“Persistent Taste Dysfunction in Long COVID: Etiology, Pathology, and Therapeutic Horizons”

John Murphy, CEO, The COVID-19 Long-haul Foundation

🧠 Abstract

Long COVID-associated taste disorders represent a persistent and underrecognized sequela of SARS-CoV-2 infection, affecting millions globally. While anosmia and dysgeusia were early hallmarks of acute COVID-19, emerging evidence suggests that taste dysfunction may persist for months or years, even in patients with mild initial symptoms. This article synthesizes current research on the etiology, pathology, benomic alterations, and clinical trajectory of taste disorders in long COVID. We examine viral persistence in taste bud basal cells, salivary gland dysfunction, neuroinflammatory cascades, and epithelial remodeling, alongside patient-reported outcomes and therapeutic interventions. Drawing from over 25 peer-reviewed sources, we propose a framework for understanding long COVID taste dysfunction as a multi-systemic, neuroepithelial disorder with implications for nutrition, mental health, and sensory rehabilitation.

🧬 Introduction

The COVID-19 pandemic, caused by SARS-CoV-2, has led to unprecedented global morbidity, with over 700 million confirmed cases and a growing population of individuals experiencing post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as long COVID. Among the constellation of long COVID symptoms, taste disorders — including ageusia, hypogeusia, dysgeusia, and phantogeusia — have emerged as persistent and debilitating conditions.

Early in the pandemic, loss of taste and smell were recognized as sentinel symptoms of acute infection. However, longitudinal studies now reveal that up to 25% of patients experience persistent taste dysfunction beyond 6 months post-infection. These symptoms are not merely sensory inconveniences; they are linked to malnutrition, depression, social withdrawal, and reduced quality of life.

Recent research from the National Institute on Aging (NIA) has demonstrated that SARS-CoV-2 can persist in taste bud basal cells for over a year, leading to misshapen, underdeveloped taste buds and reduced receptor density. This finding challenges the assumption that taste dysfunction is purely neurological and suggests a direct epithelial and benomic impact.

Moreover, studies have identified ACE2 and TMPRSS2 receptors — key viral entry points — on taste bud epithelial cells and salivary glands, implicating these structures in viral tropism and chronic inflammation. The benomic landscape of infected taste tissue reveals altered expression of genes involved in cell renewal, cytokine signaling, and neuroplasticity, suggesting a complex interplay between viral persistence, immune dysregulation, and epithelial remodeling.

This article aims to provide a comprehensive, peer-reviewed synthesis of current knowledge on long COVID taste disorders, structured as follows:

Etiology and Pathophysiology: Mechanisms of viral entry, persistence, and tissue damage
Benomic and Cellular Changes: Transcriptomic and proteomic shifts in taste bud and salivary tissue
Taste Bud Destruction and Modification: Histological and regenerative dynamics
Saliva and Oral Microenvironment: Role of xerostomia, mucosal immunity, and microbiome
Clinical Manifestations and Examples: Patient-reported outcomes and sensory profiles
Treatment Modalities: Pharmacologic, rehabilitative, and experimental interventions

By integrating molecular, clinical, and therapeutic perspectives, we aim to advance the understanding of taste dysfunction in long COVID and inform future research and care strategies.

🧪 Etiology and Pathophysiology of Taste Disorders in Long COVID

1. Overview of Taste Dysfunction in SARS-CoV-2 Infection

Taste disorders were among the earliest sensory symptoms reported during the COVID-19 pandemic, often co-occurring with anosmia. While many cases resolved within weeks, a significant subset of patients developed persistent taste dysfunction lasting months or longer, now classified under post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID.

Taste dysfunction includes:

Ageusia: complete loss of taste
Hypogeusia: reduced taste sensitivity
Dysgeusia: distorted taste perception
Phantogeusia: perception of taste without stimulus

These symptoms may occur independently or in conjunction with olfactory deficits, complicating diagnosis and treatment.

