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.

Increase in Carbohydrate Antigen 19-9 Levels without Tumor Progression after Polaprezinc Administration that Induced Deep Vein Thrombosis in a Colon Cancer Patient.

Carbohydrate antigen 19-9 (CA 19-9) is a well-known tumor marker of adenocarcinoma (reference range, 37 U/mL). It can also be used, together with computed tomography, to monitor responses and resistance to chemotherapy in cancer patients. False elevation of CA 19-9 levels is often seen in conditions such as biliary tract obstruction and cholangitis. However, whether medication might induce false elevation of CA 19-9 levels has not yet been reported. A 74-year-old man was treated with third-line CPT-11 (irinotecan) plus panitumumab for stage IV cancer of the ascending colon. The patient developed chemotherapy-induced dysgeusia and was treated with polaprezinc. After polaprezinc administration, his CA 19-9 levels gradually increased from 18.9 to 1,699.4 U/mL. He developed deep vein thrombosis (DVT), although it was not associated with progressive disease or metastasis. Upon discontinuation of polaprezinc, CA 19-9 levels gradually decreased. This case demonstrates that polaprezinc may not only induce false elevation of CA 19-9 levels but also cause development of DVT induced by increased CA 19-9 levels, both of which are very rare events.

Understanding the impact of taste changes in oncology care.

PURPOSE: Taste perception is frequently altered in cancer patients. The purpose of this review is to provide an update on advances in understanding of the basic biology and physiology of taste and how taste and flavor may be impacted in cancer and its treatment. METHODS: A succinct review of the literature on the biology and neurology of taste, taste evaluation, and the impact in oncology is provided. RESULTS: Advances have occurred in the study of the gustatory system. Taste and smell are commonly affected during cancer care, and specific chemosensory complaints may persist in large numbers of cancer survivors. Limited study in oncology patients is available despite the significant impact that taste and smell have on oral intake and general physical and social well-being. CONCLUSIONS: Taste and flavor has had limited study in cancer therapy. Impact on taste and flavor can result in changes ranging from elimination of taste to taste distortions that may be associated with taste aversions, nausea, and dietary compromise. New therapeutics and new approaches in oncology may have additional impact upon taste that requires further study. This paper reviews the current understanding of taste function, taste testing, and its potential impact on cancer care, to serve as a guide for directing further research.

The eating experience in long-term survivors of head and neck cancer: a mixed-methods study.

PURPOSE: This study explored the eating experience in long-term survivors of head and neck cancer (HNC) ≥3 years post concurrent chemoradiation. Quality of life (QOL) and the meanings and perceptions survivors had as it related to the eating experience were explored. METHODS: Purposive sampling was utilized; 10 long-term survivors of HNC participated in the study. A mixed-methods approach was used; exploratory qualitative research using content analysis and summary statistics was used to describe demographic and clinical characteristics and the Vanderbilt Head and Neck Symptom Survey version 2.0 scores (VHNSS 2.0). RESULTS: Four categories (psychological, social impact, functional status, and the current eating experience) containing 15 subthemes and 1 overarching theme (adaptation) emerged. Current health status, QOL, and QOL related to eating were viewed favorably despite the impact of treatment late effects on participants' daily lives. Adaptation and maladaptation in regard to food choice and downplaying of symptoms were recognized. Interviews as well as the VHNSS 2.0 scores indicated that xerostomia, mucosal sensitivity, swallowing difficulty, length of time required to eat, and dysgeusia remained problematic. CONCLUSION: Psychological, functional, and social losses associated with eating were identified. Participants modify or avoid foods that are challenging yet report enjoyment with eating. Challenges with eating were downplayed. Due to the potential negative nutritional and social implications of avoiding specific food/food groups, standard of care in long-term survivors of HNC should include assessment of the eating experience and functional challenges. Nutrition professional can help patients optimize dietary intake and the eating experience.

Taste alteration in breast cancer patients treated with taxane chemotherapy: experience, effect, and coping strategies.

