Therapy-Associated Saliva and Taste change Evaluation (TASTE) in head & neck cancer patients undergoing radiotherapy: a study protocol.

BACKGROUND: One of the main side effects of radiation therapy to the head and neck region is altered taste sensation. This causes significant morbidity and has profound effects on the quality of life (QoL) of patients. While radiation-associated toxicities like xerostomia and dysphagia are part of large investigations, data on taste impairment is sparse. Small cohort sizes in the majority of studies and a variety of analysis methods limit our current understanding of the underlying processes. None of the studies published to date used a taste-specific QoL questionnaire with differentiation of the different taste qualities (e.g. sour, bitter). Furthermore, data regarding the correlation of taste impairment with radiation-associated change in saliva composition is currently not available. The aim of the TASTE study is to fill this gap. Based on the acquired data, a normal tissue complication probability (NTCP) model for late radiation-associated taste impairment will be developed. METHODS: In this prospective, observational multicenter study 150 head and neck cancer patients undergoing radiation therapy will be recruited and undergo repetitive (semi-) objective and subjective assessment of their taste, smell and salivary function (questionnaires, taste and smell assessment, saliva analysis). Primary endpoint will be patient-reported taste impairment 12 months post radiation therapy using a standardized questionnaire. Secondary endpoints will include taste impairment measured using taste strips at 12 months and 2 years post radiation therapy. Differences between subgroups (radiation side, chemotherapy, etc.) and changes over time will be assessed while adjusting for confounding factors (e.g. age, sex, smoking history). DISCUSSION: This study sets out to further our understanding of taste impairment in patients undergoing radiation therapy to the head and neck region with the goal to prevent this common side effect in future patients. The results of the study may be used to evaluate taste-preserving radiotherapy for patients with head and neck cancer, which may significantly reduce the long-term burden in this patient cohort.

Brochure intervention to manage bothersome taste changes in pediatric patients receiving cancer therapy.

BACKGROUND: Primary objective was to determine if a patient informational brochure describing potentially useful strategies could help manage specific taste changes. Secondary objective was to describe the specific strategies used and whether the strategies were perceived as being helpful. PROCEDURE: This single-center study included pediatric patients with cancer or hematopoietic cell transplant recipients receiving active treatment who experienced bothersome taste changes in the last month. Participants participated in baseline and follow-up interviews conducted 14-21 days apart. A brochure that listed 16 potentially helpful strategies was provided at baseline. At follow-up, we asked about brochure use and whether it helped. At both interviews, we asked about experienced taste changes, strategies used, and whether strategy helped. RESULTS: Of 100 enrolled participants, different (87%) and bad (72%) taste were most common at baseline. Following the brochure intervention, statistically significant reductions were observed in food tasting different, bad, bland, bitter, sour, and metallic. For most strategies, the proportion of patients who used specific strategies or found them helpful was not significantly different between baseline and follow-up. However, "eating foods you like" was considered helpful in significantly more participants who used the strategy in follow-up (72 out of 89, 80.9%) compared with baseline (55 out of 95, 57.9%; p = .008). Between visits, 81.2% looked at the brochure. Among participants, 53.1% found the brochure helpful, very helpful, or extremely helpful. CONCLUSIONS: A brochure that offered strategies to manage changes in taste helped participants cope with them. Further research should evaluate the brochure using randomized and multicenter trials.

Taste disorders and alopecia in myasthenia gravis.

BACKGROUND: Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. METHODS: We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. RESULTS: Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. CONCLUSION: Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.

Taste alterations after hematopoietic cell transplantation: a scoping review.

