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Objective: While most patients with COVID-19-induced olfactory dysfunction (OD) recover spontaneously, those with persistent OD face significant physical and psychological sequelae. ChatGPT, an artificial intelligence chatbot, has grown as a tool for patient education. This study seeks to evaluate the quality of ChatGPT-generated responses for COVID-19 OD. Study Design: Quantitative observational study. Setting: Publicly available online website. Methods: ChatGPT (GPT-4) was queried 4 times with 30 identical questions. Prior to questioning, Chat-GPT was "prompted" to respond (1) to a patient, (2) to an eighth grader, (3) with references, and (4) no prompt. Answer accuracy was independently scored by 4 rhinologists using the Global Quality Score (GCS, range: 1-5). Proportions of responses at incremental score thresholds were compared using χ 2 analysis. Flesch-Kincaid grade level was calculated for each answer. Relationship between prompt type and grade level was assessed via analysis of variance. Results: Across all graded responses (n = 480), 364 responses (75.8%) were "at least good" (GCS ≥ 4). Proportions of responses that were "at least good" (P < .0001) or "excellent" (GCS = 5) (P < .0001) differed by prompt; "at least moderate" (GCS ≥ 3) responses did not (P = .687). Eighth-grade level (14.06 ± 2.3) and patient-friendly (14.33 ± 2.0) responses were significantly lower mean grade level than no prompting (P < .0001). Conclusion: ChatGPT provides appropriate answers to most questions on COVID-19 OD regardless of prompting. However, prompting influences response quality and grade level. ChatGPT responds at grade levels above accepted recommendations for presenting medical information to patients. Currently, ChatGPT offers significant potential for patient education as an adjunct to the conventional patient-physician relationship.

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Kallmann syndrome is an anosmic variety of GnRH (gonadotropin-releasing hormone) deficiency. A young adult male with anosmia since childhood presented with features of failed sexual maturation and underwent an ultrasound of the genital system and an MRI (magnetic resonance imaging) of the brain. MRI revealed absent olfactory bulbs in bilateral olfactory grooves with hypoplastic olfactory sulci on both sides. Ultrasound showed atrophic testes, while the anterior pituitary appeared normal on MRI. The clinical, hormonal, and imaging findings were characteristic of Kallmann syndrome. MRI serves as a crucial tool in its diagnosis.

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OBJECTIVES: Upper respiratory tract infections, including COVID-19, are associated with olfactory dysfunction and there is a need for novel therapeutic approaches. The aim of study was evaluating the effectiveness of adding melatonin, multivitamin and sodium citrate to olfactory training for the treatment of olfactory loss caused by COVID-19. METHODS: We evaluated olfactory function using University of Pennsylvania Smell Identification Test (UPSIT ®) scores and self-reported patient outcomes in post-infectious smell loss cases. We investigated the effectiveness involved olfactory training combined with sodium citrate, melatonin, and multivitamin supplements with zinc over a three-month period compared to an olfactory training alone. RESULTS: A total of 66 patients were included, with 33 in each group. There was no significant difference in the proportion of participants who showed improvement in UPSIT scores between the groups (OR = 1.43, 95% CI 0.43-4.8, p =  0.56). Both groups showed improvement in average test scores, but there were no significant differences in self-reported olfactory ability or discomfort with olfactory loss. Qualitative symptoms, such as parosmia and phantosmia, were reported by a similar proportion in both groups before and after the treatment (p =  0.11, p =  1, respectively). CONCLUSIONS: Olfactory training alone and olfactory training with associated with melatonin, multivitamins and topical sodium citrate did not show significant differences in improving olfactory function in post-COVID-19 patients.

