Alpha-lipoic acid does not improve olfactory training results in olfactory loss due to COVID-19: a double-blind randomized trial

Abstract Objectives Olfactory loss is a recognized long-term dysfunction after Coronavirus Disease 2019 (COVID-19) infection. This investigation aimed to assess the effect of alpha-lipoic acid as an adjuvant treatment of olfactory training on the improvement of smell loss in post-COVID-19 patients. Methods This randomized controlled trial included 128 adult outpatients who had persistent smell loss for more than 3-months after COVID-19 infection. The participants were randomly allocated into two groups: the intervention treatment group, which received alpha-lipoic acid associated to olfactory training, and comparison treatment group, which received placebo pills associated to olfactory training. The participants were followed-up for 12-weeks. Olfactory dysfunction was assessed in terms of Visual Analog Scale (VAS), and the Connecticut Chemosensory Clinical Research Center (CCCRC) test for the Brazilian population. Results A total of 100 participants completed the follow-up period and were analyzed in this study. Both groups have improved CCCRC score (p= 0.000), olfactory threshold (p= 0.000), identification score (p= 0.000) and VAS score (p= 0.000) after 12-weeks follow-up. No significant differences were determined between the intervention and comparison treatment groups in CCCRC score (p= 0.63), olfactory threshold (p= 0.50), identification score (p= 0.96) and VAS score (p= 0.97). In all these criteria, comparison treatment group went slightly worse. At the endpoint of the study, the frequency of anosmia reduced to 2% in the intervention treatment group and to 7.8% in the comparison treatment group. Also, 16.8% of the intervention group' subjects, and 15.7% of comparison treatment group's patients reached normosmia. Conclusions Overall, there was a strongly significant difference in olfactory function between baseline and endpoint for both groups. However, based on the lack of significant difference between the intervention treatment and the comparison treatment groups in terms of olfactory changes, our study appoints that the alpha-lipoic acid is not better than olfactory training alone to treat olfactory loss after COVID-19. Level of evidence Level 2.

Distúrbios do olfato, uma revisão narrativa do diagnóstico ao tratamento / Olfactory dysfunction: a narrative review from diagnosis to treatment

Os distúrbios do olfato (DO) impactam de forma significativa na qualidade de vida dos indivíduos, e o conhecimento teórico a respeito do assunto deve ser de domínio dos alergologistas e imunologistas clínicos, possibilitando, assim, o seu diagnóstico e implementação de intervenções. Suas causas podem ser variadas, entre elas estão: rinite alérgica, rinossinusite crônica com ou sem pólipos, infecções de vias aéreas superiores, exposição a substâncias químicas, doenças neurológicas, drogas, traumas e o próprio envelhecimento. O olfato pode ser avaliado e mensurado através de testes com metodologias diferentes, cujo objetivo é avaliar parâmetros como a identificação de odores, limiar e discriminação olfativa. Esses testes são de fundamental importância para caracterizar objetivamente a queixa do paciente, como também avaliar o olfato antes e após determinada aplicação terapêutica. O tratamento das desordens olfativas é baseado em sua etiologia, portanto determinar a sua causa é indispensável para uma melhor eficácia no manejo. Entre as principais opções estão os corticoides tópicos, com impacto significativo nos pacientes com doença sinusal associada, treinamento olfatório e outras intervenções como ômega 3, vitamina A intranasal, e terapias que ainda requerem mais estudos.

Olfactory dysfunction significantly impacts quality of life, and allergists and clinical immunologists must be informed about it for diagnostic and interventional purposes. The causes are varied: allergic rhinitis, chronic rhinosinusitis with or without polyps, upper airway infections, exposure to chemicals, neurological diseases, drugs, trauma, and aging itself. Olfactory function can be evaluated and measured by several tests that use different methodologies to evaluate and identify odors, olfactory threshold, and olfactory discrimination. These tests are fundamental for objectively characterizing patient complaints and evaluating olfactory function before and after therapeutic interventions. Olfactory disorders are treated according to their etiology, so determining their cause is a major factor in treatment efficacy. The main options include topical corticosteroids, which have a significant impact on patients with sinus disease, olfactory training, other therapies (such as omega 3 and intranasal vitamin A), in addition to therapies that require further research.

Effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging mice / 中国针灸

OBJECTIVE@#To observe the effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging (SAMP8) mice, and to explore the action pathway of moxa smoke.@*METHODS@#Forty-eight six-month-old male SAMP8 mice were randomly divided into a model group, an olfactory dysfunction group, a moxa smoke group and an olfactory dysfunction + moxa smoke group, with 12 mice in each group. Twelve age-matched male SAMR1 mice were used as the blank group. The olfactory dysfunction model was induced in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group by intraperitoneal injection of 3-methylindole (3-MI) with 300 mg/kg, and the moxa smoke group and the olfactory dysfunction + moxa smoke group were intervened with moxa smoke at a concentration of 10-15 mg/m3 for 30 min per day, with a total of 6 interventions per week. After 6 weeks, the emotion and cognitive function of mice was tested by open field test and Morris water maze test, and the neuronal morphology in the CAI area of the hippocampus was observed by HE staining. The contents of neurotransmitters (glutamic acid [Glu], gamma-aminobutyric acid [GABA], dopamine [DA], and 5-hydroxytryptamine [5-HT]) in hippocampal tissue of mice were detected by ELISA.@*RESULTS@#The mice in the blank group, the model group and the moxa smoke group could find the buried food pellets within 300 s, while the mice in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group took more than 300 s to find them. Compared with the blank group, the model group had increased vertical and horizontal movements (P<0.05) and reduced central area residence time (P<0.05) in the open field test, prolonged mean escape latency on days 1-4 (P<0.05), and decreased search time, swimming distance and swimming distance ratio in the target quadrant of the Morris water maze test, and decreased GABA, DA and 5-HT contents (P<0.05, P<0.01) and increased Glu content (P<0.05) in hippocampal tissue. Compared with the model group, the olfactory dysfunction group had increased vertical movements (P<0.05), reduced central area residence time (P<0.05), and increased DA content in hippocampal tissue (P<0.05); the olfactory dysfunction + moxa smoke group had shortened mean escape latency on days 3 and 4 of the Morris water maze test (P<0.05) and increased DA content in hippocampal tissue (P<0.05); the moxa smoke group had prolonged search time in the target quadrant (P<0.05) and increased swimming distance ratio, and increased DA and 5-HT contents in hippocampal tissue (P<0.05, P<0.01) and decreased Glu content in hippocampal tissue (P<0.05). Compared with the olfactory dysfunction group, the olfactory dysfunction + moxa smoke group showed a shortened mean escape latency on day 4 of the Morris water maze test (P<0.05). Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a decreased 5-HT content in the hippocampus (P<0.05). Compared with the blank group, the model group showed a reduced number of neurons in the CA1 area of the hippocampus with a disordered arrangement; the olfactory dysfunction group had similar neuronal morphology in the CA1 area of the hippocampus to the model group. Compared with the model group, the moxa smoke group had an increased number of neurons in the CA1 area of the hippocampus that were more densely packed. Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a reduced number of neurons in the CA1 area of the hippocampus, with the extent between that of the moxa smoke group and the olfactory dysfunction group.@*CONCLUSION@#The moxa smoke could regulate the contents of neurotransmitters Glu, DA and 5-HT in hippocampal tissue through olfactory pathway to improve the learning and memory ability of SAMP8 mice, and the olfactory is not the only effective pathway.

A prospective study of the effect of functional endoscopic sinus surgery on the recovery of olfactory function in patients with chronic rhinosinusitis with nasal polyposis / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the efficacy of functional endoscopic sinus surgery（FESS） in the treatment of olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps （CRSwNP） , at the same time, it provides an evidence for the prognosis evaluation of olfaction and the clinical application of oERPs to evaluate the plasticity of olfaction cortex. Methods:From October 2021 to October 2022, 45 patients with CRSwNP who underwent FESS nine-step standardized treatment in our department were recruited as the research subjects, divided into 22 patients with eosinophilic CRSwNP（ECRS）and 23 patients with non-eosinophilic CRSwNP（nECRS）. VAS-olfactory dysfunction （VAS-OD） score, SNOT-22 olfactory score, Sniffin' Sticks test and oERPs collection and processing were performed before the operation. All items were evaluated again 3 months after the operation. Results:VAS-OD and SNOT-22 olfactory score were significantly lower in all CRSwNP patients after the operation than those before the operation[F（1, 43） =357.429, P<0.001; F（1, 43） =185.657, P<0.001], the scores of T, D, I and TDI scores in Sniffin' Sticks test were significantly higher than those before the operation[F（1, 43） =126.302, P<0.001; F（1, 43） =311.301, P<0.001; F（1, 43） =131.401, P<0.001; F（1, 43） =295.885, P<0.001]; The decrease of VAS-OD and SNOT-22 olfactory score in the ECRS group was smaller than that in the nECRS group[F（1, 43） =4.825, P=0.033; F（1, 43） =9.916, P=0.003], T, D and TDI scores were significantly lower in nECRS group than those in nECRS group[F（1, 43） =6.719, P=0.013; F（1, 43） =4.890, P=0.032; F（1, 43） =4.469, P=0.040]; There was a positive correlation between preoperative eosinophil-to-lymphocyte ratio（ELR） and SNOT-22 olfactory score and how much it changes（r=0.455, P=0.002; r=-0.414, P=0.005）, a negative correlation between T, TDI score and how much they change respectively（r=-0.431, P=0.003; r=-0.385, P=0.009; r=-0.383, P=0.010; r=-0.316, P=0.035）. The latency of P3 was significantly shorter after operation than that before operation in all CRSwNP patients[F（1, 14） =24.840, P<0.001], however, the amplitude has no significant surgical effect. Conclusion:FESS could significantly improve the olfactory function of CRSwNP patients, while changes in plasticity may occur in the olfactory cortex. In addition, the preoperative peripheral blood eosinophil granulocyte level can predict the postoperative olfactory improvement.

