The sense of taste: Development, regeneration, and dysfunction.

Gustation or the sense of taste is a primary sense, which functions as a gatekeeper for substances that enter the body. Animals, including humans, ingest foods that contain appetitive taste stimuli, including those that have sweet, moderately salty and umami (glutamate) components, and tend to avoid bitter-tasting items, as many bitter compounds are toxic. Taste is mediated by clusters of heterogeneous taste receptors cells (TRCs) organized as taste buds on the tongue, and these convey taste information from the oral cavity to higher order brain centers via the gustatory sensory neurons of the seventh and ninth cranial ganglia. One remarkable aspect of taste is that taste perception is mostly uninterrupted throughout life yet TRCs within buds are constantly renewed; every 1-2 months all taste cells have been steadily replaced. In the past decades we have learned a substantial amount about the cellular and molecular regulation of taste bud cell renewal, and how taste buds are initially established during embryogenesis. Here I review more recent findings pertaining to taste development and regeneration, as well as discuss potential mechanisms underlying taste dysfunction that often occurs with disease or its treatment. This article is categorized under: Infectious Diseases > Stem Cells and Development Cancer > Stem Cells and Development Neurological Diseases > Stem Cells and Development.

[Mechanisms and Management of COVID-19-Associated Taste Disorders].

The taste buds in the human tongue contain specialized cells that generate taste signals when they are stimulated. These signals are then transmitted to the central nervous system, allowing the human body to distinguish nutritious substances from toxic or harmful ones. This process is critical to the survival of humans and other mammals. A number of studies have shown that dysgeusia, or taste disorder, is a common complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which can severely affect patients' nutritional intake and quality of life. Based on the physiological process of taste perception, the direct causes of dysgeusia include dysfunction of taste receptors and damage to the taste nervous system, while indirect causes include genetic factors, aging-related changes, bacterial and viral infections, and cancer treatments such as radiotherapy and chemotherapy. The pathogenic factors of dysgeusia are complicated, further research is needed to fully understand the underlying mechanisms, and some of the reported findings and conclusions still need further validation. All these form a great challenge for clinical diagnosis of the cause and targeted treatment of dysgeusia. Herein, we reviewed published research on the physiological process of taste perception, the potential mechanisms of taste disorders related to SARS-CoV-2 infection, and strategies for prevention and treatment, providing theoretical support for establishing and improving the comprehensive management of COVID-19 complicated by taste disorders.

A possible role for taste receptor cells in surveying the oral microbiome.

Taste receptor cells are sensory specialists that detect chemicals in food and drink. An exciting new report in PLOS Biology suggests that some taste cells could also be involved in immune surveillance like counterparts in the intestine.

Role of Aromatic Herbs and Spices in Salty Perception of Patients with Hyposmia.

Herbs and spices represent a possibility for the improvement of anosmia and ageusia. In this work we evaluated the role of Mediterranean aromatic herbs and spices in the salty taste perception of patients with hyposmia compared to healthy controls. To this goal, the salty taste perception in response to pure salt and different types of commercial flavored sea salt was assessed in patients with hyposmia, with or without a post-acute coronavirus syndrome, and healthy controls. Myrtle berries and leaves, a mixture of Mediterranean herbs and plants such as helichrysum, rosemary, liquorice, fennel seeds and myrtle leaves, oranges and saffron were used as salt flavoring ingredients. Differences in gustatory perception between 57 patients with hyposmia and 91 controls were evaluated considering the rate of the gustatory dimensions of pleasantness, intensity, and familiarity, using a 7-point hedonic Likert-type scale. At a dose of 0.04 g/mL, saline solutions of flavored salts, with an average 15% less NaCl, were perceived by patients with hyposmia as equally intense but less familiar than pure salt solution, with similar scores in the pleasantness dimension. Our study highlighted the central role of Mediterranean aromatic plants in the enhancement of salty perception in patients with hyposmia.

Salivary proteomic analysis in asymptomatic and symptomatic SARS-CoV-2 infection: Innate immunity, taste perception and FABP5 proteins make the difference.

