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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. [ABSTRACT FROM AUTHOR]

Summary: Olfaction plays a priming role in both the anticipation and consumption phases of eating behavior. Olfactory dysfunction can therefore lead to changes in various aspects of eating behavior, such as food choice, appetite, and food intake. In light of the increasing prevalence of persistent olfactory dysfunction among patients affected by Covid-19, providing proper care and dietary advice to individuals with olfactory dysfunction is imperative. Therefore, this scoping review seeks to gain a better understanding of the impact of olfactory dysfunction on eating behavior. Following the PRISMA guidelines, 49 papers were included, the outcomes were presented by dividing them into two categories: 1) anticipatory eating behavior, including (anticipatory) food liking, appetite and craving, food preferences, food neophobia, and cooking habits; and 2) consummatory behavior, including, food intake, consumption frequency, adherence to dietary guidelines, (experienced) food liking, food enjoyment, and eating habits. Our results show that in the anticipatory phase of eating behavior, food liking, and, food preferences, and in the consummatory phase, food enjoyment is most affected in people who experienced a sudden change in olfactory function rather than a gradual decline. Moreover, changes in food flavor perception due to olfactory dysfunction, result in a shift of food preferences towards more “taste-based” preferences, such as salty or savory (i.e., umami) foods. Subsequently, changes in preferences can affect food intake and adherence to dietary guidelines, but only to a limited extent. Appetite is more likely to be low in individuals with short-term olfactory dysfunction compared to those with long-term changes. Generally, eating behavior is more impacted in individuals with a distorted sense of smell than in those with smell loss, and the effect becomes more pronounced over time. Due to the heterogeneity of methods used to measure different aspects of eating behavior, this review stresses the importance of more research on olfaction and eating behavior using standardized and validated assessments. Such research is essential to better understand the effects of olfactory dysfunction on each aspect of eating behavior and provide effective interventions.

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

IntroductionThe 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.MethodsThis 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.ResultsA 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.ConclusionOlfactory 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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

Abstract 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.

Among the effects of COVID-19 are taste and smell disorders, which have occurred in a significant number of sick people. It is believed that the impairment of these senses may be long term. The aim of our research was to investigate the impact of COVID-19 disease on the ability to recognize tastes among students at the Rzeszów University of Technology. The research was conducted on a sample of students who declared that they had or had not suffered from COVID-19. The assessment of the ability to recognize flavors – that is, taste color blindness – was carried out based on the methodology recommended by the Polish Committee for Standardization [PN ISO3972]. The research, which involved 68 women and 74 men, was carried out in a laboratory adapted for this purpose, meeting the requirements specified in the standard [PN ISO 8589]. The tests took place in the morning (9 a.m.–12 p.m.). Taste recognition ability was assessed using a set of aqueous solutions of citric acid (0.43 g/L), sucrose (5.76 g/L), sodium chloride (1.19 g/L) and caffeine (0.195 g/L). The collected questionnaires were based on a standard approach to food quality analysis, and the data obtained were analyzed in the Statistica 13.3 program. It was observed that, in the studied group of students, the percentage of people who declared COVID-19 disease was high (69%). In this group, the majority of respondents (51%) described the course of the disease as mild. Among the respondents, 63.3% indicated a loss of taste, while slightly more (69.4%) declared a loss of smell. The analysis of data regarding the ability to correctly recognize individual tastes indicates that gender influenced the ability to recognize sweet and bitter tastes. Statistically, significantly more men misidentified these flavors. The impact of COVID-19 infection on the ability to identify the analyzed flavors was moderate and was confirmed only for salty and bitter tastes. Therefore, the ability to perceive important qualitative factors of food products was impaired.

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 (η2 = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 χ2 = 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 (rs = 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.

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.

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 [ABSTRACT FROM AUTHOR]

Background and objectivesCOVID-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 methodsAn 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.ResultsIn 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.ConclusionThis 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Olfactory dysfunction (OD) is a common symptom of Corona Virus Disease 2019 (COVID-19). It is defined as the reduced or distorted ability to smell during sniffing (orthonasal olfaction) and represents one of the early symptoms in the clinical course of COVID-19 infection. A large online questionnaire-based survey has shown that some post-COVID-19 patients had no improvement 1 month after discharge from the hospital. Objective: To explore the efficacy of acupuncture for OD in COVID-19 infected patients and to determine whether acupuncture could have benefits over sham acupuncture for OD in post-COVID-19 patients. Methods: This is a single-blind, randomized controlled, cross-over trial. We plan to recruit 40 post-COVID-19 patients with smell loss or smell distortions lasting for more than 1 month. Qualified patients will be randomly allocated to the intervention group (real acupuncture) or the control group (sham acupuncture) at a 1:1 ratio. Each patient will receive 8 sessions of treatment over 4 weeks (Cycle 1) and a 2-week follow-up. After the follow-up, the control group will be subjected to real acupuncture for another 4 weeks (Cycle 2), and the real acupuncture group will undergo the 4-week sham acupuncture. The primary outcomes will be the score changes on the questionnaire of olfactory functioning and olfaction-related quality of life at week 6, 8, 12, and 14 from the baseline. The secondary outcomes will be the changes in the olfactory test score at week 6 and 12 from the baseline measured by using the Traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). Discussion: The results of this trial will help to determine the effectiveness of acupuncture for OD in post-COVID-19 patients. This may provide a new treatment option for patients.

