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      甲骨易精譯NEJM論文:新冠肺炎患者入院8天被治愈全過程
      近日,權威醫學期刊《新英格蘭醫學雜志》(NEJM)在線發表了一篇關于新型冠狀病毒(2019-nCoV)的論文,向外界披露了美國首例確診病例的整個診療過程和臨床表現。
       
      我們認為,這些信息對于幫助工作在一線的醫護人員和普通大眾都有著非常重要的意義。因此,甲骨易啟動抗擊疫情翻譯專家小組,對論文的全文進行了精譯,以便于為醫務人員的臨床診療工作提供借鑒,為人們的防疫自查提供參考。
       
      該名患者在發病后的短短12天內被基本治愈:
       
      前4天:2020年1月15日結束在武漢的探親,返回美國便開始咳嗽,期間有兩天的惡心嘔吐史,但沒有感到氣短或胸痛。
       
      第5天:入院第1天,接受了支持療法,包括輸注2升生理鹽水和服用恩丹西酮緩解惡心。
       
      第6-9天:住院的第2天至第5天,除了伴有心動過速的間歇性發熱之外,患者的生命體征基本保持穩定。這段時間的治療基本上采用支持性療法。在癥狀處理方面,患者根據需要接受退熱治療,包括每隔4小時服用650毫克對乙酰氨基酚和每隔6小時服用600毫克布洛芬。
       
      第10天:住院第6天,第四次胸片顯示兩肺存在基底條紋狀渾濁,這一發現與非典型肺炎一致,聽診時發現兩肺有羅音。臨床醫生根據“同情用藥”原則,采用在研抗病毒療法。
       
      第11天:住院第7天,晚上停用萬古霉素。
       
      第12天:住院第8天,患者的臨床病情有所改善。已停止輸氧,當他呼吸環境空氣時,血氧飽和度值提高到94%至96%。先前的雙側下葉羅音不再出現?;颊叩氖秤兴纳?,除了間歇性干咳和流鼻涕之外,沒有其他癥狀。
       
      SUMMARY
       
      概述
       
      An outbreak of novel coronavirus (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 clinician sand 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.
       
      一場始于中國武漢的新型冠狀病毒(2019-nCoV)疫情已迅速蔓延,目前已在多個國家發現確診病例。我們報道的是在美國確診的首例2019-nCoV感染病例,并介紹該病例的鑒定、診斷、臨床表現和治療情況,包括患者最初出現的輕微癥狀并在發病第9天進展成肺炎的過程。本病例凸顯出臨床醫生與地方、州和聯邦各級公共衛生當局之間密切配合的重要性,以及快速宣傳這種新發傳染病相關臨床護理信息的必要性。
       
      ON DECEMBER 31, 2019, CHINA REPORTED A CLUSTEROF CASES OF pneumonia in people associated with the Huanan Seafood Whole sale Market in Wuhan, Hubei Province. On January 7, 2020, Chinese health authorities confirmed that this cluster was associated with a novel coronavirus, 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 isoccurring.3-6 As of January 30, 2020, a total of 9976 cases had been reported in at least 21 countries,7 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.
       
      2019年12月31日,中國報告了在湖北省武漢市華南海鮮批發市場相關人群中發現的一組肺炎病例。2020年1月7日,中國衛生部門證實該組群與2019-nCoV有關。雖然最初報道的病例與武漢海鮮市場接觸有關系,但最新流行病學數據表明該2019-nCoV正在發生人際傳播。截至2020年1月30日,已有至少21個國家報告了共計9,976例病例,其中包括2020年1月20日報告的美國首例2019-nCoV感染確診病例。研究正在全球范圍內展開,以便更好地了解該病毒的傳播動力學和臨床表現。本報告介紹了美國確診的首例2019-nCoV感染的流行病學特征和臨床特征。
       

      Figure 1. Posteroanterior and Lateral Chest Radiographs, January 19, 2020 (Illness Day 4).
      1. 后前位胸片和側位胸片,2020119日(發病第4天)
      No thoracic abnormalities were noted.
      未發現胸部異常。
      CASE REPORT
      病例報告
      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 traveling 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 coronavirus outbreak in China and, because of his symptoms and recent travel, decided to see a health care provider.
      2020年1月19日,一名35歲男子前往華盛頓州斯諾霍米什縣的一家急診診所就醫,他已經咳嗽了4天,并患有主觀性發熱。該患者在診所掛號和候診時就已戴好口罩。等待約20分鐘后,他進入檢查室并接受醫生的檢查。他透露自己前往中國武漢探親后于1月15日回到華盛頓州。該患者表示,他已經看到美國疾病控制與預防中心(CDC)發出的關于中國爆發2019-nCoV的健康警報,考慮到自身出現的癥狀和近期行程,他決定就醫。
       