Postinfectious Olfactory Complaints: A Follow-up Study

Abstract Introduction Acute upper respiratory infection (AURI) is the most common cause of postinfectious olfactory dysfunction (PIOD). Objective We investigated the prevalence of PIOD in a large group of patients reporting persistent smell impairment perception after the AURI resolution. Methods Olfactometry was performed within 1 month after the common cold resolution and after 1 year in 467 (299 males, mean age 41.7 years) outpatients. The Sniffin' Sticks olfactory test (Burghart instruments, Wedel, Germany) was used. Results Anosmia was documented in 28 (6%) patients, hyposmia in 33 (7%), and cacosmia in 55 (11.7%). After 1 year, PIOD improved in 82 (79.6%) patients re-tested. Conclusion The current study demonstrated that persistent olfactory dysfunction is a relevant symptom in patients with AURI, even though many patients had normal olfactometry. Thus, smell impairment deserves careful attention and requires objective documentation.

Relation between Vitamin B12 Levels and Smell Affection in COVID-19 Patients

Abstract Introduction Olfactory and gustative alterations are frequent in the initial stages of the COVID-19 infection. Vitamin B12 deficiency has been linked to olfactory dysfunction. Objective The present study aimed to assess the relationship between vitamin B12 levels and smell affection in COVID-19 patients. Methods The present study included 201 laboratory-confirmed COVID-19 patients. Smell affection was assessed using self-rated olfactory function. Serum vitamin B12 levels were assessed using commercial enzyme-linked immunosorbent assay (ELISA) kits. Results According to the smell function assessment, the patients were classified into three categories: normal osmesis (n = 77), hyposmia (n = 49), and anosmia (n = 75) (►Fig. 1). Four weeks later, 195 patients (97.0%) had their normal smell function restored. The remainder 6 patients included 4 anosmic and 2 hyposmic patients. Patients with hyposmia or anosmia had significantly lower vitamin B12 levels when compared with patients with normal osmesis (median [IQR]: 363.0 [198.0-539.0] versus 337.0 [175.0-467.0] and 491.0 [364.5-584.5] pg/ml, respectively, p < 0.001). Conclusion Vitamin B12 appears to have some contribution to smell affection in patients with COVID-19 infection.

Coronavirus disease-19 vaccination and chemosensory dysfunction

Background: Chemosensory disturbances such as altered smell and taste sensations have a strong impact on health and quality of life. The lack of awareness of these chemosensory symptoms post-coronavirus disease (COVID)-19 vaccination has led to apprehension. When adequately addressed, it can encourage people to take vaccines which are a life-saving tool in this pandemic. Aims and Objectives: This study aims to assess the prevalence and duration of altered smell and taste post-COVID-19 vaccination. Materials and Methods: The survey was conducted during January–August 2021. The Institutional Ethical Committee clearance was obtained. Data was collected from 242 COVID-19 vaccine beneficiaries majority of them being health care workers by online and offline survey questionnaires. Descriptive analysis was done using SPSS 21. Results: Out of 250 respondents, 242 completed the study. About 95% of them received CoviShield, 3.8% Covaxin, and 1.3% Pfizer. Perception of altered smell (olfactory dysfunction), taste (gustatory dysfunction), and both smell and taste was reported by 5.8%, 8.27%, and 2.61% of study participants. The mean duration was 3.43 ± 2.03 and 4 ± 1.64 days for altered smell and taste, respectively, with complete recovery. Conclusion: Chemosensory disturbances were reported in a small percentage of vaccine beneficiaries and all of them recovered within a few days completely without any medications. Vaccines are a critical tool in the battle against COVID-19 and we should emphasize on its health and lifesaving benefits and reassure those chemosensory disturbances have complete recovery.