BACKGROUND AND AIM: SARS-CoV-2 infection spawns from an asymptomatic condition to a fatal disease. Age, comorbidities, and several blood biomarkers are associated with infection outcome. We searched for biomarkers by untargeted and targeted proteomic analysis of saliva, a source of viral particles and host proteins. METHODS: Saliva samples from 19 asymptomatic and 16 symptomatic SARS-CoV-2 infected subjects, and 20 controls were analyzed by LC-MS/MS for untargeted peptidomic (flow through of 10 kDa filter) and proteomic (trypsin digestion of filter retained proteins) profiling. RESULTS: Peptides from 53 salivary proteins were identified. ADF was detected only in controls, while IL1RA only in infected subjects. PRPs, DSC2, FABP5, his-1, IL1RA, PRH1, STATH, SMR3B, ANXA1, MUC7, ACTN4, IGKV1-33 and TGM3 were significantly different between asymptomatic and symptomatic subjects. Retained proteins were 117, being 11 highly different between asymptomatic and symptomatic (fold change ≥2 or ≤-2). After validation by LC-MS/MS-SRM (selected reaction monitoring analysis), the most significant discriminant proteins at PCA were IL1RA, CYSTB, S100A8, S100A9, CA6, and FABP5. CONCLUSIONS: The differentially abundant proteins involved in innate immunity (S100 proteins), taste (CA6 and cystatins), and viral binding to the host (FABP5), appear to be of interest for use as potential biomarkers and drugs targets.

Distribution of TAS2R38 bitter taste receptor phenotype and haplotypes among COVID-19 patients.

Bitter taste receptor TAS2R38 is expressed in the respiratory tract and can respond to quorum-sensing molecules produced by pathogens, stimulating the release of nitric oxide, with biocidal activity. TAS2R38 presents two main high-frequency haplotypes: the "taster" PAV and the "non-taster" AVI. Individuals carrying the AVI allele could be at greater risk of infections, including SARS-CoV-2. The aim of this study was to assess the frequency of PAV and AVI alleles in COVID-19 patients with severe or non-severe symptoms compared to healthy subjects to further corroborate, or not, the hypothesis that the PAV allele may act as a protecting factor towards SARS-CoV-2 infection while the AVI one may represent a risk factor. After careful selection, 54 individuals were included in the study and underwent genetic analysis and PROP phenotype assessment. Our investigation could not point out at a significant relationship between single nucleotide polymorphisms responsible for PROP bitterness and presence/severity of SARS-CoV-2 infection, as previous studies suggested. Our results uncouple the direct genetic contribution of rs10246939, rs1726866 and rs713598 on COVID-19, calling for caution when proposing a treatment based on TAS2R38 phenotypes.

Altered smell and taste: Anosmia, parosmia and the impact of long Covid-19.

BACKGROUND: Qualitative olfactory (smell) dysfunctions are a common side effect of post-viral illness and known to impact quality of life and health status. Evidence is emerging that taste and smell loss are common symptoms of Covid-19 that may emerge and persist long after initial infection. The aim of the present study was to document the impact of post Covid-19 alterations to taste and smell. METHODS: We conducted exploratory thematic analysis of user-generated text from 9000 users of the AbScent Covid-19 Smell and Taste Loss moderated Facebook support group from March 24 to 30th September 2020. RESULTS: Participants reported difficulty explaining and managing an altered sense of taste and smell; a lack of interpersonal and professional explanation or support; altered eating; appetite loss, weight change; loss of pleasure in food, eating and social engagement; altered intimacy and an altered relationship to self and others. CONCLUSIONS: Our findings suggest altered taste and smell with Covid-19 may lead to severe disruption to daily living that impacts on psychological well-being, physical health, relationships and sense of self. More specifically, participants reported impacts that related to reduced desire and ability to eat and prepare food; weight gain, weight loss and nutritional insufficiency; emotional wellbeing; professional practice; intimacy and social bonding; and the disruption of people's sense of reality and themselves. Our findings should inform further research and suggest areas for the training, assessment and treatment practices of health care professionals working with long Covid.

Do Gut Microbes Taste?

Gut microbiota has emerged as a major metabolically active organ with critical functions in both health and disease. The trillions of microorganisms hosted by the gastrointestinal tract are involved in numerous physiological and metabolic processes including modulation of appetite and regulation of energy in the host spanning from periphery to the brain. Indeed, bacteria and their metabolic byproducts are working in concert with the host chemosensory signaling pathways to affect both short- and long-term ingestive behavior. Sensing of nutrients and taste by specialized G protein-coupled receptor cells is important in transmitting food-related signals, optimizing nutrition as well as in prevention and treatment of several diseases, notably obesity, diabetes and associated metabolic disorders. Further, bacteria metabolites interact with specialized receptors cells expressed by gut epithelium leading to taste and appetite response changes to nutrients. This review describes recent advances on the role of gut bacteria in taste perception and functions. It further discusses how intestinal dysbiosis characteristic of several pathological conditions may alter and modulate taste preference and food consumption via changes in taste receptor expression.

Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms.

COVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2/TMPRSS2 proteins, has been reported in non-chemosensory cells in the rodent's nose and mouth, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2/TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identify the virus target cells to be of basal and sensory origin and reveal the age-dependent appearance of viral entry-sites. Our results propose an alternative interpretation of the human viral-induced sensory symptoms and give investigative perspectives on animal models.