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The psychophysical Sniffin' Sticks test, which includes an odor identification test, is the gold standard for assessing the sense of smell in clinical and scientific practice. A necessary requirement for the odor identification test is a close familiarity with the odors used by the inhabitants of the region in which it is used. We studied 77 healthy volunteers and 51 patients with olfactory dysfunction and we found that Russians are not familiar with the three smells from the test (licorice, turpentine and anise) and are completely unfamiliar with the one proposed alternative answer (chives). Moreover, four odors demonstrated very low recognition (less than 75%). The test has been adapted for the use In Russia. In the booklet, licorice is replaced by cough syrup, turpentine by paint thinner, and chives by bay leaf. For odors with low recognition (lemon, apple, pineapple), the alternative fruity odors in the booklet were replaced with more contrasting ones. Based on the data obtained, we are going to develop a domestic version of the odor identification test.

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PURPOSE: To assess the short-term effects of topical platelet-rich plasma (PRP) injection on persistent refractory olfactory dysfunction. METHODS: A comprehensive literature search of the PubMed, SCOPUS, EMBASE, Web of Science, Google Scholar, and Cochrane databases was conducted for articles up to November 2023. The search focused on studies that compared the amelioration of olfactory dysfunction between a topical PRP treatment cohort and a control group (receiving either placebo or no treatment), along with pre- and post-treatment comparisons. Subgroup analysis of the evaluation of olfactory function was also performed. RESULTS: The improvement in olfactory scores 1-3 months post-treatment (standardized mean difference = 1.5354 [95% confidence interval: 0.7992; 2.2716], I2 = 83.8%) was greater in the treatment group than in the control group. In the treatment group, PRP increased the threshold, discrimination, and identification (TDI) score for Sniffin' Sticks by > 5.5 (minimum clinically significant difference; mean difference = 6.1789 [3.9788; 8.3789], I2 = 0.0%), indicating clinically significant improvement based on verified examinations. The rate of significant improvement among patients was 0.6683 [0.5833; 0.7436] after treatment. All TDI subdomains were significantly and similarly improved after treatment. CONCLUSION: This meta-analysis suggests that injection of PRP into the olfactory fissure or surrounding mucosal areas is an effective treatment for persistent refractory olfactory dysfunction in the short term.

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Olfactory perception is an important physiological function for human well-being and health. Loss of olfaction, or anosmia, caused by viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received considerable attention, especially in persistent cases that take a long time to recover. This review discusses the integration of different components of the olfactory epithelium to serve as a structural and functional unit and explores how they are affected during viral infections, leading to the development of olfactory dysfunction. The review mainly focused on the role of receptors mediating the disruption of olfactory signal transduction pathways such as angiotensin converting enzyme 2 (ACE2), transmembrane protease serine type 2 (TMPRSS2), neuropilin 1 (NRP1), basigin (CD147), olfactory, transient receptor potential vanilloid 1 (TRPV1), purinergic, and interferon gamma receptors. Furthermore, the compromised function of the epithelial sodium channel (ENaC) induced by SARS-CoV-2 infection and its contribution to olfactory dysfunction are also discussed. Collectively, this review provides fundamental information about the many types of receptors that may modulate olfaction and participate in olfactory dysfunction. It will help to understand the underlying pathophysiology of virus-induced anosmia, which may help in finding and designing effective therapies targeting molecules involved in viral invasion and olfaction. To the best of our knowledge, this is the only review that covered all the receptors potentially involved in, or mediating, the disruption of olfactory signal transduction pathways during COVID-19 infection. This wide and complex spectrum of receptors that mediates the pathophysiology of olfactory dysfunction reflects the many ways in which anosmia can be therapeutically managed.

