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Background: Smell loss significantly impacts the quality of life in patients. However, there is limited research on smell loss in individuals with amyotrophic lateral sclerosis (ALS), and the correlation between smell loss and cognitive impairment is unclear. This study aimed to investigate the correlation between smell loss and cognition impairment in ALS patients., Methods: The study included 216 ALS patients. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and smell identification test specifically for the Chinese population (CSIT) were administered to evaluate participants' cognitive and olfactory function, respectively., Results: After covarying for age, sex, BMI, education level, degree of hunger, dietary bias, eagerness for food, stress, smoking status, alcohol consumption, and upper respiratory tract infection (URTI) or rhinitis, CSIT scores were significantly correlated with ECAS scores (r = 0.162, p = 0.028), especially the ALS-specific scores (r = 0.158, p = 0.031). Even after excluding patients with URTI or rhinitis, the results were similar. CSIT scores were significantly correlated with ECAS scores (r = 0.224, p = 0.011), especially the ALS-specific scores (r = 0.205, p = 0.019)., Conclusion: In patients with ALS, smell loss is significantly correlated with cognitive impairment, particularly frontotemporal dysfunction. Cognitive dysfunction may lead to worse olfactory performance in ALS patients., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objectives: The aim of the present study was to follow the daily course of patients with olfactory dysfunction and healthy controls and to assess (i) how many times a day, (ii) at which time, and (iii) in which aspect of daily life participants are conscious about their sense of smell., Methods: In this longitudinal study, 49 patients with smell loss and 30 healthy participants were enrolled. Olfactory function was assessed using the Sniffin' Sticks. All participants received paper diaries designed for a 14-day period, featuring 12 rows representing 12 daily hours and six columns for various daily life aspects. They were instructed to mark their awareness of smell by indicating the relevant row and column in the diary. Following the return of the diaries, a second olfactory test was conducted within the patient group., Results: On average, patients were consciously aware of their sense of smell around 8 times daily, while healthy participants noted it about 6.5 times a day. Both groups primarily focused on their sense of smell during activities related to "eating," followed by considerations in "social life" and "personal hygiene." Interestingly, distinct patterns emerged: patients peaked in awareness at 8 a.m. and 7 p.m., whereas healthy individuals showed peaks at 6 a.m., 12 p.m., and 7 p.m. Despite regular diary use, we observed no improvement in patients' olfactory function or related quality of life., Conclusion: The olfactory diary is a valuable tool unveiling individual smell awareness patterns in patients with smell loss, aiding in counseling and patient management., Level of Evidence: 4., Competing Interests: The authors declare that there are no conflicts of interests regarding the publication of this article., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on self-reported alterations in taste and/or smell function., Methods: Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019 (post-COVID-19) chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the disease. The dependent measure-self-reported total recovery of chemosensory symptoms-was subjected to stepwise logistic regression. Independent predictors included demographic and clinical variables, in addition to specific medications used to mitigate disease symptoms (i.e., systemic corticosteroids, oseltamivir, vitamin C, ibuprofen, hydroxychloroquine, azithromycin, ivermectin, nitazoxanide, anticoagulants, and zinc)., Results: The median time between COVID-19 symptom onset and the interviews was 81 days (interquartile range: 60-104). Of the 714 subjects, 249 (34.9%) reported total recovery of their chemosensory function; 437 (61.2%) had at least one treatment since the beginning of the disease. Women and those with more comorbidities had undergone more treatments. The recovery rates of the treated and nontreated groups did not differ significantly. Nonetheless, respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell recovery. Those who took oral zinc were less likely to improve., Conclusions: No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal, although nitrazoxide trended in a positive direction. Oral zinc had a negative effect on the reported recovery of these senses., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. World Journal of Otorhinolaryngology ‐ Head and Neck Surgery published by John Wiley & Sons, Ltd on behalf of Chinese Medical Association.)

Background: Long COVID has brought numerous challenges to healthcare, with olfactory dysfunction (OD) being a particularly distressing outcome for many patients. The persistent loss of smell significantly diminishes the affected individual's quality of life. Recent attention has been drawn to the potential of platelet-rich plasma (PRP) therapy as a treatment for OD. This comprehensive review aims to evaluate the effectiveness of PRP therapy in ameliorating OD, especially when associated with long-term COVID-19. Methods: We executed a comprehensive search of the literature, encompassing clinical trials and observational studies that utilized PRP in treating OD limited to COVID-19. We retrieved and comprehensively discussed data such as design, participant demographics, and reported outcomes, focusing on the efficacy and safety of PRP therapy for OD in COVID-19 patients. Results: Our comprehensive analysis interestingly found promising perspectives for PRP in OD following COVID-19 infection. The collective data indicate that PRP therapy contributed to a significant improvement in olfactory function after COVID-19 infection. Conclusions: The evidence amassed suggests that PRP is a promising and safe therapeutic option for OD, including cases attributable to Long COVID-19. The observed uniform enhancement of olfactory function in patients receiving PRP highlights the necessity for well-designed, controlled trials. Such studies would help to refine treatment protocols and more definitively ascertain the efficacy of PRP in a broader, more varied patient cohort., Competing Interests: The authors declare no conflicts of interest.

Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID-19-associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long-term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID-19-associated olfactory dysfunction., (© 2024 British Neuropathological Society.)

