Regeneration Profiles of Olfactory Epithelium after SARS-CoV-2 Infection in Golden Syrian Hamsters

Urata, Shinji; Maruyama, Junki; Kishimoto‐Urata, Megumi; Sattler, Rachel A.; Cook, Rebecca S.; Lin, Nantian; Yamasoba, Tatsuya; Makishima, Tomoko; Paessler, Slobodan

doi:10.1021/acschemneuro.0c00649

Cited by 52 publications

(85 citation statements)

References 29 publications

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“…Second, structural instability may contribute to olfactory dysfunction. As in previous studies, most of the epithelium was desquamated, some cellular debris was present in the lumen [ 10 , 21 , 40 ], and three distinct layers were lost. Because SCs are responsible for epithelial stability, their infection and subsequent apoptosis may result in these changes.…”

Section: Discussionsupporting

confidence: 57%

The Microvillar and Solitary Chemosensory Cells as the Novel Targets of Infection of SARS-CoV-2 in Syrian Golden Hamsters

Seo

Yoon

Hwang

et al. 2021

Viruses

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Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, suffer from respiratory and non-respiratory symptoms. Among these symptoms, the loss of smell has attracted considerable attention. The objectives of this study were to determine which cells are infected, what happens in the olfactory system after viral infection, and how these pathologic changes contribute to olfactory loss. For this purpose, Syrian golden hamsters were used. First, we verified the olfactory structures in the nasal cavity of Syrian golden hamsters, namely the main olfactory epithelium, the vomeronasal organ, and their cellular components. Second, we found angiotensin-converting enzyme 2 expression, a receptor protein of SARS-CoV-2, in both structures and infections of supporting, microvillar, and solitary chemosensory cells. Third, we observed pathological changes in the infected epithelium, including reduced thickness of the mucus layer, detached epithelia, indistinct layers of epithelia, infiltration of inflammatory cells, and apoptotic cells in the overall layers. We concluded that a structurally and functionally altered microenvironment influences olfactory function. We observed the regeneration of the damaged epithelium, and found multilayers of basal cells, indicating that they were activated and proliferating to reconstitute the injured epithelium.

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Section: Discussionsupporting

confidence: 57%

The Microvillar and Solitary Chemosensory Cells as the Novel Targets of Infection of SARS-CoV-2 in Syrian Golden Hamsters

Seo

Yoon

Hwang

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…The current evidence favors alternative routes from the nose to the brain, at least in the acute phase (first two weeks) of infection. Since the viral load typically reduces rapidly within the first week of infection [94], the brain appears to be protected in the vast majority of cases with SARS-CoV-2 infection. We are concerned that studies advocating an olfactory route for SARS-CoV-2 to infect the brain may unnecessarily alarm a large number of patients suffering from anosmia.…”

Section: Discussionmentioning

confidence: 99%

The olfactory nerve is not a likely route to brain infection in COVID-19: a critical review of data from humans and animal models

et al. 2021

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One of the most frequent symptoms of COVID-19 is the loss of smell and taste. Based on the lack of expression of the virus entry proteins in olfactory receptor neurons, it was originally assumed that the new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) does not infect olfactory neurons. Recent studies have reported otherwise, opening the possibility that the virus can directly infect the brain by traveling along the olfactory nerve. Multiple animal models have been employed to assess mechanisms and routes of brain infection of SARS-CoV-2, often with conflicting results. We here review the current evidence for an olfactory route to brain infection and conclude that the case for infection of olfactory neurons is weak, based on animal and human studies. Consistent brain infection after SARS-CoV-2 inoculation in mouse models is only seen when the virus entry proteins are expressed abnormally, and the timeline and progression of rare neuro-invasion in these and in other animal models points to alternative routes to the brain, other than along the olfactory projections. COVID-19 patients can be assured that loss of smell does not necessarily mean that the SARS-CoV-2 virus has gained access to and has infected their brains.

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“…SARS-CoV-2 invades the peripheral nerves and nociceptors, as do other viruses. Urata recently reported that the olfactory epithelium (which expresses ACE2) is sloughed off for a long time after SARS-CoV-2 infection [13]. Similar to dysosmia, the most reasonable explanation of dysgeusia may be that it is a direct effect of SARS-CoV-2 on the taste buds on the tongue.…”

Section: Discussionmentioning

confidence: 99%

Oral Mucosa Could Be an Infectious Target of SARS-CoV-2

et al. 2021

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The World Health Organization reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is caused by respiratory droplets and aerosols from the oral cavity of infected patients. The angiotensin-converting enzyme 2 (ACE2) is considered the host functional protein for SARS-CoV-2 infection. In this article, we first revealed that the positive proportion of ACE2 expression in gingival cells collected from the gingival sulcus was increased to the same level as the tongue. Our data demonstrate that cells in the gingival sulcus may be a new entry point for the SARS-CoV-2 virus via a high expression of ACE2. In addition, we first evaluated the expression of ACE2 in various sites of the oral cavity with noninvasive, convenient liquid-based cytology. The liquid-based cytology evaluation of oral tissue may provide a novel preventive medical avenue against COVID-19.

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Regeneration Profiles of Olfactory Epithelium after SARS-CoV-2 Infection in Golden Syrian Hamsters

Cited by 52 publications

References 29 publications

The Microvillar and Solitary Chemosensory Cells as the Novel Targets of Infection of SARS-CoV-2 in Syrian Golden Hamsters

The Microvillar and Solitary Chemosensory Cells as the Novel Targets of Infection of SARS-CoV-2 in Syrian Golden Hamsters

The olfactory nerve is not a likely route to brain infection in COVID-19: a critical review of data from humans and animal models

Oral Mucosa Could Be an Infectious Target of SARS-CoV-2

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