PURPOSE: This review aimed to evaluate the prevalence and characteristics of dysgeusia after hematopoietic cell transplantation (HCT). METHODS: A literature search (in PubMed, Embase.com and Web of Science) for clinical studies evaluating taste before and after HCT was performed up to June 22, 2023, in collaboration with a medical information specialist. After title and abstract review (N = 807) followed by full-text review (N = 61), articles that met the inclusion criteria were summarized in a table and synthesized narratively. RESULTS: 11 articles were analyzed in this review. All studies had a prospective design and patient populations included children (N = 3) and adults (N = 8) undergoing allogeneic or autologous HCT. Taste was assessed objectively (N = 6) and/or subjectively (N = 8) between baseline and 12 months after HCT. Before HCT, the self-reported (0-31%) and objective (2.4-10%) prevalence of dysgeusia was low. During the neutropenic phase, self-reported (20-100%) and objective (21.4%) dysgeusia was highest. In the post-engraftment period, the self-reported (18%) and objective (0-33%) prevalence of dysgeusia decreased. Different taste qualities were assessed in six studies including salt, sour, bitter, sweet, and umami. CONCLUSIONS: Some patients undergoing HCT experience dysgeusia prior to treatment. During the neutropenic phase, they had highest complaints, with recovery occurring in the post-engraftment period. All basic tastes, except bitter, were affected. Umami and salt were most affected during treatment. These findings have implications for patient management.

The nutritional impact of metallic taste in head and neck cancer patients: explorations and clinical implications.

PURPOSE: Metallic taste (MT) is frequently observed during head and neck cancer treatments, but very little is known about its impact on nutritional status. The aim of this study was to explore the impact of MT on the quality of life and nutritional status in patients with head and neck cancer expressing MT. METHODS: Questionnaires on quality of life, MT, weight, and food intake were filled out by 44 patients with head and neck cancer before, during, and up to 1 year after their treatment. Patients were divided into two groups based on their reported experience of MT. RESULTS: MT was commonly observed (n = 12, 27.2%), always during the treatment phase, and mostly linked with radiotherapy or radiochemotherapy. Reported MT intensity was moderate (n = 6, 40%) to high (n = 4, 26.7%). MT had a significant negative impact on quality of life linked to dysgeusia (p = 0.025). The negative impacts of MT on food intake and on weight were not significant, possibly due to a combination of sample size, dropouts, and duration of observation. Further research in this area could provide additional insights into how to better address the issue related to MT and enhance the quality of care provided to this patient population. CONCLUSION: Metallic taste, experienced by 27.2% of the 44 patients with head and neck cancer, contributes to dysgeusia and results in a significant decline in quality of life associated with dysgeusia. TRIAL REGISTRATION: ClinicalTrials.gov trial registration number: NCT03558789.

Long-term effects of SARS-CoV-2 infection in patients with and without chemosensory disorders at disease onset: a psychophysical and magnetic resonance imaging exploratory study.

A preserved sense of smell and taste allows us to understand many environmental "messages" and results in meaningfully improvements to quality of life. With the COVID-19 pandemic, it became clear how important these senses are for social and nutritional status and catapulted this niche chemosensory research area towards widespread interest. In the current exploratory work, we assessed two groups of post-COVID-19 patients who reported having had (Group 1) or not (Group 2) a smell/taste impairment at the disease onset. The aim was to compare them using validated smell and taste tests as well as with brain magnetic resonance imaging volumetric analysis. Normative data were used for smell scores comparison and a pool of healthy subjects, recruited before the pandemic, served as controls for taste scores. The majority of patients in both groups showed an olfactory impairment, which was more severe in Group 1 (median UPSIT scores: 24.5 Group 1 vs 31.0 Group 2, p = 0.008), particularly among women (p = 0.014). No significant differences emerged comparing taste scores between Group 1 and Group 2, but dysgeusia was only present in Group 1 patients. However, for taste scores, a significant difference was found between Group 1 and controls (p = 0.005). No MRI anatomical abnormalities emerged in any patients while brain volumetric analysis suggested a significant difference among groups for the right caudate nucleus (p = 0.028), although this was not retained following Benjamini-Hochberg correction. This exploratory study could add new information in COVID-19 chemosensory long-lasting impairment and address future investigations on the post-COVID-19 patients' research.

