Long-Term Dysfunction of Taste Papillae in SARS-CoV-2.

BACKGROUND: We sought to determine whether ongoing taste disturbance in the postacute sequelae of coronavirus disease 2019 period is associated with persistent virus in primary taste tissue. METHODS: We performed fungiform papillae biopsies on 16 patients who reported taste disturbance lasting more than 6 weeks after molecularly determined severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Then, on multiple occasions, we rebiopsied 10 of those patients who still had taste complaints for at least 6 months postinfection. Fungiform papillae obtained from other patients before March 2020 served as negative controls. We performed hematoxylin and eosin staining to examine fungiform papillae morphology and immunofluorescence and fluorescence in situ hybridization to look for evidence of persistent viral infection and immune response. RESULTS: In all patients, we found evidence of SARS-CoV-2, accompanying immune response and misshapen or absent taste buds with loss of intergemmal neurite fibers. Six patients reported normal taste perception by 6 months postinfection and were not further biopsied. In the remaining 10, the virus was eliminated in a seemingly random fashion from their fungiform papillae, but four patients still, by history, reported incomplete return to preinfection taste perception by the time we wrote this report. CONCLUSIONS: Our data show a temporal association in patients between functional taste, taste papillae morphology, and the presence of SARS-CoV-2 and its associated immunological changes. (Funded by Intramural Research Program/National Institute on Aging/National Institute of Allergy and Infectious Diseases/National Institutes of Health; ClinicalTrials.gov numbers NCT03366168 and NCT04565067.).

Covid-19 and oral diseases: Crosstalk, synergy or association?

The coronavirus disease 2019 (Covid-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that clinically affects multiple organs of the human body. Cells in the oral cavity express viral entry receptor angiotensin-converting enzyme 2 that allows viral replication and may cause tissue inflammation and destruction. Recent studies have reported that Covid-19 patients present oral manifestations with multiple clinical aspects. In this review, we aim to summarise main signs and symptoms of Covid-19 in the oral cavity, its possible association with oral diseases, and the plausible underlying mechanisms of hyperinflammation reflecting crosstalk between Covid-19 and oral diseases. Ulcers, blisters, necrotising gingivitis, opportunistic coinfections, salivary gland alterations, white and erythematous plaques and gustatory dysfunction were the most reported clinical oral manifestations in patients with Covid-19. In general, the lesions appear concomitant with the loss of smell and taste. Multiple reports show evidences of necrotic/ulcerative gingiva, oral blisters and hypergrowth of opportunistic oral pathogens. SARS-CoV-2 exhibits tropism for endothelial cells and Covid-19-mediated endotheliitis can not only promote inflammation in oral tissues but can also facilitate virus spread. In addition, elevated levels of proinflammatory mediators in patients with Covid-19 and oral infectious disease can impair tissue homeostasis and cause delayed disease resolution. This suggests potential crosstalk of immune-mediated pathways underlying pathogenesis. Interestingly, few reports suggest recurrent herpetic lesions and higher bacterial growth in Covid-19 subjects, indicating SARS-CoV-2 and oral virus/bacteria interaction. Larger cohort studies comparing SARS-CoV-2 negative and positive subjects will reveal oral manifestation of the virus on oral health and its role in exacerbating oral infection.

A comparative study on the clinical features of COVID-19 with non-SARS-CoV-2 respiratory viral infections.

During this coronavirus disease 2019 (COVID-19) pandemic, physicians have the important task of risk stratifying patients who present with acute respiratory illnesses. Clinical presentation of COVID-19, however, can be difficult to distinguish from other respiratory viral infections. Thus, identifying clinical features that are strongly associated with COVID-19 in comparison to other respiratory viruses can aid risk stratification and testing prioritization especially in situations where resources for virological testing and resources for isolation facilities are limited. In our retrospective cohort study comparing the clinical presentation of COVID-19 and other respiratory viral infections, we found that anosmia and dysgeusia were symptoms independently associated with COVID-19 and can be important differentiating symptoms in patients presenting with acute respiratory illness. On the other hand, laboratory abnormalities and radiological findings were not statistically different between the two groups. In comparing outcomes, patients with COVID-19 were more likely to need high dependency or intensive care unit care and had a longer median length of stay. With our findings, we emphasize that epidemiological risk factors and clinical symptoms are more useful than laboratory and radiological abnormalities in differentiating COVID-19 from other respiratory viral infections.

Dual binding mode of "bitter sugars" to their human bitter taste receptor target.