The association of smell and taste loss with COVID-19 has been well demonstrated with high prevalence rates. In certain cases, chemosensory loss may be the only symptom of COVID-19 and may linger while other symptoms have resolved. The significance of persistent smell and taste loss and its relationship to ongoing viral shedding has yet to be investigated. In this cross-sectional study, of the 316 laboratory test-confirmed COVID-19 cases at our institution, 46 had subsequent test-based confirmation of viral clearance with 2 consecutive negative RT-PCR test results (reverse transcriptase polymerase chain reaction). Olfactory dysfunction was reported by 50% of the patients (23 of 46), with 78% (18 of 23) having subjective persistent smell loss despite negative RT-PCR test results. These preliminary data demonstrate the persistence of self-reported smell loss despite otherwise clinical resolution and undetectable nasal viral RNA.

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.

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. [ABSTRACT FROM AUTHOR]

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases.MethodsA single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity.ResultsA total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness.ConclusionIn ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus has left many health systems around the world overwhelmed, forcing triaging of scarce medical resources. Identifying indicators of hospital admission for coronavirus disease 2019 (COVID-19) patients early in the disease course could aid the efficient allocation of medical interventions. Self-reported olfactory impairment has recently been recognized as a hallmark of COVID-19 and may be an important predictor of clinical outcome.MethodsA retrospective review of all patients presenting to a San Diego Hospital system with laboratory-confirmed positive COVID-19 infection was conducted with evaluation of olfactory and gustatory function and clinical disease course. Univariable and multivariable logistic regression were performed to identify risk factors for hospital admission and anosmia.ResultsA total of 169 patients tested positive for COVID-19 disease between March 3 and April 8, 2020. Olfactory and gustatory data were obtained for 128 (75.7%) of 169 subjects, of which 26 (20.1%) of 128 required hospitalization. Admission for COVID-19 was associated with intact sense of smell and taste, increased age, diabetes, and subjective and objective parameters associated with respiratory failure. On adjusted analysis, anosmia was strongly and independently associated with outpatient care (adjusted odds ratio [aOR] 0.09; 95% CI, 0.01-0.74), whereas positive findings of pulmonary infiltrates and/or pleural effusion on chest radiograph (aOR 8.01; 95% CI, 1.12-57.49) was strongly and independently associated with admission.ConclusionNormosmia is an independent predictor of admission in COVID-19 cases. Smell loss in COVID-19 may be associated with a milder clinical course.

BackgroundOlfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia.MethodsSeven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months.ResultsAll patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI  16 but  30) at 3-month follow-up. On average, patients with baseline TDI > 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections.ConclusionPRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.Level of evidence 2b

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. [ABSTRACT FROM AUTHOR]

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. The underlying mechanisms of the loss of smell in COVID-19 can be narrowed down to five plausible scenarios in the olfactory epithelium, which are not mutually exclusive. One series of mechanisms focuses on the primary target of SARS-CoV-2 in the olfactory epithelium, the support cells, which provide the mucus to dissolve odorants and the energy required for olfactory cilia to power olfactory signal transduction, as well as a putative maintenance factor for cilia. A second set of scenarios emphasizes changes in gene expression in olfactory receptor neurons, which may be linked to the loss of cilia, causing the neurons to become immature-like. Both viral and host factors modulate the prevalence of olfactory dysfunction, with the omicron variant preferring an endosomal route that enters support cells less efficiently, resulting in a relative sparing of olfaction in patients with this variant. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Original article: Butowt R, von Bartheld CS. Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection. Neuroscientist. 2021;27(6):582-603. DOI: 10.1177/1073858420956905 The article was translated into Russian and published under the terms of the Creative Commons Attribution 4.0 license.

BackgroundThe 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).MethodsFor 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.ResultsEmotional, 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).ConclusionClinical 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.