Taste dysfunction after endoscopic endonasal resection of olfactory groove meningioma: Case series and review of the literature.

PURPOSE: The incidence of ageusia and dysgeusia after endoscopic endonasal (EEA) resection of olfactory groove meningioma (OGM) is not well established despite recognized impairment in olfactory function. METHODS: We retrospectively administered a validated taste and smell survey to patients undergoing EEA for resection of OGM at two institutions. Demographics and clinical characteristics were collected and survey responses were analyzed. RESULTS: Twelve patients completed the survey. The median time from surgery was 24 months. The average total complaint score was 5.5 out of 16 [0-13]. All patients reported a change in sense of smell while only 42 % reported a change in sense of taste. Taste changes did not consistently associate with laterality or size of the neoplasm. Significant heterogeneity existed when rating severity of symptoms. CONCLUSIONS: To our knowledge this is the first case series examining taste changes after EEA resection of OGM. Despite universal olfactory dysfunction, only a minority of patients reported a change in their sense of taste. Our findings may improve patient counseling and expectations after surgery.

Comparison of the incidence of smell and taste disorders between influenza and COVID-19.

OBJECTIVE: Smell and taste disorders among patients with COVID-19 has become increasingly reported in the literature, however the prevalence varies. Post-infectious respiratory dysfunction has also been linked to influenza. In this study, we aimed to compare the rates of smell and taste disorders between COVID-19 and Influenza in unvaccinated patients. STUDY DESIGN: Retrospective cohort study. SETTING: TriNetX research network. METHODS: Two queries were made on 7/1/2023 to include Influenza without a diagnosis of COVID-19 and a COVID-19 without a diagnosis of Influenza. The queries included patients from January 1 to December 31, 2022 from 102 Healthcare Organizations. The resultant population of patients with ICD-10 codes for COVID-19 and Influenza were matched using demographic characteristics to evaluate the risk of smell disorders. RESULTS: The overall 3-month incidence of smell and taste disorders was 0.73 % in the COVID-19 population and 0.1 % in the influenza population. The 3-month matched risk ratios were 11.1 [95 % CI (8.8,13.8)]; p < 0.001) times higher for disorders of the smell and taste secondary to COVID-19 compared to influenza. CONCLUSIONS: Disorders of the smell and taste are more common among patients with COVID-19 compared to patients with Influenza. Beyond smell loss, patients experience additional nasal and sinus-related rhinological symptoms, pointing to COVID-19's and influenza's wider impact on overall rhinological health. We believe that due to the transient nature of these disorders, they might go underreported.

The long-term effect of COVID-19 infection on olfaction and taste; a prospective analysis.

PURPOSE: To estimate long-term prognosis of chemosensory dysfunctions among patients recovering from COVID-19 disease. METHODS: Between April 2020 and July 2022, we conducted a prospective, observational study enrolling 48 patients who experienced smell and/or taste dysfunction during the acute-phase of COVID-19. Patients were evaluated for chemosensory function up to 24 months after disease onset. RESULTS: During the acute-phase of COVID-19, 80% of patients reported anosmia, 15% hyposmia, 63% ageusia, and 33% hypogeusia. At two years' follow-up, 53% still experienced smell impairment, and 42% suffered from taste impairment. Moreover, 63% of patients who reported parosmia remained with olfactory disturbance. Interestingly, we found a negative correlation between visual analogue scale scores for smell and taste impairments during the acute-phase of COVID-19 and the likelihood of long-term recovery. CONCLUSION: Our study sheds light on the natural history and long-term follow-up of chemosensory dysfunction in patients recovering from COVID-19 disease. Most patients who initially suffered from smell and/or taste disturbance did not reach full recovery after 2 years follow-up. The severity of impairment may serve as a prognostic indicator for full recovery.

Predictive factors of involuntary weight loss in patients with smell and taste disorders.

