Olfactory Disorders Research Articles

Analysis Descriptive of Anosmia and Dysgeusia in SARS CoV-2 Patients: Overview of Epidemiology, Pathogenesis, Prognosis, and Treatment Options

Introduction: SARS CoV-2 (COVID-19) is a respiratory infectious disease whose cause has been identified as the seventh type of the coronavirus family that attacks humans. Common symptoms among patients with COVID-19 include fever, dry cough, shortness of breath (dyspnea), muscle aches (myalgia), confusion, headache, sore throat, rhinorrhea, chest pain, diarrhea, nausea / vomiting, conjunctival congestion, nose. congestion, sputum production, fatigue (malaise), hemoptysis, and shivering. However, the spread of COVID-19 infection has shown new symptoms of the disease: patients with dysfunction of smell, taste and indigestion. Methods: Literature review by taking libraries from 34 journals and 2 textbook. The journal obtained from the Google, NCBI and Pubmed search engine, as well as processing research materials into new information related to the research objectives. Results: One hypothesis currently developing is that SARS-CoV-2 will cause olfactory changes through direct access and damage to the CNS through its penetration by the cribriform plate. Another hypothesis that is also developing suggests direct viral damage to olfactory cells and taste receptors. Glial cells, neurons, and the oral cavity present the ACE-2 receptor which appears to be a mechanism of cell invasion by viruses. Conclusion: People who have lost their smell or taste are six times more likely to become positive for COVID-19. Likewise, people who have anosmia have a 10-fold higher chance of being diagnosed with COVID-19. Taste and smell disorders with ageusia have a 10 times higher chance of catching COVID-19.

Olfactory dysfunction in patients with Wilson's Disease.

Many neurodegenerative disorders are associated with olfactory dysfunction (OD), but little is known about OD in Wilson's Disease (WD). We evaluated olfactory function in patients with WD. OD was examined in 68 patients with WD and 70 sex- and age-matched healthy controls using subjective testing with 'Sniffin Sticks'. Threshold discrimination identification (TDI) score and its three components (odour detection threshold, discrimination, and identification) were assessed. Compared to controls, patients with WD had a significantly weaker sense of smell in terms of TDI (p < 0.01), odour discrimination (p < 0.01), and identification (p < 0.01), but not in terms of odour detection threshold (p = 0.27). Patients with predominantly neurological symptoms were characterised by greater OD by TDI (p < 0.01), odour detection threshold (p = 0.01), and discrimination (p = 0.03). The presence of pathological lesions (p = 0.04) in brain magnetic resonance imaging and generalised brain atrophy (p = 0.02) predisposed to worse TDI. In the WD group, weak inverse correlations between age and TDI score (r = -0.27), odour detection threshold (r = -0.3), and discrimination (r = -0.3) were found. Male gender was a risk factor for abnormal TDI in both WD and controls (both p = 0.02). Patients with WD, particularly older individuals, more frequently had OD than healthy volunteers. Predominantly neurological symptoms, and the presence of typical brain MRI changes, predisposed patients with WD to smell disorders.

Olfactory and gustatory outcomes following endoscopic transsphenoidal hypophysectomy

ObjectiveThe aim of this study was to evaluate olfactory, gustatory, and quality-of-life outcomes in patients who underwent endonasal transsphenoidal hypophysectomy.MethodsIn this prospective study, the patients were assessed subjectively using the Malay version of sQOD-NS (short questionnaire of olfactory disorders in a negative statement) and objectively using the culturally adapted Sniffin’ Sticks smell test and taste test preoperatively and 3 months postoperatively. The Sniffin’ Sticks smell test consists of odor identification, odor discrimination, and odor threshold tests. The taste test consists of different sweet, salt, sour, and bitter concentrations.ResultsTwenty patients were enrolled in the study. The study comprises 45% female and 55% male. On average patients’ ages were 49.5 years. In this study we found a significantly reduced in odor identification score (p = 0.049) post-surgery; however, there was no statistically significant difference in odor threshold, odor discrimination, and taste. The olfactory quality of life outcome based on the Malay version of sQOD-NS (p = 0.001) was significantly reduced after surgery. There was no significant difference in the Sniffin’ Sticks smell test (p < 0.178) and taste test (p < 0.425) pre-surgery and post-surgery. The tumor’s location, either sellar or suprasellar, did not influence the smell outcome of patients postoperatively (p = 0.056).ConclusionThe study showed that the endoscopic transsphenoidal technique for pituitary surgery does not pose permanent olfactory disability.