      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 coronavirus strains known to cause illness in humans (HKU1, NL63, 229E, and OC43).
      除了患有高甘油三酯血癥病史之外,該患者是一名注重健康的不吸煙者。體檢結果顯示患者呼吸環境空氣時的體溫為37.2攝氏度,血壓134/87毫米汞柱,心率每分鐘110跳,呼吸頻率每分鐘16次,氧飽和度96%?;颊咴诮邮芊尾柯犜\時發現有羅音,并接受了胸片檢查,但報告顯示沒有異常(圖1)。甲型和乙型流感的快速核酸擴增檢測(NAAT)結果均為陰性。醫務人員收集了患者的鼻咽拭子樣本,并將其送去進行病毒性呼吸道病原體的檢測(通過核酸擴增檢測);所有病原體的檢測報告在48小時內送回,結果均為陰性,包括甲型和乙型流感、副流感、呼吸道合胞病毒、鼻病毒、腺病毒和四種已知會導致人類疾病的常見冠狀病毒株(HKU1、NL63、229E和OC43)。
       
      Given the patient’s travel 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 travel 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.
      考慮到患者的旅行史,該診所立即通知了當地及州衛生部門。華盛頓州衛生署與急診臨床醫師一起通知了疾病預防控制中心(CDC)的應急行動中心。雖然患者稱并未到過華南海鮮市場,在中國旅行期間也未曾與已知患病者有過接觸,但疾病預防控制中心的工作人員一致認為需要按照目前疾病預防控制中心對“受調查人員”病例定義對患者進行2019-nCoV檢測。檢測樣本按照疾病預防控制中心的指導收集,包括血清、鼻咽和口咽拭子樣本。樣本收集好后,患者出院回家,并在當地衛生部門的嚴密監控下在家中進行自我隔離。
       
      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.
      2020年1月20日,疾病預防控制中心通過實時逆轉錄-聚合酶鏈反應(rRT-PCR)檢測,證實患者的鼻咽和口咽拭子檢測結果均呈現2019-nCoV陽性。在與疾病預防控制中心主題專家、州及地方衛生官員、緊急醫療服務部門以及醫院領導和工作人員的配合下,患者被送入普羅維登斯地區醫療中心的空氣隔離病房進行臨床觀察,所有醫護人員遵循疾病預防控制中心提出的關于接觸、飛沫、空氣傳播預防措施的建議,并佩戴眼部防護用品。
       
      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 have 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.
      入院時,患者報稱持續干咳,且有兩天的惡心嘔吐史,但沒有感到氣短或胸痛。生命體征也在正常范圍之內。經體檢,發現患者粘膜干燥。其余的檢查結果都很平常。入院后,患者接受了支持療法,包括輸注2升生理鹽水和服用恩丹西酮緩解惡心。



      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.
      住院的第2天至第5天(發病第6天至第9天),除了伴有心動過速的間歇性發熱之外,患者的生命體征基本保持穩定(圖2)?;颊呃^續報稱干咳,且感覺很疲勞。住院第2天的下午,患者出現腹瀉現象,并感到腹部不適?;颊咴谝归g發生第二次腹瀉;此次腹瀉的糞便樣本被收集,同時再次收集呼吸道樣本(鼻咽和口咽)以及血清,用于rRT-PCR檢測。糞便和兩個呼吸道樣本的rRT-PCR檢測結果均呈現2019-nCoV陽性,但血清檢測結果仍然呈陰性。
       
      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.
      這段時間的治療基本上采用支持性療法。在癥狀處理方面,患者根據需要接受退熱治療,包括每隔4小時服用650毫克對乙酰氨基酚和每隔6小時服用600毫克布洛芬。在住院的前6天,他還因持續咳嗽服用了600毫克愈創甘油醚并輸注了約6升生理鹽水。
       
