Giving a Voice to Patients With Smell Disorders Associated With COVID-19: Cross-Sectional Longitudinal Analysis Using Natural Language Processing of Self-Reports.

BACKGROUND: Smell disorders are commonly reported with COVID-19 infection. The smell-related issues associated with COVID-19 may be prolonged, even after the respiratory symptoms are resolved. These smell dysfunctions can range from anosmia (complete loss of smell) or hyposmia (reduced sense of smell) to parosmia (smells perceived differently) or phantosmia (smells perceived without an odor source being present). Similar to the difficulty that people experience when talking about their smell experiences, patients find it difficult to express or label the symptoms they experience, thereby complicating diagnosis. The complexity of these symptoms can be an additional burden for patients and health care providers and thus needs further investigation. OBJECTIVE: This study aims to explore the smell disorder concerns of patients and to provide an overview for each specific smell disorder by using the longitudinal survey conducted in 2020 by the Global Consortium for Chemosensory Research, an international research group that has been created ad hoc for studying chemosensory dysfunctions. We aimed to extend the existing knowledge on smell disorders related to COVID-19 by analyzing a large data set of self-reported descriptive comments by using methods from natural language processing. METHODS: We included self-reported data on the description of changes in smell provided by 1560 participants at 2 timepoints (second survey completed between 23 and 291 days). Text data from participants who still had smell disorders at the second timepoint (long-haulers) were compared with the text data of those who did not (non-long-haulers). Specifically, 3 aims were pursued in this study. The first aim was to classify smell disorders based on the participants' self-reports. The second aim was to classify the sentiment of each self-report by using a machine learning approach, and the third aim was to find particular food and nonfood keywords that were more salient among long-haulers than those among non-long-haulers. RESULTS: We found that parosmia (odds ratio [OR] 1.78, 95% CI 1.35-2.37; P<.001) as well as hyposmia (OR 1.74, 95% CI 1.34-2.26; P<.001) were more frequently reported in long-haulers than in non-long-haulers. Furthermore, a significant relationship was found between long-hauler status and sentiment of self-report (P<.001). Finally, we found specific keywords that were more typical for long-haulers than those for non-long-haulers, for example, fire, gas, wine, and vinegar. CONCLUSIONS: Our work shows consistent findings with those of previous studies, which indicate that self-reports, which can easily be extracted online, may offer valuable information to health care and understanding of smell disorders. At the same time, our study on self-reports provides new insights for future studies investigating smell disorders.

Assessment of smell disturbances 6 months after COVID-19 in Polish population.

Considering the frequency and severity of olfactory disorders associated with SARS-CoV-2 infection, attention to the olfactory loss has expanded. The aim of our study was to assess of smell disturbances 6 months after COVID-19. The study population consisted of 2 groups: 196 Post-COVID-19 patients who were hospitalized because of COVID-19, control sample-130 patients without reported smell disorders from general population-Bialystok PLUS study. People from both groups were asked to participate in the Sniffin Sticks Test (half year after the disease). Sniffin Sticks Test consisted of 12 standardized smell samples. The participant's test score was counted based on correct scent recognition. Middle/older age was related with lower likelihood of olfaction recovery. The biggest differences in recognition of particular fragrances were observed for: orange and lemon, lemon and coffee (p.adj < 0.001). Patients had the greatest problem in assessing smell of lemon. The comparison of scores between Delta, Omicron, Wild Type, Wild Type Alpha waves showed statistically significant difference between Delta and Wild Type waves (p = 0.006). Duration of the disease (r = 0.218), age (r = -0.253), IL-6 (r = -0.281) showed significant negative correlations with the score. Statistically significant variables in the case of smell disorders were Omicron wave (CI = 0.045-0.902; P = 0.046) and Wild Type wave (CI = 0.135-0.716; P = 0.007) compared to Delta wave reference. Moreover, patients with PLT count below 150 000/µl had greater olfactory disorders than those with PLT count over 150 000/µl. There are: smell differences between post-COVID-19 patients and healthy population; statistically significant difference between Delta and Wild Type waves in Post-COVID-19 group in score of the Sniffin Sticks Test. Smell disturbances depend on the age, cognitive impairments, clinical characteristics of the COVID-19 disease and sex of the patient.