Possible effects of low testosterone levels on olfactory function in males / Possíveis efeitos dos baixos níveis de testosterona na função olfativa em homens

Abstract Introduction: Functions attributed to androgens have increased, ranging from the role in hypothalamic-pituitary-gonadal axis and reproductive behaviors to modulation of cognition, mood and some other functions. Sex differences and changes in circulating sex hormones affect human sensory function. In the literature, authors reported this kind of influence for olfaction predominantly in females. Objective: To investigate the effects of low testosterone levels on olfactory functions in males, in this prospective clinical study. Methods: Male patients diagnosed with prostate cancer were included. Thirty-nine patients with prostate cancer whose testosterone levels were lower than 50 ng/dL due to castration, were the study group. Thirty-one patients with prostate cancer who were not castrated with testosterone levels higher than 50 ng/dL were selected as the control group. Acoustic rhinometry and peak nasal inspiratory flow tests were performed for all participants; and for evaluation of olfactory function, both groups completed the Connecticut chemosensory clinical research center olfactory test. Results: The mean ages of the patients and controls were 69.6 ± 7.2 (57-89) and 66.3 ± 5.8 (50-78) years, respectively (= 0.039). There was a significant difference between groups in terms of testosterone levels (p < 0.0001). The multivariate logistic regression revealed testosterone level as the only predictive factor determining the difference between the groups. In terms of olfactory parameters, all scores were lower in the emasculated group (butanol threshold test p = 0.019, identification p = 0.059, and Connecticut center score p = 0.029) There was a significant correlation between testosterone levels and olfactory parameters (p = 0.023; p = 0.025 for identification and Connecticut center scores, respectively). Conclusion: Low testosterone levels in males have negative effects on olfactory functions. Further molecular research is required to understand the connection between testosterone and olfaction.

Resumo Introdução: As funções atribuídas aos andrógenos aumentaram, variam desde o papel no eixo hipotálamo-hipófise-gonadal e comportamentos reprodutivos até a modulação da cognição, humor e outras funções. As diferenças entre os sexos e as mudanças nos hormônios sexuais circulantes afetam a função sensorial humana. Na literatura, os autores relataram esse tipo de influência para o olfato, principalmente no sexo feminino. Objetivo: Investigar os efeitos dos baixos níveis de testosterona nas funções olfativas em homens, neste estudo clínico prospectivo. Método: Pacientes do sexo masculino com diagnóstico de câncer de próstata foram incluídos no estudo. Compreenderam o grupo de estudo 39 pacientes com câncer de próstata cujos níveis de testosterona eram inferiores a 50 ng/dL devido à castração. Foram determinados como grupo controle 31 pacientes com câncer de próstata que não foram emasculados, com níveis de testosterona superiores a 50 ng/dL. Testes de rinometria acústica e pico de fluxo inspiratório nasal foram feitos para todos os participantes; e para avaliação da função olfativa, ambos os grupos concluíram o teste olfativo do Connecticut chemosensory clinical research center. Resultados: A média da idade dos pacientes e controles foi de 69,6 ± 7,2 (57 ± 89) e 66,3 ± 5,8 (50 ± 78) anos, respectivamente (= 0,039). Houve uma diferença significante entre os grupos em relação a níveis de testosterona (p < 0,0001). A regressão logística multivariada revelou o nível de testosterona como o único fator preditivo que determinou a diferença entre os grupos. Em termos de parâmetros olfativos, todos os escores foram menores no grupo castrado (teste do limiar de butanol p = 0,019, identificação p = 0,059 e escore do Connecticut center p = 0,029). Houve uma correlação significante entre o nível de testosterona e os parâmetros olfativos (p = 0,023; p = 0,025 para identificação e escore do Connecticut center, respectivamente). Conclusão: Baixos níveis de testosterona em homens têm efeito negativo na função olfativa. Mais pesquisas moleculares são necessárias para entender a conexão entre testosterona e olfação.

