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.

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.
Психофизический тест Sniffin’ Sticks, включающий тест на идентификацию запахов, принято считать «золотым стандартом» для оценки обоняния в клинической и научной практике. Необходимое требование к тесту на идентификацию запахов — близкое знакомство с используемыми запахами жителей региона, в котором проводится исследование. Мы обследовали 77 здоровых добровольцев и 51 пациента с ольфакторной дисфункцией и пришли к выводу, что россияне плохо знакомы с тремя запахами из теста (лакрица, скипидар и анис) и совсем не знакомы с одним предлагаемым альтернативным ответом (шнитт-лук). Кроме того, 4 запаха имеют очень низкое распознавание (менее 75%). Тест адаптирован для применения в России. В буклете «лакрица» заменена «сиропом от кашля», «скипидар» — «растворителем краски», «шнитт-лук» — «лавровым листом». У запахов с низким распознаванием (лимон, яблоко, ананас) альтернативные фруктовые запахи в буклете заменены более контрастными. На основании полученных данных предложена разработка отечественного теста на идентификацию запахов, в котором все запахи будут хорошо знакомы россиянам.

OBJECTIVE: 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.
CONCLUSIONS: 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.

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]).
CONCLUSIONS: 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.
METHODS: 3 Laryngoscope, 2024.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

The common cold, the flu, and the 2019 coronavirus disease (COVID-19) have many symptoms in common. As such, without testing for severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2), it is difficult to conclude whether or not one is infected with SARS-CoV-2. The aim of the current study was to compare the presence and severity of COVID-19-related symptoms among those who tested positive or negative for the beta variant of SARS-CoV-2 (B.1.351) and identify the clinical presentation with the greatest likelihood of testing positive for SARS-CoV-2. n = 925 individuals that were tested for SARS-CoV-2 at Dutch mass testing sites (i.e., test streets) were invited to complete a short online survey. The presence and severity of 17 COVID-19-related symptoms were assessed. In addition, mood, health correlates, and quality of life were assessed for the week before the test. Of the sample, n = 88 tested positive and n = 837 tested negative for SARS-CoV-2. Individuals who tested positive for SARS-CoV-2 reported experiencing a significantly greater number, as well as greater overall symptom severity, compared to individuals who tested negative for SARS-CoV-2. A binary logistic regression analysis revealed that increased severity levels of congestion, coughing, shivering, or loss of smell were associated with an increase in the odds of testing positive for SARS-CoV-2, whereas an increase in the severity levels of runny nose, sore throat, or fatigue were associated with an increase in the odds of testing negative for SARS-CoV-2. No significant differences in mood or health correlates were found between those who tested positive or negative for SARS-CoV-2, except for a significantly higher stress score among those who tested negative for SARS-CoV-2. In conclusion, individuals that tested positive for SARS-CoV-2 experienced a significantly greater number and more severe COVID-19-related symptoms compared to those who tested negative for SARS-CoV-2. Experiencing shivering and loss of smell may be the best indicators for increased likelihood of testing positive for SARS-CoV-2.

Long COVID presents with diverse symptoms after COVID-19. Different clusters of symptoms have been reported; however, their persistence beyond 2 years after COVID-19 remains unclear. In this cohort study, we prospectively evaluated individuals with previous severe COVID-19 presenting with long COVID at a two-year follow-up. We characterized the included patients and performed a cluster analysis of symptoms through multiple correspondence analysis and hierarchical clustering. A total of 199 patients with long COVID were included. The median age was 58 years (48-69), 56% were male, and the median follow-up time since the COVID-19 diagnosis was 26 months (IQR: 25, 27). Three symptom clusters were identified: Cluster 1 is characterized by fatigue, myalgia/arthralgia, a low prevalence of symptoms, and a lack of specific symptoms; Cluster 2 is defined by a high prevalence of fatigue, myalgia/arthralgia, and cardiorespiratory symptoms, including palpitations, shortness of breath, cough, and chest pain; and Cluster 3 is demonstrated a high prevalence of ageusia, anosmia, fatigue, and cardiorespiratory symptoms. Our study reinforces the concept of symptom clustering in long COVID, providing evidence that these clusters may persist beyond two years after a COVID-19 diagnosis. This highlights the chronic and debilitating nature of long COVID and the importance of developing strategies to mitigate symptoms in these patients.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.
CONCLUSIONS: 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.

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.
METHODS: Level 4.