The 25 human bitter taste receptors (hTAS2Rs) are responsible for detecting bitter molecules present in food, and they also play several physiological and pathological roles in extraoral compartments. Therefore, understanding their ligand specificity is important both for food research and for pharmacological applications. Here we provide a molecular insight into the exquisite molecular recognition of bitter ß-glycopyranosides by one of the members of this receptor subclass, hTAS2R16. Most of its agonists have in common the presence of a ß-glycopyranose unit along with an extremely structurally diverse aglycon moiety. This poses the question of how hTAS2R16 can recognize such a large number of "bitter sugars". By means of hybrid molecular mechanics/coarse grained molecular dynamics simulations, here we show that the three hTAS2R16 agonists salicin, arbutin and phenyl-ß-D-glucopyranoside interact with the receptor through a previously unrecognized dual binding mode. Such mechanism may offer a seamless way to fit different aglycons inside the binding cavity, while maintaining the sugar bound, similar to the strategy used by several carbohydrate-binding lectins. Our prediction is validated a posteriori by comparison with mutagenesis data and also rationalizes a wealth of structure-activity relationship data. Therefore, our findings not only provide a deeper molecular characterization of the binding determinants for the three ligands studied here, but also give insights applicable to other hTAS2R16 agonists. Together with our results for other hTAS2Rs, this study paves the way to improve our overall understanding of the structural determinants of ligand specificity in bitter taste receptors.

Prospective assessment of taste impairment and nausea during radiotherapy for head and neck cancer.

Dysgeusia and nausea are common side effects observed in head and neck cancer patients treated with either exclusive radiotherapy or combined modality treatment. The aim of the present study was to prospectively evaluate dysgeusia, during treatment and follow-up, using the chemotherapy-induced taste alteration scale (CiTAS), a metrics based on 18-items exploring three dimensions (quantitative and qualitative changes in taste perception, and diet-related issues) identified through a four-factor analysis: decline in basic taste, discomfort, phantogeusia-parageusia, and general taste alterations. Moreover, we scored, according to Common Toxicity Criteria Adverse Events, nausea and other treatment-related toxicities. Since, ginger is traditionally used to prevent and/or treat nausea and vomiting, we prophylactically employed a ginger-based supplement named Naumix/Naugin (Gamfarma, Milan, Italy), to potentially mitigate both nausea and taste impairment. Using the CiTAS scale, we highlighted a progressive increase in all dysgeusia dimensions, peaking at the VII week of treatment and a subsequent partial late recovery. In particular, we observed a recovery for discomfort, phantogeusia-parageusia, and general taste alterations at 6 months. Grade 2 nausea, observed to be as low as 12.9% potentially due to the use of ginger, peaked at the III week of treatment. Finally, for patients experiencing nausea, the dysgeusia dimension of discomfort was also relevant.

Radiation-Related Alterations of Taste Function in Patients With Head and Neck Cancer: a Systematic Review.

OPINION STATEMENT: Taste sensation is vital for a healthy body as it influences our food intake, acts as a defense mechanism and elicits pleasure. Majority of the head and neck cancer (HNC) patients undergoing radiotherapy suffer from altered taste function and often complain of inability to taste their food, reduced food intake, and weakness. However, there are not many studies conducted to assess this commonly reported side effect. Furthermore, clinical research on radiotherapy-induced taste alterations has proven to be difficult, considering a lack of reliable and validated study tools for assessing objective and subjective outcomes. Developing standardized tools for assessment of taste function and conducting prospective studies in larger population of HNC is the need of the hour. Taste sensation being critically important for sustenance, we need to focus on ways to preserve it. The physical properties of proton particle enable localization of the radiation dose precisely to the tumor and minimizing the exposure of the adjacent healthy tissues. By using Intensity-Modulated Proton Therapy in HNC patients, we anticipate preserving the taste sensation by reducing the dose of radiation to the taste buds.

Unlocking the Complex Flavors of Dysgeusia after Hematopoietic Cell Transplantation.

Dysgeusia is a frequently occurring symptom after hematopoietic cell transplantation (HCT) that has important long-term effects on physical, nutritional, and immunologic recovery, as well as on quality of life. Despite the relevance of this symptom, the study of dysgeusia in patients undergoing HCT has been limited, owing in part to its complexity. In this article, we review normal taste function and its clinical evaluation, discuss how dysgeusia uniquely affects patients undergoing HCT, and examine distinct, transplantation-related contributors to dysgeusia that may help elucidate strategies to ultimately reduce this symptom burden after transplantation.

Recovery of taste organs and sensory function after severe loss from Hedgehog/Smoothened inhibition with cancer drug sonidegib.