2. Viral Entry and Tropism

SARS-CoV-2 enters host cells via the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2). These receptors are expressed not only in the respiratory tract but also in:

Taste bud epithelial cells
Salivary gland acini
Oral mucosa
Cranial nerves VII, IX, and X

This distribution suggests that taste dysfunction may result from direct viral invasion, not merely secondary to olfactory loss.

3. Taste Bud Damage and Epithelial Remodeling

Recent histological studies have shown:

Misshapen and underdeveloped taste buds in long COVID patients
Reduced density of taste receptor cells
Delayed regeneration of basal cells

A landmark study by the National Institute on Aging found persistent SARS-CoV-2 RNA in taste bud basal cells up to 12 months post-infection. This suggests a mechanism of chronic epithelial disruption, possibly driven by viral persistence and immune dysregulation.

4. Neuroinflammation and Cranial Nerve Involvement

Taste perception is mediated by cranial nerves:

Facial nerve (VII): anterior two-thirds of the tongue
Glossopharyngeal nerve (IX): posterior third
Vagus nerve (X): epiglottis and pharynx

SARS-CoV-2 has been shown to induce neuroinflammation, with evidence of:

Microglial activation
Cytokine-mediated demyelination
Axonal transport disruption

These effects may impair signal transmission from taste receptors to the brainstem, contributing to dysgeusia and ageusia.

5. Salivary Gland Dysfunction and Oral Microenvironment

Saliva plays a critical role in taste by:

Solubilizing tastants
Maintaining mucosal integrity
Transporting ions and enzymes

SARS-CoV-2 infects salivary gland epithelial cells, leading to:

Xerostomia (dry mouth)
Altered salivary composition
Reduced flow rate

These changes impair taste perception and may exacerbate epithelial damage.

6. Benomic Alterations

Benomic profiling (transcriptomic and proteomic analysis) of infected taste tissue reveals:

Downregulation of taste receptor genes (e.g., TAS1R, TAS2R families)
Upregulation of inflammatory cytokines (IL-6, TNF-α)
Altered expression of neuroplasticity markers (BDNF, NGF)

These changes suggest a multi-layered disruption involving:

Sensory cell renewal
Neural connectivity
Immune signaling

Such benomic shifts may underlie the chronicity and variability of taste dysfunction in long COVID.

7. Examples of Taste Distortion

Patient-reported examples include:

Metallic taste when eating fruit
Bitterness in water
Loss of sweetness perception
Persistent phantom tastes (e.g., smoke, rot)

These distortions often correlate with specific receptor dysfunction and neural misfiring, reinforcing the need for multi-modal assessment.

🧬 Benomic and Cellular Changes in Long COVID Taste Disorders

1. Introduction to Benomics in Taste Dysfunction

Benomics — encompassing transcriptomics, proteomics, and metabolomics — offers a molecular lens into the persistent taste dysfunction observed in long COVID. Unlike acute viral damage, long COVID appears to involve chronic alterations in gene expression, cell signaling, and tissue regeneration, particularly in taste bud epithelium and salivary glands.

2. Transcriptomic Alterations in Taste Buds

Studies using RNA sequencing of taste papillae from long COVID patients reveal:

Downregulation of taste receptor genes: TAS1R (sweet/umami), TAS2R (bitter), and ENaC (salt) channels show reduced expression.
Upregulation of inflammatory mediators: IL-6, TNF-α, and IFN-γ are elevated, suggesting ongoing immune activation.
Suppression of stem cell renewal pathways: SOX2, LGR5, and SHH — key regulators of taste bud regeneration — are downregulated.

These changes imply a failure of epithelial turnover, leading to atrophic or malformed taste buds.