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OBJECTIVE: To compare, using state-of-the-art psychophysical tests, the olfactory function of patients complaining and not complaining of olfactory hypersensitivity. STUDY DESIGN: Retrospective cross-sectional. SETTING: The Smell and Taste Center at the University of Pennsylvania. METHODS: University of Pennsylvania Smell Identification Test (UPSIT) scores were obtained from 148 patients complaining of hyperosmia and 494 patients with no such complaints; detection threshold test scores were obtained from 77 and 483 patients of these respective groups. The effects of subject group, age, and sex on the test scores were assessed using analyses of variance. Categorical variables were evaluated by χ2. Responses to items within a detailed intake questionnaire, for example, the Beck Depression Inventory (BDI-II), were also evaluated. RESULTS: Unexpectedly, those complaining of hyperosmia had lower olfactory test scores than those with no such complaints (respective UPSIT means [95% confidence interval [CIs]] = 27.86 (26.85, 28.87) and 32.19 (31.67, 32.71); P < .001; respective threshold means (log vol/vol) = -4.49 (-4.89, -4.09) and -5.22 (-5.36, -5.06); P < .001). Remarkably, 70.95% of the self-identified hyperosmics exhibited mild to severe microsmia. The hyposmia complainers also exhibited elevated BDI scores (11.02 [9.53, 12.51] vs 7.58 [6.80, 8.34]). CONCLUSION: When objectively tested, many patients who complain of hypersensitivity to odors are actually less sensitive to them. The basis of this phenomenon is unclear. It could reflect the presence of emotionally disturbing altered smell sensations, or one or more comorbidities, such as hypochondria or osmophobia. These findings point to the importance of objective testing of persons with complaints of chemosensory dysfunction and reiterate the inaccuracy of self-reports.

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INTRODUCTION: Persistent post-COVID olfactory dysfunction continues to be studied due to the controversy in its pathophysiology and neuroimaging. MATERIALS AND METHODS: The patients had confirmed mild COVID-19 infection with olfactory dysfunction of more than one month of evolution and they were compared to controls with normal olfaction, assessed using the Sniffin' Sticks Olfactory Test and underwent brain, magnetic resonance imaging (MRI) of the olfactory bulb and olfactory function. RESULTS: A total of 8 patients and 2 controls participated. The average age of the patients was 34.5 years (SD 8.5), and that of the controls was 28.5 (SD 2.1). The average score in the patients' olfactory test was 7.9 points (SD 2.2). In brain and olfactory bulb MRI tests, no morphological differences were found. When evaluated by functional MRI, none of the patients activated the entorhinal area in comparison to the controls, who did show activation at this level. Activation of secondary olfactory areas in cases and controls were as follows: orbitofrontal (25% vs 100%), basal ganglia (25% vs 50%) and insula (38% vs 0%) respectively. CONCLUSIONS: There were no observed morphological changes in the brain MRI. Unlike the controls, none of the patients activated the entorhinal cortex in the olfactory functional MRI.

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Background: Isolated hypogonadotropic hypogonadism is a heterogeneous clinical entity. There is a growing list of molecular defects that are associated with hypogonadotropic hypogonadism (HH). TCF12, a recently identified molecular defect, causes craniosynostosis and is suggested to be used as a biomarker for prognosis in various cancer types. Recently, TCF12 variants were shown in a cohort with HH. Case presentation: A 15.3 years old female patient was referred to the endocrinology clinic for obesity. She had been gaining weight from mid-childhood. She had her first epileptic seizure at the age of 15.1 years and mildly elevated thyroid autoantibodies were detected during evaluation for etiology of seizures. She had not experienced menarche yet. She was operated for left strabismus at the age of 7 years. School performance was poor and she was receiving special education. Tanner stage of breast was 1 and pubic hair was 3. The endocrine workup revealed hypogonadotropic hypogonadism. Also, the Sniffin' Sticks test detected anosmia. Thyroid ultrasonography was performed due to the mildly elevated thyroid autoantibodies, and thyroid nodules with punctate calcifications were detected. Total thyroidectomy and central lymph node dissection were performed regarding the cytological findings of the nodules and multicentric papillary thyroid carcinoma with no lymph node metastasis was detected on pathology specimens. Regarding the phenotypic features of the patients, whole exome sequencing was performed and heterozygous deletion of exon 1 and exon 6-8 in TCF12 was detected. Conclusion: Haploinsufficiency of TCF12 causes anosmic HH. Probably due to the incomplete penetrance and variable expressivity of the disease, patients could display variable phenotypic features such as intellectual disability, developmental delay, and craniosynostosis. Further description of new cases with TCF12 variations could enhance our understanding of craniosynostosis and its potential link to Kallmann syndrome associated with this gene.