Striking taste disturbances are reported in cancer patients treated with Hedgehog (HH)-pathway inhibitor drugs, including sonidegib (LDE225), which block the HH pathway effector Smoothened (SMO). We tested the potential for molecular, cellular, and functional recovery in mice from the severe disruption of taste-organ biology and taste sensation that follows HH/SMO signaling inhibition. Sonidegib treatment led to rapid loss of taste buds (TB) in both fungiform and circumvallate papillae, including disruption of TB progenitor-cell proliferation and differentiation. Effects were selective, sparing nontaste papillae. To confirm that taste-organ effects of sonidegib treatment result from HH/SMO signaling inhibition, we studied mice with conditional global or epithelium-specific Smo deletions and observed similar effects. During sonidegib treatment, chorda tympani nerve responses to lingual chemical stimulation were maintained at 10 d but were eliminated after 16 d, associated with nearly complete TB loss. Notably, responses to tactile or cold stimulus modalities were retained. Further, innervation, which was maintained in the papilla core throughout treatment, was not sufficient to sustain TB during HH/SMO inhibition. Importantly, treatment cessation led to rapid and complete restoration of taste responses within 14 d associated with morphologic recovery in about 55% of TB. However, although taste nerve responses were sustained, TB were not restored in all fungiform papillae even with prolonged recovery for several months. This study establishes a physiologic, selective requirement for HH/SMO signaling in taste homeostasis that includes potential for sensory restoration and can explain the temporal recovery after taste dysgeusia in patients treated with HH/SMO inhibitors.

Might Helicobacter pylori infection be associated with distortion on taste perception?

Helicobacter pylori (H. pylori) has been found in dental plaque, saliva and lingual sites. To date, taste or olfaction disorders related to H. pylori infections have never been reported. In a review of the literature we found two papers just referring to a sour taste sensation during H. pylori infection. Studies in animal models suggest that changes in taste perception may relate to infections which damage taste buds. We observed an interesting clinical case of a 24-year-old Ghanaian woman with documented H. pylori gastric infection, complaining of cacosmia and cacogeusia. Taste evaluation indicated hypogeusia and highlighted a specific difficulty in discriminating between bitter and acid tastes. Saliva fluid was found positive for the ureA gene (H. pylori ureasi A). On the basis of this report, we hypothesize that taste perception might be correlated with a documented H. pylori infection. So, in a dyspeptic clinical picture in both pre and post diagnostic phase when H. pylori infection is suspected, taste evaluation might be important. Further studies are certainly needed in a large patient population to clarify the possible connection between H. pylori infection and smell-taste distortion.

Contact endoscopic comparison of morphology of human fungiform papillae of healthy subjects and patients with transected chorda tympani nerve.

BACKGROUND: The chorda tympani nerve (CTN) carries gustatory fibers from taste buds of fungiform papillae (fPap) of the anterior portion of the tongue. Accordingly, middle ear surgery with transection of the CTN may result in gustatory impairment. With use of contact endoscopy, the present study aimed to compare number and shape of fPap and subepithelial vessel formation in patients after CTN transection with that of healthy controls. MATERIAL AND METHODS: The number of fPap per square centimeter was obtained in addition to measures of gustatory sensitivity using electrogustometry and intensity ratings of natural taste stimuli. Data from 32 healthy subjects (mean age 40 yr; 16 female, 16 male) were compared with those from 14 patients whose CTN had been cut and partly resected during middle ear surgery because of cholesteatoma (mean age 38 yr; 7 female, 7 male). Middle ear surgery was performed by two of the authors. RESULTS: In healthy subjects, a higher fPap density was found on the tongue's tip compared with its edge; younger subjects had higher densities than older subjects. No sex-related differences were observed. Patients with transected CTN exhibited a significant decrease of taste function as measured with both natural and electric stimuli. In patients, we found significantly fewer and flatter fPap on the side of the tongue where surgery had been performed in comparison with the contralateral side. In addition, fPap density at the ipsilateral side was significantly lower compared with fPap density on the respective side in healthy controls. CONCLUSION: As established through contact endoscopy, the number of fPap decreases in relation to deafferentation and also in relation to the subjects' age, both of which are accompanied by a decreased gustatory sensitivity.

Posttonsillectomy taste distortion: a significant complication.

