骆驼从业者可能是MERS病毒传播的途径之一

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近日，广州医科大学呼吸疾病国家重点实验室赵金存和肇静娴团队与沙特阿拉伯利雅得国王沙特大学Abdulaziz N. Alagaili教授及美国爱荷华大学Stanley Perlman教授合作研究发现在沙特阿拉伯工作的骆驼从业者约50%感染过中东呼吸综合征冠状病毒（Middle East Respiratory Syndrome coronavirus, MERS-CoV），并首次提出了骆驼从业者可能是MERS病毒传播的途径之一的猜想，填补了MERS传播研究领域空白。该成果于2018年10月30日发表于《mBio》杂志上。




中东呼吸综合征冠状病毒（MERS-CoV）是一种新发突发、高致病性、经呼吸道传播的冠状病毒，于2012年首发于沙特。MERS的出现给全球公共卫生安全带来新挑战。截至2018年9月，MERS-CoV引起的中东呼吸综合征（MERS）已有2260例实验室确诊病例，其中803例死亡，死亡率约为35.5%。目前MERS疫情仍在流行中，已传播到包括我国在内共27个国家和地区，尚无有效的治疗药物和预防疫苗。在前期研究中，骆驼被认为是MERS-CoV的传播源头之一，早期感染MERS的病人多数为直接接触过骆驼，或为院内感染。然而在后续爆发的MERS病例中，绝大多数病人都未曾接触过骆驼。骆驼从业者是一个可能长时间直接接触骆驼口鼻腔分泌物的群体，因此作者猜测，后续的MERS爆发有可能是由感染MERS-CoV的骆驼从业者与健康人接触传播所致。







机体在病毒感染后主要通过天然免疫应答和获得性免疫应答发挥抗病毒作用。病毒特异性抗体和T细胞为获得性免疫应答最重要的两个主要组分。在前期研究中，主要是通过血清学的方法来检测MERS-CoV特异性抗体在人体中的水平来判断机体是否感染过MERS-CoV，然而这些抗体，特别是在那些轻症以及无症状的人群体内存在的时间很短，水平也较低，因而此方法存在局限性。本文作者在其前期研究中发现，病毒特异性T细胞可在人体内长期存在，甚至在一些血清学阴性的样本中也能检出MERS-CoV特异性的T细胞。因此，为阐明骆驼从业者是否感染过MERS-CoV，作者综合利用血清学及流式细胞术等方法检测了30份来自于沙特阿拉伯与骆驼长期密切接触的骆驼养殖和运输人员的血样以及44份沙特阿拉伯和美国的健康人群血样。结果显示约有50%的骆驼工人样本血清学实验阳性，约有60%骆驼工人样本T细胞反应阳性。而在对健康人群的检测中，血清学检测及T细胞反应均为阴性。此项研究不仅再次证明血清学以及T细胞联合检测有助于鉴别轻度或无症状的MERS患者，从而更好地确定感染的发生率和流行情况，而且在一定程度上表明携带MERS-CoV的骆驼从业者可能是病毒人际传播的途径之一。



ABSTRACT
Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.



IMPORTANCE The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure. Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease. Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community.

来源：呼吸疾病国家重点实验室