An estimated 1 in 10 000 people are born without the ability to smell, a condition known as congenital anosmia, and about one third of those people have non-syndromic, or isolated congenital anosmia (ICA). Despite the significant impact of olfaction for our quality of life, the underlying causes of ICA remain largely unknown. Using whole exome sequencing (WES) in 10 families and 141 individuals with ICA, we identified a candidate list of 162 rare, segregating, deleterious variants in 158 genes. We confirmed the involvement of CNGA2, a previously implicated ICA gene that is an essential component of the olfactory transduction pathway. Furthermore, we found a loss-of-function variant in SREK1IP1 from the family gene candidate list, which was also observed in 5% of individuals in an additional non-family cohort with ICA. Although SREK1IP1 has not been previously associated with olfaction, its role in zinc ion binding suggests a potential influence on olfactory signaling. This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Sudden smell loss is one of the early symptoms of COVID-19. Although it is stated that the loss of smell and taste following COVID-19 improves within a few weeks, there are also cases that do not improve for a long time. The aim of this study is to reveal long-term smell loss experiences after COVID-19., Methods: A qualitative approach was adopted. We conducted semistructured interviews with 11 participants who had smell loss for at least 3 months. Interviews were recorded, transcribed and evaluated using a thematic analysis for qualitative data., Results: Nutrition and appetite, personal hygiene, threats to safety and emotional changes were the main themes created by the authors and were the areas where participant expressions focused. The participants used oral/nasal corticosteroid therapy for smell loss and received short-term olfactory training, but could not find a solution., Conclusions: Long-term smell loss problems, which were neglected during the pandemic period, should be carefully evaluated due to their negative effects. Understanding and focusing on the negative effects of loss of smell may contribute to the solution of long-term smell loss problems., Patient and Public Contribution: Eleven participants who experienced long-term loss of smell following COVID-19 contributed to the study. They enriched the study by describing the effects of their experiences. There was no other participation or contribution from the public to the research., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: With promising outcomes, platelet-rich plasma (PRP) has recently been suggested as a treatment for olfactory dysfunction (OD)., Methods: Clinical studies utilizing PRP in OD caused by COVID-19, trauma, anesthetic exposure, viral infection, and chronic rhinosinusitis were included in a systematic review., Results: Ten clinical studies were qualitatively analyzed. Six of these studies used the PRP for OD caused by COVID-19, one on OD after functional endoscopic sinus surgery, and three on post-infectious or post-trauma OD. The population included 531 patients, ranging in age from 15 to 63., Conclusion: The use of PRP may be a risk-free and efficient therapeutic option with very encouraging outcomes. Indeed, it enhances olfactory perception in patients who not only exhibit COVID-19 infection aftereffects, but also in those who have lost their sense of smell due to trauma, rhinosinusitis, rhinitis, or even surgery. To evaluate the PRP's therapeutic benefits in OD patients and to compare the efficacy of different therapeutic protocols with regard to treatment schedules, there is an urgent need for focused controlled trials.

Introduction: Although previous studies have examined olfactory dysfunction in children, the novel coronavirus SARS-CoV-2 has certainly had an unprecedented effect on their olfaction, which could not be taken into consideration. The aim of this report was to present data on the epidemiology of olfactory dysfunction during the pandemic and compare this dataset with a pre-pandemic set. We hypothesized an increase in URTI-related olfactory dysfunction., Methods: Data of paediatric patients consulting a smell and taste clinic between March 2020 and June 2022 were retrospectively analysed. The frequency of major causes of olfactory dysfunction was examined and compared with three subsets of an older dataset., Results: A total of 52 patients were included in the analysis. Most children presented with olfactory dysfunction due to upper respiratory tract infection (URTI) (52%). Congenital olfactory dysfunction was present in 34% of cases. Sinonasal disorders and idiopathic cases accounted for 6 and 4%, respectively, whereas head trauma was the least common cause (2%). This was in contrast with the results of the older set. The frequency of URTI-related olfactory dysfunction increased significantly. The frequency of head-trauma-related or congenital olfactory dysfunction showed marked reductions. There were no significant differences regarding the other aetiologies between our patient cohort and the three subsets., Conclusion: The COVID-19 pandemic has resulted in differences regarding the prevalence of aetiologies between our dataset and the subsets of pre-pandemic times. The surge of the frequency of URTI-related olfactory dysfunction may be ascribed to a novel pathomechanism involving sustentacular cells in the olfactory epithelium., (© 2024 S. Karger AG, Basel.)

Objective: Develop and validate a quality-of-life (QoL) outcome measure for patients with dysosmia., Study Design: Cross-sectional survey study., Setting: Otolaryngology clinics, research registries, and Facebook support groups., Methods: A 59-item pilot survey with questions addressing parosmia concerns was developed using input from subjects with parosmia and clinical expertise from Otolaryngologists. After item reduction, the Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR) was reduced to its final 29 items. DisODOR maximum score is 116 (each item score 0-4) with higher scores indicating a higher degree of dysfunction from smell distortion. DisODOR was validated using participants with parosmia persisting >3 months after severe acute respiratory syndrome coronavirus 2 (cases) and healthy controls. Reliability, face and content validity, internal consistency, convergent validity, discriminative validity, sensitivity to change, and the minimal clinically important difference (MCID) were assessed., Results: A total of 134 cases and 20 controls completed DisODOR. The mean (SD) age was 45.9 (12.2) for cases and 29.6 (8.9) for controls. The mean score difference between cases and controls was 45.0 (95% confidence interval, 40.5-49.5) displaying good discriminative validity. DisODOR showed strong test-retest reliability (r = .942) with high internal consistency (Cronbach's α = .971). DisODOR had a moderate correlation with SNOT-22 scores (r = .619) indicating good convergent validity. There is an excellent association with the global impression of severity categories (η 2  = 0.447). Based on the distribution method, the MCID is 15., Conclusion: DisODOR is a valid, reliable QoL instrument for parosmia that can be used to measure the functional impact and QoL impairment for parosmia patients. DisODOR is sensitive to change and thus can be used in studies investigating treatments for parosmia., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Chemosensory losses have long been considered a cardinal symptom of COVID-19 infection. Recent studies have shown changing symptom profiles with COVID-19, including decreasing incidence of olfactory losses. We accessed the National COVID Cohort Collaborative database to identify patients with and without smell and taste loss within 2 weeks of COVID-19 diagnosis. Peak prevalence time intervals for variants were determined from Covariants.org. Using rates of chemosensory loss during the peak time interval for "Untyped" variants as baseline (4/27/2020-6/18/2020), odds ratios for COVID-19-associated smell or taste disturbance fell for each of the Alpha (0.744), Delta (0.637), Omicron K (0.139), Omicron L (0.079), Omicron C (0.061), and Omicron B (0.070) peak intervals. These data suggest that during the recent Omicron waves and potentially moving forward, the presence or absence of smell and taste disturbances may no longer have predictive value in the diagnosis of COVID-19 infection., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background and Objectives: COVID-19 has emerged as a public health emergency caused by the coronavirus 2 (SARS-CoV2). However, only a few studies have reported that anosmia is an early predictor of COVID-19. Therefore, this study aimed to assess the current level of knowledge regarding smell dysfunction in COVID-19 era in Saudi community., Materials and Methods: An online survey was conducted using Survey Monkeys in Saudi Arabia. The survey was distributed through Twitter and WhatsApp. The questionnaire included individuals' demographic information, such as sex, age, residence, income, and qualifications, as well as their knowledge of the early symptoms of COVID-19. ANOVA and Mann-Whitney U- test were conducted to analyze the data. There were twelve items on knowledge dimensions which were assessed through five-point Likert scale., Results: In total, 809 respondents completed the questionnaire. Among them, 658 (81.3%) had no knowledge of how sudden loss of or change in the sense of smell can be the only symptom of COVID-19. However, most participants, 738 (91.2%), knew that fever was a symptom of COVID-19. Similarly, 707 (87.4%) and 772 (95.5%) participants knew that cough and shortness of breath were the major symptoms of COVID-19, respectively. In addition, 395 (48.3%) participants had no information regarding taste changes as a symptom of COVID-19. Notably, participants who were female, married, or diagnosed with COVID-19 had significantly greater knowledge of smell-related issues due to COVID-19 than males, unmarried, and healthy/those without COVID-19., Conclusion: This study revealed that the Saudi population has an fairly good level of knowledge regarding common COVID-19 symptoms as more than 90% of the participants understood symptoms of COVID-19, but less acceptable knowledge regarding smell and taste dysfunction as more than 80% had no knowledge of change in olfactory and taste function was due to COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Aldrees, Almatrafi, Mokhatrish and Aldriweesh.)