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Despite the recent advances in understanding the mechanisms of olfaction, no tools are currently available to noninvasively identify loss of smell. Because of the substantial increase in patients presenting with coronavirus disease 2019-related loss of smell, the pandemic has highlighted the urgent need to develop quantitative methods. Methods: Our group investigated the use of a novel fluorescent probe named Tsp1a-IR800P as a tool to diagnose loss of smell. Tsp1a-IR800P targets sodium channel 1.7, which plays a critical role in olfaction by aiding the signal propagation to the olfactory bulb. Results: Intuitively, we have identified that conditions leading to loss of smell, including chronic inflammation and coronavirus disease 2019, correlate with the downregulation of sodium channel 1.7 expression in the olfactory epithelium, both at the transcript and at the protein levels. We demonstrated that lower Tsp1a-IR800P fluorescence emissions significantly correlate with loss of smell in live animals-thus representing a potential tool for its semiquantitative assessment. Currently available methods rely on delayed subjective behavioral studies. Conclusion: This method could aid in significantly improving preclinical and clinical studies by providing a way to objectively diagnose loss of smell and therefore aid the development of therapeutic interventions.

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OBJECTIVES: The new corona virus infection, has a wide range of clinical manifestations. Fever and cough are the most common symptoms. The olfactory function may be also affected with COVID-19. In this randomized clinical trial, we wanted to evaluate the therapeutic effect of olfactory training with and without oral vitamin A for COVID-19-related olfactory dysfunction. METHODS: Patients answered to the standard Persian version of anosmia reporting tool and performed the quick smell test before and after 12 weeks and at the end of the 12 months follow up. The patients were randomly allocated to three groups; Group A treatment with olfactory training, Group B treatment with oral vitamin A and olfactory training, and Group C as control group which only underwent nasal irrigation twice a day. Patients were treated for 3 months and followed up for 12 months. RESULTS: Totally 90 patients were included in three groups. After interventions, 76.9% of patients in Group A, 86.7% of patients in Group B, and 26.7% of patients in Group C completely improved. The average intervention time was statistically significant in relationship with the final olfactory status of the patients in the 12 months follow-up. The olfactory training has significantly improved the smell alteration at the end of 3- and 12- months follow-up in A and B groups. CONCLUSION: A three-months olfactory training is effective for improvement of COVID-19-related olfactory dysfunction. Adding daily oral vitamin A to olfactory training did not lead to better results in improving olfactory dysfunction. LEVEL OF EVIDENCE: Step 2 (Level 2*): Randomized trial.

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OBJECTIVE: This study aimed to investigate the prevalence and factors associated with olfactory dysfunction in individuals exposed to Isotretinoin (ISO) for the treatment of acne, using the University of Pennsylvania Smell Identification Test (UPSIT®). METHODS: This cross-sectional study enrolled age and sex-matched patients with acne who were current users of oral ISO and unexposed controls without olfactory complaints. UPSIT® and a validated questionnaire (Nasal Obstruction Symptom Evaluation) were administered to evaluate nasal obstruction in patients exposed to ISO. RESULTS: A total of seventy patients were recruited, with 35 in the exposed group and 35 in the unexposed group, consisting of 18 males and 17 females in each group, aged from 17 to 47 years. The prevalence of olfactory dysfunction was higher in the exposed group compared to the non-exposed group (62.9% vs. 17.1%), yielding a Prevalence Ratio (PR) of 3.7 (95% CI 1.9-7.1). However, no participants were categorized as anosmia or severe hyposmia and the majority of dysfunction was mild hyposmia compared to moderate hyposmia (51.5% vs. 11.4%). Among the exposed individuals, gasoline, orange, coffee, and wood exhibited the highest rates of identification errors (≥54%). Olfactory function demonstrated a negative correlation with treatment duration (p = 0.01), cumulative dose (p = 0.02), and nasal obstruction (p = 0.02). CONCLUSIONS: Olfactory dysfunction was more prevalent among ISO users, despite the patients being unaware of the disorder. Olfactory changes were correlated with treatment duration, cumulative dose, and nasal obstruction. LEVEL OF EVIDENCE: Level 4.