Coincidence of COVID-19 Infection and Smell-Taste Perception Disorders.

Many reports by physicians and patients during the 2019 to 2020 pandemic indicate that COVID-19 is associated with elevated levels of odor and taste perception disorders (anosmia, hyposmia, ageusia, and/or dysgeusia). Recent increase in olfactory dysfunction in patients referred to ear nose and throat clinics and COVID-19 infection at the same time encouraged us to examine anosmic/hyposmic patients to establish any association between these signs. It has been shown that the COVID-19 virus exploits the uses angiotensin-converting enzyme 2 receptor to obtain cell entry. This result increases the interest to examine the expression of angiotensin-converting enzyme 2 in neurological tissue, and to assess the possible contribution of damage. This mini review provides fundamental knowledge on coincidence of COVID-19 infection and smell-taste perception disorders from an objective perspective.

COVID-19: Recovery from Chemosensory Dysfunction. A Multicentre study on Smell and Taste.

OBJECTIVE/HYPOTHESIS: With the COVID-19 pandemic, chemosensory dysfunction are among the most prevalent symptoms. Most reports are subjective evaluations, which have been suggested to be unreliable. The objective is to test chemosensory dysfunction and recovery based on extensive psychophysical tests in COVID-19 during the course of the disease. STUDY DESIGN: Prospective cohort study. METHODS: A total of 111 patients from four centers participated in the study. All tested positive for SARS-COV-2 with RT-PCR. They were tested within 3 days of diagnosis and 28 to 169 days after infection. Testing included extensive olfactory testing with the Sniffin' Sticks test for threshold, discrimination and identification abilities, and with the Taste Sprays and Taste Strips for gustatory function for quasi-threshold and taste identification abilities. RESULTS: There was a significant difference in olfactory function during and after infection. During infection 21% were anosmic, 49% hyposmic, and 30% normosmic. After infection only 1% were anosmic, 26% hyposmic, and 73% normosmic. For gustatory function, there was a difference for all taste qualities, but significantly in sour, bitter, and total score. Twenty-six percent had gustatory dysfunction during infection and 6.5% had gustatory dysfunction after infection. Combining all tests 22% had combined olfactory and gustatory dysfunction during infection. After infection no patients had combined dysfunction. CONCLUSIONS: Chemosensory dysfunction is very common in COVID-19, either as isolated smell or taste dysfunction or a combined dysfunction. Most people regain their chemosensory function within the first 28 days, but a quarter of the patients show persisting dysfunction, which should be referred to specialist smell and taste clinics for rehabilitation of chemosensory function. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1095-1100, 2021.

Alteration, Reduction and Taste Loss: Main Causes and Potential Implications on Dietary Habits.

Our sense of taste arises from the sensory information generated after compounds in the oral cavity and oropharynx activate taste receptor cells situated on taste buds. This produces the perception of sweet, bitter, salty, sour, or umami stimuli, depending on the chemical nature of the tastant. Taste impairments (dysgeusia) are alterations of this normal gustatory functioning that may result in complete taste losses (ageusia), partial reductions (hypogeusia), or over-acuteness of the sense of taste (hypergeusia). Taste impairments are not life-threatening conditions, but they can cause sufficient discomfort and lead to appetite loss and changes in eating habits, with possible effects on health. Determinants of such alterations are multiple and consist of both genetic and environmental factors, including aging, exposure to chemicals, drugs, trauma, high alcohol consumption, cigarette smoking, poor oral health, malnutrition, and viral upper respiratory infections including influenza. Disturbances or loss of smell, taste, and chemesthesis have also emerged as predominant neurological symptoms of infection by the recent Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus strain 2 (SARS-CoV-2), as well as by previous both endemic and pandemic coronaviruses such as Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and SARS-CoV. This review is focused on the main causes of alteration, reduction, and loss of taste and their potential repercussion on dietary habits and health, with a special focus on the recently developed hypotheses regarding the mechanisms through which SARS-CoV-2 might alter taste perception.

Self-reported loss of smell without nasal obstruction to identify COVID-19. The multicenter Coranosmia cohort study.

OBJECTIVES: To determine the frequency of SARS-CoV-2 positive samples in a subset of patients consulting for primarily isolated acute (<7 days) loss of smell and to assess the diagnostic accuracy of olfactory/gustatory dysfunction for COVID-19 diagnosis in the overall population tested for COVID-19 in the same period. METHODS: Prospective multicentric cohort study in four olfactory ENT units and a screening center for COVID-19. RESULTS: i) Among a subset of 55 patients consulting for primarily recent loss of smell, we found that 51 (92.7%) had a COVID-19 positive test (median viral load of 28.8 cycle threshold). Loss of smell was mostly total (anosmia), rarely associated with nasal obstruction but associated with a taste disorder in 80%. Olfactory dysfunction occurred suddenly, either as first complaint or preceded by mild symptoms occurring a median of 3 days. The majority of patients (72.9%) partially recovered the sense of smell within 15 days. ii) In a population of 1824 patients tested for COVID-19, the positive predictive value and the specificity of loss of smell and/or taste were 78.5% and 90.3% respectively (sensitivity (40.8%), negative predictive value (63.6%)). CONCLUSIONS: Self-reported loss of smell had a high predictive positive value to identify COVID-19. Making this sign well known publicly could help to adopt isolation measures and inform potential contacts.