Objective: The aim of this study was to quantify the impact of COVID-19 on olfactory and gustatory function in US adults., Methods: From the 2021 Adult National Health Interview Survey, demographic and survey-specific module data concerning COVID-19 diagnoses, testing and disease severity, and data quantifying disturbances and eventual recovery of smell and taste were extracted. Sample weights were applied to obtain nationally representative statistics. The overall rate of COVID-19 infection was determined, and those diagnosed with COVID-19 were analyzed with respect to disease severity, smell and taste disturbance, and respective recoveries., Results: In 2021, 35.8 million or 14% of the adult population (95% CI 13.5-14.7%; mean age, 43.9 years; 53.8% female) had been diagnosed with COVID-19. Among those, 60.5% (58.6-62.5%) and 58.2% (56.2-60.1%) reported accompanying losses  in smell or taste, respectively; there was a significant association between overall COVID-19 symptom severity and smell (p < 0.001) and taste disturbance (p < 0.001). Following infection, 72.2% (69.9-74.3%), 24.1% (22.2-26.2%), and 3.7% (3.0-4.6%) of the patients experienced complete, partial, and no smell recovery, respectively. Recovery rates for gustatory function paralleled olfaction, with 76.8% (74.6-78.9%), 20.6% (18.7-22.7%), and 2.6 (1.9-3.4%) reporting complete, partial, and no recovery of taste, respectively. When sensory disturbance was present, severity of overall symptomatology was negatively associated with smell and taste recovery (p < 0.001 for each)., Conclusion: The majority of adults infected with COVID-19 in 2021 experienced olfactory or gustatory dysfunction with a non-negligible population reporting incomplete or no near-term sensory recovery. Our results are useful for providers counseling patients and suggest that interventions lessening overall COVID-19 symptom burden may prevent prolonged sensory dysfunction., Level of Evidence: 4 Laryngoscope, 133:2357-2361, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Anosmia and hyposmia significantly affect patients' quality of life and have many etiologies, including trauma, inflammatory conditions including chronic rhinosinusitis, neoplasm, and viral infections, such as rhinovirus and SARS-CoV-2., Objective: Our purpose was to establish whether a consensus exists regarding optimal management of olfactory dysfunction and to provide insight into the treatment of anosmia in the current climate of increased prevalence secondary to COVID-19. Thus, we aimed to systematically review the literature on the management of non-Chronic-rhinosinusitis- related anosmia/hyposmia., Methods: PubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990 using terms combined with Medical Subject Headings (MeSH). We included articles evaluating management of anosmia and hyposmia written in the English language, with original data, a minimum of 3 months of follow-up except for COVID-related studies, at least 2 patients, and well-defined and measurable outcomes., Results: A total of 3013 unique titles were returned upon the initial search. Of these, 297 abstracts were examined, yielding 19 full texts meeting inclusion criteria (8 with level 1 evidence, 3 with level 2, 1 with level 3, and 7 with level 4). The studies included a total of 1522 subjects, with follow up ranging from 3 to 72 months, with an exception for COVID related studies. Endpoints were based on clinically significant improvements of olfactory functions as measured through validated smell tests. Treatments with the most robust data were intranasal corticosteroids and olfactory training., Conclusion: The literature on the treatment of anosmia and hyposmia includes randomized trials showing the efficacy of a few modalities. While further research is needed to expand therapeutic options for this debilitating condition, the current literature supports the use of olfactory training and topical corticosteroids.

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs-fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment ( n = 10), standard care ( n = 9), or control ( n = 5). Median OD duration was 157 days (IQR 127-175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control ( p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care ( p = 0.009) groups. Interval SIT scores increased significantly ( p = 0.009) in the combination group. rs-fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT ( r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.

Introduction: The current study evaluated the use of platelet-rich plasma (PRP), an autologous blood product with supraphysiologic concentrations of growth factors, in the treatment of prolonged coronavirus disease 2019 (COVID-19)-related smell loss., Methods: This multi-institutional, randomized controlled trial recruited patients with COVID-19 who had objectively measured smell loss (University of Pennsylvania Smell Identification Test [UPSIT] ≤ 33) between 6 and 12 months. Patients were randomized to three intranasal injections of either PRP or sterile saline into their olfactory clefts. The primary outcome measure was change in Sniffin' Sticks score (threshold, discrimination, and identification [TDI]) from baseline. The secondary end point measures included responder rate (achievement of a clinically significant improvement, ≥5.5 points TDI), change in individual TDI olfaction scores, and change in subjective olfaction via a visual analog scale., Results: A total of 35 patients were recruited and 26 completed the study. PRP treatment resulted in a 3.67-point (95% CI: 0.05-7.29, p = 0.047) greater improvement in olfaction compared with the placebo group at 3 months and a higher response rate (57.1% vs 8.3%, odds ratio 12.5 [95% exact bootstrap confidence interval, 2.2-116.7]). There was a greater improvement in smell discrimination following PRP treatment compared with placebo but no difference in smell identification or threshold. There was no difference in subjective scores between PRP and placebo. No adverse effects were reported., Conclusion: Olfactory function following COVID-19 can improve spontaneously after 6 months and can improve to a greater extent with PRP injection. These data build on the promise of PRP to be a safe potential treatment option for patients with COVID-19-related smell loss, and larger-powered studies will help further assess its efficacy., (© 2022 ARS-AAOA, LLC.)

During COVID-19 pandemic, clinicians have had to deal with an ever-increasing number of cases of olfactory disturbances after SARS-CoV-2 infections and in some people this problem persisted for long time after negativization from virus. This a prospective randomized controlled trial aims at evaluating the efficacy of ultramicronized palmitoylethanolamide (PEA) and Luteolin (LUT) (umPEA-LUT) and olfactory training (OT) compared to OT alone for the treatment of smell disorders in Italian post-COVID population. We included patients with smell loss and parosmia who were randomized and assigned to Group 1 (intervention group; daily treatment with umPEA-LUT oral supplement and OT) or Group 2 (control group; daily treatment with placebo and OT). All subjects were treated for 90 consecutive days. The Sniffin' Sticks identification test was used to assess the olfactory functions at the baseline (T0) and the end of the treatment (T1). Patients were queried regarding any perception of altered olfaction (parosmia) or aversive smell, such as cacosmia, gasoline-type smell, or otherwise at the same observational points. This study confirmed the efficacy of combination of umPEA-LUT and olfactory training as treatment of quantitative smell alteration COVID-19 related, but the efficacy of the supplement for parosmia was limited. UmpEA-LUT is useful for the treatment of brain neuro-inflammation (origin of quantity smell disorders) but has limited/no effect on peripheral damage (olfactory nerve, neuro-epithelium) that is responsible of quality disorders.