3. Proteomic Shifts in Salivary Glands

Proteomic analysis of saliva from long COVID patients shows:

Reduced levels of salivary amylase and mucins: impairing tastant solubilization and mucosal protection.
Elevated proteases and oxidative stress markers: including MMP-9 and 8-isoprostane, which may degrade epithelial integrity.
Altered neuropeptides: such as substance P and CGRP, which modulate taste perception and pain.

These findings suggest that salivary dysfunction contributes to taste distortion, not just dryness.

4. Cellular Remodeling and Taste Bud Architecture

Histological studies reveal:

Flattened fungiform papillae with reduced taste pore density.
Disorganized basal cell layers, with impaired mitotic activity.
Loss of innervation: reduced synaptic markers (e.g., synaptophysin, neurofilament) in taste bud afferents.

This structural degradation correlates with clinical hypogeusia and dysgeusia, especially in patients with prolonged symptoms.

5. Epigenetic and Metabolic Reprogramming

Emerging evidence suggests:

DNA methylation changes in taste receptor genes and immune regulators.
Altered mitochondrial function in taste bud cells, with reduced ATP production and increased ROS.
Metabolomic shifts in saliva, including elevated lactate and reduced glutamate — both of which affect taste signaling.

These changes may reflect a metabolic exhaustion state, consistent with other long COVID findings.

6. Clinical Implications

Benomic profiling can help:

Stratify patients by molecular phenotype (e.g., inflammatory vs. neurodegenerative)
Guide targeted therapies (e.g., anti-inflammatory agents, neuroprotective peptides)
Monitor recovery via salivary biomarkers

For example, patients with elevated IL-6 and low TAS1R expression may benefit from IL-6 inhibitors or taste receptor agonists.

🧫 Taste Bud Destruction and Modification in Long COVID

1. Anatomy of Taste Buds

Taste buds are specialized sensory organs located primarily on:

Fungiform papillae (anterior tongue)
Foliate papillae (posterior lateral tongue)
Circumvallate papillae (posterior tongue)

Each bud contains 50–100 taste receptor cells, supported by basal cells and innervated by cranial nerves VII, IX, and X. These cells undergo rapid turnover, typically every 10–14 days, making them vulnerable to viral, inflammatory, and metabolic insults.

2. Histological Evidence of Damage

Postmortem and biopsy studies in long COVID patients reveal:

Flattened papillae with reduced taste pore openings
Disorganized epithelial layers, lacking clear stratification
Loss of taste receptor cell markers, including gustducin and PLCβ2
Reduced innervation, with diminished synaptophysin and neurofilament staining

These findings suggest structural collapse of the taste bud microenvironment, impairing both detection and signal transmission.

3. Mechanisms of Destruction

Several mechanisms contribute to taste bud damage:

Direct viral cytopathy: SARS-CoV-2 infects taste bud basal cells via ACE2, leading to apoptosis and impaired renewal.
Immune-mediated injury: Persistent cytokine exposure (IL-6, TNF-α) induces epithelial thinning and fibrosis.
Neurotropic effects: Viral particles may travel retrograde along cranial nerves, disrupting trophic support and synaptic integrity.
Vascular compromise: Microthrombi and endothelial dysfunction reduce perfusion to taste tissue, exacerbating ischemic damage.

4. Regeneration Failure

In healthy individuals, taste buds regenerate via:

Basal stem cell proliferation
Differentiation into receptor and support cells
Reinnervation by cranial nerves

In long COVID, this process is disrupted by:

Downregulation of SHH, SOX2, and LGR5 — key stem cell regulators
Persistent inflammation, which inhibits mitosis and promotes senescence
Loss of neural input, which impairs cell fate signaling

This leads to atrophic, non-functional taste buds, often visible on tongue examination as smooth, depapillated areas.

5. Clinical Correlates

Patients with taste bud destruction report:

Complete loss of taste (ageusia)
Selective deficits (e.g., inability to taste sweet or bitter)
Delayed taste recovery, often >6 months
Taste distortions, such as metallic or rotten flavors

These symptoms correlate with histological severity, suggesting that structural damage is a key driver of persistent dysfunction.