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COVID-19 (Coronavirus), an acute respiratory disorder, is caused by SARS-CoV-2 (coronavirus severe acute respiratory syndrome). The high prevalence of COVID-19 infection has drawn attention to a frequent illness symptom: olfactory and gustatory dysfunction. The primary purpose of this manuscript is to create a Computer-Assisted Diagnostic (CAD) system to determine whether a COVID-19 patient has normal, mild, or severe anosmia. To achieve this goal, we used fluid-attenuated inversion recovery (FLAIR) Magnetic Resonance Imaging (FLAIR-MRI) and Diffusion Tensor Imaging (DTI) to extract the appearance, morphological, and diffusivity markers from the olfactory nerve. The proposed system begins with the identification of the olfactory nerve, which is performed by a skilled expert or radiologist. It then proceeds to carry out the subsequent primary steps: (i) extract appearance markers (i.e., 1 s t and 2 n d order markers), morphology/shape markers (i.e., spherical harmonics), and diffusivity markers (i.e., Fractional Anisotropy (FA) & Mean Diffusivity (MD)), (ii) apply markers fusion based on the integrated markers, and (iii) determine the decision and corresponding performance metrics based on the most-promising classifier. The current study is unusual in that it ensemble bags the learned and fine-tuned ML classifiers and diagnoses olfactory bulb (OB) anosmia using majority voting. In the 5-fold approach, it achieved an accuracy of 94.1%, a balanced accuracy (BAC) of 92.18%, precision of 91.6%, recall of 90.61%, specificity of 93.75%, F1 score of 89.82%, and Intersection over Union (IoU) of 82.62%. In the 10-fold approach, stacking continued to demonstrate impressive results with an accuracy of 94.43%, BAC of 93.0%, precision of 92.03%, recall of 91.39%, specificity of 94.61%, F1 score of 91.23%, and IoU of 84.56%. In the leave-one-subject-out (LOSO) approach, the model continues to exhibit notable outcomes, achieving an accuracy of 91.6%, BAC of 90.27%, precision of 88.55%, recall of 87.96%, specificity of 92.59%, F1 score of 87.94%, and IoU of 78.69%. These results indicate that stacking and majority voting are crucial components of the CAD system, contributing significantly to the overall performance improvements. The proposed technology can help doctors assess which patients need more intensive clinical care.

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OBJECTIVE: To investigate the platelet-rich plasma (PRP) effectiveness in patients with a long-lasting postviral olfactory dysfunction (LPOD). METHODS: Forty-three consecutive patients with a long-lasting postviral OD were prospectively recruited. The injection of 1 mL of PRP was carried out in both olfactory clefts. The pre- to 6-month post-PRP injection change in olfaction was assessed with the olfactory disorder questionnaire (ODQ) and the threshold, discrimination, and identification (TDI) tests. RESULTS: Forty-three patients received bilateral PRP injections (24 females). The mean age of patients was 58.9 ± 16.8 years. The mean duration of LPOD was 8.7 years. The pre to 6-month post-injection mean TDI significantly improved from 10.3 ± 10.2 to 20.12 ± 12.07 (p = 0.001). The mean ODQ significantly decreased from 29.8 ± 13.0 to 23.4 ± 11.3 (p = 0.013). The average change of the TDI and the ODQ were 9.8 and 6.4, respectively. Age was inversely associated with the 6-month threshold score. CONCLUSION: PRP appears to be a promising therapeutic strategy for long-lasting postviral OD. Our findings support the conduction of controlled randomized trial in this population of patients.

