Even after the virus disappears, some people continue to experience altered taste. New research suggests that subtle molecular changes in taste receptor cells, not visible damage, may explain why sweet, umami, and bitter flavors remain disrupted long after COVID-19 infection.
Study: Taste dysfunction in long COVID. Image credit: DimaBerlin/Shutterstock.com
Some people with long COVID-19 report persistent taste alterations, but the objective deficits and their underlying disease processes remain unclear. A recent study published in the journal Chemical Senses investigates these areas.
How SARS-CoV-2 infection disrupts taste perception
Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which drove the recent coronavirus disease 2019 (COVID-19) pandemic, was prominently associated with olfactory and taste dysfunction. This typically normalizes within weeks, but in a small proportion of people it persists for months.
Symptoms lasting for over three months are classified as part of the long COVID-19 syndrome, also termed post-acute COVID-19 syndrome (PACS). It may be the solitary remaining symptom. The loss of taste, as occurs in extreme cases, as well as a noticeable reduction in taste, significantly affects safety and the quality of life, impairing appetite and nutritional intake. Thus, it requires specific intervention.
The frequency of these symptoms was higher with earlier SARS-CoV-2 variants than with Omicron and its subvariants. The current study included mostly individuals infected by the earlier variants. Variations in taste-related symptoms may reflect different degrees of viral affinity for taste receptor cells and differences in the immune responses, potentially altering the taste-related outcome.
Taste buds are epithelial sensory organs with up to 100 taste cells, of which half are taste receptor cells. Different types of taste receptor cells correlate with specific taste subtypes, such as sweet, umami, and bitter.
This involves PLCβ2-mediated signaling triggered by an array of specific receptors, such as TAS1R2/R3 for sweet and TAS1R1/R3 for umami taste. These are type II receptor cells. In contrast, type III receptor cells detect tastes via ionic transduction, such as sour and very salty. Taste bud cells undergo rapid turnover, but differentiate only when they come into contact with the related nerve fiber. The high proportion of taste bud cells that synapse with nerve fibers, at 80 %, emphasizes the potentially key role of nerve-taste cell connectivity in post-viral taste loss.
Type II cells contain ACE2 and TMPRSS2 molecules, the receptors that mediate SARS-CoV-2 attachment to and entry into the host epithelial cell. This might contribute to taste bud damage. Other putative factors contributing to taste dysfunction in long COVID-19 include associated inflammation, immunologic abnormalities, and salivary alterations.
The current study sought to examine these different areas.
Testing long COVID-19 taste loss with WETT and biopsies
The study included 28 people diagnosed with COVID-19 who had persistent taste dysfunction for over a year after testing positive for the virus, recruited specifically because of ongoing taste complaints, although one participant reported no taste loss but had an active infection at sampling and served as a comparator in tissue analyses. The Waterless Empirical Taste Test (WETT) was used to provide objective, quantitative measures of taste dysfunction for each of the five basic tastes: sweet, bitter, umami, sour, and salty.
In addition, fungiform taste papillae were biopsied for microscopic examination in 20 of the 28 individuals. These papillae were chosen for their accessibility, as they are on the tip of the tongue. The structure of the taste bud and the nervous supply were evaluated. Quantitative mRNA analysis was performed for each taste receptor cell.
Selective loss of sweet, umami, and bitter tastes
All subjects reported normal taste pre-COVID-19. The mean age at the time of the study was 50 years. The time from first infection to the current taste test ranged from 13.5 to 27 months. Only three of the subjects had subnormal overall taste scores (below the tenth percentile), adjusted for age and sex. However, 11 of them had totally lost one or more of the basic tastes. Thus, a normal composite taste score does not preclude dysfunction of one or more basic tastes.
No uniform pattern of taste loss was observed, but only two subjects had a profoundly reduced sense of sourness. Interestingly, during the acute phase of the illness, sour taste is reported to be most affected.
Conversely, total and profound taste loss involved the PLCβ2-mediated receptors: sweet, umami, and bitter. This was associated with a lower expression of PLCβ2 and TAS1R3 mRNAs, which are key to type II taste cell function. While neither sweet nor umami taste scores correlated with mRNA expression individually, their combined average scores showed a significant correlation.
The study reports what the authors describe as the first evidence linking psychophysical taste dysfunction in long COVID-19 with reduced expression of key taste-receptor cell mRNAs, including PLCβ2 and TAS1R3.
Anatomically, most papillae appeared grossly normal, but a few showed disorganized structure and isolated PLCβ2-positive cells in the epithelium. These abnormal cells were observed in seven of the biopsies from long COVID-19 subjects, but were never observed in normal individuals. These findings suggest that long-term taste dysfunction is a relatively rare but measurable sequel of COVID-19 and is more commonly linked to PLCβ2-dependent tastes mediated by type II taste receptor cells.
Previous studies have suggested that viral infection of taste bud epithelium may disrupt taste bud organization and nerve connectivity, with recovery occurring after viral clearance. However, in the current study, viral RNA was not detected in taste papilla biopsies despite persistent taste dysfunction. Some scientists think that reinfection or delayed viral clearance, and possibly the associated inflammation, affect taste bud regrowth and the recovery of taste function in long COVID-19.
Despite a normal-appearing taste-sensing apparatus, taste disruption was observed. The authors hypothesize that this may reflect longer-lasting molecular changes, including a phenomenon termed “inflammatory memory,” an epigenetic alteration that can leave a prolonged mark on chromatin structure. Widespread disruption of nerve transmission has also been proposed as a possible contributor to taste loss.
Strengths and limitations
This study was a single-timepoint retrospective study and, as such, has no control group. It uses self-reported taste reports for pre-pandemic history and lacks pre-infection taste measurements for comparison, instead relying on established normative taste-test datasets.
However, its use of integrated subjective and objective taste data is a major strength. In addition, it coupled mRNA assessment with tissue-level examination of structural integrity in taste buds in individuals with long COVID-19.
Long COVID-19 taste loss linked to PLCβ2 pathway disruption
This study demonstrates a predominant loss of sweet, umami, and bitter taste in this sample, all of which involve the PLCβ2-dependent taste pathway. However, other mechanisms may be at work, as suggested by the few who lost other taste qualities.
Overall, this small, targeted cohort of individuals with persistent symptoms underscores the prevalence of long-term taste loss or decrease in long COVID-19, offering quantitative evidence while highlighting the need for larger, controlled studies to clarify underlying mechanisms and prevalence.
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