Post-COVID syndrome: analysis of the prevalence of chemosensory dysfunction and predictive factors of recovery in COVID-19 long-haulers in Jordan.

OBJECTIVE: One of the major concerns of the post-COVID-19 era is elucidating and addressing the long-term complications of COVID-19. SUBJECTS AND METHODS: A web-based questionnaire was distributed in Jordan to assess the prevalence and recovery from chemosensory dysfunction among COVID-19 long-haulers in Jordan. RESULTS: A total of 611 respondents complained of chemosensory dysfunction (age range = 18-68 years), and the majority of the respondents were female (88.4%). Parosmia was the most prevalent olfactory dysfunction reported (n = 337, 33.3%), and parageusia was the most frequently reported gustatory dysfunction (n = 239, 36.4%). Medications were not reported to be associated with a better perception of smell or taste by nearly half of those who had been treated (n = 146, 46.1%). Among participants who had received olfactory rehabilitation/training (n = 215, 35.2%), 43.7% (n = 94) reported modest improvement, with the most frequently helpful scents being coffee (n = 80, 24.8%), aromatic oils (n = 74, 23%), and perfumes/colognes (n = 73, 22.7%). Age was found to have a significant negative correlation with complete recovery. In addition, age (p < .05), anosmia (p < .001), hyperosmia (p < .001), ageusia (p < .05), and duration of olfactory dysfunction (p < .001) were all independent predictors of complete recovery. CONCLUSIONS: Chemosensory dysfunctions are largely subjective; therefore, more objective examinations are required to draw more definite conclusions.

Long-Term Taste and Smell Outcomes After COVID-19.

Importance: Self-report surveys suggest that long-lasting taste deficits may occur after SARS-CoV-2 infection, influencing nutrition, safety, and quality of life. However, self-reports of taste dysfunction are inaccurate, commonly reflecting deficits due to olfactory not taste system pathology; hence, quantitative testing is needed to verify the association of post-COVID-19 condition with taste function. Objective: To use well-validated self-administered psychophysical tests to investigate the association of COVID-19 with long-term outcomes in taste and smell function. Design, Setting, and Participants: This nationwide cross-sectional study included individuals with and without a prior history of COVID-19 recruited from February 2020 to August 2023 from a social media website (Reddit) and bulletin board advertisements. In the COVID-19 cohort, there was a mean of 395 days (95% CI, 363-425 days) between diagnosis and testing. Exposure: History of COVID-19. Main Outcomes and Measures: The 53-item Waterless Empirical Taste Test (WETT) and 40-item University of Pennsylvania Smell Identification Test (UPSIT) were used to assess taste and smell function. Total WETT and UPSIT scores and WETT subtest scores of sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate were assessed for groups with and without a COVID-19 history. The association of COVID-19 with taste and smell outcomes was assessed using analysis of covariance, χ2, and Fisher exact probability tests. Results: Tests were completed by 340 individuals with prior COVID-19 (128 males [37.6%] and 212 females [62.4%]; mean [SD] age, 39.04 [14.35] years) and 434 individuals with no such history (154 males [35.5%] and 280 females [64.5%]; mean (SD) age, 39.99 [15.61] years). Taste scores did not differ between individuals with and without previous COVID-19 (total WETT age- and sex-adjusted mean score, 33.41 [95% CI, 32.37-34.45] vs 33.46 [95% CI, 32.54-34.38]; P = .94). In contrast, UPSIT scores were lower in the group with previous COVID-19 than the group without previous COVID-19 (mean score, 34.39 [95% CI, 33.86-34.92] vs 35.86 [95% CI, 35.39-36.33]; P < .001]); 103 individuals with prior COVID-19 (30.3%) and 91 individuals without prior COVID-19 (21.0%) had some degree of dysfunction (odds ratio, 1.64 [95% CI, 1.18-2.27]). The SARS-CoV-2 variant present at the time of infection was associated with smell outcomes; individuals with original untyped and Alpha variant infections exhibited more loss than those with other variant infections; for example, total to severe loss occurred in 10 of 42 individuals with Alpha variant infections (23.8%) and 7 of 52 individuals with original variant infections (13.5%) compared with 12 of 434 individuals with no COVID-19 history (2.8%) (P < .001 for all). Conclusions and Relevance: In this study, taste dysfunction as measured objectively was absent 1 year after exposure to COVID-19 while some smell loss remained in nearly one-third of individuals with this exposure, likely explaining taste complaints of many individuals with post-COVID-19 condition. Infection with earlier untyped and Alpha variants was associated with the greatest degree of smell loss.