Frecuencia de disfunción olfatoria en mujeres embarazadas con infección por SARS-CoV-2 / Frequency of olfactory dysfunction in pregnant women with SARS-CoV-2 infection

Resumen Introducción: En pacientes con COVID-19 se ha reportado disfunción olfatoria y anosmia; en la mujer embarazada se presenta hasta en 24.2 %. Objetivo: Conocer la frecuencia con la que las mujeres embarazadas e infección por SARS-CoV-2 tienen disfunción olfatoria. Métodos: Se preguntó edad, edad gestacional, temperatura, presencia de constipación nasal o rinorrea, mialgias, cefalea, tos o dolor torácico, además de evaluar si las mujeres percibían e identificaban el aroma de jugo de uva, café en polvo y mentol. Se utilizaron medidas de tendencia central y dispersión, frecuencias y porcentajes. Se calculó sensibilidad, especificidad, valor predictivo positivo y negativo. La U de Mann-Whitney y el contraste de proporciones sirvieron para las comparaciones entre los grupos. Resultados: Hubo mayor proporción de mujeres con tos, cefalea, disnea, mialgias, odinofagia, rinorrea, dolor torácico y anosmia en mujeres positivas a SARS-CoV-2. De las pacientes sin COVID-19, 88.9 % detectó cada uno de los aromas; solo 31.8 % del grupo positivo detectó el aroma a uva, 47.7 % el de café y 59.1 % el de mentol, el cual tuvo los porcentajes más altos en sensibilidad (40 %), especificidad (21 %), valores predictivos positivo (59 %) y negativo (11 %). Conclusión: la disfunción olfatoria se presenta en un porcentaje importante de las mujeres embarazadas con COVID-19.

Abstract Introduction: In patients with COVID-19, olfactory dysfunction and anosmia have been reported, which in pregnant women occur in up to 24.2 %. Objective: To know the frequency in which pregnant women with SARS-CoV-2 infection have olfactory dysfunction. Methods: Age, gestational age, temperature, presence of nasal constipation or rhinorrhea, myalgia, headache, cough or chest pain were asked. Whether patients perceived and identified the scent of grape juice, coffee powder and menthol was evaluated. Central tendency and dispersion measures, frequencies and percentages were used. Sensitivity, specificity, positive and negative predictive value were calculated. Mann-Whitney's U-test and contrast of proportions were used for comparisons between groups. Results: There was a higher proportion of women with cough, headache, dyspnea, myalgia, odynophagia, rhinorrhea, chest pain, and anosmia in SARS-CoV-2-positive women. In patients without COVID-19, 88.9 % detected each one of the scents; only 31.8 % of the positive group detected grapes scent, 47.7 % coffee and 59.1 % menthol, which had the highest percentages of sensitivity (40 %), specificity (21 %), positive predictive value (59 %) and negative predictive value (11 %). Conclusion: Olfactory dysfunction occurs in a significant percentage of pregnant women with COVID-19.

Anosmia/Hyposmia is a Good Predictor of Coronavirus Disease 2019 (COVID-19) Infection: A Meta-Analysis

Abstract Introduction The number of positive cases and deaths from the coronavirus disease 2019 (COVID-19) is still increasing. The early detection of the disease is very important. Olfactory dysfunction has been reported as the main symptom in part of the patients. Objective To analyze the potential usefulness of anosmia or hyposmia in the detection of the COVID-19 infection. Data Synthesis We systematically searched the PubMed Central database using specific keywords related to our aims until July 31st, 2020. All articles published on COVID-19 and anosmia or hyposmia were retrieved. A statistical analysis was performed using the Review Manager (RevMan, Cochrane, London, UK) software, version 5.4. A total of 10 studies involving 21,638 patients were included in the present analysis. The meta-analysis showed that anosmia or hyposmia is significantly associated with positive COVID-19 infections (risk ratio [RR]: 4.56; 95 % confidence interval [95 %CI]: 3.32-6.24; p < 0.00001; I2 = 78 %, random-effects modeling). Conclusion The presence of anosmia or hyposmia is a good predictor of positive COVID-19 infections. Patients with onset of anosmia or hyposmia should take the test or undergo screening for the possibility of COVID-19 infection.