      The nature of the patient isolation unit permitted only point-of-care laboratory testing initially; complete blood counts and serum chemical studies were available 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 have shown no growth to date.
      患者隔離單元的性質最初只允許進行即時實驗室測試;從住院第3天開始,可以進行完整的血液計數和血清化學研究。住院第3天和第5天(發病第7天和第9天)的實驗室結果反映出白細胞減少、輕度血小板減少和肌酸激酶水平升高(表1)。此外,肝功能指標也有變化:住院第5天的堿性磷酸酶(68單位/升)、丙氨酸轉氨酶(105單位/升)、天冬氨酸轉氨酶(77單位/升)和乳酸脫氫酶(465單位/升)水平均有所升高??紤]到患者反復發燒,在第4天進行了血培養;到目前為止,相關指標沒有任何增長。
       
      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 intravenously every 8 hours) and cefepime (administered intravenously every 8 hours) was initiated.
      住院第3天(發病第7天)拍攝的胸片顯示沒有浸潤或異常跡象(圖3)。然而,住院第5天(發病第9天)晚上的第二次胸片顯示左肺下葉有肺炎跡象(圖4)。這些X光檢查結果與住院第5天晚上開始的呼吸系統狀況變化相吻合,即當患者呼吸環境空氣時,通過脈搏血氧儀測得的氧飽和度值跌至90%。第6天,患者開始接受補充氧氣,以每分鐘2升的速度通過鼻導管進行輸氧??紤]到臨床表現的變化和對醫院獲得性肺炎的擔憂,開始使用萬古霉素(1750毫克負荷劑量,隨后每隔8小時靜脈給藥1克)和頭孢吡肟(每隔8小時靜脈給藥一次)進行治療。



      Figure 3. Posteroanterior and Lateral Chest Radiographs, January 22, 2020 (Illness Day 7, Hospital Day 3).
      圖3. 后前位胸片和側位胸片,2020年1月22日(發病第7天,住院第3天)
      No acute intrathoracic plain-film abnormality was noted.
      未發現急性胸內平片異常。

      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 intravenous remdesivir (a novel nucleotide analogue 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.
      住院第6天(發病第10天),第四次胸片顯示兩肺存在基底條紋狀渾濁,這一發現與非典型肺炎一致(圖5),聽診時發現兩肺有羅音。根據X光檢查結果,醫護人員決定給患者輸氧,患者持續高燒,且多個部位持續呈陽性的2019-nCoV檢測結果;再者,同時期已發表的重癥肺炎發展報告與該患者胸片中顯示的肺炎發展情況相一致,因此,臨床醫生根據“同情用藥”原則,采用在研抗病毒療法。第7天晚上開始靜脈輸注remdesivir(一種正在研發中的新型核苷酸類似物前藥),未觀察到與輸注相關的不良事件。在第7天晚上停用萬古霉素,次日,在對耐甲氧西林金黃色葡萄球菌進行連續的降鈣素原陰性水平和鼻腔陰性PCR測試后,停用頭孢吡肟。
       
      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 have resolved with the exception of his cough, which is decreasing in severity.
      住院第8天(發病第12天),患者的臨床病情有所改善。已停止輸氧,當他呼吸環境空氣時,血氧飽和度值提高到94%至96%。先前的雙側下葉羅音不再出現?;颊叩氖秤兴纳?,除了間歇性干咳和流鼻涕之外,沒有其他癥狀。截至2020年1月30日,患者仍在住院治療,但已經退燒,除咳嗽外,其他癥狀均已消退,咳嗽的嚴重程度也在減輕。

      Figure 4. Posteroanterior Chest Radiograph, January 24, 2020 (Illness Day 9, Hospital Day 5).
      圖4. 后前位胸片,2020年1月24日(發病第9天,住院第5天)
      Increasing left basilar opacity was visible, arousing concern about pneumonia.
      左側基底部的可見渾濁增加,引發對肺炎的擔憂。

