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中东呼吸综合征冠状病毒感染病例的临床特征和病毒学分析。

Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection.

机构信息

Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.

出版信息

Lancet Infect Dis. 2013 Sep;13(9):745-51. doi: 10.1016/S1473-3099(13)70154-3. Epub 2013 Jun 17.

Abstract

BACKGROUND

The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus involved in cases and case clusters of severe acute respiratory infection in the Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the UK. We provide a full description of a fatal case of MERS-CoV infection and associated phylogenetic analyses.

METHODS

We report data for a patient who was admitted to the Klinikum Schwabing (Munich, Germany) for severe acute respiratory infection. We did diagnostic RT-PCR and indirect immunofluorescence. From time of diagnosis, respiratory, faecal, and urine samples were obtained for virus quantification. We constructed a maximum likelihood tree of the five available complete MERS-CoV genomes.

FINDINGS

A 73-year-old man from Abu Dhabi, United Arab Emirates, was transferred to Klinikum Schwabing on March 19, 2013, on day 11 of illness. He had been diagnosed with multiple myeloma in 2008, and had received several lines of treatment. The patient died on day 18, due to septic shock. MERS-CoV was detected in two samples of bronchoalveolar fluid. Viral loads were highest in samples from the lower respiratory tract (up to 1·2 × 10(6) copies per mL). Maximum virus concentration in urine samples was 2691 RNA copies per mL on day 13; the virus was not present in the urine after renal failure on day 14. Stool samples obtained on days 12 and 16 contained the virus, with up to 1031 RNA copies per g (close to the lowest detection limit of the assay). One of two oronasal swabs obtained on day 16 were positive, but yielded little viral RNA (5370 copies per mL). No virus was detected in blood. The full virus genome was combined with four other available full genome sequences in a maximum likelihood phylogeny, correlating branch lengths with dates of isolation. The time of the common ancestor was halfway through 2011. Addition of novel genome data from an unlinked case treated 6 months previously in Essen, Germany, showed a clustering of viruses derived from Qatar and the United Arab Emirates.

INTERPRETATION

We have provided the first complete viral load profile in a case of MERS-CoV infection. MERS-CoV might have shedding patterns that are different from those of severe acute respiratory syndrome and so might need alternative diagnostic approaches.

FUNDING

European Union; German Centre for Infection Research; German Research Council; and German Ministry for Education and Research.

摘要

背景

中东呼吸综合征冠状病毒(MERS-CoV)是一种新兴病毒,与阿拉伯半岛、突尼斯、摩洛哥、法国、意大利、德国和英国的严重急性呼吸道感染病例和病例群有关。我们提供了一例致命性 MERS-CoV 感染病例的详细描述,并进行了相关的系统发育分析。

方法

我们报告了一名因严重急性呼吸道感染而入住慕尼黑 Schwabing 医院(德国)的患者的数据。我们进行了诊断性 RT-PCR 和间接免疫荧光检测。从诊断之日起,我们获得了呼吸道、粪便和尿液样本以进行病毒定量。我们构建了 5 个可用的完整 MERS-CoV 基因组的最大似然树。

结果

一名来自阿拉伯联合酋长国阿布扎比的 73 岁男性,于 2013 年 3 月 19 日(发病第 11 天)转入 Schwabing 医院。他于 2008 年被诊断为多发性骨髓瘤,并接受了多种治疗。患者于第 18 天因感染性休克死亡。在两份支气管肺泡灌洗液样本中检测到 MERS-CoV。下呼吸道样本中的病毒载量最高(高达 1.2×10^6 拷贝/毫升)。尿液样本中病毒浓度最高的时间是第 13 天,达到 2691 RNA 拷贝/毫升;第 14 天肾功能衰竭后,尿液中不再检测到病毒。第 12 天和第 16 天获得的两份粪便样本中含有病毒,含量达到每克 1031 RNA 拷贝(接近检测方法的最低检测限)。第 16 天获得的两份咽拭子中的一份呈阳性,但仅获得少量病毒 RNA(5370 拷贝/毫升)。血液中未检测到病毒。在最大似然系统发育树上,我们将完整的病毒基因组与其他 4 个可用的全基因组序列组合在一起,将分支长度与分离日期相关联。共同祖先的时间在 2011 年中旬。添加德国埃森 6 个月前治疗的一例无关联病例的新基因组数据显示,来自卡塔尔和阿拉伯联合酋长国的病毒聚集在一起。

解释

我们提供了首例 MERS-CoV 感染完整病毒载量谱。MERS-CoV 的脱落模式可能与严重急性呼吸综合征不同,因此可能需要替代的诊断方法。

资金

欧盟;德国感染研究中心;德国研究委员会;德国联邦教育和研究部。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9274/7164791/816f475193f4/gr1_lrg.jpg

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