An Extrapulmonary Manifestation of Coronavirus Disease 2019:Olfactory Dysfunction / 中国医学科学院学报

In addition to acute respiratory symptoms,coronavirus disease 2019(COVID-19)could cause olfactory dysfunction,which becomes the only clinical manifestation of COVID-19 in some cases.We review the epidemiological characteristics,pathological mechanism,screening value,treatment and prognosis of olfactory dysfunction in patients with COVID-19,aiming to achieve an in-depth understanding of the early diagnosis,quarantine,scientific treatment and prognosis of COVID-19.

Association of anosmia and positive SARS-CoV-2 (COVID-19) RT-PCR Test results among patients in the Quezon City General Hospital

Objective@#To determine the association of anosmia and positive SARS-CoV-2 (COVID-19) RT-PCR test results among patients in a tertiary government hospital in Metro Manila.@*Methods@#Design: Cross-Sectional Study. Setting: Tertiary Government Hospital. Participants: Patients aged 18 years old and above who consulted or were admitted with COVID-19 symptoms at the Quezon City General Hospital in the Philippines from July to September 2020 answered an offline version of the American Academy of Otolaryngology-Head and Neck Surgery AAO-HNS COVID-19 Anosmia Reporting Tool prior to undergoing (COVID-19) RT-PCR testing.@*Results@#Out of 172 participants, 63 (36.6%) presented with anosmia. Sixty (95.2%) out of 63 of those with anosmia had a positive COVID-19 RT-PCR test result. Forty-one (65%) participants reported anosmia as the first symptom while the most common associated symptoms were fever (59%), cough (50%), and rhinorrhea (31%). There was a significant association between anosmia and positive SARS-CoV-2 (COVID-19) RT-PCR tests (X2 =33.85, df=1, p<.0001). @*Conclusion@#Anosmia was associated with a positive SARS-CoV-2 (COVID-19) RT-PCR test in more than 95% of those who reported the symptom. Anosmia should be considered as a red flag sign which should be included in the screening of persons suspected of being infected with COVID-19 to help mitigate further spread of the virus.

Prevalence of olfactory dysfunction among COVID-19 patients with self-reported smell loss versus objective olfactory tests: A systematic review and meta-analysis

Background@#Olfactory dysfunction (OD) in COVID-19 presents as a sudden onset smell loss commonly seen in mild symptomatic cases with or without rhinitis but can occur as an isolated symptom. The reported prevalence of OD among COVID-19 patients ranged from 5% to 98%. Although numerous studies have been conducted about their association, these were mainly based on self-reported cases and subjective questionnaires. @*Objective@#This study investigates whether there is a significant difference in the prevalence of olfactory dysfunction between self-reported and objective testing using validated objective olfactory tests among RT-PCR confirmed COVID-19 patients. @*Methods@#PubMed (MEDLINE), Cochrane, Web of Science, and Google Scholar were searched for studies investigating the prevalence of OD by using objective olfactory tests among patients who self-reported OD (November 1, 2019 to July 31, 2020). All studies were assessed for quality and bias using the Cochrane bias tool. Patient demographics, type of objective olfactory test, and results of self-reported OD and objective testing were reported. @*Results@#Nine studies encompassing 673 patients met the inclusion criteria. Validated objective olfactory tests used in the included studies were CCCRC, SST and SIT. Overall prevalence of OD among patients who self-reported was higher after objective testing (71% versus 81%). This was also seen in when we performed subgroup analysis based on the objective tests that were used. However, meta-analysis using random effects model showed no significant difference in the overall prevalence of OD (p value=.479, 95% CI 56.6 to 84.0 versus 71.2 to 89.8) as well as in the subgroups. @*Conclusion@#To the best of our knowledge, this is the first meta-analysis that statistically reviewed articles that evaluated the difference between self-reported and objective tests done on the same patients. Results showing that self-reporting OD approximates the results of the objective tests among COVID-19 positive patients may imply that self-reporting can be sufficient in contact tracing and triggering swabbing and self quarantine during the time of COVID-19 and objective tests can be used as an adjunct in the diagnosis particularly in research. However, this study was limited by small sample size and articles done in European countries hence, interpretation and application of the results of this study must be approached with care. Further studies documenting the difference between self-reporting and objective test in large scale setting involving different countries may be helpful in establishing a definitive consensus.

Association of Anosmia and Positive SARS-CoV-2 (COVID-19) RT-PCR Test Results Among Patients in the Quezon City General Hospital

AbstractObjective: To determine the association of anosmia and positive SARS-CoV-2 (COVID-19) RT-PCR test results among patients in a tertiary government hospital in Metro Manila.Methods: Design: Cross-SectionalStudy Setting: Tertiary Government Training HospitalParticipants: Patients aged 18 years old and above who consulted or were admitted with COVID-19 symptoms at the Quezon City General Hospital in the Philippines from July to September 2020 answered an offline version of the American Academy of Otolaryngology - Head and Neck Surgery AAO-HNS COVID-19 Anosmia Reporting Tool prior to undergoing (COVID-19) RT-PCR testing.Results: Out of 172 participants, 63 (36.6%) presented with anosmia. Sixty (95.2%) out of 63 of those with anosmia had a positive COVID-19 RT-PCR test result. Forty-one (65%) participants reported anosmia as the first symptom while the most common associated symptoms were fever (59%), cough (50%), and rhinorrhea (31%). There was a significant association between anosmia and positive SARS-CoV-2 (COVID-19) RT-PCR tests (X2 =33.85, df=1, pConclusion: Anosmia was associated with a positive SARS-CoV-2 (COVID-19) RT-PCR test in more than 95% of those who reported the symptom. Anosmia should be considered as a red flag sign which should be included in the screening of persons suspected of being infected with COVID-19 to help mitigate further spread of the virus.Keywords: anosmia; olfactory dysfunction; loss of sense of smell; coronavirus; SARS-CoV-2; pandemic; 2019-NCoV; COVID-19

The Impact of Olfactory Dysfunction on the Psychological Status and Quality of Life of Patients with Nasal Obstruction and Septal Deviation

Abstract Introduction Olfactory dysfunctionmay be present in patients with nasal obstruction and septal deviation. The impact of olfactory dysfunction on the psychological profile and quality of life (QoL) of these patients remains unexplored. Objective The present study aimed to investigate the emotional status and QoL of patients with olfactory dysfunction and septal deviation and to identify predictors associated with clinically significant improvement of psychological status and QoL, focusing mainly on the role of olfactory recovery after septoplasty. Methods The olfactory function was quantitatively assessed using the ''Sniffin' sticks'' test (Burghart Messtechnik GmbH, Wedel, Germany) in 60 patients and 25 controls enrolled in this prospective study. The participants completed validated questionnaires specific for general health (Short Form-36), nasal-symptom related QoL (SinoNasal Outcome Test-22), olfaction-associated QoL (Questionnaire of Olfactory Deficits) and for assessing their psychological state (Short Anxiety Screening Test and Beck Depression Inventory) preoperatively and 6 months postoperatively. The patients used the Glasgow Benefit Inventory to evaluate their personal benefit after septoplasty with. Results Septoplasty led to significantly improved olfactory function. Patients with olfactory impairment had significantly lower nasal-symptom related QoL, higher stress levels, andmore depressivemood compared with normosmics and controls before and after septoplasty. Postoperatively, personal benefit from surgery was higher in normosmic patients. Improvement of nasal-symptom related QoL was significantly associated with higher likelihood of clinically significant improvement of patients' psychological profile and more personal benefit from surgery. Olfactory dysfunction was negatively correlated with the emotional status of the patients. Conclusion Olfactory dysfunction appears to significantly affect the psychological status of patients with nasal obstruction, and olfactory recovery improves the patients' perception of personal benefit from septoplasty.

Evaluating the olfactory dysfunction and cognitive deficits induced by intracerebroventricular injection of Amyloid beta (1–42) in female C57BL/6 mice

Amyloid-β (Aβ) is a key pathological hallmark of Alzheimer's disease (AD), the most common form of dementiamajorly occurring in the geriatrics. Aβ accumulation is observed in the brains of AD patients and is reported toproduce long-term effects on cognitive functions leading to neurodegeneration, and subsequently, to AD. Olfactorydeficits are reported in AD and are proposed to be another consequence of these accumulations. The present studywas performed to primarily investigate the olfactory behavior and neurochemical changes in olfactory bulb uponintracerebroventricular (i.c.v) injection of Aβ (1–42) in female C57BL/6 mice. The study also assessed the cognitivechanges of i.c.v injected animals and recorded the subsequent changes in their hippocampus. All behavioral andneurochemical variations were noted separately on 7th, 17th, and 28th day after i.c.v injection. Results from thebehavioral analysis indicated prominent olfactory deficit from the 7th day. Reactive oxygen species levels increasedin both the tissues after Aβ injection. Neurotransmitter data showed that pathological accumulation of Aβ increasesglutamate levels in bulb and hippocampus. Additionally, histopathological evidence supported the neurochemical data.Data from the present study confirmed an olfactory dysfunction associated with AD and reported the neurochemicalchanges leading to these deficits in a non-transgenic model.