      Figure 5. Anteroposterior and Lateral Chest Radiographs, January 26, 2020 (Illness Day 10, Hospital Day 6).
      5. 前后位胸片和側位胸片,2020126日(發病第10天,住院第6天)
      Stable streaky opacities in the lung bases were visible, indicating likely atypical pneumonia; the opacities have steadily increased in density over time.
      肺底出現可見的穩定條紋狀渾濁,表明可能是非典型肺炎;渾濁的密度隨時間穩步增加。
      METHODS
      SPECIMEN COLLECTION
      Clinical specimens for 2019-nCoV diagnostic testing were obtained in accordance with CDC guidelines.12 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.
      方法
      樣本采集
      新型冠狀病毒診斷檢測的臨床樣本采集遵循CDC指南的要求。使用合成纖維拭子采集了鼻咽拭子和口咽拭子樣本,將各個拭子分別放入含有2至3毫升病毒運送培養液的無菌試管。根據CDC指南的要求用血清分離管采集血清,然后進行離心。用無菌樣本容器分別采集尿液樣本和糞便樣本。在運往CDC前,樣本的儲存溫度為20C至80C。在患病第7、11及12天進行了2019-nCoV復測樣本的采集,包括鼻咽拭子、口咽拭子、血清、尿液和大便樣本。
       
      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 coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (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 available on the CDC Laboratory Information website for 2019-nCoV.
      2019-nCoV的診斷檢測
      根據公開發布的病毒序列開發出了rRT-PCR測定法,用該測定法檢測了臨床樣本。與以往針對急性重癥呼吸綜合征冠狀病毒(SARS-CoV)和中東呼吸綜合征冠狀病毒(MERS-CoV)的診斷檢測相似,2019-nCoV的診斷檢測有三個核衣殼基因靶點及一個陽性對照靶點。該測定法的說明及rRT-PCR引物和探針的序列信息,請參見美國CDC實驗室信息網關于2019-nCoV的內容。
       
      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 available 2019-nCoV reference sequence (GenBank accession number NC_045512.2).
      基因測序
      2020年1月7日,中國研究人員在美國國立衛生研究院基因庫數據庫和全球流感數據共享計劃(GISAID)數據庫共享了2019-nCoV的完整基因序列;之后又發表了分離2019-nCoV的報告。從rRT-PCR陽性樣本(口咽部和鼻咽部)提取出核酸,并用桑格測序法和新一代測序平臺(Illumina和MinIon)進行了全基因組測序。序列組裝采用Sequencer軟件5.4.6版(桑格);minimap軟件2.17版(MinIon)和freebayes軟件1.3.1版(MiSeq)。將完整基因組與已發布的2019-nCoV參考序列(GenBank登錄號NC_045512.2)進行了比較。
       
      RESULTS
      SPECIMEN TESTING FOR 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.
      結果
      2019-NCOV的樣本檢測
      在患者發病第4天采集的初始呼吸道樣本(鼻咽拭子和口咽拭子)呈2019-nCoV 陽性(表2)。雖然患者的初期癥狀較輕,發病第4天的低循環閾值(Ct)(鼻咽樣本為18-20,口咽樣本為21-22)表明,這些樣本中的病毒載量較高。發病第7天采集的兩份上呼吸道樣本仍呈2019-nCoV陽性,鼻咽拭子樣本的病毒載量仍然高(循環閾值為23-24)。發病第7天采集的大便樣本也呈2019-nCoV陽性(循環閾值為36-38)。在兩個采樣日采集的血清樣本均呈2019-nCoV陰性。發病第11天和第12天采集的鼻咽樣本和口咽樣本顯示病毒載量呈下降趨勢?;疾〉?2天采集的口咽樣本呈2019-nCoV陰性。在上述日期采集的血清樣本的rRT-PCR檢測尚未出結果。
       
      Table 2. Results of Real-Time Reverse-Transcriptase-Polymerase-Chain-Reaction Testing for the 2019 Novel Coronavirus (2019-nCoV).*
      Specimen Illness Day 4 Illness Day 7 Illness Day 11 Illness Day 12
      Nasopharyngeal swab Positive (Ct, 18-20) Positive (Ct, 23-24) Positive (Ct, 33-34) Positive (Ct, 37-40)
      Oropharyngeal swab Positive (Ct, 21-22) Positive (Ct, 32-33) Positive (Ct, 36-40) Negative
      Serum Negative Negative Pending Pending
      Urine NT Negative NT NT
      Stool NT Positive (Ct, 36-38) NT NT
      * Lower cycle threshold (Ct) values indicate higher viral loads. NT denotes not tested.
       