PURPOSE: This study examined the experience and coping strategies for taste alteration in female breast cancer patients treated with docetaxel or paclitaxel. METHODS: A purposive sample of 25 patients currently receiving docetaxel or paclitaxel or within 6 months of having completed treatment was recruited. Semi-structured interviews and patient-level data were utilized for this exploratory descriptive study. Interview data were analyzed with the constant comparative method; patient-level data were abstracted from the electronic medical record. RESULTS: Of all side effects reported from taxanes, the most common was taste alteration (8 of 10 docetaxel patients, 3 of 15 paclitaxel patients). Women that experience taste alteration chose not to eat as much, ate on an irregular schedule, and/or lost interest in preparing meals for themselves and/or their family. Women adopted a variety of new behaviors to deal with the taste alteration and its effects, including trying new recipes, eating strongly flavored foods, honoring specific food cravings, eating candy before meals, cutting food with lemon, drinking sweetened drinks, using plastic eating utensils, drinking from a straw, brushing their teeth and tongue before meals, and using baking soda and salt wash or antibacterial mouthwash. CONCLUSIONS: Taste alteration affects breast cancer patients' lives, and they develop management strategies to deal with the effect. While some self-management strategies can be seen as positively adaptive, the potential for increased caloric consumption and poor eating behaviors associated with some coping strategies may be a cause for concern given the observation of weight gain during breast cancer treatment and association of obesity with poor treatment outcomes in breast cancer patients. Further studies are warranted to determine the overall burden of this symptom and measurement of cancer and non-cancer-related consequences of these behavioral adaptations.

The Pathogenesis of COVID-19-Related Taste Disorder and Treatments.

COVID-19, mainly manifested as acute respiratory distress syndrome, has afflicted millions of people worldwide since 2019. Taste dysfunction is a common early-stage symptom of COVID-19 infection that burdens patients for weeks or even permanently in some cases. Owing to its subjectivity and complexity, the mechanism of taste disorder is poorly studied. Previous studies have reported that the COVID-19 entry receptors are highly expressed in taste buds, thereby intensifying the cytocidal effect. Taste receptor cells are vulnerable to inflammation, and the COVID-19-induced cytokine storm causes secondary damage to taste function. Interferon and various proinflammatory cytokines can trigger cell apoptosis and disrupt the renewal of taste bud stem cells. This immune response can be further enhanced by the accumulation of Angiotensin II (Ang II) caused by an unbalanced local renin-angiotensin system (RAS) system. In addition, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is neurotropic and can invade the brain through the olfactory bulb, affecting the nervous system. Other factors, such as host zinc deficiency, genetic susceptibility, sialic acid, and some neurotransmitters, also contribute to the pathogenesis process. Although several medical interventions have displayed effectiveness, only a few strategies exist for the treatment of postinfectious dysgeusia. Stem cell-based taste regeneration offers promise for long-term taste disorders. Clinical studies have demonstrated that stem cells can treat long COVID-19 through immune regulation. In dysgeusia, the differentiation of taste bud stem cells can be stimulated through exogenous epithelial-derived and neural-derived factors to regenerate taste buds. Tongue organoids are also emerging as functional taste buds, offering new insights into the study of taste regeneration. This review presents the current evidence of the pathogenesis of COVID-19-related dysgeusia, summarizes currently available treatments, and suggests future directions of taste regeneration therapy.

Effect of nutritional status before radiotherapy on radiation-induced acute toxicities in patients with nasopharyngeal carcinoma.

BACKGROUND: To investigate the effect of nutritional status on radiation-induced acute toxicities in nasopharyngeal carcinoma (NPC) patients before radiotherapy. METHODS: Nutritional status of 228 patients with NPC who received intensity-modulated radiotherapy was retrospectively analyzed by modified nutrition index (m-NI). Cumulative grading score of six common acute toxicities were defined as total score for acute toxicities. RESULTS: M-NI ≤6 is a risk factor for xerostomia (p = 0.016, OR = 0.208, 95% CI 0.058-0.743), oral mucositis (p = 0.016, OR = 0.287, 95% CI 0.104-0.793), dysgeusia (p = 0.001, OR = 0.028, 95% CI 0.004-0.217), and dysphagia (p = 0.015, OR = 0.251, 95% CI 0.083-0.764) as well in patients with NPC. Total score of radiation-induced acute toxicities of patients with malnutrition (13.6 ± 1.7) was significantly higher than that of patients with normal nutrition (12.0 ± 2.4) (t = -5.464, p < 0.001). CONCLUSIONS: NPC patients with malnutrition before radiotherapy develop more serious dysgeusia, oral mucositis, dysphagia, and xerostomia after intensity-modulated radiotherapy.

