Taste dysfunction in Long COVID

Abstract

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 and who experienced taste disturbances more than 12 months after testing positive for SARS-CoV-2. To objectively establish the nature of taste deficit, we used the WETT taste test, which quantifies the subject's ability to taste each of the five taste qualities: sweet, umami, bitter, sour, and salty. We then biopsied five to eight fungiform taste papillae (FP) in 20 of the 28 subjects. The FPs were analyzed histologically for overall taste bud 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 three showed overall taste scores below the 10^th 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, bitter) was significantly more common and was correlated with reduced expression of PLCβ2 and Tas1R3 mRNAs. Histological analysis revealed generally preserved taste bud structure and innervation, but with occasional disorganized taste buds 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.

Figure 1:

Correlation of relative mRNA expression levels with taste scores. The point indicated in orange is the data from Subject SWE17 who was used for comparison. A) The mRNA levels for PLCß2 (r(18)=−.51, p= .023) and TAS1R3(r(18)=.43, p= .056) correlated with the overall taste score for each subject. B) The mRNA level for TAS1R3 correlates with the combined taste score for the related taste qualities (Sweet and brothy) (r(18)=.51, p= .02).

Figure 2:

Appearance of normal taste buds sectioned in different planes from different subjects. Red = PLCß2 immunoreactivity showing Type II taste cells; Green = TUJ1 immunoreactivity for nerve fibers. Typical taste buds have more than one PLCß2+ cell surrounded by a dense network of TUJ1-stained nerve fibers. Green profiles outside of taste buds are extragemmal nerve fibers typical of lingual epithelium (Moayedi et al. 2021). a, b. Taste buds sectioned longitudinally appear similar in shape to garlic bulbs or onions (from Subject (SWE) 15. c) Taste buds sectioned perpendicular to their long axis appear circular (from subject (SWE) 29 who reported a total absence of taste perception (taste score of 13, showing no correct responses to any tastant). Scale bar in panel (b) applies to all panels.

Figure 3:

Examples of abnormal PLCß2+ taste-like cells from 4 cases. (A & B). Subject (SWE) 12 had a taste score of 35 (54%). (C) From subject (SWE) 13 who had a score of 22 (21%). In both cases (A & C), innervated PLCß2+ (red arrows) cells occur in relative isolation within the epithelium. Innervation of these cells (green: TUJ1) is sparse unlike innervation of taste buds (cf Fig. 2). These cells may represent very small taste buds or simply PLCß2+ cells lying outside of a taste bud structure. Panel B shows a higher magnification of one such isolated PLCß2+ cell and its innervation stained for the presence of P2X3, a neural receptor predominantly on nerve fibers that innervate taste buds. Panels D-E are from case (SWE) 24 with a taste score of 17 (4%) showing examples of aberrant PLCß2+ cells (red arrows) outside of a taste bud structure. Panel F: A disorganized taste bud from case SWE 29 who reported a total absence of taste perception (taste score of 13, showing no correct responses to any tastant). The heavy innervation is typical of taste buds, but the cellular structure revealed by PLC-staining (red) does not show typical taste bud organization.