COVID-19 associated anosmia in pediatric patients: subject publications review.

OBJECTIVE: Aim: To review the publications subject to the problem of COVID-19 associated anosmia incidence in pediatric patients as well as its pathogenesis, diagnostics, treatment and recovery. The peculiarity of pediatric COVID-19 anosmia is due to children accounting for very low percentage of COVID-19 patients (comparing to one in adults), mostly with milder course of the disease. Awareness of anosmia and its proper diagnostics is crucial in children and adolescents, considering it can be the only manifestation in COVID-19 positive pediatric patients. PATIENTS AND METHODS: Materials and Methods: In order to achieve this goal a meta-analysis of information from databases followed by statistical processing and generalisation of the obtained data was carried out. CONCLUSION: Conclusions: Publications on COVID-19 anosmia in children and adolescents are less numerous than those concerning adult patients, so it is important to use every single trustworthy one. Anosmia/ageusia may be the only symptom, early identifier and the strongest predictor of COVID-19 infection in pediatric patients. Prospects for further scientific researches. Further researches regarding differential diagnostics of COVID-19 and other infections, including seasonal influenza, manifesting with both olfactory and taste dysfunction as well as anosmia diagnostics in children and adolescents with autistic spectrum and different types of mental disorders are possible.

Factors influencing olfactory function in an adult general population sample: the CHRIS study.

The sense of smell allows for the assessment of the chemical composition of volatiles in our environment. Different factors are associated with reduced olfactory function, including age, sex, as well as health and lifestyle conditions. However, most studies that aimed at identifying the variables that drive olfactory function in the population suffered from methodological weaknesses in study designs and participant selection, such as the inclusion of convenience sample or only of certain age groups, or recruitment biases. We aimed to overcome these issues by investigating the Cooperative Health Research in South Tyrol (CHRIS) cohort, a population-based cohort, by using a validated odor identification test. Specifically, we hypothesized that a series of medical, demographic and lifestyle variables is associated with odor identification abilities. In addition, our goal was to provide clinicians and researchers with normative values for the Sniffin' Sticks identification set, after exclusion of individuals with impaired nasal patency. We included 6,944 participants without acute nasal obstruction and assessed several biological, social, and medical parameters. A basic model determined that age, sex, years of education, and smoking status together explained roughly 13% of the total variance in the data. We further observed that variables related to medical (positive screening for cognitive impairment and for Parkinson's disease, history of skull fracture, stage 2 hypertension) and lifestyle (alcohol abstinence) conditions had a negative effect on odor identification scores. Finally, we provide clinicians with normative values for both versions of the Sniffin' Sticks odor identification test, i.e. with 16 items and with 12 items.

Relationship between olfactory and gustatory functions: The Iwaki health promotion project 2019.