Stricter Postoperative Oropharyngeal Cancer Radiation Therapy Normal Tissue Dose Constraints Are Feasible.

PURPOSE: Although dose de-escalation is one proposed strategy to mitigate long-term toxicity in human papillomavirus associated oropharyngeal cancer, applying more stringent normal tissue constraints may be a complementary approach to further reduce toxicity. Our study demonstrates that in a postoperative setting, improving upon nationally accepted constraints is achievable and leads to reductions in normal tissue complication probabilities (NTCP) without compromising disease control. METHODS AND MATERIALS: We identified 92 patients at our institution between 2015 and 2019 with p16+ oropharyngeal cancer who were treated with adjuvant volumetric modulated arc therapy. We included patients treated to postoperative doses and standard volumes (including bilateral neck). Doses delivered to organs at risk were compared with recommended dose constraints from a recent cooperative group head and neck cancer trial of radiation therapy to 60 Gy. We applied validated and published NTCP models for dysphagia, dysgeusia, esophagitis, oral mucositis, and xerostomia relevant to oropharyngeal cancer. RESULTS: Achievable and delivered mean doses to most normal head and neck tissues were well below national recommended constraints. This translates to notable absolute NTCP reductions for salivary flow (10% improvement in contralateral parotid, 35% improvement in submandibular gland), grade ≥ 2 esophagitis (23% improvement), grade ≥ 3 mucositis (17% improvement), dysgeusia (10% improvement), and dysphagia (8% improvement). Locoregional control at a median follow-up of 26.3 months was 96.7%, with only 3 patients experiencing locoregional recurrence (1 local, 2 regional). CONCLUSIONS: Modern radiation therapy planning techniques allow for improved normal tissue sparing compared with currently established dose constraints without compromising disease control. These improvements may lead to reduced toxicity in a patient population expected to have favorable long-term outcomes. Stricter constraints can be easily achieved and should be used in conjunction with other evolving efforts to mitigate toxicity.

Multiple Types of Taste Disorders among Patients with COVID-19.

Objective Based on the increasing incidence of smell and taste dysfunction among coronavirus disease 2019 (COVID-19) patients, such issues have been considered an early symptom of infection. However, few studies have investigated the type of taste components that are most frequently affected in COVID-19 patients. This study investigated the difference in frequencies of the types of taste component disorders among hospitalized COVID-19 patients. Methods In this retrospective, single-center, observational study, patients' background characteristics, clinical course, laboratory and radiological findings, and details on taste and/or smell disorders were collected and analyzed from medical records. Patients A total of 227 COVID-19 patients were enrolled, among whom 92 (40.5%) complained of taste disorders. Results Multiple types of taste disorders (hypogeusia/ageusia and hypersensitivity, or hypersensitivity and changing tastes) were reported in 10 patients. In particular, 23 patients reported hypersensitivity to at least 1 type of taste, and 2 patients complained of a bitter taste on consuming sweet foods. Impairment of all taste components was found in 48 patients (52.2%). The most frequent taste disorder was salty taste disorder (81 patients, 89.0%). Hypersensitivity to salty taste was most frequently observed (19 patients, 20.9%). Conclusion Patients with COVID-19 develop multiple types of taste disorders, among which salty taste disorder was the most frequent, with many patients developing hypersensitivity to salty taste. As smell and taste are subjective senses, further studies with the combined use of objective examinations will be required to confirm the findings.

The relation between serum D-dimer, ferritin and vitamin D levels, and dysgeusia symptoms, in patients with coronavirus disease 2019.