Can Sodium Citrate Effectively Improve Olfactory Function in Non-Conductive Olfactory Dysfunction? / 대한이비인후과학회지

The objective of this study was to perform a systematic review of the literature for application of intranasal sodium citrate in the patients with olfactory dysfunction to help determine the sodium citrate treatments for this condition. Two authors independently searched the data base (Medline, Scopus, and the Cochrane database) for relevant studies from inception to January 2018. Included studies were randomized controlled studies published in English comparing topical sodium citrate application (treatment group) with saline (control group) in patients who had olfactory dysfunction. Outcomes of interest included the change of olfactory identification and threshold during 2 hours post-treatment. Three studies were enrolled in the meta-analysis. Compared with control group, treatment group did not increase posttreatment score of olfactory identification [standardized mean difference (SMD)=-0.03; 95% confidence interval (CI)=-0.29-0.24; I²=0%] and olfactory threshold (SMD=0.18; 95% CI=-0.09-0.45; I²=0%) significantly. In the degree of pre-post improvement of two outcomes, although treatment group statistically showed the significant improvement in olfactory threshold (SMD=0.30; 95% CI=0.05-0.55; I²=17%), the clinical significance of this outcome was meaningless. Similarly, there was no significant difference in olfactory identification between two groups (SMD=0.17; 95% CI=-0.11-0.45; I²=22%). Unlike the recent favorable results, our summated results presented the uselessness for the local application of sodium citrate in improving patient's olfactory function. However, we also had some limitation such as small sample size and inconsistent application methods. Therefore, larger trials and standardized methodology are needed to reach more stronger and exact results.

Discussion on Standardization of Forensic Assessment of Olfactory Dysfunction / 法医学杂志

With the development of society, the improvement of living standards and the advancement of research methods, olfactory function has been paid more and more attention. Therefore, higher requirements for the forensic identification of olfactory function have also been put forward. Standardization construction of forensic medical examination and identification of olfactory dysfunction is urgently needed. Based on a comprehensive review of olfactory function and forensic assessment of olfactory dysfunction, this paper elaborates on problems related to the principles and timing of forensic assessment of olfactory dysfunction, the requirements of identification of traumatic olfactory dysfunction, the subjective and objective methods of examination of olfactory function. Strict control of the above issues is an important mean of standardization of forensic assessment of olfactory dysfunction.

Pay attention to the early evaluation and diagnosis for cognitive decline in type 2 diabetes / 中华内分泌代谢杂志

Cognitive decline in diabetes is the main manifestation of diabetic central neuropathy. Such cognitive decrements can be grouped as mild cognitive decline and dementia according to the disease severity, which would seriously threaten to the patients′ quality of late life. Current treatment is not able to reverse the dementia process, thus early diagnosis is essential. Sensory retrogression such as olfactory dysfunction seems to be an early warning indicator of the neurodegenerative diseases. Functional magnetic resonance imaging is an important tool for noninvasive detection of early brain pathophysiological changes. Therefore, the multidisciplinary cooperation among diabetes, neurocognition and neuroimage, and the construction of a quantitative assessment platform for olfactory function would be helpful to the early evaluation and diagnosis of cognitive decline in diabetes, and may also provide new ideas and targets for the early prevention and treatment of the cognitive complications in diabetes.

Pay attention to the early evaluation and diagnosis for cognitive decline in type 2 diabetes / 中华内分泌代谢杂志

Cognitive decline in diabetes is the main manifestation of diabetic central neuropathy. Such cognitive decrements can be grouped as mild cognitive decline and dementia according to the disease severity, which would seriously threaten to the patients' quality of late life. Current treatment is not able to reverse the dementia process, thus early diagnosis is essential. Sensory retrogression such as olfactory dysfunction seems to be an early warning indicator of the neurodegenerative diseases. Functional magnetic resonance imaging is an important tool for noninvasive detection of early brain pathophysiological changes. Therefore, the multidisciplinary cooperation among diabetes, neurocognition and neuroimage, and the construction of a quantitative assessment platform for olfactory function would be helpful to the early evaluation and diagnosis of cognitive decline in diabetes, and may also provide new ideas and targets for the early prevention and treatment of the cognitive complications in diabetes.