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Oxford University Press - PMC COVID-19 Collection logoLink to Oxford University Press - PMC COVID-19 Collection
. 2020 Jul 15:ciaa995. doi: 10.1093/cid/ciaa995

SARS-CoV-2 infects and damages the mature and immature olfactory sensory neurons of hamsters

Anna Jinxia Zhang 1,2,3,#, Andrew Chak-Yiu Lee 2,#, Hin Chu 1,2,3,#, Jasper Fuk-Woo Chan 1,2,3,4,#, Zhimeng Fan 2, Can Li 2, Feifei Liu 2, Yanxia Chen 2, Shuofeng Yuan 1,2,3, Vincent Kwok-Man Poon 2, Chris Chung-Sing Chan 2, Jian-Piao Cai 2, Kenneth Lap-Kei Wu 5,6, Siddharth Sridhar 1,2,3,4, Ying-Shing Chan 5,6, Kwok-Yung Yuen 1,2,3,4,
PMCID: PMC7454453  PMID: 32667973

Abstract

Background

Coronavirus Disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction of uncertain underlying mechanism which can be severe and prolonged. The roles of inflammatory obstruction of the olfactory clefts leading to conductive impairment, 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

In this study, we investigated the location for the pathogenesis of SARS-CoV-2 from the olfactory epithelium (OE) of the nasopharynx to the olfactory bulb of 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 which peaked between 2 to 4 days post-infection with the highest viral load detected at day 2 post-infection. Besides the nasopharyngeal pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the more superficial mature olfactory sensory neurons labeled by olfactory marker protein (OMP), the less mature olfactory neurons labelled by Tuj1 at more basal position, and the sustentacular cells which provide metabolic and physical support for the olfactory neurons, resulting in apoptosis and severe destruction of the OE. During the whole course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb.

Conclusions

Besides acute inflammation at OE, infection of mature and immature olfactory neurons, and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction of COVID-19 which is not reported with SARS-CoV.


Articles from Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America are provided here courtesy of Oxford University Press

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