Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters
Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters
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DOI：
10.1016/j.bbi.2020.06.032
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发表时间：
2020-10-01
影响因子：
15.1
通讯作者：
Meunier, Nicolas
中科院分区：
文献类型：
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作者：
Bryche, Bertrand;St Albin, Audrey;Meunier, Nicolas
嗅觉缺失是COVID-19大流行期间SARS-CoV-2感染的最常见症状之一。然而，嗅觉突然丧失背后的细胞机制尚未被研究。气味检测的初始步骤发生在假复层嗅觉上皮（OE）中，其主要由被称为支持细胞的支持细胞包围的嗅觉感觉神经元组成。嗅觉神经元将其轴突投射到中枢神经系统的嗅球，为病原体通过绕过血脑屏障进入中枢神经系统提供了潜在的途径。在本研究中，我们探讨了SARS-CoV-2感染对金黄色叙利亚仓鼠嗅觉系统的影响。我们观察到，早在SARS-CoV-2鼻滴注后2天，OE就出现了大规模损伤，导致气味检测所需的纤毛大量丧失。这些损害与大部分支持细胞的感染有关，但与嗅神经元无关，我们在嗅球中没有检测到任何病毒的存在。我们观察到大量的免疫细胞浸润的OE和固有层的感染动物，这可能有助于脱屑的OE。OE部分恢复感染后14天。因此，在COVID-19患者中观察到的嗅觉缺失可能与支持细胞感染SARS-CoV-2后OE的大量快速脱皮以及随后OE和固有层中免疫细胞的募集有关。
Anosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-CoV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria.