检验每一次或许与许多其他类似于传染病没明显区分，尤其是在夏季则颤动道病原秋冬季。
另均，本随之而来率病征在传染病的第9天演进为心肌梗塞的时机与近期呕吐的心脏病（发病后之当年位数为8天）相反。尽管根据病征的检验持续性衰弱暂时是否给予remdesivir慈爱的用到，但仍必需展开研究性飞行测试以明确remdesivir和任何其他研究工作抑制剂放射治疗2019-nCoV细菌感染的安正因如此性和确实。
我们年度报告了加拿大月所年度报告的2019-nCoV细菌感染病征的检验形态。
该随之而来率的不可或缺不足之处之外病征在朗读有关随之而来的医疗卫生保健指示后暂时寻求卫生；由当地卫生ISP证实病征都只到长沙的之旅历通史背景，随后在当地，俄克拉荷马州和联邦医疗卫生保健高级官员二者之间展开协调；并明确或许的2019-nCoV细菌感染，从而可以急剧强制病征并随后对2019-nCoV展开的实验室证实，并而无须病征病情衰弱再进一步指标和管理制度。
该随之而来率年度报告特别强调了检验心理医生对于任何经常成现急性传染病疼痛的就诊病征，要论述成都只的之旅亲身经历或沾染病患的不可忽视性，为了确保准确识别系统和第一时间强制或许导致2019-nCoV细菌感染风险的病征，并协助减少再进一步的传播方式。
最后，本年度报告特别强调必需明确与2019-nCoV细菌感染相关的检验传染病，发病机理和病原裂开持续时间的
正因如此部范围和自然环境历通史背景，以为检验管理制度和医疗卫生保健决策获取依据。
请注意为英文原版
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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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