OBJECTIVE: Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well understood. In this study, we aimed to investigate the relationship between the olfactory and gustatory functions based on the results of a large-scale epidemiological study (Iwaki Health Promotion Project) of the general local population. METHODS: We analyzed 565 participants who underwent taste and olfactory tests in the 2019 Iwaki Project. Gustatory function was tested for four taste qualities (sweet, sour, salty, and bitter) using whole-mouth taste tests. Olfactory function was tested using the University of Pennsylvania Smell Identification Test modified for Japanese (UPSIT-J). We evaluated sex-related differences between olfactory and gustatory functions and the effects of various factors on olfactory identification using multivariate analysis. Furthermore, we compared the percentage of accurate UPSIT-J responses between the normal and hypogeusia groups. We also analyzed the effects of taste and olfactory functions on eating. RESULTS: Olfactory and gustatory functions were lower in men than in women. Among the four taste qualities, salty taste was the most closely associated with olfactory identification ability, with lower olfactory scores of salty taste in the hypogeusia group than in the normal group. Moreover, the hyposmia group had higher daily salt intake than the normal olfaction group in women. CONCLUSION: These results suggest that olfactory identification tests may be useful in predicting elevated salt cognitive thresholds, leading to a reduction in salt intake, which may contribute to hypertension prevention.

Composite Dietary Antioxidant Index is negatively associated with olfactory dysfunction among adults in the United States: A cross-sectional study.

The Comprehensive Dietary Antioxidant Index (CDAI) plays a crucial role as an indicator of diets rich in antioxidants. Despite its importance, the clinical significance of CDAI concerning olfactory dysfunction (OD) remains unknown. Our study aims to investigate whether there is an association between CDAI and OD within the general adult population aged 20 years and older. We hypothesized a negative correlation between CDAI and OD in the general adult population. A cross-sectional study used data from the National Health and Nutrition Examination Survey (n = 1624; >20 y of age). A multivariate logistic regression model examined the connection between CDAI and OD. Smooth-fitted curves were used to investigate the nonlinear relationship between CDAI and OD. A threshold effect analysis was then used to pinpoint the inflection point. Subgroup analyses were conducted based on gender and age. Multivariate regression analysis revealed a negative correlation between CDAI and OD. After controlling for variables, the risk of OD in the highest quartile of CDAI was significantly lower than in the lowest quartile (Q1) (odds ratio = 0.64; 95% confidence interval, 0.44-0.92; P = .0148). Stratified analysis indicated a significant association between CDAI and OD in individuals younger than age 60 years and male. This research suggests that increasing the co-ingestion of antioxidants within a moderate range can reduce the incidence of OD.

Association between peripheral eosinophilia, JESREC score, and olfactory dysfunction in patients with chronic rhinosinusitis.

Objective: The purpose was to evaluate the relationship between peripheral eosinophilia, Japan Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, and olfactory dysfunction in chronic rhinosinusitis (CRS) patients and to explore the accuracy and specific cut points of the JESREC score in predicting olfactory dysfunction. Methods: In this cross-sectional, retrospective study, olfactory function was assessed by the Sniffin' Sticks 12-item test and multivariate logistic regression analyses were carried out. Receiver operating characteristic curves were plotted to derive accuracy and cutoff values for the JESREC scores of the olfactory dysfunction criterion. Results: A total of 354 patients [mean (SD) age, 50.0 (14.9) years; 41.8% women] were included in the final analysis. The prevalence of olfactory dysfunction was 46.3%. Individuals who had olfactory dysfunction were more likely to be male (64.6% vs. 52.6%), have eosinophilic chronic rhinosinusitis (ECRS) (39.0% vs. 7.9%), have a longer course of CRS (2.3 years vs. 1.5 years), have higher JESREC scores (8.5 vs. 4.5), and have higher proportions of nasal polyps (78.7% vs. 18.9%) and peripheral eosinophilia (3.3% vs. 1.4%). In logistic analysis, the percentage of eosinophils (1.25, 1.13-1.37), JESREC score (1.31, 1.22-1.40), bilateral lesion (2.06, 1.25-3.41), nasal polyps (15.83, 9.23-27.16), CT shadow (2.73, 1.69-4.43), and ECRS (6.86, 3.68-12.80) were associated with olfactory dysfunction in CRS patients after controlling for covariates, while peripheral neutrophils were not significant. In addition, the area under the curve was 0.778 and the cutoff value for JESREC score for olfactory dysfunction was defined as 5.5. Conclusions: Peripheral eosinophilia and high JESREC scores were significantly associated with the risk of olfactory dysfunction in CRS patients, and special attention should be paid to patients with a JESREC score ≥6.

