Lancet Infect Dis：中东呼吸综合征冠状病毒与SARS病毒存在重要差异

发表在《The Lancet Infectious Diseases》上的新文章提供了第一个关于病毒载量的完整描述——对一位感染中东呼吸综合征冠状病毒（MERS-CoVer）病人体内病毒的循环部位及数量的描述。报告的对象是一位来自Abu Dhabi的73岁老人，其在感染MERS-CoV几周后，于2013年4月份死于慕尼黑。

关于该新病毒的综合临床数据匮乏，只有一个医学杂志对第15个病人的病毒进展及特征进行了描述。在新研究中，病人在流感样症状持续2天后就入住了Abu Dhabi的医院，被诊断为肺炎并且接受抗生素和人工通气治疗。在病程12天时，被送到位于慕尼黑的医院。病人在经历呼吸症状恶化和肾衰后，在病程的第18天死亡。

病人入住慕尼黑医院后，研究者对其病毒载量进行了日常测量，发现下呼吸道中病毒载量最高，佐证了前期的结果，也为当前WHO关于尽可能搜集感染区资料用于诊断的建议提供了支持。同样的，在尿和粪便中，也存在着可检测的低病毒载量，但在病人血中却没有。

病毒存在于尿液中，这表明其可能在肾脏中进行复制，这可能是这位病人及其他新近在Lancet文章中提及的来自法国的2位病人肾衰的原因。然而，研究者指出，病程前期使用抗生素也可能影响肾脏功能，因此需要更多的研究来明确感染后病毒增殖的部位和机制。

粪便中低浓度的病毒也预示着，新病毒与易在粪便中发现的SARS冠状病毒在体内的循环中存在着关键的差异。进一步研究病毒在体内的循环机制将对诊断和控制感染有重要的作用。

此研究的第一作者Christian Drosten教授说，“像这样的实验数据对于达到临床诊断建议、做出病人预后计划及估计感染风险是非常关键的。”

在明确记载MERS病例的定性实验数据缺乏的情况下，大部分情况都从与SARS类似的假设来考虑。但是，我们正在明确的基础实验基础上证明MERS病毒和SARS之间存在差异。“

根据研究的共同第一作者Clemens-Martin Wendtner教授的说法，“由于只有5个可用的全基因组序列，因此紧迫需要更多的基因数据来揭示病人的空间及时间分布和估计独立的人传播链的数量，以便更好地评估此病毒对世界健康的威胁。”

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