Antibody response, associated symptoms and profile of patients presumably infected by SARS-CoV-2 with taste or smell disorders in the SAPRIS multicohort study

BackgroundTaste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and antibody response intensity associated with taste or smell disorders.MethodsWe used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave.ResultsThe analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05–1.58] for women), smoking (OR = 1.54 [95% CI 1.13–2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06–1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26–1.36], OR = 1.37 [95% CI 1.33–1.42] and OR = 1.34 [95% CI 1.29–1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea.ConclusionsAmong patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with an antibody response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

Smell and Taste Disorder in the COVID-19 Pandemic

Smell and Taste Disorder in the COVID-19 Pandemic

Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial

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.

Peripheral smell regions in patients with central vertigo: An MRI evaluation

Abstract OBJECTIVES. We investigated peripheral smell regions in patients with central vertigo by cranial magnetic resonance imaging (MRI). MATERIAL AND METHODS. In this study, 137 adult patients were included by selecting cranial MRI images from the hospital’s PACS system, covering both recent and past records. The first group included 68 adult patients suffering from central vertigo, and the control group (Group 2) 69 healthy individuals, who had no central vertigo. Measurements of olfactory bulb (OB) volume and olfactory sulcus (OS) depth were taken from all groups. RESULTS. The study found that the OB volume of the group with central vertigo was significantly lower compared to the control group (p&lt;0.05). However, there were no significant differences in the OS depth between the two groups (p&gt;0.05). In both groups, there were no significant variations in OB volume between the right and left sides (p&gt;0.05). Additionally, both the central vertigo group and the control group showed that the left OS depth was lower than the right side (p&lt;0.05). Positive correlation was seen between OB volume and OS depth on both left and right sides as well as bilateral OB volume and OS depth in the central vertigo group. However, there were no significant correlations between OB volume, OS depth and age and gender in the central vertigo group. CONCLUSION. We concluded that OB volume got lower in patients with central vertigo. However, there were no side differences between OB volumes. As central vertigo secondary to cerebral ishchemia causes olfactory disorders, measures should be taken to prevent central vascular problems. From another perspective, olfactory problems may be one of the initial signs of central vascular problems and central vertigo.

Olfactory Impairment Is the Main Predictor of Higher Scores at REM Sleep Behavior Disorder (RBD) Screening Questionnaire in Parkinson's Disease Patients.

Olfactory impairment and REM sleep behavior disorder (RBD) are common non-motor symptoms in Parkinson's disease (PD) patients, often preceding the onset of the specific motor symptoms and, thus, crucial for strategies directed to anticipate PD diagnosis. In this context, the specific interaction between olfactory impairment and RBD has not been clearly defined. The aim of this study was to determine the possible role of olfactory impairment and other clinical characteristics as possible predictors of higher scores at RBD screening questionnaire (RBDSQ) in a large population of PD patients. In this study, 590 PD patients were included from the Parkinson's Progression Markers Initiative. Demographic and clinical features were registered. All participants completed motor and non-motor evaluations at the baseline visit. For motor assessments, the disease severity was evaluated by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pars III. Regarding non-motor symptoms assessment, Montreal Cognitive Assessments (MoCA), University of Pennsylvania Smell Identification Test (UPSIT) and RBD screening questionnaire (RBDSQ) were registered. Among 590 PD patients included in this study, 111 patients with possible RBD were found (18.8%). RBD was less frequent in female PD patients (p ≤ 0.011). Among patients with or without possible RBD diagnosis, statistically significant differences in MDS-UPDRS III (23.3 ± 11.4 vs. 19.7 ± 9.1, respectively, p ≤ 0.002) and in UPSIT score (19.7 ± 8.3 vs. 22.6 ± 8.0, respectively, p ≤ 0.001) were found. Moreover, significant correlations between RBDSQ versus UPDRS III score and versus UPSIT score were observed. Multivariate linear regression analysis showed that UPSIT was the most significant predictor of higher scores at RBDSQ, while the other significant predictors were UPDRS III and age. The severity of olfactory impairment appears tightly correlated to RBD symptoms, highlighting the role of these biomarkers for PD patients. Additionally, according to this large study, our data confirmed that RBD in PD patients exhibits peculiar gender differences.

