Research Identifies Molecular Basis for Persistent Taste Loss in Long COVID

Years into the postpandemic era, millions of US individuals continue to live with the lingering effects of COVID-19. Long COVID is now estimated to affect between 10% and 30% of those who contract SARS-CoV-2, with a change in smell or taste recognized as one of its defining symptom subtypes. In a study published in Chemical Senses, researchers have taken an important step toward explaining why some patients never fully recover. The study authors noted that the findings carry practical implications for pharmacists on the front lines of long COVID care.¹

Researchers from the University of Colorado Anschutz School of Medicine, Uppsala University Hospital, and the Swedish University of Agricultural Sciences studied 28 nonhospitalized patients who reported persistent taste disturbances more than 1 year after a confirmed SARS-CoV-2 infection. Using the Waterless Empirical Taste Test (WETT), a validated 53-strip psychophysical instrument, investigators objectively quantified each participant's ability to detect all 5 basic taste qualities: sweet, umami, bitter, sour, and salty. Fungiform papilla biopsies were then collected from 20 participants and analyzed by histology and quantitative PCR for taste cell molecular markers.²

What the Study Found

The central finding was a significant reduction in messenger RNA encoding PLCβ2, which is a signal-amplifying protein expressed in type 2 taste receptor cells that are responsible for detecting sweet, umami, and bitter flavors. Expression levels of PLCβ2 messenger RNA (mRNA) correlated significantly with overall taste scores (r = −0.51, P = .023), as did TAS1R3 mRNA, a receptor subunit shared by both sweet and umami transduction pathways, which correlated with the combined sweet-umami score (r = 0.51, P = .02). Salty and sour taste qualities, which depend on a distinct type 3 cell pathway that does not require PLCβ2, were largely preserved.²

Taste Buds Look Normal, But Don't Work Normally

Histological analysis revealed that taste bud architecture and innervation were generally intact across subjects, even in individuals who reported total loss of 1 or more taste qualities. However, 7 of the 19 post-COVID biopsy subjects displayed disorganized taste buds or abnormally isolated PLCβ2-positive cells scattered throughout the lingual epithelium—a pattern not observed in any of the 12 healthy control subjects (P < .03). The authors suggest these aberrant cells may reflect disrupted nerve-to-taste-cell signaling, a mechanism demonstrated previously in animal models.²

Critically, no SARS-CoV-2 RNA was detected in any of the tissue samples, even though subjects were tested a mean of 21 months after initial infection. This finding aligns with prior work showing that taste bud cells are replaced every 2 to 4 weeks, meaning none of the cells present at the time of biopsy would have existed during the acute infection. Yet the molecular deficit persisted. The investigators propose that epigenetic mechanisms, possibly involving persistent immune dysregulation, may be sustaining the functional impairment long after viral clearance.²

Implications for Pharmacy Practice

Because many patients and even some clinicians dismiss persistent taste complaints as subjective or flavor confusion rooted in smell loss, the Chemical Senses study provides important validation. The ACE2 receptor and TMPRSS2 protease, which SARS-CoV-2 uses to infect cells, are expressed on type 2 taste receptor cells—the very cell population that showed reduced PLCβ2 and TAS1R3 mRNA in long COVID subjects. This biological plausibility should inform how pharmacists counsel patients reporting that sweet, bitter, or umami tastes are diminished or absent.²

Despite these findings, treatment options remain limited. Olfactory retraining, where patients systematically sniff essential oils twice daily, has shown promise for smell recovery and may have some relevance to integrated flavor perception. Ongoing research into whether targeted molecular therapies could restore PLCβ2 signaling is needed, and the authors call for future studies to determine whether the observed mRNA deficits are reversible.³

Pharmacists can play a role by screening long COVID patients for nutritional risk since diminished taste is associated with reduced appetite, poor dietary intake, and potential drug-food interaction blind spots.³

"Our findings offer measurable evidence of long-term taste disruption in some post-COVID patients long after the virus has been cleared," the study authors concluded. “For the millions still living with this invisible symptom, those words represent meaningful progress—and a call for more targeted clinical attention.”²

REFERENCES

1. Hou Y, Gu T, Ni Z, Shi X, Ranney ML, Mukherjee B. Global prevalence of long COVID, its subtypes, and risk factors: an updated systematic review and meta-analysis. Open Forum Infect Dis. 2025;12(9):ofaf533. doi:10.1093/ofid/ofaf533

2. Morad H, Vanhala T, Kisiel MA, et al. Taste dysfunction in long COVID. Chem Senses. 2026;51:bjaf068. doi:10.1093/chemse/bjaf068

3. Handler R. From smell loss to brain fog: unpacking the long COVID puzzle. Stanford Medicine Department of Medicine. September 30, 2025. Accessed March 4, 2026. https://med.stanford.edu/medicine/news/current-news/standard-news/long-covid-care-2025.html