SARS-CoV-2 Receptors and Entry Genes Are Expressed in the Human Olfactory Neuroepithelium and Brain

Fodoulian, Leon; Tuberosa, Joël; Rossier, Daniel; Boillat, Madlaina; Kan, Chenda; Pauli, Véronique; Égervári, Kristóf; Lobrinus, Johannes Alexander; Landis, Basile Nicolas; Carleton, Alan; Rodríguez, Iván

doi:10.1016/j.isci.2020.101839

Cited by 195 publications

(216 citation statements)

References 79 publications

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“…Both proteins are mainly expressed in the upper part of the respiratory tract ( Hou et al, 2020 ) and the highest density of these proteins is found in the olfactory epithelium. Sustentacular cells express most of ACE2 and TMPRSS2 and these proteins are absent from OSN ( Bilinska et al, 2020 ; Fodoulian et al, 2020 ). Both are also expressed to a lesser extent in Bowman’s gland, microvillar cells and basal stem cells ( Brann et al, 2020 ).…”

Section: Sars-cov-2 and Anosmia: Cellular Tropism In Olfactory Epithementioning

confidence: 99%

COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology

et al. 2021

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Smell and taste impairments are recognized as common symptoms in COVID 19 patients even in an asymptomatic phase. Indeed, depending on the country, in up to 85–90% of cases anosmia and dysgeusia are reported. We will review briefly the main mechanisms involved in the physiology of olfaction and taste focusing on receptors and transduction as well as the main neuroanatomical pathways. Then we will examine the current evidences, even if still fragmented and unsystematic, explaining the disturbances and mode of action of the virus at the level of the nasal and oral cavities. We will focus on its impact on the peripheral and central nervous system. Finally, considering the role of smell and taste in numerous physiological functions, especially in ingestive behavior, we will discuss the consequences on the physiology of the patients as well as management regarding food intake.

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Section: Sars-cov-2 and Anosmia: Cellular Tropism In Olfactory Epithementioning

confidence: 99%

COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology

et al. 2021

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“…1b). Ace2 is strongly expressed in a specific area of the main olfactory epithelium (MOE), the dorsal part (MOED) which is directly exposed to the environment and specialized in sensing volatile chemical cues 14,15 . Moreover, we observed a previously unreported expression of Ace2, in the most rostral sensory subsystem, the Grueneberg ganglion (GG), mostly implicated in volatile danger cues detection [34][35][36] and in the circumvallate taste papilla (CV) involved in water-soluble tastant perception 29 .…”

Section: Sars-mentioning

confidence: 99%

“…Selected slices were then blocked for 3 h at room temperature in a PBS solution containing 5% normal donkey serum (NDS; Jackson ImmunoResearch) and 1% of non-ionic detergent (Triton ® X-100; Fluka). A double and indirect immunostaining approach using specific primary antibodies was then used to simultaneously localize ACE2 expression with other marker proteins 14,15 . The primary antibodies used were directed against ACE2 (Goat anti-ACE2; PA5-47488; Invitrogen; (which was not certified by peer review) is the author/funder.…”

Section: Chemosensory Epithelia Isolationmentioning

confidence: 99%

Age-dependent appearance of SARS-CoV-2 entry cells in mouse chemosensory systems reflects COVID-19 anosmia and ageusia symptoms

Brechbühl

Wood

Bouteiller

et al. 2021

Preprint

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COVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2 and the TMPRSS2 proteins, has been reported in non-chemosensory cells in the nose and mouth of the rodents, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2 and TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identified the virus target cells to be of basal and sensory origin and we revealed their age-dependent appearance. Our results not only clarify human viral-induced sensory symptoms but also propose new investigative perspectives based on ACE2-humanized mouse models.

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“…Briefly, the pathogenesis of the olfactory dysfunctions can be explained by two theories of direct viral cytopathy and systemic inflammatory cascade of events. According to recent studies, SARS-CoV-2 may affect directly the olfactory epithelium through perturbation of supporting cells which maintain the integrity of the olfactory sensory neurons and express ACE2 protein and cell surface protease TMPRSS2 which are both necessary for the virus entry into the target cells (Brann et al, 2020; Fodoulian et al, 2020). However, systematic studies on the histopathology of the olfactory epithelium in patients with COVID-19 are lacking (Deshmukh et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

High prevalence of long-term psychophysical olfactory dysfunction in patients with COVID-19

Boscolo‐Rizzo

Menegaldo

Fabbris

et al. 2021

Preprint

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This study prospectively assessed the long-term prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 54 (37.2) being mildly microsmic, 16 (11.0%) moderately microsmic, 7 (4.8%) severely microsmic, and 10 patients (6.9%) being anosmic. At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of sense of smell or taste and olfactory test scores (Spearman’s r=-0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of SARS-CoV-2 infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-CoV-2 infection.

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SARS-CoV-2 Receptors and Entry Genes Are Expressed in the Human Olfactory Neuroepithelium and Brain

Cited by 195 publications

References 79 publications

COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology

COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology

Age-dependent appearance of SARS-CoV-2 entry cells in mouse chemosensory systems reflects COVID-19 anosmia and ageusia symptoms

High prevalence of long-term psychophysical olfactory dysfunction in patients with COVID-19

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