BACKGROUND: Chemosensory dysfunction (olfaction, taste, and trigeminal) affects quality of life, potentially impacting eating behaviors. We investigated which factors are associated with weight loss in patients with smell and taste disorders. METHODS: Retrospective study of consecutive adult patients seen in the smell and taste clinic during a 10-year period. Patients were asked about smell, flavor and taste impairment. Psychophysically, smell was assessed with Sniffin' Sticks, flavor with a retronasal test, and taste with Taste Strips. RESULTS: A total of 554 patients (313 females) were included with a median age of 51 years (IQR 23). Seventy-six (13.7%) reported involuntary weight loss (median 6 kg, IQR 6) due to chemosensory disorders. The odds of losing weight were 2.1 times higher when patients reported subjective changes in flavor perception. Parosmia was a significant predictor of weight loss. Patients with symptoms lasting longer than two years were less likely to present with weight loss. Post-traumatic chemosensory dysfunction was a significant predictor of losing weight. On psychophysical testing, the probability of a patient losing weight increased by 8% for every 1-unit reduction in Taste Strips score. CONCLUSION: Factors associated with weight loss were self-reported changes in flavor perception, parosmia, duration of symptoms for less than two years, head injury, and psychophysically measured low Taste Strips score. These data help to identify patients at risk of weight loss from smell or taste impairment.

Taste loss in COVID-19 â€" psychophysical evidence supporting a low prevalence.

Much - possibly even too much - has been published about chemosensory dysfunction as a consequence of COVID-19. Studies have reported prevalence of taste loss in up to 89.9%, which is in a similar range as COVID-19 related smell loss. However, most of these publications rely solely on patients' self-reports. Only few studies used validated psychophysical tests to specifically address olfaction and gustation. Especially for gustation, it is evident that subjective reporting does not correlate well with more objective psychophysical findings, often leading to an overestimation of subjectively impaired taste.

Effect of hyperbaric oxygen therapy on diabetes-related oral complications.

Background: Diabetes Mellitus is a chronic disease characterized by uncontrolled blood sugar levels, which lead to end-organ damage. While the diagnosis and treatment of its complications have been extensively studied, the effect of Hyperbaric Oxygen Therapy (HBO2) on diabetes-related oral complications remains unexplored. Aim: This prospective clinical study aims to investigate the effect of HBO2 on diabetes-related oral complications. Methods: Twenty patients diagnosed with diabetic foot ulcers and scheduled for HBO2 were included in this study. We recorded stimulated and unstimulated saliva pH, buffering capacity, flow rate, and subjective symptoms such as dry mouth, halitosis, taste loss, difficulty swallowing, and clinical examination findings before HBO2 and after the 21st session. Results: Upon comparing the findings, we observed a significant decrease in dry mouth and halitosis, periodontal disease severity, and healing of candida-related stomatitis and angular cheilitis. Despite not reaching statistical significance for other saliva parameters, the unstimulated salivary flow rate increased to normal limits (0.3-0.4 ml/min) in 6 out of 8 patients with a flow rate of less than 0.25 ml/min. Conclusion: Our study investigated the effect of HBO2 on diabetes-related oral complications for the first time, highlighting symptomatic relief for dry mouth and halitosis. Although our results are insufficient to report a definitive benefit, they underscore the need for further research on the oral health effects of HBO2.

Factors associated with impaired psychophysical gustatory function.