Clinical aspects and cytomorphological and functional features of the nasal mucosa in chronic pathology of the intranasal structures and their verification from CT data

Background. Approximately 30% of the general human population suffers from chronic pathology of intranasal structures, the main manifestations of which are impaired nasal breathing and sense of smell. The main instrumental diagnostic methods for this pathology are X-ray computed tomography (CT), which allows obtaining data on the architecture of the anatomical structures of the upper respiratory tract, and rhinomanometry, based on the results of which it is possible to assess the functional capacity of the nasal cavity during breathing. Also, a thorough study of the cytological material of the mucous membrane of the upper respiratory tract is an important component in determining the functional state of the nasal cavity, clarifying the diagnosis and choosing a treatment method. This allows the doctor to determine the composition and number of cellular elements in the material, assess their condition (destruction, proliferation, dystrophy, necrosis, etc.), ascertain the intensity of the body’s reactive abilities, monitor the dynamics of tissue recovery or the healing process in them, and encourages researchers to study in more detail and comparing the materials of clinical, radiological and cytological studies with the aim of developing a pathogenetically directed complex treatment of patients with nasal breathing disorders. Therefore it is necessary to know aspects of correlation between the results of rhinocytography and CT data in typical pathological conditions with nasal congestion are considered. Purpose – is to study the clinical aspects and cytomorphological and functional features of the nasal mucosa in patients with pathology of intranasal structures with respiratory and olfactory disorders and research their independent verification based on the CT data. Materials and Methods. Clinical examination of patients included the study of complaints, anamnesis of the disease, examination of the ENT organs, rhinomanometry, endoscopic examination of the nasal cavity and nasopharynx, The CT of the paranasal sinuses using 3D cone beam tomography on the Vatech PaX-i3D device, as well as cytological examination of the nasal mucosa. The criteria for participation in the study were the absence of chronic diseases of the cardiovascular, respiratory, digestive, urinary systems, as well as heredity burdened by these diseases. Results. Formation of a different nature of the course and severity of disorders is associated with inflammatory, dyscirculatory and trophic disorders in the nasal mucosa, which weaken both mucociliary clearance and local immunity. This applies mainly to the I group of observations. The consequence of a decrease in local immunity factors in the nasal mucosa is microbial contamination, which is associated with a long-term nasal breathing disorder in the I and II groups of observations, up to five years and six months, respectively. The results of rhinocytography mostly correspond with the aerodynamic models data of nasal сavity from the CT datasets. Conclusions. Despite the reliability of the examinations carried out by us, the cytological examination of the nasal mucosa is only an additional analysis, the interpretation of which should be based on the clinical picture of a particular patient. Proposed aerodynamic model from CT-datasets actually provides an independent verification of the aerodynamic characteristics of the nasal cavity, obtained from rhinomanometry data, and may indicate a violation of nasal breathing according to changes in the internal anatomical configuration of the nasal chanel.

Treatment of Olfactory Disorders After SARS - CoViD 2 Virus Infection.

The benefit of a nasal corticosteroid in the treatment of persistent post-infectious smell disorders is not as clear in previous studies as is assumed for olfactory training. This study would therefore like to describe the treatment strategies using the example of a persistent olfactory dysfunction as a result of a proven infection with SARS-CoViD-2-virus. Twenty patients (average age of 33.9 ± 11.9years) with hyposmia were included in this study from December 2020 to July 2021. Every second patient received additionally a nasal corticosteroid. The two resulting randomized groups of equal size were screened with the TDI test, a 20-item taste powder test for the assessment of retronasal olfaction and otorhinolaryngological examination. The patients were asked to train twice daily using a standardized odor training kit and followed up after 2months and 3months, respectively. We documented a significant overall improvement in olfactory ability over the investigation period in both groups. While the TDI score steadily increased on average under the combination therapy, the rise under olfactory training alone was initially steeper. This short-term interaction effect over mean two months was not statistically significant. According to Cohen, however, a moderate effect (eta2 = 0.055, Cohen`s d = 0.5) can still be assumed. This effect could be explained by a possibly higher compliance at the beginning of the sole olfactory training due to the lack of further drug treatment offers. When the training intensity decreases, the recovery of the sense of smell stagnates. Adjunctive therapy ultimately outweighs this short-term benefit. The results reinforce the recommendation of early and consistent olfactory training on patients with dysosmia due to COVID-19. For continuous improvement of the sense of smell, an accompanying topical treatment seems at least to be worth consideration. The results should be optimized with larger cohorts and using new objective olfactometric methods.

