Pathogenesis of taste impairment and salivary dysfunction in COVID-19 patients

Olfactory Disorders in Post-Acute COVID-19 Syndrome

“…ACE2 can act as a primary receptor, and, after virus attachment, the spike protein in its surface is cleaved and dissociated by furin, after which the subunit S2 is cleaved by TMPRSS2, changing the structure of the S2 subunit, which ultimately leads to membrane fusion and viral RNA transferring to host cell cytoplasm. An alternative pathway can also be initiated by ACE2 binding and the internalization process involving clathrin and cathepsin L, and, in this case, the virus releases its genetic material directly after endocytosis, as an alternative independent from TMPRSS2 to invade cells [19].…”

“…After entering the mouth through salivary particles, the virus can infect cells in filiform and vallate papillae, lingual epithelium and taste buds, all cells that express ACE2, starting its replication, which in turn causes taste impairment [19]. Other potential targets for cell infection due to ACE2 are vascular endothelial cells and adipocytes in parotid and salivary glands.…”

“…Other potential targets for cell infection due to ACE2 are vascular endothelial cells and adipocytes in parotid and salivary glands. The damage in these cells affects both blood and nutritional supplies and, indirectly, it can change taste perception [19].…”

“…High levels of ACE2 were found in sustentacular cells of the olfactory system, which are in intimate contact with dendrites of olfactory receptor neurons, and also other olfactory epithelium cells such as ductal cells of Bowman's gland, microvillar cells, globose and horizontal basal cells, and olfactory bulb pericytes [19,21]. It is hypothesized that infection of mesenchymal stromal and vascular cells in the nose and bulb and their subsequent inflammation affects the neuronal conduction, reduces nutritional and water supplies and, therefore, causes the death of olfactory sensory neurons (OSNs) and damage to olfactory bulb function [20] (Figure 1).…”

“…It is hypothesized that infection of mesenchymal stromal and vascular cells in the nose and bulb and their subsequent inflammation affects the neuronal conduction, reduces nutritional and water supplies and, therefore, causes the death of olfactory sensory neurons (OSNs) and damage to olfactory bulb function [20] (Figure 1). Although OSNs are surprisingly not an ACE2 expressing tissue, it has already been described that the spike protein can bind to neural cell receptors, possibly due to cell-to-cell transmission through tunneling nanotubes (TNTs), filamentous cellular projections that form a communication and transportation net between cells [19].…”