OBJECTIVE: To investigate the clinical characteristics associated with measured gustatory dysfunction in patients with chemosensory (smell and taste) discomfort. STUDY DESIGN: Retrospective study. DESIGN: Hospital-based cohort. SETTING: The clinical characteristics associated with the measured diagnosis of gustatory dysfunction were statistically analysed. PARTICIPANTS: Patients who underwent all the psychophysical olfactory and chemical gustatory function tests (YSK olfactory function test and chemical gustometry exam) and the subjective questionnaires between October 2021 and February 2023. MAIN OUTCOME MEASURES: YSK olfactory function test and chemical gustometry results, subjective questionnaire score about chemosensory (smell and taste) functions. The Medical records of patients who visited the smell and taste centre in a tertiary. RESULTS: A total of 219 patients were enrolled; 180 were diagnosed as having normal gustatory function, and 39 were diagnosed as having gustatory dysfunction. Subjective recognition of gustatory function was not associated with the measured gustatory function. Age, sex, measured olfactory function and the threshold and discrimination scores for the olfactory function test were significant factors in the multivariate analysis. When the patients were further divided according to age, the threshold test scores rather than other subsets in the olfactory function test were significantly associated with measured gustatory dysfunction in patients 60 and older. CONCLUSION: In older adult male patients with olfactory dysfunction, gustatory function should be considered regardless of subjective gustatory dysfunction.

Taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

Long-term Consequences of COVID-19: Chemosensory Disorders.

PURPOSE OF REVIEW: A number of sequelae after acute coronavirus disease 2019 (COVID-19) significantly affect the quality of life of patients. The chemosensory disorders including olfactory dysfunction (OD) and gustatory dysfunction (GD) are two of the commonest symptoms complained by patients with COVID-19. Although chemosensory function has been reported improved in over 60% of COVID-19 patients in a short time after acute infection, it may last as a major symptom for patients with long COVID-19. This narrative review discussed current literatures on OD and GD in long COVID-19 including the prevalence, risk factors, possible mechanisms, and potential therapies. RECENT FINDINGS: Although the prevalence of OD and GD has declined continuously after acute COVID-19, a considerable number of patients had persistent chemosensory disorders 3 months to 2 years after symptom onset. Female gender, initial severity of dysfunction, nasal congestion, emotional distress and depression, and SARS-CoV-2 variants have been identified as risk factors for persistent OD and GD in long COVID-19. The pathogenesis of OD and GD in long COVID-19 remains unknown, but may be analogous to the persistent OD and GD post common respiratory viral infection. Corticosteroids and olfactory training might be a potential choice regarding the treatment of lasting OD and GD after SARS-CoV-2 infection; however, more studies are needed to prove it. OD and GD are common long-term consequences of COVID-19 and influenced by gender, initial severity of dysfunction, emotional distress and depression, and SARS-CoV-2 variants. More studies are needed to illustrate their pathogenesis and to establish therapeutic strategies.

Antibody response, associated symptoms and profile of patients presumably infected by SARS-CoV-2 with taste or smell disorders in the SAPRIS multicohort study.

BACKGROUND: Taste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and antibody response intensity associated with taste or smell disorders. METHODS: We used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave. RESULTS: The analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea. CONCLUSIONS: Among patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with an antibody response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study.

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

Taste loss in cancer patients: clinicians' perceptions of educational materials and diagnostic tools.

PURPOSE: Cancer therapy is essential and lifesaving; however, it can have short- and long-term consequences on patients' health. Up to 87% of cancer patients report changes in taste function, yet patients report a lack of support from clinicians regarding their experience with taste loss during and following treatment. Thus, the objective of this study was to assess clinicians' knowledge and experience with managing patients with taste loss and identify potential gaps in the availability of educational materials and diagnostic tools. METHOD: In an online survey, sixty-seven participants who identify as clinicians and practice in the United States and work with cancer patients that complain of taste problems answered questions on their knowledge and experience supporting cancer patients experiencing changes in taste function and provided their opinion on access to educational materials. RESULTS: The current study reports gaps in participants' knowledge of taste and taste disorder terminology, with 15.4% correctly defining both taste and flavor and roughly half were familiar with specific taste disorder classifications. Over half of the participants reported not having access to adequate information to help their patients manage taste alterations. Only two-thirds of participants reported routinely asking patients if they are experiencing changes in taste function. CONCLUSION: Clinicians' responses emphasized the need to improve access to educational materials regarding taste changes and increase the availability of information regarding management strategies. Addressing these inequities in education and improving the standard of care is the first step in improving the care for cancer patients suffering from altered taste function.