Comparison of prevalence and evolution of COVID-19 olfactory disorders in patients infected by D614 (wild) and B.1.1.7. Alpha variant: a brief report.

To investigate the prevalence and the evolution of olfactory disorders (OD) related to coronavirus disease 2019 (COVID-19) in patients infected during the first and the second European waves. From March 2020 to October 2020, COVID-19 patients with OD were recruited and followed over the 12-month post-infection. The following data were collected: demographic, treatments, vaccination status, and olfactory function. Olfaction was assessed with the Olfactory Disorder Questionnaire (ODQ), and threshold, discrimination, and identification (TDI) test. Outcomes were compared between patients of the first wave (group 1: wild/D614G virus) and the second wave (group 2: B.1.1.7. Alpha variant) at 1-, 3- and 12-month post-infection. Sixty patients completed the evaluations accounting for 33 and 27 patients in group 1 and 2, respectively. The 1-month TDI score (23.7 ± 5.3) was significantly lower in group 2 compared to group 1 (29.8 ± 8.7; p = 0.017). Proportion of normosmic patients at 1-month post-infection was significantly higher in group 1 compared to group 2 (p = 0.009). TDI scores only significantly increased from 1- to 3-month post-infection in anosmic and hyposmic patients. Focusing on There was a negative association between the 1-month ODQ and the 1-month TDI (rs = - 0.493; p = 0.012). ODQ was a significant predictor of TDI scores at 3- and 12-month post-infection. The 12-month prevalence of parosmia was 60.6% in group 1 and 42.4% in group 2, respectively. There was no significant influence of oral corticosteroid treatment, adherence to an olfactory training and vaccination status on the olfactory outcomes. Patients of the second wave (Alpha B.1.1.7. variant) reported significant higher proportion of psychophysical test abnormalities at 1-month post-infection than patients infected during the first wave (D614G virus).

Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System

Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58-12.54), olfactory nerve disorders (8.02; 2.44-26.33), and hallucinations (22.96; 8.45-62.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs.

A parosmia severity index based on word-classification predicts olfactory abilities and impairment

Parosmia is an olfactory disorder that involves distortions of specific odors that may co-occur with anosmia, loss of smell of other odors. Little is known about which odors frequently trigger parosmia, and measures of parosmia severity are lacking. Here, we present an approach to understand and diagnose parosmia that is based on semantic properties (e.g., valence) of words describing odor sources (“fish”, “coffee”, etc.). Using a data-driven method based on natural language data, we identified 38 odor descriptors. Descriptors were evenly dispersed across an olfactory-semantic space, which was based on key odor dimensions. Parosmia patients (n = 48) classified the corresponding odors in terms of whether they trigger parosmic or anosmic sensations. We investigated whether these classifications are related to semantic properties of the descriptors. Parosmic sensations were most often reported for words describing unpleasant odors of inedibles that are highly associated to olfaction (e.g., “excrement”). Based on PCA modeling, we derived the Parosmia Severity Index—a measure of parosmia severity that can be determined solely from our non-olfactory behavioral task. This index predicts olfactory-perceptual abilities, self-reported olfactory impairment, and depression. We thus provide a novel approach for investigating parosmia and establishing its severity that does not require odor exposure. Our work may enhance our understanding of how parosmia changes over time and how it is expressed differently across individuals.

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders.

Current approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission. We measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria®/Astrazeneca and/or Comirnaty®/Pfizer). While serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19. As breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Our results encourage further studies to explore the prognosis potential of anti-Spike-NTD IgA in saliva at predicting persistent smell and taste disorders.