OBJECTIVE: This study aimed to evaluate the association between serum D-dimer, ferritin and vitamin D levels, and dysgeusia symptoms, in patients with coronavirus disease 2019. METHODS: The present study was conducted with the medical records of 300 patients positive for coronavirus disease 2019, hospitalised between 28 March and 15 August 2020. The patients were divided into two groups regarding the presence or absence of dysgeusia symptoms. RESULTS: Fever and sore throat rates, and the mean D-dimer level, were considerably higher in the dysgeusia group than in the non-dysgeusia group (32.1 vs 21.6 per cent, p = 0.04; 43.6 vs 20.7 per cent, p < 0.001; and 0.54 ± 0.32 vs 0.49 ± 0.51 mg/l FEU, p = 0.008, respectively). The mean age was significantly lower in the dysgeusia group than in the non-dysgeusia group (42.83 ± 12.31 vs 50.51 ± 13.67 years, p < 0.001). CONCLUSION: Younger age, fever and shortness of breath could be observed in patients with dysgeusia symptoms. In addition, the D-dimer level was significantly higher in the dysgeusia group.

[Impaired gustatory sensitivity of the tongue to table salt as a risk factor of arterial hypertension].

The study included 630 patients with verified diagnosis of arterial hypertension (AH) in whom 24 hr AP monitoring was performed, threshold gustatory sensitivity of the tongue to table salt (TGS) measured, and habit to add salt to the cooked food evaluated. Measurement of Na in daily urine of 442 patients was followed by estimation of salt consumption. The results were compared with those obtained in 100 patients with newly diagnosed AH. The control group comprised 288 subjects. TGS in AH patients was significantly higher than in controls and directly related to clinical features of the disease, high AP values, age, smoking habits, hypercholesterolemia, abdominal-type obesity, and hereditary predisposition. TGS positively correlated with daily urinary excretion of NaCl (r = 0.4-0.7; p < 0.05-0.01). High TGS decreased under effect of hypotensive therapy.

Peculiar Unpleasant Dysgeusia as the Sole Initial Symptom of Guillain-Barré Syndrome.

Dysgeusia is rare in Guillain-Barré syndrome, particularly as the initial symptom. We herein report the case of a 59-year-old woman who presented with only dysgeusia as the initial symptom of Guillain-Barré syndrome, followed by gradually worsening muscle weakness and bilateral sensory disturbances in the extremities. Her dysgeusia was so unpleasant that she could not eat anything, so she received nasogastric tube feeding without dysphasia. We speculate that the dysgeusia in our patient was mainly caused by inflammation of the chorda tympani nerves. Guillain-Barré syndrome should be considered a possible cause of acute dysgeusia.

Defects of taste and smell in patients with hypothyroidism.

Taste and smell functions were measured in 18 unselected patients with untreated primary hypothyroidism, and in 15 of the 18 patients after treatment with thyroid hormones. Before treatment, 9 of the 18 patients (50 per cent) were aware of some alteration in their sense of taste, and 7 of the 18 patients (39 per cent) were aware of some alteration in their sense of smell. Distoritions of tase (dysgeusia) and smell (dysosmia) were frequent complaints among the untreated patients; dysgeusia was observed by 7 patients (39 per cent) and dysosmia by 3 patients (17 per cent). Median detection and recognition thresholds for four taste stimuli salt (sodium chloride), sweet (sucrose), sour (hydrochloric acid) and bitter (urea), and for two smell stimuli (pyridine and nitrobenzene), were determined in each patient before and after treatment with thyroid hormones. Before treatment, decreased taste acuity (hypogeusia) for at least one stimulus was observed in 14 of the patients (83 per cent); the most common abnormalities were in the detection and recognition of bitter stimuli. Median detection thresholds for both smell stimuli were also markedly elevated (hyposmia) before therapy. Treatment with throid hormones largely reversed both the taste and smell defects. In one patient, taste and smell abnormalities were completely corrected after 16 days of treatment with thyroxine. This study indicates that taste and smell defects are common clinical abnormalities in primary hypothyroidism, and suggests that these defects may contribute to the anorexia and lack of interest in eating which are frequently observed.