6. Imaging and Biomarkers

Emerging tools include:

Confocal microscopy of tongue epithelium to assess papillae morphology
Salivary cytokine panels to track inflammation
Taste strip testing for quantitative assessment of taste thresholds

These modalities may help stratify patients, monitor recovery, and guide treatment.

💧 Saliva and the Oral Microenvironment in Long COVID

1. Role of Saliva in Taste Perception

Saliva is essential for taste function because it:

Solubilizes tastants, allowing molecules to interact with taste receptors.
Maintains mucosal integrity, protecting taste buds from mechanical and chemical stress.
Provides ions and enzymes (e.g., sodium, amylase) that modulate taste signaling.
Supports microbiome balance, influencing oral health and sensory perception.

Disruption of salivary flow or composition can therefore profoundly alter taste.

2. SARS-CoV-2 Infection of Salivary Glands

ACE2 and TMPRSS2 receptors are expressed in salivary gland epithelial cells, making them susceptible to viral entry. Studies have shown:

Direct viral replication in salivary acini.
Persistent viral RNA in saliva months after acute infection.
Histological evidence of glandular inflammation and fibrosis.

This leads to xerostomia (dry mouth), a common symptom in long COVID, which exacerbates taste dysfunction.

3. Altered Salivary Composition

Proteomic and metabolomic studies of saliva in long COVID patients reveal:

Reduced mucins (MUC5B, MUC7) → impaired tastant solubilization.
Decreased salivary amylase → altered carbohydrate breakdown and sweet taste perception.
Elevated inflammatory cytokines (IL-6, TNF-α) → local immune dysregulation.
Oxidative stress markers (8-isoprostane, malondialdehyde) → epithelial damage.

These changes create a hostile oral environment, impairing both taste bud function and receptor signaling.

4. Oral Microbiome Dysbiosis

Long COVID patients often exhibit oral microbiome shifts, including:

Reduced diversity of commensal bacteria.
Overgrowth of opportunistic pathogens (e.g., Candida, Prevotella).
Altered metabolite profiles (e.g., increased lactate, reduced short-chain fatty acids).

Microbiome dysbiosis may contribute to taste distortion (metallic, bitter, or rotten flavors) and oral discomfort.

5. Clinical Manifestations

Patients with salivary dysfunction report:

Dry mouth with difficulty swallowing.
Loss of sweetness or saltiness due to impaired ion transport.
Persistent metallic or bitter taste linked to inflammatory metabolites.
Burning mouth syndrome in severe cases.

These symptoms often overlap with taste bud destruction, compounding sensory loss.

6. Therapeutic Approaches

Interventions targeting saliva and oral environment include:

Saliva substitutes and stimulants (pilocarpine, cevimeline).
Hydration and oral hygiene to reduce microbial overgrowth.
Anti-inflammatory rinses (chlorhexidine, corticosteroid mouthwashes).
Probiotics and microbiome modulation to restore balance.
Nutritional support to compensate for altered taste perception.

🩺 Clinical Course and Patient Examples in Long COVID Taste Disorders

1. Symptom Onset and Acute Phase

Early presentation: Taste loss often appears within the first 3–5 days of acute SARS-CoV-2 infection, sometimes preceding respiratory symptoms.
Common acute symptoms: Sudden ageusia, metallic dysgeusia, or inability to distinguish sweet and salty flavors.
Overlap with olfactory dysfunction: Many patients experience combined anosmia and ageusia, complicating sensory attribution.

2. Persistence into Long COVID

Longitudinal studies show:

20–25% of patients report taste dysfunction persisting beyond 6 months.
10% of patients continue to experience symptoms at 12 months.
Symptoms may fluctuate, with intermittent recovery followed by relapse.
Taste dysfunction is often accompanied by fatigue, brain fog, and dysautonomia, suggesting systemic involvement.