Association between dietary zinc intake and olfactory dysfunction: a study based on the NHANES database.

OBJECTIVE: The primary objective of this study was to find the association between dietary zinc intake and the prevalence of olfactory disorders using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: A cross-sectional study was conducted using the 2013-2014 NHANES data. A linear regression model was constructed with dietary zinc intake as the independent variable and olfactory dysfunction as the dependent variable. Initially, in the unadjusted model, weighted logistic regression analysis was carried out for continuous variables, and stratified analysis was conducted for categorical variables. Subsequently, three models were created to perform subgroup analysis by adjusting for different confounding factors, further investigating the relationship between dietary zinc intake and olfactory dysfunction. Finally, restricted cubic spline (RCS) models adjusting for all confounding factors were utilized to study the nonlinear associations of age and dietary zinc intake with olfactory dysfunction and their relevant thresholds. RESULTS: A total of 2958 samples were analyzed in this study. Weighted logistic regression analysis displayed a negative relationship between dietary zinc intake and the prevalence of olfactory dysfunction in the population of non-Hispanic whites and other Hispanics, as well as in individuals with body mass index (BMI) ≥ 25 kg/m2 (OR < 1, P < 0.05). The P values for the multiplicative interaction terms adjusting for all confounding factors were not significant (P for interaction > 0.05). In the three regression models adjusting for different confounding factors, dietary zinc intake was significantly negatively related to olfactory dysfunction in all populations (Crude: OR 0.63, 95% CI 0.44-0.91; Model I: OR 0.58, 95% CI 0.38-0.90; Model II: OR 0.59, 95% CI 0.35-1.00). Subgroup analysis based on BMI showed a remarkable negative relationship between dietary zinc intake and olfactory dysfunction in the group with BMI of 25-30 kg/m2 (Crude: OR 0.50, 95% CI 0.28-0.90, P = 0.012; Model I: OR 0.49, 95% CI 0.24-1.00, P = 0.021) and the group with BMI ≥ 30 kg/m2 (Crude: OR 0.55, 95% CI 0.33-0.92, P = 0.013; Model I: OR 0.51, 95% CI 0.29-0.88, P = 0.005; Model II: OR 0.51, 95% CI 0.29-0.91, P = 0.004). RCS analysis revealed a remarkable nonlinear association of age and dietary zinc intake with olfactory dysfunction (P-non-linear < 0.05). The prevalence of olfactory dysfunction was considerably higher in individuals aged 60 and above compared to those under 60 years old. Daily dietary zinc intake within the range of 9.60-17.45 mg was a protective factor for olfactory dysfunction, while intake outside this range increased the prevalence of olfactory dysfunction. CONCLUSION: Daily dietary zinc intake within the range of 9.60-17.45 mg has a protective effect against olfactory dysfunction. Intake outside this range increases the prevalence of olfactory dysfunction. The prevalence of olfactory dysfunction is significantly higher in individuals aged 60 and above compared to those under 60 years old. For individuals with a BMI of 25-30 kg/m2 and a BMI ≥ 30 kg/m2, dietary zinc intake is negatively correlated with olfactory dysfunction. Therefore, it is recommended that these populations increase their dietary zinc intake to develop healthier lifestyles and maintain olfactory health.

Associations between olfactory dysfunction and cognition: a scoping review.

