Reduced Salivary Gustin and Statherin in Long-COVID Cohort with Impaired Bitter Taste

Abstract

Background/Objectives: Taste dysfunction is a frequent symptom of acute coronavirus disease (COVID)-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While the majority of those affected reported recovery over time, emerging data suggest that 20-25% of individuals experience persistent taste dysfunction, constituting a common symptom of long COVID. Gustation is mediated by continuously renewing taste bud cells. A balance between the counteracting processes of cell generation and cell death maintains the homeostatic turnover. Sonic hedgehog (SHH) is a morphogenic protein that promotes taste cell proliferation and differentiation. Enzymatic proteins such as gustin modulate the environment around the taste receptors and influence taste perception. Hence, we hypothesized that increased taste cell turnover and reduced taste-related salivary proteins contribute to the taste dysfunction in long COVID. Methods: Unstimulated whole saliva (UWS) was collected from individuals with long COVID experiencing taste dysfunction after obtaining informed consent. The normal control included archived saliva samples catalogued prior to 2019. Taste perception was objectively determined by the waterless empirical taste test. The SHH, gustin, and inflammatory cytokines in UWS were determined with ELISA. The expressions of epithelial and taste-cell-specific markers in cellular saliva were assessed by immunoflurorescence. Results: Impaired bitter taste was the most common dysfunction in the long-COVID cohort. Salivary gustin was significantly lower in those with long COVID and correlated with lower bitter taste score. Cellular saliva showed keratin-10- and small-proline-rich protein-positive epithelial cells as well as SHH-, occluding- and KCNQ1-positive taste cells. Conclusions: Salivary gustin could be a marker for impaired bitter taste in long COVID.