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

Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection.
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DOI:
10.1016/s1473-3099(13)70154-3
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发表时间:
2013-09
期刊:
The Lancet. Infectious diseases
影响因子:
--
通讯作者:
Wendtner CM
Wendtner CM
中科院分区:
其他
文献类型:
--
作者:
Drosten C;Seilmaier M;Corman VM;Hartmann W;Scheible G;Sack S;Guggemos W;Kallies R;Muth D;Junglen S;Müller MA;Haas W;Guberina H;Röhnisch T;Schmid-Wendtner M;Aldabbagh S;Dittmer U;Gold H;Graf P;Bonin F;Rambaut A;Wendtner CM

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中东呼吸综合征冠状病毒(MERS-CoV)是一种新出现的病毒,涉及阿拉伯半岛、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。我们提供了一个完整的描述MERS冠状病毒感染的致命病例和相关的系统发育分析。我们报告一名因严重急性呼吸道感染而入住Klinikum Schwabing(慕尼黑,德国)的患者的数据。我们做了诊断RT-PCR和间接免疫荧光。从诊断开始,采集呼吸道、粪便和尿液样本进行病毒定量。我们构建了五个可用的完整MERS-CoV基因组的最大似然树。2013年3月19日,一名来自阿拉伯联合酋长国阿布扎比的73岁男子在患病第11天被转移到Klinikum Schwabing。他在2008年被诊断出患有多发性骨髓瘤,并接受了几种治疗。患者在第18天死于感染性休克。在两个支气管肺泡液样本中检测到MERS-CoV。下呼吸道样本中的病毒载量最高(高达1.2 × 106拷贝/mL)。  第13天尿样中的最大病毒浓度为2691 RNA拷贝/mL;第14天肾衰竭后尿液中不存在病毒。在第12天和第16天获得的粪便样品含有病毒,每克高达1031个RNA拷贝(接近测定的最低检测限)。第16天获得的两份口鼻拭子中有一份呈阳性,但几乎没有产生病毒RNA(5370拷贝/mL)。血液中未检出病毒。全病毒基因组与其他四个可用的全基因组序列在最大似然同源性中组合,将分支长度与分离日期相关联。共同祖先的时间是2011年的一半。添加来自之前在德国埃森治疗6个月的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类。我们提供了MERS-CoV感染病例的第一个完整的病毒载量谱。MERS-CoV可能具有与严重急性呼吸系统综合征不同的脱落模式,因此可能需要替代诊断方法。欧洲联盟、德国感染研究中心、德国研究理事会和德国教育和研究部。
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. 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. 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 × 106 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. 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. European Union; German Centre for Infection Research; German Research Council; and German Ministry for Education and Research.