INTRODUCTION: Strong evidence suggests that olfactory dysfunction (OD) can predict additional neurocognitive decline in neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. However, research exploring olfaction and cognition in younger populations is limited. The aim of this review is to evaluate cognitive changes among non-elderly adults with non-COVID-19-related OD. METHODS: We performed a structured comprehensive literature search of PubMed, Ovid Embase, Web of Science, and Cochrane Library in developing this scoping review. The primary outcome of interest was the association between OD and cognitive functioning in adults less than 60 years of age. RESULTS: We identified 2878 studies for title and abstract review, with 167 undergoing full text review, and 54 selected for data extraction. Of these, 34 studies reported on populations of individuals restricted to the ages of 18-60, whereas the remaining 20 studies included a more heterogeneous population with the majority of individuals in this target age range in addition to some above the age of 60. The etiologies for smell loss among the included studies were neuropsychiatric disorders (37%), idiopathic cause (25%), type 2 diabetes (7%), trauma (5%), infection (4%), intellectual disability (4%), and other (18%). Some studies reported numerous associations and at times mixed, resulting in a total number of associations greater than the included number of 54 studies. Overall, 21/54 studies demonstrated a positive association between olfaction and cognition, 7/54 demonstrated no association, 25/54 reported mixed results, and only 1/54 demonstrated a negative association. CONCLUSION: Most studies demonstrate a positive correlation between OD and cognition, but the data are mixed with associations less robust in this young adult population compared to elderly adults. Despite the heterogeneity in study populations and outcomes, this scoping review serves as a starting point for further investigation on this topic. Notably, as many studies in this review involved disorders that may have confounding effects on both olfaction and cognition, future research should control for these confounders and incorporate non-elderly individuals with non-psychiatric causes of smell loss.

Olfactory and Gustatory Function 3 Years After Mild COVID-19-A Cohort Psychophysical Study.

This case-control study estimates the 3-year prevalence of measured olfactory dysfunction and gustatory dysfunction associated with SARS-CoV-2 infection.

The combination of olfactory dysfunction and depression increases the risk of incident dementia in older adults.

OBJECTIVES: Olfactory dysfunction and depression are common in later life, and both have been presented as risk factors for dementia. Our purpose was to investigate the associations between these two risk factors and determine if they had an additive effect on dementia risk. DESIGN: Olfactory function was assessed using the Brief Smell Identification Test (BSIT), and depression was classified using a combination of the 15-item Geriatric Depression Scale (GDS) score and current antidepressant use. Cross-sectional associations between depression and olfactory function were examined using correlations. Cox regression analyses were conducted to examine the longitudinal relationship between olfaction and depression and incident dementia across 12-years of follow-up. PARTICIPANTS: Participants were 780 older adults (aged 70-90 years; 56.5% female) from the Sydney Memory and Ageing Study (MAS) without a diagnosis of dementia at baseline. RESULTS: Partial correlation revealed a nonsignificant association between baseline depression and olfactory function after accounting for covariates (r = -.051, p = .173). Cox regression showed that depression at baseline (hazard ratio = 1.706, 95% CI 1.185-2.456, p = .004) and lower BSIT scores (HR = .845, 95%CI .789-.905, p < .001) were independently associated with a higher risk of incident dementia across 12 years. Entering both predictors together improved the overall predictive power of the model. CONCLUSIONS: Lower olfactory identification scores and depressive symptoms predict incident dementia over 12 years. The use of BSIT scores and depression in conjunction provides a greater ability to predict dementia than either used alone. Assessment of olfactory function and depression screening may provide clinical utility in the early detection of dementia.

Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

An Explanation for Reports of Increased Prevalence of Olfactory Dysfunction With Omicron: Asymptomatic Infections.

The prevalence of olfactory dysfunction (OD) in people infected with the Omicron variant is substantially reduced compared with previous variants. However, 4 recent studies reported a greatly increased prevalence of OD with Omicron. We provide a likely explanation for these outlier studies and reveal a major methodological flaw. When the proportion of asymptomatic infections is large, studies on the prevalence of OD will examine and report predominantly on nonrepresentative cohorts, those with symptomatic subjects, thereby artificially inflating the prevalence of OD by up to 10-fold. Estimation of the true OD prevalence requires representative cohorts that include relevant fractions of asymptomatic cases.

Reduction in olfactory dysfunction prevalence among patients with diabetes taking metformin.

