Even after the virus disappears, some people continue to experience changes in taste. A new study suggests that subtle molecular changes in taste receptor cells, rather than visual damage, may explain why sweet, umami, and bitter tastes remain disrupted after infection with the coronavirus.
Study: Taste disturbance in long-term COVID-19 infection. Image credit: DimaBerlin/Shutterstock.com
Some long-term patients with COVID-19 report persistent taste changes, but the objective deficit and the underlying disease process remain unclear. Recent research published in journals chemical sense Investigate these areas.
How SARS-CoV-2 infection disrupts taste sensation
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which caused the recent coronavirus disease 2019 (COVID-19) pandemic, was significantly associated with olfactory and gustatory dysfunction. This usually normalizes within a few weeks, but in a small number of people it persists for several months.
Symptoms that last more than three months are classified as part of the long-term coronavirus disease (COVID-19) syndrome, also known as post-acute COVID-19 syndrome (PACS). It can be a symptom of loneliness. Loss of taste, which occurs in extreme cases, and a marked reduction in taste has a significant impact on safety and quality of life, impairing appetite and nutritional intake. Therefore, special intervention is required.
The frequency of these symptoms was higher in earlier SARS-CoV-2 variants than in Omicron and its subvariants. The current study primarily included individuals infected with earlier variants. Changes in taste-related symptoms may reflect differences in the degree of virus tropism for taste receptor cells or in immune responses, which may alter taste-related outcomes.
Taste buds are epithelial sensory organs with up to 100 taste cells, half of which are taste receptor cells. Different types of taste receptor cells are correlated with specific taste subtypes, such as sweet, umami, and bitter.
This involves PLCβ2-mediated signaling triggered by a set of specific receptors, including TAS1R2/R3 for sweet taste and TAS1R1/R3 for umami taste. These are type II receptor cells. In contrast, type III receptor cells detect tastes such as sour or very salty through ionic transport. Taste bud cells rapidly turn over, but only differentiate when they come into contact with associated nerve fibers. The high proportion of taste bud cells forming synapses with nerve fibers (80%) highlights the potentially important role of nerve-taste cell connections in taste loss after viral infection.
Type II cells contain ACE2 and TMPRSS2 molecules, which are receptors that mediate the attachment and entry of SARS-CoV-2 into host epithelial cells. This can contribute to taste bud damage. Other factors that may contribute to taste disturbances during prolonged COVID-19 include associated inflammation, immunological abnormalities, and changes in saliva.
The current study aims to investigate these different areas.
Testing for long-term COVID-19 taste loss with WETT and biopsy
The study included 28 people diagnosed with COVID-19 who suffered from a taste disorder that persisted for more than a year after testing positive for COVID-19 and were recruited specifically for ongoing taste complaints, although one participant did not report a taste disorder but had an active infection at the time of sampling and was the subject of comparison for tissue analysis. Anhydrous Empirical Taste Testing (WETT) was used to provide objective and quantitative measurements of taste dysfunction for each of the five basic tastes: sweet, bitter, umami, sour, and salty.
In addition, fungiform papillae were biopsied for microscopic examination in 20 of 28 patients. These papillae were chosen for ease of access as they are located at the tip of the tongue. The structure and nerve supply of the taste buds were evaluated. Quantitative mRNA analysis was performed for each taste receptor cell.
Selective loss of sweet, umami, and bitter tastes
All participants reported normal taste sensation before the coronavirus outbreak. The average age at the time of the study was 50 years. The time period between initial infection and current taste test ranged from 13.5 to 27 months. Only three of the participants had an age- and gender-adjusted overall taste score below normal (below the 10th percentile). However, 11 of them had completely lost one or more of their basic tastes. Therefore, a normal composite taste score does not exclude one or more basic taste dysfunctions.
No uniform pattern of taste loss was observed, although only two subjects had significantly reduced sour taste sensation. Interestingly, acidity has been reported to be most affected during the acute phase of the disease.
Conversely, complete and profound taste loss involved PLCβ2-mediated receptors for sweet, umami, and bitter tastes. This was associated with decreased expression of PLCβ2 and TAS1R3 mRNA, which are key to type II taste cell function. Sweetness or umami scores individually did not correlate with mRNA expression, but their combined average score showed a significant correlation.
This study reports what the authors describe as the first evidence linking psychophysical taste disturbances in prolonged COVID-19 with decreased expression of key taste receptor cell mRNAs, such as PLCβ2 and TAS1R3.
Anatomically, most papillae appeared normal overall, but some papillae showed disorganized architecture and had isolated PLCβ2-positive cells within the epithelium. These abnormal cells were observed in seven of the biopsies from subjects with long-term coronavirus infection (COVID-19), but never in normal people. These findings suggest that long-term taste impairment is a relatively rare but measurable sequela of COVID-19 infection and is more commonly associated with PLCβ2-dependent taste sensation mediated by type II taste receptor cells.
Previous studies have suggested that viral infection of the taste bud epithelium disrupts taste bud tissue and neural connections, and that recovery may occur after viral clearance. However, in the present study, despite persistent taste disturbance, no viral RNA was detected in taste papilla biopsies. Some scientists believe that reinfection, delayed viral clearance, and perhaps associated inflammation, may influence taste bud regrowth and recovery of taste function in long-term COVID-19 infections.
Taste disturbances were observed despite the taste sensing apparatus appearing normal. The authors hypothesize that this may reflect more long-term molecular changes, including a phenomenon called “inflammatory memory,” an epigenetic change that can leave a long-term imprint on chromatin structure. It is thought that widespread impairment of neurotransmission may also contribute to taste loss.
strengths and limitations
This study is a single-time point retrospective study, so there is no control group. Using self-reported taste reports for pre-pandemic medical history, pre-infection taste measurements are lacking for comparison, relying instead on established normative taste testing datasets.
However, the use of integrated subjective and objective taste data is a major strength. Additionally, they combined mRNA assessment with tissue-level testing of the structural integrity of taste buds in people with long-term COVID-19 infections.
Long-term COVID-19-induced taste loss associated with disruption of the PLCβ2 pathway
This study demonstrated a predominant loss of sweet, umami, and bitter tastes in this sample, all of which involve PLCβ2-dependent taste pathways. But other mechanisms may be at work, as suggested by the small number of people who have lost other taste traits.
Overall, this small, targeted population with persistent symptoms highlights the prevalence of taste loss or reduction in long-term COVID-19 and provides quantitative evidence, while highlighting the need for large-scale controlled studies to elucidate the underlying mechanisms and prevalence.
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