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

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Objective: Olfactory dysfunction (OD) is a condition primarily affecting older adults. Several factors have been implicated in OD, such as age, socioeconomic status, and neurodegenerative disease; however, the effect of military service still requires additional investigation. Here, we aim to determine if there is an association between prior military service and OD among older adults. Methods: This cross-sectional study included 2268 adults from Round 1 of the National Social Life, Health, and Aging Project. OD was defined as 0-3 odors correctly identified on the 5-item Sniffin' Sticks test. Bivariate analysis was conducted to calculate crude odds ratios (cOR) for the association of prior military service with OD and identify covariates for regression. Associations between prior military service and OD were assessed using logistic regression, and adjusted odds ratios (aOR) were calculated controlling for age, gender, race/ethnicity, education, stroke history, dementia, diabetes, and mental health. All analyses were weighted using survey weights to account for sampling design. Results: OD was present in 489 adults (21.6%). Among those with OD, the average age was 71.0 ± 7.9 years, whereas the average age in those without OD was 67.0 ± 7.2 years. Among adults with OD, 34.4% reported prior military service, compared to 27.7% of adults without OD (cOR = 1.37; 95% CI: 1.05-1.79). However, after adjusting for covariates, prior military service was not associated with OD (aOR: 1.09; 95% CI: 0.79-1.50). Older age (aOR: 1.07; 95% CI: 1.05-1.09) and worse mental health (aOR: 1.68; 95% CI: 1.14-2.49) were associated with OD. Conclusion: Prior military service was not associated with OD among older adults after controlling for covariates. More nuanced research is needed to examine correlations between OD and specific elements of military service such as duration, toxin exposure, and head trauma.Level of Evidence: Level 4.

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OBJECTIVE: Although olfactory dysfunction is one of the most common presenting signs of COVID-19 infection, little is known about which populations are most susceptible. The aim of this study is to evaluate the risk of COVID-19-induced chemosensory dysfunction in malnourished individuals. METHODS: The N3C database was queried for adults having positive COVID-19 test result, diagnosis of chemosensory dysfunction within 2 weeks of positive test date, and overnutrition or undernutrition (i.e., deficiency or excess of micro- and macronutrients) related diagnoses prior to COVID-19 infection. Individuals previously diagnosed with chemosensory dysfunction were excluded. COVID-19-positive adults without olfactory dysfunction were similarly analyzed. Statistical analysis was performed using odds ratio calculations (95% confidence interval [CI]). RESULTS: Of 3,971,536 patients with COVID-19, 73,211 adults were identified with a diagnosis of undernutrition and 428,747 adults were identified with a diagnosis of overnutrition prior to infection. Of those with undernutrition, 264 (0.36%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. Of those with overnutrition, 2851 (0.66%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. The calculated odds ratio for undernutrition and olfactory dysfunction was 0.731 (p < 0.0001, 95% CI [0.0647, 0.0825]). The calculated odds ratio for overnutrition and olfactory dysfunction was 1.419 (p < 0.0001, 95% CI [1.3359, 1.5081]). CONCLUSION: Overnutrition may increase the risk of COVID-19-related olfactory dysfunction, while undernutrition may slightly protect. While reasons are unclear, baseline differences in metabolic, inflammatory, and structural biochemistry deserve closer inspection. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

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INTRODUCTION: Olfactory symptoms have been reported as particular in COVID-19 patients. OBJECTIVE: To synthesize and analyze the existing evidence on the monitoring loss of sense of smell and taste in COVID-19 patients, and for how long symptoms persist after the virus is no longer active in the organism. METHODS: A search was implemented in PubMed, Embase, Scopus, Science Direct, and Web of Science databases. This systematic review and meta-analysis were conducted according to PRISMA, and the risk of bias was assessed through the Newcastle-Ottawa Scale. The review protocol is registered in PROSPERO. RESULTS: Our systematic review included data from 14 articles with a total of 2143 participants. The most reported sensory symptom of COVID-19 was anosmia, which was detected in 1499 patients, being the only symptom to appear in all studies. Ageusia was detected in 595 patients, dysgeusia in 514 patients, and hyposmia in 209 patients. The studies provided the number of 729 patients with sensory symptoms during the acute COVID-19 infection of 15 days, and 1020 patients with lasting sensory symptoms, presenting sensory dysfunctions after the average latent period of 15 days of the acute COVID-19 infection. CONCLUSION: Evidence points to the loss or dysfunction of taste and smell as one of the symptoms of COVID-19 persisting for an average time of 15 days, with 44% of COVID-19 patients with persistent symptoms for more than 15 days. Nevertheless, most studies do not perform a follow-up with those patients. Therefore, further research on sensory symptoms and their follow-up is required.

