Taste dysfunction in Long COVID.

Persistent taste dysfunction may occur both as acute and long-term symptoms of SARS-CoV-2 infection (Long COVID), yet the underlying mechanisms are unknown at the histological, cellular, and molecular levels. This study investigates the underlying pathology in 28 non-hospitalized subjects who reported persistent taste disturbances for over 12 months after testing positive for SARS-CoV-2. To assess taste function, subjects completed the Waterless Empirical Taste Test (WETT), which quantifies the subject's ability to taste each of the five human taste qualities: sweet, umami, bitter, sour, and salty. Biopsies of fungiform papillae were collected from 20 participants and analyzed histologically for overall taste bud structure and innervation and by quantitative PCR (qPCR) for expression of markers for different taste receptor cells (TRCs). Although all subjects reported subjective taste dysfunction, only five scored below the 20th percentile on overall taste sensitivity. However, 12 subjects exhibited total loss of one or more taste qualities and another 13 subjects tested below the 95% confidence interval for at least one taste modality. Notably, loss of sweet, umami, or bitter tastes -- qualities mediated by a PLCβ2-transduction cascade -- was significantly more common than loss of sour and salty, and this loss correlated with reduced expression of PLCβ2 mRNA. Histological analysis revealed generally preserved taste bud structure and innervation in all cases, with occasional disorganization resulting in isolated PLCβ2-immunoreactive cells. Our findings suggest long-term taste dysfunction after COVID-19 disproportionately impacts PLCβ2-dependent taste qualities and is not due to widespread structural damage of the taste periphery.