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SARS-CoV-2 infection causes transient olfactory dysfunction in mice

By Cheng-Feng Qin, Qing Ye, Jia Zhou, Guan Yang, Rui-Ting Li, Qi He, Yao Zhang, Shu-Jia Wu, Qi Chen, Jia-Hui Shi, Rong-Rong Zhang, Hui-Min Zhu, Hong-Ying Qiu, Tao Zhang, Yong-Qiang Deng, Xiao-Feng Li, Ping Xu, Xiao Yang

Posted 10 Nov 2020
bioRxiv DOI: 10.1101/2020.11.10.376673

Olfactory dysfunction caused by SARS-CoV-2 infection represents as one of the most predictive and common symptoms in COVID-19 patients. However, the causal link between SARS-CoV-2 infection and olfactory disorders remains lacking. Herein we demonstrate intranasal inoculation of SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), resulting in transient olfactory dysfunction in humanized ACE2 mice. The sustentacular cells and Bowman's gland cells in OE were identified as the major targets of SARS-CoV-2 before the invasion into olfactory sensory neurons. Remarkably, SARS-CoV-2 infection triggers cell death and immune cell infiltration, and impairs the uniformity of OE structure. Combined transcriptomic and proteomic analyses reveal the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptors in OE from the infected animals. Overall, our mouse model recapitulates the olfactory dysfunction in COVID-19 patients, and provides critical clues to understand the physiological basis for extrapulmonary manifestations of COVID-19. ### Competing Interest Statement The authors have declared no competing interest.

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