INTRODUÇÃO: Sintomas olfativos foram relatados como específicos em pacientes com COVID-19. OBJETIVO: Sintetizar e analisar as evidências existentes sobre o monitoramento da perda de olfato e paladar em pacientes com COVID-19 e por quanto tempo os sintomas persistem. MÉTODOS: Foi realizada uma busca nas bases de dados PubMed, Embase, Scopus, Science Direct e Web of Science. Esta revisão sistemática e metanálise foi realizada de acordo com o PRISMA, e o risco de viés foi avaliado por meio da Escala de Newcastle-Ottawa. O protocolo de revisão está registrado no PROSPERO. RESULTADOS: Nossa revisão sistemática incluiu dados de 14 artigos com um total de 2143 participantes. O sintoma sensorial mais comumente relatado de COVID-19 foi anosmia, detectado em 1.499 pacientes, sendo o único sintoma a aparecer em todos os estudos. Ageusia foi detectada em 595 pacientes, disgeusia em 514 pacientes e hiposmia em 209 pacientes. Os estudos forneceram o número de 729 pacientes com sintomas sensoriais por 15 dias durante a infecção aguda por COVID-19 e 1020 pacientes com sintomas sensoriais duradouros, apresentando disfunções sensoriais após o período latente médio de 15 dias da infecção aguda por COVID-19. CONCLUSÃO: Evidências apontam a perda ou disfunção do paladar e olfato como um dos sintomas da COVID-19 persistindo por um tempo médio de 15 dias, com 44% dos pacientes com COVID-19 com sintomas persistentes por mais de 15 dias. No entanto, a maioria dos estudos não realiza acompanhamento desses pacientes. Portanto, mais pesquisas sobre sintomas sensoriais e seu acompanhamento são necessárias.

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Post-Acute Sequelae of COVID-19 (PASC) encompasses persistent neurological symptoms, including olfactory and autonomic dysfunction. Here, we report chronic neurological dysfunction in mice infected with a virulent mouse-adapted SARS-CoV-2 that does not infect the brain. Long after recovery from nasal infection, we observed loss of tyrosine hydroxylase (TH) expression in olfactory bulb glomeruli and neurotransmitter levels in the substantia nigra (SN) persisted. Vulnerability of dopaminergic neurons in these brain areas was accompanied by increased levels of proinflammatory cytokines and neurobehavioral changes. RNAseq analysis unveiled persistent microglia activation, as found in human neurodegenerative diseases. Early treatment with antivirals (nirmatrelvir and molnupiravir) reduced virus titers and lung inflammation but failed to prevent neurological abnormalities, as observed in patients. Together these results show that chronic deficiencies in neuronal function in SARS-CoV-2-infected mice are not directly linked to ongoing olfactory epithelium dysfunction. Rather, they bear similarity with neurodegenerative disease, the vulnerability of which is exacerbated by chronic inflammation.

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Smell loss affects around 15-20% of the population, with a major effect on the quality of life. The most common complaint is the impairment of the eating experience, with around 90% of patients reporting this issue. A study conducted at a specialised Taste and Smell Clinic investigated if food and cooking can positively affect the enjoyment of food, subjective cooking skills, and quality of life in patients with smell loss. The 49 participants in the study received a 5-week cooking school course that focused on emphasizing the other senses to regain the enjoyment of food. Participants gained more confidence in cooking, and their quality of life improved significantly. Positively evaluated recipes were adjusted based on feedback and published as free e-books in Danish, German, and English. Eating and cooking are multisensory experiences, and the perception of food depends on the complex interaction of senses and surroundings. If the olfactory input is reduced or absent, both the enjoyment and cooking experience can be negatively affected. Therefore, focusing on food and cooking can have a positive impact on patients with smell loss.