Objective: This study aimed to evaluate the efficacy of corticosteroid irrigation compared to saline to no nasal irrigation in COVID-19 patients with olfactory loss., Design and Setting: A randomised controlled study was conducted at the Otolaryngology-Head & Neck Surgery Department, Ramathibodi Hospital, Faculty of Medicine, Mahidol University., Participants: Two hundred thirty-seven COVID-19 participants with a new-onset smell loss were recruited into the study. Two hundred twenty-two participants met the inclusion criteria and were randomised into three groups: corticosteroid irrigation, saline irrigation and no treatment., Main Outcome Measures: The primary outcome was the mean difference in the smell sensation score among the groups after treatment at 1, 2 and 6 weeks. The secondary outcomes measurements included (1) a self-rating quality of life (QOL)-related smell dysfunction score, (2) the change over time in smell sensation score and self-rating QOL-related smell dysfunction score and (3) the median time to complete recovery of smell loss., Results: The mean differences in smell sensation scores among the three groups were not statistically significant at any follow-up period. The mean score of self-rating QOL-related smell dysfunction in the corticosteroid group was significantly better than the other groups at 1 week. The change of outcome scores showed significant improvement over time, regardless of the treatments. The median time to complete smell recovery was similar: 3 weeks., Conclusion: This study emphasised that corticosteroid nasal irrigation is not superior to saline or no nasal irrigation in restoring the sense of smell in COVID-19-associated olfactory loss., (© 2022 John Wiley & Sons Ltd.)

The mechanisms of olfactory dysfunction in COVID-19 are still unclear. In this review, we examine potential mechanisms that may explain why the sense of smell is lost or altered. Among the current hypotheses, the most plausible is that death of infected support cells in the olfactory epithelium causes, besides altered composition of the mucus, retraction of the cilia on olfactory receptor neurons, possibly because of the lack of support cell-derived glucose in the mucus, which powers olfactory signal transduction within the cilia. This mechanism is consistent with the rapid loss of smell with COVID-19, and its rapid recovery after the regeneration of support cells. Host immune responses that cause downregulation of genes involved in olfactory signal transduction occur too late to trigger anosmia, but may contribute to the duration of the olfactory dysfunction., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: A subset of individuals suffering from Coronavirus Disease 2019 (COVID-19) will experience ongoing symptoms that last longer than three months (i.e., long-haul COVID). This includes olfactory dysfunction (OD), which is currently estimated to occur in 1-63.5% of patients at one-year post-infection. However, OD in individuals with long-haul COVID-19 is poorly understood, and there is little information regarding how initial SARS-CoV-2 variants correlate with long-haul symptoms. In this study, we investigated the prevalence and severity of OD in patients with long-haul COVID-19 and investigated how OD severity varied with SARS-CoV-2 variants., Methods: Patients were recruited from the University of North Carolina-Chapel Hill COVID Recovery Clinic. Each patient completed the University of Pennsylvania Smell Identification Test (UPSIT). The dominant strain at the time of infection was determined using the date of COVID-19 diagnosis, and Centers for Disease Control and Prevention, World Health Organization, and North Carolina Department of Health and Human Services databases., Results: Nearly 85% of patients with long-haul COVID-19 reported some degree of OD, which persisted in some patients for two or more years from the date of the initial infection. There was no association between the time since COVID-19 infection and severity of OD. No difference was detected between OD in patients with long-haul COVID-19 based on the dominant variant at the time of infection (p=0.0959)., Conclusion: A vast majority of patients with long-haul COVID-19 had some degree of ongoing olfactory complications, although the severity of symptoms was not dependent on the dominant SARS-CoV-2 variant at the time of infection., Competing Interests: CONFLICT OF INTEREST: The Author(s) declare(s) that there is no conflict(s) of interest. Financial Disclosures: No authors have any financial conflicts of interest.

Background: The objective of this study was to determine how clinical characteristics and validated quality of life (QoL)-measures are associated with eating behavior in patients with olfactory dysfunction (OD)., Methods: For this cross-sectional study, 150 OD patients of different causes were retrospectively recruited. Olfactory function was measured using the Sniffin' Sticks (TDI), while olfactory-related QoL was evaluated with the Questionnaire of OD negative and positive statements (QOD-NS and QOD-PS). The importance of olfaction was measured using the Importance of Olfaction Questionnaire (IOQ). The Dutch Eating Behavior Questionnaire (DEBQ) assessed eating behavior based on emotional, external, and restrained eating. Associations were sought between eating behavior metrics (as dependent variables) with clinical characteristics and olfactory-related outcome measures., Results: Emotional, external, and restrained eating behavior deviating from normative standards were reported in 54%, 71.3%, and 68% of patients, respectively. Multivariate regression modeling revealed that emotional eating was associated with age (ß = -0.227, p = 0.032), the body mass index (BMI, ß = 0.253, p = 0.005), the TDI (ß = 0.190, p = 0.046), and the QOD-NS (ß = 0.203, p = 0.049). External eating was associated with OD duration (ß = 0.291, p = 0.005), the TDI (ß = 0.225, p = 0.018), the QOD-PS (ß = -0.282, p = 0.008), and the IOQ (ß = 0.277, p = 0.004). Restrained eating was associated with age (ß = 0.216, p = 0.033), the BMI (ß = 0.257, p = 0.003), male gender (ß = -0.263, p = 0.002), and the IOQ (ß = 0.332, p < 0.001)., Conclusion: Clinical characteristics and olfactory outcome measures differentially impact eating styles in OD patients. Our study's results highlight the importance of considering unfavorable changes in eating behavior during clinical counseling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Prem, Sharma, Kaiser, Besser and Mueller.)

The objective of this study was to identify specific olfactory phenotypes-patterns of olfactory performance-across distinct cohorts with or without olfactory dysfunction (OD). Adult patients underwent testing via a novel olfactory testing methodology in 1 of 4 groups based on health status: sinonasal inflammatory condition (chronic rhinosinusitis or allergic rhinitis), ≥4 weeks of self-reported OD after resolved COVID-19 infection, Alzheimer's disease, and healthy control. Participants' scores for each scent were normalized on a scale of 0 to 1 relative to their worst and best scores. Agglomerative hierarchal cluster analysis was performed on normalized data for the COVID-19 and sinonasal cohorts. Resulting clusters from the penultimate merger revealed a sensitivity of 81% and specificity of 63% for the detection of patients with COVID-19. These results support that there are olfactory phenotypes that may discriminate COVID-19 OD from sinonasal inflammatory disease. These phenotypes will likely become increasingly leveraged in the workup and treatment of patients with OD.

