Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

Abstract

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.

Hamster and ferret experimental infection with intranasal low dose of a single strain of SARS-CoV-2

“…The pathogenicity of SARS-CoV2 in the nasal cavity of the hamsters infected in this study involved respiratory and olfactory epithelium, including sustentacular cells (17). In ferrets, similar infection pattern has also been observed (9).…”

Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection

“…There is now an emerging consensus that mature olfactory neurons do not express the virus entry proteins, ACE2 and TMPRSS2, at least not at significant levels, and not in the large majority of the mature olfactory neurons in mouse and human (Baxter and others 2020; Bilinska and others 2020; Brann and others 2020; Chen and others 2020b; Fodoulian and others 2020; Gupta and others 2020; Klingenstein and others 2020; Ziegler and others 2020-see Table 2). A recent study that localized the SARS-CoV-2 virus in the hamster olfactory epithelium confirmed this notion by showing that sustentacular cells contained the virus, but not olfactory neurons (Bryche and others 2020). This means that the olfactory neurons are not the initial and primary target of the virus.…”

Characterization of cells susceptible to SARS-COV-2 and methods for detection of neutralizing antibody by focus forming assay

“…Further studies are warranted to determine what factors are necessary and sufficient for viral egress and could therefore serve as potential therapeutic targets. Multiple groups have demonstrated success using golden Syrian hamsters to model SARS-CoV-2 infection, pathogenesis, and possibly transmission[35,[52][53][54], which may reflect differing susceptibility of hamster cell types based on anatomical location of the isolated cells.…”