Smell and taste dysfunction in patients with SARS-CoV-2 infection: A review of epidemiology, pathogenesis, prognosis, and treatment options.

During the initial pandemic wave of COVID-19, apart from common presenting symptoms (cough, fever, and fatigue), many countries have reported a sudden increase in the number of smell and taste dysfunction patients. Smell dysfunction has been reported in other viral infections (parainfluenza, rhinovirus, SARS, and others), but the incidence is much lower than SARS-CoV-2 infection. The pathophysiology of post-infectious olfactory loss was hypothesized that viruses may produce an inflammatory reaction of the nasal mucosa or damage the olfactory neuroepithelium directly. However, loss of smell could be presented in COVID-19 patients without other rhinologic symptoms or significant nasal inflammation. This review aims to provide a brief overview of recent evidence for epidemiology, pathological mechanisms for the smell, and taste dysfunction in SARS-CoV-2 infected patients. Furthermore, prognosis and treatments are reviewed with scanty evidence. We also discuss the possibility of using "smell and taste loss" as a screening tool for COVID-19 and treatment options in the post-SARS-CoV-2 infectious olfactory loss.

Prevalence and Recovery From Olfactory and Gustatory Dysfunctions in Covid-19 Infection: A Prospective Multicenter Study.

BACKGROUND: Covid-19 is defined by an association of multiple symptoms, including frequently reported olfactory and gustatory disorders. OBJECTIVE: The main purpose of this study was to analyze the prevalence of these neurosensory impairments in patients with Covid-19, and to assess short-term recovery. METHODS: We performed a multicenter case series study during the Covid-19 epidemic. All patients presenting a RT-PCR-confirmed SARS-CoV-2 infection were included, whether hospitalized or treated at home. To analyze the prevalence and features of olfactory and gustatory dysfunctions, a phone interview was conducted 5 days after the positive PCR result. The questionnaire was submitted again 10 days later to patients having reported olfactory and gustatory disorders, in order to assess their recovery. RESULTS: 115 patients were included in our study. 81 patients (70%) reported olfactory and gustatory disorders without nasal obstruction or rhinorrhea. These impairments were more frequently reported in the female population, young people, and house-bound patients with mild symptomatic forms. Short-term recovery assessed at Day 15 was complete for 64% of the patients, and incomplete in 33%. Median recovery time was 15 days (4-27 days) after olfactory or gustatory symptom onset. CONCLUSION: Olfactory and gustatory dysfunctions related to Covid-19 are frequently reported and prevalent in mild symptomatic forms of the disease. Recovery in most cases seems rapid and complete.

Olfactory and gustatory dysfunctions in 100 patients hospitalized for COVID-19: sex differences and recovery time in real-life.

PURPOSE: COVID-19 displays a variety of clinical manifestations; in pauci-symptomatic patients olfactory (OD) and gustatory dysfunctions (GD) may represent the first or only symptom. This topic is currently arousing great interest, and a growing number of papers are being published. Aim of this study is to investigate the timing of recovery from OD and GD in a real-life population hospitalized for COVID-19. METHODS: We followed up by a phone interview the first 100 patients discharged a month earlier from three Italian non-intensive care wards. RESULTS: All 100 patients were Caucasian, mean age was 65 years, 60% were males. Forty-two patients (mean age 63 years) experienced subjective chemosensory dysfunctions (29 OD and 41 GD): the male/female ratio was 2:1; 83% reported a complete or near complete recovery at follow-up. The recovery rate was not significantly different between males and females. The mean duration of OD and GD was 18 and 16 days, respectively. The mean recovery time from OD or GD resulted significantly longer for females than for males (26 vs 14 days, P = 0.009). Among the 42 symptomatic, the mean age of males was significantly higher than that of females (66 vs 57 years, P = 0.04), while the opposite was observed in the 58 asymptomatic patients (60 vs 73 years, P = 0.0018). CONCLUSIONS: Recovery from OD or GD was rapid, occurring within 4 weeks in most patients. Chemosensory dysfunctions in women was less frequent, but longer lasting. The value of our study is its focus on a population of hospitalized patients significantly older than those previously described, and the additional data on gender differences.