Self-reported oral complaints in older mentally ill patients.

AIM: The aim of this study was to investigate the prevalence of self-reported oral complaints in older hospitalized mentally ill patients and relate them to the primary psychiatric diagnosis. METHODS: A total of 89 older hospitalized psychiatric patients consented to participate in the study, and were interviewed and clinically examined. The medical data were obtained from the hospital's medical records. RESULTS: The mean age of the patients was 73 years (range 59-94 years). A total of 54% suffered from psychotic disorders, 26% from dementia and 20% from mood disorders. The most common oral complaint was xerostomia (45%), followed by dysgeusia (28%), oral malodor (26%), pain when chewing (25%), burning mouth (23%), chewing difficulties (12%) and sialorrhoea (2%). The prevalence of burning mouth, dysgeusia and oral malodor differed significantly among psychiatric diagnoses and was increased in patients with mood disorders. A close association was recorded between burning mouth, dysgeusia, xerostomia and oral malodor complaints. Stepwise logistic regression showed that the use of antidepressants and burning mouth complaints were significantly associated with mood disorders. CONCLUSIONS: An increased prevalence of oral complaints was recorded in the elderly psychiatric patients with mood disorders. Those patients should be systematically evaluated and managed for oral complaints, and particularly for burning mouth. The close association between burning mouth complaints and mood disorders requires further investigation to clarify the potential diagnostic value of the symptom for mood disorders.

Genetic variation in taste perception: does it have a role in healthy eating?

Taste is often cited as the factor of greatest significance in food choice, and has been described as the body's 'nutritional gatekeeper'. Variation in taste receptor genes can give rise to differential perception of sweet, umami and bitter tastes, whereas less is known about the genetics of sour and salty taste. Over twenty-five bitter taste receptor genes exist, of which TAS2R38 is one of the most studied. This gene is broadly tuned to the perception of the bitter-tasting thiourea compounds, which are found in brassica vegetables and other foods with purported health benefits, such as green tea and soya. Variations in this gene contribute to three thiourea taster groups of people: supertasters, medium tasters and nontasters. Differences in taster status have been linked to body weight, alcoholism, preferences for sugar and fat levels in food and fruit and vegetable preferences. However, genetic predispositions to food preferences may be outweighed by environmental influences, and few studies have examined both. The Tastebuddies study aimed at taking a holistic approach, examining both genetic and environmental factors in children and adults. Taster status, age and gender were the most significant influences in food preferences, whereas genotype was less important. Taster perception was associated with BMI in women; nontasters had a higher mean BMI than medium tasters or supertasters. Nutrient intakes were influenced by both phenotype and genotype for the whole group, and in women, the AVI variation of the TAS2R38 gene was associated with a nutrient intake pattern indicative of healthy eating.

Carcinoid tumor of the thymus associated with Cushing's syndrome and dysgeusia: case report and review of the literature.

A 30-year-old man was hospitalized with edema, polyuria, and abnormalities in taste. ACTH and cortisol levels at admission were markedly elevated, even after attempted suppression with 8 mg dexamethasone. A thoracic-abdominal CT revealed an anterior mediastinal lesion and hyperplasia of both adrenal glands. After excision of the mediastinal mass, which confirmed the presence of a carcinoid thymic tumor, the patient became totally asymptomatic, with normal ACTH and cortisol levels. A carcinoid thymic tumor has a poor prognosis, especially when it is associated with Cushing's syndrome. Most patients will present recidivism or metastasis within 5 years after surgery. However, the low number of cases available for analysis makes it difficult to establish optimum therapeutic approaches.

Dysgeusia limited to sweet taste in myasthenia gravis.

Total dysgeusia, an inability to interpret all of the basic tastes, often occurs with zinc deficiency. Partial dysgeusia (dissociation dysgeusia) is a rare inability to interpret a limited number of these basic tastes. We present the case of a patient with myasthenia gravis who became unable to discern sweet taste, but other basic tastes were unaffected. Such dysgeusia can be explained by obstruction of selective taste receptors in taste cells. We considered that this symptom was induced by an autoimmune mechanism related to myasthenia gravis.