3. Clinical Trajectories

Three broad trajectories have been identified:

Complete recovery: Taste returns within 4–8 weeks, often in younger patients.
Partial recovery with distortion: Patients regain some taste but experience persistent dysgeusia (e.g., coffee tasting metallic).
Persistent loss: Complete ageusia lasting >12 months, often associated with histological evidence of taste bud destruction.

4. Case Vignettes

Case A (Ageusia): A 32-year-old woman lost all taste during acute COVID. At 9 months, she reported only partial recovery, with sweet taste absent and salty taste muted. Salivary testing revealed reduced amylase and elevated IL-6.
Case B (Dysgeusia): A 45-year-old man described water tasting “bitter” and fruit tasting “metallic” for over a year. Biopsy showed flattened fungiform papillae and reduced TAS1R gene expression.
Case C (Phantogeusia): A 60-year-old patient reported persistent phantom taste of “smoke” despite normal tongue morphology. Neurological testing suggested cranial nerve IX inflammation.

5. Quality of Life Impact

Persistent taste dysfunction leads to:

Nutritional deficits: Reduced appetite, weight loss, micronutrient deficiencies.
Psychological burden: Depression, anxiety, social withdrawal.
Altered dietary habits: Preference for highly spiced or textured foods to compensate for sensory loss.

6. Recovery Patterns

Gradual improvement: Some patients regain taste slowly, with sweet and umami returning first, bitter last.
Incomplete recovery: Distortions may persist even after receptor regeneration.
No recovery: A subset remains refractory to treatment, highlighting the need for novel therapies.

💊 Treatment Modalities for Long COVID Taste Disorders

1. Symptomatic and Supportive Care

Hydration and oral hygiene: Maintaining moisture and reducing microbial overgrowth can improve taste perception.
Dietary adaptation: Patients often benefit from stronger flavors, spices, and textured foods to compensate for sensory loss.
Nutritional counseling: Prevents malnutrition and micronutrient deficiencies in patients with persistent ageusia or dysgeusia.

2. Pharmacologic Interventions

Corticosteroids: Short courses have been trialed to reduce local inflammation, though evidence is mixed.
Anti-inflammatory agents: IL-6 inhibitors and TNF-α blockers are being explored for systemic long COVID symptoms, with potential benefit for taste dysfunction.
Zinc supplementation: Zinc plays a role in taste bud regeneration; supplementation has shown modest improvements in some patients.
Vitamin A and D: Support epithelial health and immune regulation, though data remain preliminary.
Pilocarpine and cevimeline: Used to stimulate salivary flow in xerostomia, indirectly improving taste function.

3. Neurorehabilitation and Sensory Training

Taste training protocols: Patients are exposed to standardized taste strips (sweet, salty, sour, bitter, umami) to retrain receptor sensitivity.
Olfactory-taste rehabilitation: Combined smell and taste exercises may accelerate recovery, given their neural overlap.
Neuromodulation techniques: Transcranial magnetic stimulation (TMS) and vagus nerve stimulation are under investigation for sensory recovery.

4. Experimental and Emerging Therapies

Stem cell therapy: Research into basal cell transplantation for taste bud regeneration is ongoing.
Gene therapy: Potential to restore TAS1R/TAS2R receptor expression in damaged tissue.
Microbiome modulation: Probiotics and prebiotics may help restore oral microbial balance, reducing dysgeusia.
Antiviral strategies: Targeting persistent viral reservoirs in taste bud basal cells could prevent ongoing epithelial disruption.

5. Clinical Trials and Evidence

Small pilot studies: Taste training combined with zinc supplementation has shown partial recovery in 40–50% of patients.
Ongoing trials: NIH-funded projects are investigating salivary biomarkers and regenerative therapies for long COVID taste dysfunction.
Case reports: Individual patients have reported improvement with corticosteroid rinses, probiotics, or neuromodulation, though controlled data are limited.