KEY POINTS: Metformin treatment is associated with reduced olfactory dysfunction (OD) in diabetic patients Metformin may possess potential protective effects on olfaction beyond glycemic control.

Evidence for a role of metformin in preventing olfactory dysfunction among older adults.

BACKGROUND: Olfactory dysfunction (OD) is increasingly recognized as a hallmark of unhealthy aging and is intimately associated with mortality, but therapies remain elusive. Recognizing the increased prevalence of OD in individuals with diabetes, and the potential anti-aging effects of metformin, we studied the association of metformin use with OD. METHODS: Cross-temporal study of participants from Waves 2 (2010-11) and 3 (2015-16) of the National Social Life, Health, and Aging Project (NSHAP), a nationally representative cohort study of community-dwelling older adults. We included participants with diabetes who had complete data on olfaction and relevant covariates at Wave 2 and were not lost to follow-up at Wave 3. Olfactory identification (OI), the ability to identify the odorant, and olfactory sensitivity (OS), the ability to detect the presence of an odorant, were tested. Weighted multivariable logistic regression was used to study the association between metformin use at Wave 2 (baseline) and odds of having impaired OI/OS at Wave 3, adjusted for age, sex, race/ethnicity, education, smoking, BMI, HbA1c, years since diabetes diagnosis, and insulin use. RESULTS: Among 228 participants with diabetes (mean age=70 years, 53% female, 21% Black), 112 (49%) used metformin at baseline. Relative to nonusers, users had 58% lower odds of impaired OI and 67% lower odds of impaired OS at Wave 3. Among participants with normal baseline OS (N=62), users had 97% lower odds of impaired OS at Wave 3. CONCLUSIONS: Metformin use is associated with lower odds of OD among individuals with diabetes, suggesting a potential protective effect on olfaction. Future work including a larger sample and additional information on metformin use is needed to establish whether these findings are independent of diabetic control.

Olfactory-Related Adverse Events: An Analysis of the Food and Drug Administration Adverse Events Reporting System.

OBJECTIVE: Olfactory dysfunction has gained considerable interest with its association to the coronavirus pandemic. Due to the limited literature on olfactory-related adverse events (ORAE) associated with medications, this study investigated ORAE reported in the Food and Drug Administration Adverse Event Reporting System (FAERS) to identify the most frequent medications associated with these reactions. STUDY DESIGN: Cross-sectional analysis SETTING: FAERS database. METHODS: The FAERS database was accessed to obtain ORAEs from 2012 to 2022. Disproportionality analysis was conducted by calculating the proportional reporting ratios (PRR) and reporting odds ratio (ROR) for anosmia, parosmia, hyposmia, and olfactory dysfunction. A PRR > 2 or ROR > 1 was significant. A multivariate logistical model was used to estimate adjusted ROR for gender and country of origin. RESULTS: Our final study population consisted of 1111 cases with the following symptoms: anosmia (672), parosmia (364), hyposmia (71), and olfactory dysfunction (4). The most significant ROR signal scores were found for secukinumab (3.42; 95% confidence interval, CI [1.9, 4.01]) for anosmia, levofloxacin (8.86; 95% CI [2.83, 9.8]) for hyposmia, and pregabalin (6.88; 95% CI [2.23, 8.01]) for parosmia. No significant PRR signal scores were found for anosmia, but significant signals were found for citalopram hydrobromide (17.25; 95% CI [17.01, 17.49]) in hyposmia, and dimethyl fumarate (3.18; 95% CI [3.09, 3.27]) in parosmia. No valid PRR or ROR values were found for olfactory dysfunction. Multivariate analysis did not reveal statistically significant differences between genders for any symptoms, but individuals from non-US countries did exhibit statistically significant elevated risk of anosmia (1.3 (95% CI [1.01, 1.68]). CONCLUSION: Pharmacovigilance studies provide an opportunity to evaluate the safety profile of medications regarding ORAE, particularly for those commonly prescribed for sinonasal symptoms. Findings from this study may function as a resource for prescribers and patients.