OBJECTIVE/HYPOTHESIS: Tonsillectomy is among the most commonly performed procedures. As with any surgery, head and neck surgeons must be aware of possible complications and their potential affects. At our smell and taste center, we have been referred several patients in a 6-month period with the complaint of taste distortion after tonsillectomy. We report in this article a patient that complains of taste distortion after a right tonsillectomy for unilateral tonsillar hypertrophy. STUDY DESIGN: A prospective study documenting taste distortion after tonsillectomy using clinical, subjective, and objective evaluation. METHODS: The clinical course of a patient with taste distortion after a tonsillectomy is described. The gustatory function was investigated by conducting electrogustometry and spatial taste testing. Threshold measurements were determined at three left- and three right-side tongue regions: 1) the tongue tip region (innervated by the chorda tympani branch of the facial nerve), 2) the lateral margin of the tongue (anterior to the foliate papillae), and 3) the posterior tongue region (innervated by the lingual branch of the glossopharyngeal nerve). RESULTS: After a complete clinical evaluation and taste testing, it was found that the patient suffered an injury to the right lingual branch of the glossopharyngeal nerve. The close anatomic relationship between the palatine tonsil and lingual branch of the glossopharyngeal nerve makes the nerve vulnerable during tonsillectomy. This injury has caused the patient to suffer ageusia to the right posterior one third of the tongue, compensated by a contralateral phantogeusia (phantom taste) with clinical dysgeusia. The phantogeusia was abolished by application of anesthetic to the area where the phantom was perceived. We propose that the phantogeusia is the result of release-of-inhibition in the contralateral glossopharyngeal nerve. CONCLUSION: Taste distortion (including, phantogeusia and dysgeusia) after tonsillectomy is rarely reported as a complication but has a significant impact on quality of life. This article examines the taste distortion presence as a complication after tonsillectomy to make head and neck surgeons aware of this serious complication and the pathophysiology of taste distortion.

Unusual complication of tonsillectomy: taste disturbance and the lingual branch of the glossopharyngeal nerve.

Taste disturbance is an unusual complication of tonsillectomy of which there are very few reports in the literature. The possible causes of this rare complication are: (1) direct or indirect damage to the glossopharyngeal nerve or its lingual branch (LBGN), (2) lack of dietary zinc, and (3) habitual drug intake. We report a 41-year-old man, who complained of taste disturbance following tonsillectomy that was performed for chronic tonsillitis and unilateral (left) tonsillar hypertrophy. During surgery, hypertrophic tonsils were found to be sited deeply into the tonsillar bed, especially at the lower pole of the left tonsil. Pathologic examination following tonsillectomy revealed a keratinous cyst and chronic infection at the left tonsil, and lymphoid hyperplasia and chronic infection at the right tonsil. Although his complaint had been getting better, qualitative examination of his taste function revealed bilateral impairment of the sense of sweet taste on the base of his tongue two months after the surgery, and a taste disturbance of sweet taste on the left side persisted the 10th month after the surgery. His serum zinc value was normal, and he did not take any drug that could affect his sense of taste. Depending on the literature data, possible indirect damage to the LBGN was suspected as the cause of the taste disturbance. This symptom may be reversible within two years after tonsillectomy, but it can also be irreversible. Therefore, tonsillectomy should be performed with minimal trauma to the tonsillar bed, especially when there is an additional pathology extending into the lower pole, and such a patient should be informed of the risk of post-operative taste disturbance after tonsillectomy as being one of the rare complications of this surgery.

Search for correlation between symptoms and signs of changes in the oral mucosa and presence of fungi.

The aim of the present study was to determine the relationship between the symptoms and signs of oral mucosal changes and the presence of fungi. The investigation comprised 235 subjects. Fungi were detected in the oral cavities of 196 of these subjects. The fungi belonged to different species of the genus Candida. A significant correlation was found between the presence of fungi in the oral cavity and the existence of burning sensation, xerostomia, dysgeusia and non-idiopathic bleeding from the surface of the oral mucosa. A similar correlation was observed between the fungal colonization and atrophic changes, as well as reddened oral mucosa with lesions, ulceration and keratotic problems.

[Dysgeusia in clinical practice. 2. Pathology]. / Le disgeusie nella pratica clinica. Parte II. Patologia.

The various types of dysgeusia are discussed and a clinical classification is proposed. Dysgeusia are divided according to the modifications of the intensity of the perception: ipergeusia and ipogeusie/ageusia. The latter are the most frequent and important ones; they are divided in congenital ones, rapidly developing ones, and slow developing ones. A practical way to distinguish among the rapidly arousing ones is to consider the duration of the symptom. If it lasts more than a week the probabilities of an underlying serious illness grow, mainly of CNS. The slow onset ones are most commonly due to general metabolic alterations, among which diabetes, and to common habits, like smoking.