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Bilinska et al report high expression of ACE2 and TMPRSS2 in sustentacular cells of the olfactory epithelium and less expression in OSNs (Bilinska et al , 2020) Since sustentacular cells play key roles in supporting OSN metabolism and odor sensing, any virus-mediated damage to these cells could lead to olfactory deficits (Heydel et al , 2013) Overall, these studies offer several hypotheses as to how viral mechanisms could lead to smell loss in COVID-19 patients: one ACE2 mechanisms in olfactory neurons lead to a direct modulation of olfactory sensitivities or even cell death;two ACE2 mechanisms in non-neural olfactory cells lead to indirect modulation of OSN function and;three ACE2 mechanisms in neighboring glial cells lead to increased inflammatory response, whose downstream effects could alter OSN function and reduce olfactory sensitivities [ ]a SARS-CoV-2/ACE2-mediated dysregulation of insulin signaling could further aggravate symptoms in diabetics [ ]highest density of central insulin receptors and highest concentration of insulin in mammalian brain are found in the olfactory bulb (Havrankova et al , 1981)
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Frontiers_in_Human_Neuroscience
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Loss of Smell in COVID-19 Patients: Lessons and Opportunities
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