Taste dysfunction in long COVID.

Persistent taste dysfunction is frequently reported in individuals with post-acute sequelae of infection by SARS-CoV-2 (long COVID). The mechanisms and pathological correlates underlying this taste dysfunction are unknown. This study investigates the underlying pathology in 28 non-hospitalized subjects diagnosed with COVID-19 who experienced taste disturbances more than 12 mo after testing positive for SARS-CoV-2. To objectively establish the nature of the taste deficit, we used the WETT taste test, which quantifies the subject's ability to taste each of the 5 taste qualities: sweet, umami, bitter, sour, and salty. We then biopsied 5 to 8 fungiform taste papillae (FP) in 20 of the 28 subjects. The FPs were analyzed histologically for overall taste bud (TB) structure and innervation and by quantitative PCR (qPCR) for mRNA expression of markers for different taste receptor cells. Although all subjects had reported taste dysfunction, only 3 showed overall taste scores below the 10th percentile for a normal population adjusted for age and sex. However, 11 of the 28 subjects exhibited total loss of one or more taste qualities. Loss of PLCβ2-dependent taste qualities (sweet, umami, and bitter) was significantly more common and was correlated with reduced expression of PLCβ2 and Tas1R3 mRNAs. Histological analysis revealed generally preserved TB structure and innervation but with occasional disorganized TBs and abnormal, isolated PLCβ2-positive cells in the epithelium. Our findings suggest long-term taste dysfunction after COVID-19 occurs rarely-more frequently involving PLCβ2-dependent taste qualities-but is not due to wholesale disruption of the taste periphery.