Severe Acute Respiratory Syndrome Coronavirus 2 Infects and Damages the Mature and Immature Olfactory Sensory Neurons of Hamsters
Severe Acute Respiratory Syndrome Coronavirus 2 Infects and Damages the Mature and Immature Olfactory Sensory Neurons of Hamsters
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DOI：
10.1093/cid/ciaa995
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发表时间：
2021-07-15
影响因子：
11.8
通讯作者：
Yuen, Kwok-Yung
中科院分区：
文献类型：
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作者：
Zhang, Anna Jinxia;Lee, Andrew Chak-Yiu;Yuen, Kwok-Yung
背景2019冠状病毒病（COVID-19）主要是一种急性呼吸道感染。值得注意的是，很大一部分COVID-19患者会出现嗅觉功能障碍。特别是在年轻患者中，嗅觉丧失可能是第一个或唯一的症状。嗅裂炎性阻塞、影响嗅神经元功能的炎性细胞因子、嗅神经元或其支持细胞的破坏以及嗅球的直接侵入在引起嗅觉功能障碍中的作用尚不确定。本研究以金黄色叙利亚仓鼠为实验动物，观察了严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）在嗅上皮至嗅球中的致病部位。鼻内接种SARS-CoV-2后，鼻甲骨组织中可检测到炎性细胞浸润和促炎细胞因子/趋化因子反应。反应在感染后2 - 4天达到峰值，在感染后第2天检测到最高病毒载量。除假柱状纤毛呼吸道上皮细胞外，在嗅觉标记蛋白标记的成熟嗅觉感觉神经元、神经元特异性III类β-微管蛋白标记的较不成熟嗅觉神经元、支持细胞中也检测到SARSCoV-2病毒抗原，导致细胞凋亡和OE严重破坏，在整个感染过程中，嗅球中未检测到SARS-CoV-2病毒抗原。除了OE处的急性炎症外，SARS-CoV-2对成熟和未成熟嗅觉神经元以及支持支持细胞的感染可能导致与COVID-19相关的独特嗅觉功能障碍，这在SARS-CoV-2中没有报道。
Background. Coronavirus disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction. Especially in young patients, loss of smell can be the first or only symptom. The roles of inflammatory obstruction of the olfactory clefts, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs in causing olfactory dysfunction are uncertain.Methods. We investigated the location for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the olfactory epithelium (OE) to the olfactory bulb in golden Syrian hamsters.Results. After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues. The responses peaked between 2 and 4 days postinfection, with the highest viral load detected at day 2 postinfection. In addition to the pseudo-columnar ciliated respiratory epithelial cells, SARSCoV-2 viral antigens were also detected in the mature olfactory sensory neurons labeled by olfactory marker protein, in the less mature olfactory neurons labeled by neuron-specific class III beta-tubulin at the more basal position, and in the sustentacular cells, resulting in apoptosis and severe destruction of the OE. During the entire course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb.Conclusions. In addition to acute inflammation at the OE, infection of mature and immature olfactory neurons and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction related to COVID-19, which is not reported with SARS-CoV-2.