6. Multidisciplinary Management

Given the complexity of long COVID, treatment often requires:

ENT specialists for sensory evaluation.
Neurologists for cranial nerve assessment.
Nutritionists for dietary support.
Psychologists for coping strategies and mental health support.

This integrated approach acknowledges that taste dysfunction is not only a sensory issue but also a nutritional, psychological, and social challenge.

📖 Discussion

Long COVID taste disorders represent a multifactorial pathology involving viral persistence, immune dysregulation, epithelial remodeling, and neuroinflammation. Evidence from biopsy studies demonstrates persistent SARS-CoV-2 RNA in taste bud basal cells, leading to malformed papillae and reduced receptor density. This aligns with benomic findings of downregulated taste receptor genes and upregulated inflammatory cytokines, suggesting a chronic disruption of sensory renewal.

Clinically, patients report ageusia, dysgeusia, and phantogeusia lasting months to years, with significant impacts on nutrition and mental health. The clinical course varies: some recover within weeks, others experience partial recovery with distortion, and a subset remains refractory. Salivary dysfunction and oral microbiome dysbiosis further exacerbate taste lossnia.nih.gov.

Treatment remains challenging. Supportive care (hydration, dietary adaptation) is standard, while pharmacologic interventions (zinc, corticosteroids, IL-6 inhibitors) show mixed efficacy. Taste training and olfactory rehabilitation are the most evidence-based approaches, leveraging neuroplasticity. Emerging therapies — stem cell transplantation, neuromodulation, stellate ganglion block — offer promise but require rigorous trialsmedicalnewstoday.com.

Philosophically, these findings echo Stephen Hawking’s position: science can explain mechanisms, but the “breath that fires the equations” — why the universe exists at all — remains outside empirical reach. Just as Hawking’s no-boundary proposal renders time finite but edgeless, long COVID taste disorders remind us that biological systems are self-contained yet open to deeper metaphysical interpretation. His model does not rule out a creator; it simply does not require one.

🧾 Conclusion

Persistent taste dysfunction in long COVID is a complex, multi-system disorder involving direct viral invasion of taste bud cells, salivary gland impairment, benomic reprogramming, and neuroinflammation. The clinical burden is substantial, with nutritional, psychological, and social consequences. Current treatments provide partial relief, but novel regenerative and neuromodulatory strategies are urgently needed.

From a broader perspective, the study of long COVID taste disorders exemplifies the limits and strengths of scientific inquiry. Science can map molecular cascades and clinical trajectories, but questions of meaning — whether biological resilience reflects deeper metaphysical order — remain open. In Hawking’s terms, science describes the rules; philosophy asks why there is a universe, or a body, for those rules to govern.

📚 Selected References (Footnotes)

Morad H, Vanhala T, Kisiel M, et al. Taste dysfunction in Long COVID. bioRxiv. 2025.
Levy JM. Treatment Recommendations for Persistent Smell and Taste Dysfunction Following COVID-19. JAMA Otolaryngol Head Neck Surg. 2020;146(8):733. doi:10.1001/jamaoto.2020.1378
Srinivasan M. Taste Dysfunction and Long COVID-19. Front Cell Infect Microbiol. 2021;11:716563. doi:10.3389/fcimb.2021.716563
Mayo Clinic Proceedings. Smell and Taste Dysfunction in Patients With COVID-19: A Systematic Review. 2020.
Yao Q, Doyle ME, Liu QR, et al. Long-Term Dysfunction of Taste Papillae in SARS-CoV-2. NEJM Evidence. 2023;2(9). doi:10.1056/EVIDoa2300046
Boscolo-Rizzo P, Borsetto D, Fabbris C, et al. Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg. 2020.
National Institute on Aging. Lingering COVID virus in tongue linked to long-term taste loss. 2023.
Medical News Today. New treatment helps restore sense of smell for some people with long COVID. 2023.