      2. 2019新型冠狀病毒 (2019-nCoV) 實時熒光定量-反轉錄聚合酶鏈反應檢測結果.*
      樣本 發病第4 發病第7 發病第11 發病第12
      鼻咽拭子 陽性 (循環閾值為 18-20) 陽性 (循環閾值為 23-24) 陽性 (循環閾值為 33-34) 陽性 (循環閾值為 37-40)
      口咽拭子 陽性 (循環閾值為 21-22) 陽性 (循環閾值為 32-33) 陽性 (循環閾值為 36-40) 陰性
      血清 陰性 陰性 未出結果 未出結果
      尿液 未檢測 陰性 未檢測 未檢測
      大便 未檢測 陽性 (循環閾值為 36-38) 未檢測 未檢測
      *循環閾值(Ct)較低表示病毒載量較高。
      GENETIC SEQUENCING
      The full genome sequences from oropharyngeal and nasopharyngeal specimens were identical to one another and were nearly identical to other available 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 available through GenBank (accession number MN985325).
      基因測序
      口咽樣本和鼻咽樣本的全基因組序列完全相同,與已發布的其他2019-nCoV序列幾乎相同。該患者的病毒和2019-nCoV參考序列(NC_045512.2)之間,只有開放閱讀框8處的3個核苷酸和1個氨基酸存在差異。該參考序列來自GenBank(登錄號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 traveled 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 have been identified, but monitoring of close contacts continues.
      討論
      我們報道的美國首例2019-nCoV 確診病例說明此新暴發疫情尚有幾方面未完全清楚,包括傳播動力學和臨床疾病的發展全貌。此病例患者曾去過中國武漢,但在武漢期間未去過海鮮批發市場和醫療機構,也未接觸過任何病患。盡管該病患的2019-nCoV感染來源不明,但已公開了人傳人的證據。截至2020年1月30日,尚未發現與該病例相關的2019-nCoV繼發病例,但仍在繼續監控其密切接觸者。
       
      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.
      發病第4天和第7天上呼吸道樣本中檢出2019-nCoV核糖核酸,且循環閾值較低,提示病毒載量高,有潛在的傳播性。值得注意的是,我們還在發病第7天采集的大便樣本中也檢測到了2019-nCoV核糖核酸。盡管該病患血清樣本屢次呈2019-nCoV陰性,但在中國,重癥患者血液內已檢測到病毒核糖核酸。不過,肺外檢測到病毒核糖核酸不一定意味著存在傳染性病毒,目前還不清楚呼吸道外檢測到病毒核糖核酸的臨床意義。
       
      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, have 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.
      目前,我們對2019新型冠狀病毒感染的臨床情況了解非常有限。中國已報告了并發癥,如重度肺炎、呼吸衰竭、急性呼吸窘迫綜合征(ARDS)和心臟損傷,包括死亡。不過,值得注意的是,這些病例是在肺炎診斷的基礎上確定的,因此可能偏向報告更嚴重的結果。
       
      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 having 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.
      我們的病患最初表現為輕微咳嗽和間斷性低熱,發病第4天胸片無肺炎表現,在發病第9天時發展為肺炎。2019-nCoV感染病程早期,輕癥患者的這些非特異性癥狀和體征在臨床上可能與許多其他常見傳染病無法區分,尤其是在呼吸道病毒感染高發的冬季。此外,該病患在患病第9天發展為肺炎,這一時間與最近發表的文章中報道的遲發性呼吸困難(中位時間為發病第8天)相符。盡管因患者臨床狀況惡化而決定使用瑞德西韋進行同情用藥,但需要進行隨機對照試驗以確定瑞德西韋及治療2019-nCoV感染患者的其它試驗藥的安全性和療效。
       
      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 travel 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 travel 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.
      本文報道了美國首例報告的2019-nCoV感染患者的臨床特征。該病例要點包括患者看到關于疫情的公共衛生警告后決定就醫;當地醫務人員了解到患者近期曾去過武漢,隨后當地、州和聯邦公共衛生官員彼此協調;識別出可能感染2019-nCoV,從而能夠迅速隔離患者,隨后實驗室確認2019-nCoV,以及將患者收入院進一步檢查和治療。此病例報告凸顯出臨床醫師詢問因急性病癥而就診的患者的近期旅行史或與其他患者接觸史的重要性,從而確保正確識別和迅速隔離可能感染2019-nCoV的患者,降低進一步傳播風險。最后,此報告還強調,我們需要確定與2019-nCoV感染相關臨床疾病的全部表現和自然病程、發病機制以及病毒釋出體外的病毒散發期,從而指導臨床治療和公共衛生決策。

      本文原文來源于NEJM.org,版權歸原作者所有,譯文由甲骨易提供。
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