The COVID-19 pandemic caused by SARS-CoV-2 virus quickly spread globally, infecting over half a billion individuals, and killing over 6 million*. One of the more unusual symptoms was patients' complaints of sudden loss of smell and/or taste, a symptom that has become more apparent as the virus mutated into different variants. Anosmia and ageusia, the loss of smell and taste, respectively, seem to be transient for some individuals, but for others persists even after recovery from the infection. Causes for COVID-19-associated chemosensory loss have undergone several hypotheses. These include non-functional or destroyed olfactory neurons and gustatory receptors or of their supporting cells, disruption of the signaling protein Neuropilin-1, and disruption in the interaction with semaphorins, key molecules in the gustatory and olfactory axon guidance. The current paper will review these hypotheses and chart out potential therapeutic avenues., (© 2022 Wiley Periodicals LLC.)

The sense of smell is interrelated with psychosocial functioning. Olfactory disorders often decrease quality of life but treatment options for people with olfactory loss are limited. Additionally, olfactory loss accompanies and precedes psychiatric and neurodegenerative diseases. Regular, systematic exposure to a set of odors, i.e., olfactory training (OT) has been offered for rehabilitation of the sense of smell in clinical practice. As signals from the olfactory bulb are directly projected to the limbic system it has been also debated whether OT might benefit psychological functioning, i.e., mitigate cognitive deterioration or improve emotional processing. In this review we synthesize key findings on OT utility in the clinical practice and highlight the molecular, cellular, and neuroanatomical changes accompanying olfactory recovery in people with smell loss as well as in experimental animal models. We discuss how OT and its modifications have been used in interventions aiming to support cognitive functions and improve well-being. We delineate main methodological challenges in research on OT and suggest areas requiring further scientific attention., Competing Interests: Conflict of interest Authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Our aim is to determine prevalence, severity, duration of otorhinolaryngologic symptoms related to coronavirus disease 2019 (COVID-19), and correlation between the test results obtained by oronasopharyngeal swab and the symptoms of these regions by evaluating differences in ear, nose, and throat (ENT) symptoms between laboratory-confirmed COVID-19 patients and clinically and computed tomography (CT)-diagnosed COVID-19 patients., Methods: The study enrolled patients with a positive polymerase chain reaction (PCR) test diagnosed with COVID-19 that grouped as PCR (+), and those with repeated negative PCR tests but COVID-19 Reporting and Data System (CO-RADS) chest CT findings with high (CO-RADS 5) or very high (CO-RADS 6) similarity to COVID-19 that grouped as PCR(-)/CT(+). Demographic features, general symptoms, and otorhinolaryngological symptoms and severity of disease were evaluated and compared., Results: The most common ENT symptoms in the PCR(+) group were loss of taste (n=77), loss of smell, and sore throat with respective frequencies of 34.5%, 31.8%, 26.0%, and in PCR(-) CT (+) group loss of taste, loss of smell, and sore throat with respective frequencies 24.6%, 21.1%, and 18.4%. ENT symptom rates were found higher in PCR (+) group (65.0%) according to PCR(-)/CT(+) group (49.1%) with statistically significant difference (p=0.008). Loss of smell rates were found higher in PCR (+) group according to PCR(-)/CT(+) group with statistically significant difference (p=0.037)., Conclusion: Loss of smell and taste were most common ENT symptoms in laboratory-confirmed COVID-19 cases. The presence of COVID-19 should definitely be considered in patients presenting with sudden loss of smell or taste. In addition, loss of smell and otolaryngologic symptoms were more common in laboratory-confirmed COVID-19 according to clinically and computed tomograpy diagnosed COVID-19 cases. There can be a correlation between positive sample region and symptom region. Location of symptoms must be considered for decision of sampling location., Competing Interests: None declared., (© Copyright 2022 by The Medical Bulletin of Sisli Etfal Hospital.)

Objectives: Patients with olfactory dysfunction (OD) frequently report symptoms of depression. The objective of this study was to determine how clinical characteristics and olfactory-related quality of life (QoL) measures associate with the likelihood for major depressive disorders (MDDs)., Methods: A total of 192 OD patients were included. Olfactory function was measured using all three subtests of the Sniffn' Sticks test. Olfactory-related quality of life (QoL) was evaluated using the Questionnaires of Olfactory Dysfunction (QOD)-negative (NS) and -positive statement (PS). The likelihood for MDD was assessed using the Patients Health Questionnaire-2 (PHQ-2). Demographics and disease-specific variables (etiology and duration of OD) were collected. Univariate and multivariable analyses were used to associate disease-specific variables and the QOD with the outcome of the PHQ-2. Additionally, the predictive ability of the QOD-NS to predict depressive symptoms was calculated., Results: In univariate analysis, COVID-19 related smell loss, the QOD-NS, and the QOD-PS were significantly associated with the PHQ-2. In multivariable analyses adjusting for QoL measures, the QOD-NS (ß = 0.532, p < 0.001) and sinonasal OD (compared with postinfectious OD) were significantly associated with the PHQ-2 (ß = 0.146, p = 0.047). When omitting QoL measures from multivariable analyses, only COVID-19 related OD (compared with postinfectious OD) was significantly associated with the PHQ-2 (ß = 0.287, p = 0.009). A QOD-NS score > 20.5 had 70.13% sensitivity and 76.32% specificity for detecting symptoms of depression., Conclusion: Our results suggest that COVID-19 related OD might be associated with a higher likelihood for MDD. Furthermore, we showed that the QOD-NS score might be helpful to predict symptoms of depression in OD patients., Level of Evidence: 4 Laryngoscope, 132:1829-1834, 2022., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To report long-term patterns of recovery and non-recovery in a large nationwide cohort of subjects with COVID-19 associated smell loss., Study Design: Prospectively, longitudinal questionnaires., Setting: Web-based national survey., Methods: A longitudinal survey of adults with COVID-19 and/or sudden change in smell or taste since January 1, 2020 was launched April 10, 2020. Participants were queried again in late May 2022 regarding recovery. Data from respondents with >2 years since loss were analyzed and compared to recovery status of those more recently effected., Results: 1103 responded to the survey of whom 946 met inclusion criteria. Among the 267 respondents for whom at least 2 years of follow up was available, 38.2 % reported full recovery, 54.3 % partial, and 7.5 % no recovery. For the entire cohort (all with ≥3 months since smell loss), 38.7 % reported complete recovery, 51.0 % reported partial recovery (ranging from mild complaints to severe phantosmia or dysosmia), and 10.3 % reported no improvement at all. Complete recovery of smell function was significantly higher in those under 40 years old (45.6 % compared to 32.9 % in those over 40)., Conclusion: Although the vast majority of subjects who do recover do so within the first 3 months, long-term spontaneous recovery can occur. Rates of recovery do not seem to differ depending on when during the pandemic the loss first occurred., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of olfactory dysfunction on the course and severity of COVID-19 and its prognostic and predictive significance for COVID-19., Study Design: Prospective case-control study., Setting: Ondokuz Mayıs University School of Medicine., Methods: Reverse transcription polymerase chain reaction (PCR)-positive patients, patients with COVID-19-related symptoms who had a negative PCR result, and healthy controls were included in the study. Clinicodemographic characteristics, inflammatory markers, and computed tomography stages were recorded. Disease progression and intensive care unit admission were registered. The visual analog scale (0, worst; 10, best) was used to evaluate subjective olfactory, taste, and nasal breathing ability, and the Sniffin' Sticks identification (SS-ID) test was used for psychophysical olfactory assessment., Results: Mean SS-ID scores were significantly lower in the positive group (8.77) than in the negative (10.43) and healthy control (12.17) groups. VAS-smell scores were significantly lower and anosmia was more prevalent in PCR-positive patients ( P < .01). SS-ID and VAS-smell scores were significantly correlated ( r = 0.681, P < .001). The inflammatory parameters, pulmonary infiltration stage, disease progression, and ICU admission were not associated with SS-ID scores. A cutoff SS-ID score <9 resulted in 55.56% sensitivity in predicting COVID-19 positivity, and a cutoff VAS-smell score <8 yielded 72.22% sensitivity., Conclusion: Olfactory dysfunction was detected objectively and subjectively in the PCR-positive group, and no difference was found in terms of taste function and nasal breathing. The severity and prognosis of COVID-19 are not exclusively dependent on olfactory dysfunction. The degree of olfactory dysfunction can be useful in predicting PCR positivity.

