Epithelial-neuro-immune dynamics in dysgeusia triggered by chronic viral infection 3795

Abstract Description SARS-CoV2 infection is uniquely characterized by the sudden onset of anosmia and dysgeusia in many individuals. While most recover, a subset continues to experience persistent symptoms known as long-COVID, with 30% reporting dysgeusia. In our long-COVID cohort, objective testing revealed significant distortion in the perception of bitter and sweet tastes. Although polymorphisms in TAS2R38 and gustin genes are linked to bitter taste perception, haplotype analysis in our long-COVID cohort was inconclusive. We hypothesized that a disrupted homeostasis between taste cell loss and replenishment due to chronic inflammation leads to dysgeusia. Single cell transcriptomic analysis revealed cellular heterogeneity including epithelial cells (such as KRT14, KRT15, SPRR3), cells exhibiting neuronal markers (such as SNAP25, SNAP47, KCNQ2) suggestive of taste receptor cells and immune cells in saliva. However, differences in marker expressions between the long-COVID and healthy cohort were not significant except for inflammatory chemokine and interleukin genes. Immunofluorescence and flow cytometry confirmed the presence of epithelial cells, taste receptor like cells and immune cells in saliva. Elevated proinflammatory cytokine expression in saliva indicated persistent localized inflammatory immune response. Collectively these findings suggest that persistent epithelial-neuro-immune response locally in the tongue following SARS-CoV2 infection contributes to the dysgeusia in long-COVID. Funding Sources DENTAL RESEARCH FOUNDATION #44-76-254 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)