Pericytes may facilitate SARS-CoV-2 entry into the nervous system

Objective: Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system. Methods: We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens. Results: The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue; this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue; ciliated cells and goblet cells in bronchial tissue; and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue. Conclusion: Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood–brain barrier via pericytes. Additionally, SARS-CoV-2–induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.

Comparison between olfactory training and curcumin therapy in improving olfactory dysfunction in patients with chronic kidney disease

ObjectiveOlfactory dysfunction can be seen in chronic kidney disease (CKD) patients. We aimed to investigate the effects of olfactory training and curcumin on olfactory dysfunction in CKD patients and compare their impact with a placebo. MethodsWe conducted a double-blind, randomized, placebo-controlled trial in CKD patients, 2021–2022. We enrolled 60 participants in our study into three groups (curcumin, training, and control). Participants were randomized into trials and control groups and assessed using the Iran-smell identification test (Iran-SIT), a questionnaire of olfactory disorders (QOD), and a self-assessment tool. P-value < 0.05 was considered statistically significant. ResultsWe gathered 58 participants (mean age of 56.1 ± 2.5, 56.9% men). All the tests showed that curcumin improved olfactory function after the trial, though it was significant in QOD (17.5 ± 11.8 vs. 13.1 ± 9.7, p = 0.045) and self-assessment results (8.5 ± 3.1 vs. 9.5 ± 4.0, p = 0.047). Moreover, compared to baseline, training patients experienced an increase in their olfactory function in Iran-SIT (15.3 ± 4.9 vs. 18.8 ± 2.7, p = 0.001), QOD (19.0 ± 10.4 vs. 12.2 ± 9.9, p = 0.003), and self-assessment tools (6.8 ± 1.8 vs. 8.2 ± 3.1, p = 0.027). In contrast, the olfactory function was unchanged in control in all the tests (p > 0.05). Also, the improved change of Iran-SIT and QOD scores during the trial was more significant in training compared to the curcumin group (p < 0.002). ConclusionThe findings of this study indicate that olfactory training, even more than curcumin, can improve olfactory function in CKD patients. This information may help manage olfactory dysfunction in the CKD population.

Zika virus leads to olfactory disorders in mice by targeting olfactory ensheathing cells.

Zika virus (ZIKV) is an emerging arbovirus of the genus flavivirus that is associated with congenital Zika syndrome (CZS) in newborns. A wide range of clinical symptoms including intellectual disability, speech delay, coordination or movement problems, and hearing and vision loss, have been well documented in children with CZS. However, whether ZIKV can invade the olfactory system and lead to post-viral olfactory dysfunction (PVOD) remains unknown. We investigated the susceptibility and biological responses of the olfactory system to ZIKV infection using mouse models and human olfactory organoids derived from patient olfactory mucosa. We demonstrate that neonatal mice infected with ZIKV suffer from transient olfactory dysfunction when they reach to puberty. Moreover, ZIKV mainly targets olfactory ensheathing cells (OECs) and exhibits broad cellular tropism colocalizing with small populations of mature/immature olfactory sensory neurons (mOSNs/iOSNs), sustentacular cells and horizontal basal cells in the olfactory mucosa (OM) of immunodeficient AG6 mice. ZIKV infection induces strong antiviral immune responses in both the olfactory mucosa and olfactory bulb tissues, resulting in the upregulation of proinflammatory cytokines/chemokines and genes related to the antiviral response. Histopathology and transcriptomic analysis showed typical tissue damage in the olfactory system. Finally, by using an air-liquid culture system, we showed that ZIKV mainly targets sustentacular cells and OECs and support robust ZIKV replication. Our results demonstrate that olfactory system represents as significant target for ZIKV infection, and that PVOD may be neglected in CZS patients. Stated in the acknowledgment.

