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

Bryche, Bertrand; Albin, Audrey St; Murri, Séverine; Lacôte, Sandra; Pulido, Coralie; Gouilh, Meriadeg Ar; Lesellier, Sandrine; Servat, Alexandre; Wasniewski, Marine; Picard-Meyer, Evelyne; Monchâtre-Leroy, Élodie; Volmer, Romain; Rampin, Olivier; Goffic, Ronan Le; Marianneau, Philippe; Meunier, Nicolas

doi:10.1016/j.bbi.2020.06.032

Cited by 271 publications

(349 citation statements)

References 28 publications

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“…In keeping with the work of Brann et al ., 28 Bryche et al . 21 demonstrated infection of the supporting sustentacular cells, but not the olfactory neurons themselves. Desquamation, however, affected both infected and non-infected cells, with the olfactory neurons showing loss of cilia.…”

Section: Discussionmentioning

confidence: 96%

Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia

et al. 2020

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Background. Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated. Case report. This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2. Conclusion. The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.

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Section: Discussionmentioning

confidence: 96%

Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia

et al. 2020

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“…First, the infection of sustentacular cells may disrupt signaling from olfactory sensory neurons (OSN) to the olfactory bulb. For example, sustentacular cells provide support to OSN by maintaining ion balance 28 , which may be altered either directly by sustentacular cell infection or indirectly via disorganization of the olfactory epithelium (OE), leading to loss of cilia from OSN and deficient signal transduction 29 . The second possibility is collateral damage to OSN resulting from pro-inflammatory cytokine secretion by SARS-CoV-2 infected sustentacular cells.…”

Section: Discussionmentioning

confidence: 99%

K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia

Perlman

Zheng

Wong

et al. 2020

Preprint

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The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. While much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation and many patients with this finding show no or only minor respiratory signs. Studies in animals experimentally infected with SARS-CoV-2, the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. COVID-19 severity ranges from asymptomatic to lethal. Most experimental infections provide insights into mild disease. Here, using K18-hACE2 mice that we originally developed for SARS studies, we show that infection with SARS-CoV-2 causes severe disease in the lung, and in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Further, we show that infusion of convalescent plasma (CP) from a recovered COVID-19 patient provided protection against lethal disease. Mice developed anosmia at early times after infection. Notably, while treatment with CP prevented significant clinical disease, it did not prevent anosmia. Thus K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.

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“…Of note, such a model does not imply that SARS-CoV-2 travels from the olfactory epithelium to the brain along the olfactory axons. Indeed, no axonal transport of SARS-CoV-2 to the brain has been demonstrated in the hamster model during the first two weeks after infection [89], and no viral accumulation or persistence has been reported in cerebral olfactory regions of autopsy material from patients with COVID-19 [90]. On the other hand, rapid SARS-CoV-2 accumulation in the brain after intranasal injection was recently shown using the new humanized ACE2 knock-in mouse [91].…”

Section: Smell and Taste Disordersmentioning

confidence: 99%

SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

Pennisi

Lanza

Falzone

et al. 2020

IJMS

131

129

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Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

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

Cited by 271 publications

References 28 publications

Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia

Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia

K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia

SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

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