Background: Previous studies provided the first evidence that the importance of olfaction decreases with the duration of olfactory dysfunction (OD)., Objective: To evaluate differences in olfactory-related quality of life (QoL) between patients with new-onset and persistent smell loss (>4 weeks) during the coronavirus-19 (COVID-19) pandemic and patients with persistent postinfectious OD (PIOD) that were recruited before the pandemic., Methods: This was a retrospective study that included 149 patients with self-reported OD. The olfactory-related QoL was measured using the questionnaire of OD (QOD). The QOD measures the degree to which patients (i) adjust and cope with smell loss (QOD-positive statement [QOD-PS]), (ii) suffer from distorted odor perceptions (QOD-parosmia [QOD-PAR]), and (iii) suffer from smell loss in general (QOD-negative statement [QOD-NS]). Self-perceived chemosensory function, demographics, olfactory function, and duration of smell loss were evaluated. Analyses of variance were used to depict differences in QoL-outcomes between different OD groups., Results: All patients included during the COVID-19 pandemic reported an extensive loss of chemosensory functions of smell, taste, and flavor perception. Psychophysical retronasal screening testing showed olfactory impairments in more than half of these patients. One-way analysis of variance and posthoc tests revealed that the QOD-NS was significantly higher in the new-onset OD group than the PIOD group. At the same time, the QOD-PS score was significantly higher in the PIOD and the persistent COVID-19 OD group than in the new-onset OD group., Conclusion: We showed that patients with persistent OD experienced better olfactory-related adjustment and lower QoL-impairment scores than those with recent-onset smell loss, suggesting that the olfactory-related QoL might change as a function of time after symptom onset.

The unexpected onset smell and taste disability was being recognized as a COVID-19 related symptom. Loss of smell might occur alone or be followed by other COVID-19 symptoms, such as a dry cough, fever, headache, and shortness of breath. Other virus infections have been linked to anosmia (parainfluenza, rhinovirus, SARS, and others), affecting up to 20% of the adult population, which is much less common than SARS-CoV-2 infection. A hypothesis about the pathophysiology of post-infectious olfactory loss is that viruses could make an inflammatory response of the nasal mucosa or directly damage the olfactory neuroepithelium. However, in patients with COVID-19, loss of smell may occur without other rhino logic symptoms or suggestive nasal inflammation. According to evidence, anosmia-related SARS-CoV-2 could be a new viral syndrome unique to COVID-19. Furthermore, through experimental intranasal inoculation in mice, SARS-CoV-2 can be inoculated into the olfactory neural circuitry. This disease has not had the required focus, most likely because it is not life-threatening in and of itself. Though patients' quality of living is significantly reduced as their olfactory ability is lost, resulting in lowering and inadequate appetite, excessive or unbalanced food consumption, as well as an overall sense of insecurity. This review aims to give a quick overview of the latest epidemiological research, pathological mechanisms for the dysfunction of smell, and taste in patients infected with SARS-CoV-2. In addition, the initial diagnosis and treatment options for dysfunction are also discussed., (© 2022 The Authors.)

Introduction: Smell disorders are common in the general population and occur e.g., after infections, trauma or idiopathically Treatment strategies for smell loss range from surgery, medication to olfactory training, depending on the pathology, but they are limited This study examined the effect of acupuncture on olfactory function., Methods: Sixty patients with smell loss following infections of the upper respiratory tract were included in this investigation Half of the study group were randomly assigned to verum acupuncture and the other half to sham acupuncture Olfaction was measured by means of the "Sniffin' Sticks" test battery (odour threshold, discrimination and identification)., Results: Compared to sham acupuncture, verum was associated with an improvement of smell function as measured by the TDI score (p = 0.039) The improvement was largely determined by improvement in odour discrimination, and was significantly better in patients with a shorter duration of the disorder., Conclusion: The present results suggest that acupuncture is an effective supplementary treatment option for patients with olfactory loss., (© 2021. The Author(s).)

Purpose of Review: Olfactory dysfunction is a prevalent condition affecting 5-15% of the general population, with significant impact on quality of life. This review summarizes the most recent and relevant literature in the treatment of olfactory dysfunction., Recent Findings: Current evidence supports the short-term use of topical corticosteroids and systemic therapy. These treatments may occur in conjunction with olfactory training, which is well supported by the literature. While there are several additional treatments currently under investigation, meaningful conclusions are not yet able to be made regarding their efficacy. The treatment of olfactory dysfunction is targeted at the suspected etiology when possible. After normal aging, chronic rhinosinusitis, post-infectious sequelae including as a result SARS-CoV-2 infection (COVID-19), and head trauma are the most common causes. Current evidence supports the short-term use of topical corticosteroids and systemic therapy. Several additional treatments are under investigation but recommendations for their use cannot currently be made., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Recent research shows that the human sense of smell seems to be more efficient than previously believed and to have a major impact on our health condition and quality of life. During the COVID-19 pandemic, an increased clinical interest has become evident for the SARS-CoV-2 related impact on olfactory function. This article highlights important aspects in the diagnosis and therapy of the chemical senses., (© 2021. The Author(s).)