SARS-CoV-2 neurotropism and other possible causes of olfactory disorders in COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease (AIRD) caused by infection with the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first cases were diagnosed and reported in Wuhan, central China, in November 2019. The disease initially occurred locally. However, the number of infected individuals increased dynamically and spread worldwide. The most common symptoms of the SARS-CoV-2 infection include malaise, fever, dry cough and dyspnoea. Over time, reports of new COVID-19 symptoms included taste and smell disorders. A potential cause of these disorders is related to neurotropism, i.e. the affinity of SARS-CoV-2 to the nervous system. Angiotensin-converting enzyme 2 receptor is essential in the pathogenesis of SARS-CoV-2 infection. The receptor is found in many tissues and organs, including the olfactory epithelium, neurons and neuroglial cells. Another potential cause is neuroinvasiveness, i.e. the ability of the virus to invade the central nervous system, and thereby damage its structures. As a result, olfactory disorders may occur. Other concepts, such as the inflammatory response of the body and the concept of stroke or damage to olfactory supporting cells, are also considered.

Neurological Manifestations of Non-Severe COVID-19—A Multidirectional Approach

COVID-19 remains a significant clinical issue worldwide, with frequent neurological manifestations. In this study, the authors combine data obtained from the patient's medical history, physical examinations, and additional test results in the pursuit of any clinically relevant connections. Fifty-eight adult patients hospitalized in the Department of Neurology and Infectiology over a five-months period were retrospectively enrolled in this study. On admission, all patients included in this study were classified as mild or moderate COVID-19 cases, according to the World Health Organization (WHO) guidelines. Laboratory tests, Electroencephalography (EEG), and Magnetic Resonance Imaging (MRI) were performed. There was no statistically significant difference in the Neutrophil-Lymphocyte Ratio (NLR), C-reactive protein (CRP), and Interleukin 6 (IL-6) in patients who reported to the hospital within a week from the symptoms' onset and in those who reported later. In total, 49.06% of patients with eligible EEG recordings presented abnormal brain activity, while 27.59% of the study population had COVID-19-associated MRI findings. EEG and MRI abnormality occurrence did not correlate with the incidence of mild neurological symptoms (headache, olfactory, and gustatory disorders) of the SARS-CoV-2 infection. In three patients in this study population, unprovoked generalized epileptic seizures occurred for the first time in their life. Non-severe SARS-CoV-2 infection causes functional and structural abnormalities within the central nervous system. Brain microhemorrhages are frequently present in non-severe COVID-19 patients. There is no significant association between mild neurological symptoms of COVID-19 and additional test abnormalities. The time from SARS-CoV-2 infection's onset to hospital admission does not seem to influence the prognostic value of CRP, IL-6, and NLR in non-severe COVID-19. Mild-to-moderate SARS-CoV-2 infection can be a trigger factor for epilepsy and epileptic seizures.

Self-assessment of olfactory function using the “Sniffin’ Sticks”

BackgroundA precise and reliable test of the olfactory function is indispensable for the diagnosis of the olfactory disorder (OD). Despite of this, in a clinical context, often there is no place in daily routine for time-consuming procedures. This study aimed to examine if the assessment of olfactory function using the “Sniffin’ Sticks” is suitable for self-assessment.MethodsParticipants comprised 84 healthy control subjects (HC) and 37 OD patients. The “Sniffin’ Sticks” test battery consisting of odor threshold (T), discrimination (D) and identification (I) tests was used for self- and assisted assessments. To save time, we applied the 8-item wide step version of the T test and the 8-item D test, whereas the I task remained the same as the original version. The whole test included two sessions, with each session comprising a self-assessment part performed by the participants themselves, and an assisted-assessment part performed by the examiner.ResultsSniffin’ Sticks self-assessment was efficient in distinguishing between self-reported HC subjects and OD patients (p’s < 0.01), and the scores did not differ significantly from the assisted-assessment (p’s > 0.05). In the self-administered I and TDI tests, there was a moderate to excellent test–retest reliability (ICC = 0.51–0.93, p’s < 0.01), and a strong to excellent correlation with the assisted assessment (r = 0.71–0.92, p’s < 0.01). However, the self-administered T and D tests only exhibited low to moderate test–retest reliability (ICC = 0.30–0.72, p’s < 0.05) and correlations with the assisted test (r = 0.31–0.62, p’s < 0.05).ConclusionsThe Identification self-test is appropriate to be solely applied, and is therefore an easy-to-use alternative for olfactory screening in a larger segment of patients. The whole “Sniffin’ Sticks” self-test also shows good measurement properties and is therefore a suitable backup in clinical practice, but improvement is needed due to the simplified D and T self-test.