Of those 85 patients, 14 patients (16.5%, male to female = 1:13, mean age 41.2 [16-67] years, mean pretreatment UPSIT score = 20.9 ± 7.5) identified parosmia as a major complaint after COVID-19 infection. Keywords: coronavirus 2019; COVID19; gabapentin; olfaction; olfactory dysfunction; parosmia; smell Loss EN coronavirus 2019 COVID19 gabapentin olfaction olfactory dysfunction parosmia smell Loss 1034 1036 3 05/29/23 20230601 NES 230601 INTRODUCTION Postviral olfactory dysfunction (PVOD) has significantly increased in incidence since the rise of coronavirus disease 2019 (COVID-19), resulting in anosmia (complete loss), hyposmia (partial loss), phantosmia (dysfunction of smell in the absence of an odor), or parosmia (distorted perception of smell) with limited evidence for proposed treatments.[[1]] Olfactory disorders have been linked with a negative impact on emotions, interpersonal relationships, and overall health, as well as increased mortality.[[3]] Parosmia, typically a foul or rotten odor, can be significantly distressing and dangerous as patients may no longer enjoy or tolerate previously pleasant or innocuous scents that they regularly encounter. Gabapentin improves parosmia after COVID-19 infection. [Extracted from the article]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Evidence regarding prevalence of COVID-19 related Olfactory dysfunction (OD) among ambulatory patients is highly variable due to heterogeneity in study population and measurement methods. Relatively few studies have longitudinally investigated OD in ambulatory patients with objective methods. Methods: We performed a longitudinal study to investigate OD among COVID-19 ambulatory patients compared to symptomatic controls who test negative. Out of 81 patients enrolled, 45 COVID-19 positive patients and an age- and sex-matched symptomatic control group completed the BSIT and a questionnaire about smell, taste and nasal symptoms. These were repeated at 1 month for all COVID-19 positive patients, and again at 3 months for those who exhibited persistent OD. Analysis was performed by mixed-effects linear and logistic regression. Results: 46.7% of COVID-19 patients compared to 3.8% of symptomatic controls exhibited OD at 1-week post diagnosis. At 1 month, 16.7%, (6 of 36), of COVID-19 patients had persistent OD. Mean improvement in BSIT score in COVID-19 patients between 1-week BSIT and 1 month follow-up was 2.0. OD did not correlate with nasal congestion. Conclusions: Ambulatory COVID-19 patients exhibited OD significantly more frequently than symptomatic controls. Most patients regained normal olfaction by 1 month. The BSIT is a simple validated and objective test to investigate the prevalence of OD in ambulatory patients. OD did not correlate with nasal congestion which suggests a congestion-independent mechanism of OD.

Post-COVID syndrome can be defined as symptoms of COVID-19 that persist for longer than 12 weeks, with several studies reporting persistent symptoms relating to the sensory organs (eyes, ears, and nose). The aim of this systematic review was to examine the prevalence of persistent anosmia, hyposmia, ageusia, and hypogeusia, as well as eye/vision and ear/hearing related long-COVID symptoms. Authors searched the electronic databases from inception to November 2021. Search terms included words related to long-COVID, smell, taste, eyes/vision, and ears/hearing, with all observational study designs being included. A random effects meta-analysis was undertaken, calculating the prevalence proportions of anosmia, hyposmia, ageusia, and hypogeusia, respectively. From the initial pool, 21 studies met the inclusion criteria (total n 4,707; median n per study 125; median age = 49.8; median percentage female = 59.2%) and 14 were included in the meta-analysis The prevalence of anosmia was 12.2% (95% CI 7.7–16.6%), hyposmia 29.9% (95% CI 19.9–40%), ageusia 11.7% (95% CI 6.1–17.3%), and hypogeusia 31.2% (95% 16.4–46.1%). Several eye/vision and ear/hearing symptoms were also reported. Considering that changes in the sensory organs are associated with decreases in quality of life, future research should examine the etiology behind the persistent symptoms.Systematic review registration[www.crd.york.ac.uk/prospero], identifier [CRD42021292804].

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.

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.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has caused recurring and major outbreaks in multiple human populations around the world. The plethora of clinical presentations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been described extensively, of which olfactory dysfunction (OD) was established as an important and common extrapulmonary manifestation of COVID-19 infection. The aim of this protocol is to conduct a systematic review and meta-analysis on peer-reviewed articles which described clinical data of OD in COVID-19 patients. Methods This research protocol has been prospectively registered with the Prospective Register of Systematic Reviews (PROSPERO; CRD42020196202). CINAHL, ClinicalTrials.gov, Cochrane Central, EMBASE, MEDLINE and PubMed, as well as Chinese medical databases China National Knowledge Infrastructure (CNKI), VIP and WANFANG, will be searched using keywords including ‘COVID-19’, ‘coronavirus disease’, ‘2019-nCoV’, ‘SARS-CoV-2’, ‘novel coronavirus’, ‘anosmia’, ‘hyposmia’, ‘loss of smell’, and ‘olfactory dysfunction’. Systematic review and meta-analysis will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines. Articles will be screened according to pre-specified inclusion and exclusion criteria to extract studies that include new clinical data investigating the effect of COVID-19 on olfactory dysfunction. Included articles will be reviewed in full; data including patient demographics, clinical characteristics of COVID-19-related OD, methods of olfactory assessment and relevant clinical outcomes will be extracted. Statistical analyses will be performed using the Comprehensive Meta-Analysis version 3. Discussion This systematic review and meta-analysis protocol will aim to collate and synthesise all available clinical evidence regarding COVID-19-related OD as an important neurosensory dysfunction of COVID-19 infection. A comprehensive search strategy and screening process will be conducted to incorporate broad clinical data for robust statistical analyses and representation. The outcome of the systematic review and meta-analysis will aim to improve our understanding of the symptomatology and clinical characteristics of COVID-19-related OD and identify knowledge gaps in its disease process, which will guide future research in this specific neurosensory defect. Systematic review registration PROSPERO registration number: CRD42020196202.