Purpose of Review: To summarize and critically review the recent literature on novel treatments for olfactory disorders (OD)., Recent Findings: Emerging therapies in the management of OD include multiple vitamins and supplements, biologics, neuromodulators, and intranasal agents. There is also an active investigation into treatments that harness the neuroregenerative properties of the olfactory epithelium, such as platelet-rich plasma and stem cell transplantation., Summary: Successful management of OD is multimodal and tailored to the underlying etiology. As the findings of further investigations accrue, the management of OD will undoubtedly continue to be advanced and refined, and likely harness the intrinsic neuroregenerative properties of the olfactory system., Competing Interests: Conflict of InterestMichael T. Chang declares that he has no conflict of interest. Zara M. Patel reports royalties or licenses from Springer and Wolters Kluwer; consulting fees from Medtronic, Wyndly, Dianosic, Ethicon/Johnson & Johnson, Mediflix, and Consumer Medical; patent pending (S15-465 63/076,656 [S31-06935.PRO]); participation on a Data Safety Monitoring Board or Advisory Board for Optinose and Regeneron/Sanofi; and stock or stock options for Olfera Therapeutics., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In recent months it has emerged that the novel coronavirus-responsible for the COVID-19 pandemic-causes reduction of smell and taste in a large fraction of patients. The chemosensory deficits are often the earliest, and sometimes the only signs in otherwise asymptomatic carriers of the SARS-CoV-2 virus. The reasons for the surprisingly early and specific chemosensory dysfunction in COVID-19 are now beginning to be elucidated. In this hypothesis review, we discuss implications of the recent finding that the prevalence of smell and taste dysfunction in COVID-19 patients differs between populations, possibly because of differences in the spike protein of different virus strains or because of differences in the host proteins that enable virus entry, thus modifying infectivity. We review recent progress in defining underlying cellular and molecular mechanisms of the virus-induced anosmia, with a focus on the emerging crucial role of sustentacular cells in the olfactory epithelium. We critically examine the current evidence whether and how the SARS-CoV-2 virus can follow a route from the olfactory epithelium in the nose to the brain to achieve brain infection, and we discuss the prospects for using the smell and taste dysfunctions seen in COVID-19 as an early and rapid diagnostic screening tool.

Background: The clinical course of coronavirus disease 2019 (COVID-19) olfactory dysfunction remains poorly characterized, often limited by self-reported measures. Given the logistical challenges of psychophysical testing, understanding the longitudinal relationship between self-reported and quantitative measures can help accurately identify patients with persistent olfactory dysfunction. This study aimed to longitudinally correlate measured and subjective olfactory function in COVID-19 subjects., Methods: A prospective, longitudinal study evaluating subjective and measured olfaction was conducted on ambulatory COVID-19 subjects. Olfaction scores were obtained using a visual analogue scale (VAS) (0 = anosmia, 10 = normosmia) and the validated 12-item Brief Smell Identification Test (BSIT). Weekly testing was performed until recovery (BSIT ≥ 9/12 and/or VAS = 10/10) or study completion., Results: Eighty-six polymerase chain reaction (PCR)-positive COVID-19 subjects were recruited ≤3 days from diagnosis and 52 completed longitudinal testing. Among those with self-reported smell loss at recruitment, similar levels (75.8%) of objective (BSIT ≥ 9/12) and subjective recovery were obtained using a VAS cutoff ≥8, yet only 30.3% reported complete subjective recovery (VAS = 10). Median times to objective and complete subjective olfactory recovery were 12 ± 2.3 and 24 ± 3.5 days, respectively. Although both measures showed chemosensory improvement, the distributions of objective and full subjective olfactory recovery differed significantly (log rank test χ 2 = 6.46, degrees of freedom [df] = 1, p = 0.011). Overall correlation between BSIT and VAS scores was moderate to strong across longitudinal follow-up (r s = 0.41-0.65)., Conclusion: Self-reported and psychophysically measured COVID-19 olfactory dysfunction improve at similar levels and are moderately correlated longitudinally, yet there is a significant delay in complete subjective recovery. Psychophysical testing in conjunction with qualitative assessments may be considered for counseling and follow-up of patients with COVID-19 smell loss., (© 2021 ARS-AAOA, LLC.)

The temporal course and the severity of the involution of sensory systems through aging can be critical since they ensure the ability to perceive and recognize the world. In older people, sensory impairments significantly increase their risk of biological, psychological, and social impoverishment. Besides this, olfactory loss is considered an early biomarker in Alzheimer's disease (AD) neurodegenerative process. Here we studied olfactory ethograms in middle-aged male and female gold-standard C57BL/6 mice and 3xTg-AD mice, a genetic model of AD that presents cognitive dysfunction and a conspicuous neuropsychiatric-like phenotype. A paradigm involving 1-day food deprivation was used to investigate the ethological patterns shown in the olfactory inspection of a new cage and the sniffing, finding, and eating of hidden food pellets. The sniffing-find-eat temporal patterns were independent of the loss of weight and unveiled (fast) olfactory signatures in Alzheimer's disease, differing from those (slow progressive) in normal aging. Male 3xTg-AD mice exhibited an early signature than female mice, opposite to animals with normal aging. The sequence of actions was correlated in male and female 3xTg-AD mice in contrast to control mice. Social isolation, naturally occurring in male 3xTg-AD due to the death of cage mates, emphasized their olfactory patterns and disrupted the behavioral correlates. The paradigm provided distinct contextual, sex, and genotype olfactory ethogram signatures useful to investigate olfactory function in normal and AD-pathological aging. Isolation had an impact on enhancing the changes in the olfactory signature here described, for the first time, in the 3xTg-AD model of Alzheimer's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Marín-Pardo and Giménez-Llort.)