Perspectives on the Pathophysiology, Management, and Relevance of Olfactory and Gustatory Dysfunction to COVID-19, Part One.

Context: Amelioration of olfactory and gustatory dysfunction (OGD) disorders has become a common requirement due to COVID-19. Although it's hardly exclusive to COVID-19, OGD's prevalence requires exploration of therapeutic and restorative modalities, on the broadest scale possible. No specific medication or treatment of any noteworthy efficacy exists for OGD. Objective: As Part 1 of a three-part article, a narrative review intended to examine the known causes of OGD, not restricted to COVID-19, and frame their relevance for development of new treatments or the repurposing of existing ones. Design: The researcher performed a narrative review by searching databases including PubMed, Sciencedirect, Google Scholar, Old Dominion University Libraries, and the websites of various medical journals. Searches included numerous combinations of keywords accompanied by the phrases, loss of sense of smell and taste, olfactory and gustatory dysfunction disorders, as well as the terms anosmia, parosmia, ageusia, and parageusia. Such keywords included viruses, bacteria, fungi, protozoa, parasites, infection, COVID-19, treatments, medications, steroids, supplements, nutrients, alternative medicine, acupuncture, olfactory training, clinical trials, cranial nerves, pathogenesis, pathophysiology, and etiology. Setting: The Liebell Clinic, Virginia Beach, VA, USA. Results: Scientific investigation into mechanisms and treatment of OGD appears to be historically limited and unremarkable. Medical literature spanning decades reports a bleak clinical outlook with an abundance of speculation and hypotheses. Limited evidence of effective or reliable treatment exists, especially for chronic cases. Conclusions: With a dismal lack of medical support for a suddenly prevalent, but hardly novel set of maladies of taste and smell perception; the imperative for multifaceted and broad investigations across all medical disciplines is without question. Global urgency for the development of any treatment capable of reducing or resolving OGD triggered by COVID-19 is unprecedented. Part 2 of the current author's three-part series will address the details of current and past treatment approaches and clinical trials.

Part Two: Perspectives on Olfactory and Gustatory Dysfunction Pathophysiology, Management, and Relevance to COVID-19: Current Approaches.

Context: The phenomena of olfactory and gustatory dysfunction disorders (OGD) are hardly unique to COVID-19. However, the widespread incidence of OGD as sequelae of COVID-19 has provoked rejuvenated interest in these long existing, but poorly studied maladies. Objective: This second of a three-part review discusses past and current approaches for treatment of OGD, not restricted to those that COVID-19 has caused, with the intention to lay a foundation for consideration of new paradigms for evaluation and management of OGD. Design: The researcher performed a narrative review by searching databases including PubMed, Sciencedirect, Google Scholar, Old Dominion University Libraries, and the websites of various medical journals. Searches included numerous combinations of keywords accompanied by the phrases, loss of sense of smell and taste, olfactory and gustatory dysfunction disorders, as well as the terms anosmia, parosmia, ageusia, and parageusia. Such keywords included viruses, bacteria, fungi, protozoa, parasites, infection, COVID-19, treatments, medications, steroids, supplements, nutrients, alternative medicine, acupuncture, olfactory training, clinical trials, cranial nerves, pathogenesis, pathophysiology, and etiology. Setting: The Liebell Clinic, Virginia Beach, VA, USA. Conclusions: The epidemiology and hypotheses of pathophysiology of post-COVID OGD has been addressed via numerous studies and reviews. However, extremely limited evidence of effective treatment for chronic OGD, in general, exists, Global demand for any treatment capable of reducing or resolving it is unprecedented. Past and present treatment approaches and recently initiated clinical trials, since the onset of the pandemic, have yet to yield any significant results.