Background: Social determinants of health (SDoH) include the socioeconomic, demographic, and social conditions that influence differences in health status among individuals and groups. The impact of these conditions on olfactory function remains poorly understood. In this scoping review, we systematically review the available literature to synthesize the association between SDoH and olfactory function., Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR) guidelines, we performed systematic search queries in PubMed, Embase, and Ovid databases and categorized articles according to themes that emerged regarding SDoH. The primary outcomes included self-reported and objective measurements of smell., Results: We identified 722 unique references that underwent title and abstract review by two independent reviewers, with 70 articles undergoing full-text review and 57 relevant for data extraction. Six themes emerged in our review, under which we categorized the studies and synthesized respective associations with olfactory function. These include studies exploring socioeconomic status (n = 19, 33%), education status (n = 27, 47%), occupational exposures (n = 26, 46%), racial/ethnic disparities (n = 12, 21%), and lifestyle/behavioral factors (n = 33, 58%)., Conclusions: Within the context of this scoping review, olfactory dysfunction is significantly more prevalent in patients with lower socioeconomic status, exposure to environmental and occupational toxins, and of minority race/ethnicity, whereas the associations between olfactory dysfunction and education level and lifestyle factors such as smoking and drinking seem to be much more elusive. This review highlights the importance of accounting for SDoH in observational studies examining olfactory outcomes. Given the increased awareness of olfactory loss, special consideration should be given to understanding olfactory dysfunction in the context of these factors., (© 2021 ARS-AAOA, LLC.)

Purpose: To determine the prevalence of objective gustatory (GD) and olfactory (OD) dysfunction in COVID-19 patients., Methods: This is a prospective, cross-sectional study of 51 COVID-19 positive patients diagnosed using RT-PCR-based testing. Of these study participants, 41 reported having present GD and OD at the time of enrollment and ten patients were without symptomatic OD and GD. All participants were objectively tested for OD by Brief Smell Identification Test (BSIT) and for GD by Burghart taste strip test, which were mailed to the participants. The subjective presence and severity of COVID-19 symptoms of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough and shortness of breath were also assessed., Results: Of the 41 patients with GD and OD, only 25.6% (10/39; p ≤ 0.0001) objectively presented GD and 39.1% (16/41; p ≤ 0.0001) OD at the time of their subjective dysfunction. Regarding GD, 23.1% (9/39) suffered from total hypogeusia, 2.6% (1/39) from ageusia. A significant loss of sour (33.3% (13/39)) and salty taste (17.9% (7/39)) could be recognized. Only 10.3% (4/39) showed a reduction in sweet and bitter taste. Concerning OD, 9.8% (4/41) showed a deficit relative to younger age in the BSIT and 29.3% (12/41) results abnormal relative to age., Conclusion: Subjective and objective findings in GD and OD differ significantly. Most patients suffering from objective dysgeusia present a deficit in sour and salty taste., Trial Registration Number: DRKS00021516; 22/04/2020., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Anosmia and hyposmia have many etiologies, including trauma, chronic sinusitis, neoplasms, and respiratory viral infections such as rhinovirus and SARS-CoV-2. We aimed to systematically review the literature on the diagnostic evaluation of anosmia/hyposmia., Methods: PubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990 using terms combined with Medical Subject Headings (MeSH). We included articles evaluating diagnostic modalities for anosmia, written in the English language, used original data, and had two or more patients., Results: A total of 2065 unique titles were returned upon the initial search. Of these, 226 abstracts were examined, yielding 27 full-text articles meeting inclusion criteria (Level of evidence ranging from 1 to 4; most level 2). The studies included a total of 13,577 patients. The most utilized diagnostic tools were orthonasal smell tests (such as the Sniffin' Sticks and the UPSIT, along with validated abridged smell tests). Though various imaging modalities (including MRI and CT) were frequently mentioned in the workup of olfactory dysfunction, routine imaging was not used to primarily diagnose smell loss., Conclusion: The literature includes several studies on validity and reliability for various smell tests in diagnosing anosmia. Along with a thorough history and physical, validated orthonasal smell tests should be part of the workup of the patient with suspected olfactory dysfunction. The most widely studied modality was MRI, but criteria for the timing and sequence of imaging modalities was heterogenous., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objectives/hypothesis: As a cardinal symptom of chronic rhinosinusitis (CRS), hyposmia has been recommended to be assessed as a component of CRS disease control. Herein we determine the significance of hyposmia in CRS in the context of nasal obstruction and drainage symptoms., Study Design: Prospective, cross-sectional METHODS: Cross-sectional study of 308 CRS patients (102 CRSwNP, 206 CRSsNP) without prior endoscopic sinus surgery. The burden of nasal obstruction and hyposmia were assessed using the corresponding item scores on the 22-item Sinonasal Outcome Test (SNOT-22). Burden of nasal discharge was assessed using the mean of "thick nasal discharge" and "thick post-nasal discharge" SNOT-22 item scores. Patients were all asked to rate their CRS symptom control as "not at all," "a little," "somewhat," "very," or "completely.", Results: In CRSwNP, only 4.9% had a hyposmia score > 1 with nasal obstruction and drainage scores less than or equal to 1. In CRSsNP, only 1.9% had a hyposmia score > 1 with nasal obstruction and drainage scores less than or equal to 1. On univariate association, CRS symptom control was significantly associated with nasal obstruction, hyposmia, and drainage in both CRSwNP and CRSsNP (P < .05 in all cases). Using multivariable regression to account for all nasal symptoms, only nasal obstruction and nasal discharge scores (but not hyposmia) were significantly associated with CRS symptom control., Conclusions: Hyposmia rarely occurs without nasal obstruction or nasal drainage, and may therefore be redundant to assess for CRS disease control. Moreover, hyposmia was not associated with patient-reported CRS symptom control when accounting for the burden of nasal obstruction and drainage., Level of Evidence: 3 Laryngoscope, 131:E2116-E2120, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objective: To evaluate associations between self-perceived chemosensory functions of smell, taste, and flavor perception with olfactory-specific quality of life (QoL) in patients with olfactory dysfunction (OD) and whether these associations would be influenced by other factors, such as duration or etiology of smell loss., Study Design: Retrospective cohort study., Setting: Tertiary care, academic center., Methods: Olfactory-specific QoL was measured with the Questionnaire of Olfactory Disorders (QOD). The QOD measures the impact of OD on QoL (QOD-negative statements) and the ability of patients to cope with smell loss (QOD-positive statements). Orthonasal olfactory function, patients' demographics, self-perceived chemosensory perception, and duration and etiology of OD were retrospectively collected in a cohort of patients with quantitative OD. Correlations and multivariable linear regression models were computed to determine possible associations with the outcome measure of QOD-negative and QOD-positive statement scores., Results: A total of 133 patients with OD were included. Analysis revealed a positive correlation between self-perceived taste and flavor perception with QOD-negative statement scores, while self-perceived smell showed no significant correlation. Similarly, longer duration of smell loss and higher age were also correlated with higher QOD-positive statement scores. Multivariable regression models confirmed that self-perceived taste was independently associated with the QOD-negative statement score, while age and duration of OD were independently associated with the QOD-positive statement score., Conclusions: These findings suggest that the impact of diminished flavor perception during eating and drinking has a stronger impact on the QoL of patients with OD as compared with decreased orthonasal olfaction.