Prevalence and Magnitude of Olfactory Dysfunction in Allergic Rhinitis.

BACKGROUND: Although allergic rhinitis (AR) can negatively impact the ability to smell, the degree to which this occurs is not clear and prevalence estimates vary among studies. This study had 4 main objectives: (1) To estimate the prevalence and the degree of olfactory dysfunction in AR patients; (2) To compare olfactory perception between AR patients with different persistence and severity of symptoms and determine if olfactory testing may aid in differentiating among Allergic Rhinitis and its Impact on Asthma (ARIA) groups; (3) To determine whether allergic reactions to different allergens differentially impact olfactory function, and (4) Verify possible changes in the olfactory epithelium (OE) caused by AR. METHODS: One hundred thirty-three patients with AR and one hundred controls were tested. The main outcome was the score in University of Pennsylvania Smell Identification Test (UPSIT®). The OE was examined using immunofluorescence markers for neuronal activity, apoptosis, oxidative stress, signal transduction, eosinophils, and epithelial thickness. RESULTS: Prevalence of olfactory dysfunction in the AR patients was higher (AR: 42.9% vs controls: 9%, P < .001). No difference was found either between intermittent and persistent disease cases (P = .58) or between cases with mild and those with moderate/severe symptomatology (P = .33). Lower olfactory capacity was not associated with the reaction to more (P = .48) or diverse types of allergens (Ps > .05). Although not significant, patients with AR had a greater amount of eosinophilia and a lower amount of cAMP (cyclic adenosine monophosphate) in the OE. CONCLUSION: The study highlights a higher prevalence of olfactory dysfunction in AR patients compared to controls, but olfactory testing may not effectively differentiate AR severity or allergen sensitivities. Although trends suggest potential pathophysiological changes in the OE of AR patients, further research is needed to validate these findings.

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

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.

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.

Healthcare Workers (HCWs) and non-HCWs reaction to Bacillus Calmette-Guérin (BCG) in the BATTLE trial.

OBJECTIVES: Healthcare workers (HCWs) may have different response to Bacillus Calmette-Guérin (BCG) vaccination due to previous occupational exposure to Mycobacterium particles. We report subgroup analysis of the BATTLE trial, comparing BCG effects in HCWs vs non-HCWs. This was a secondary analysis of a trial. METHODS: The BATTLE trial was a double-blind placebo-controlled phase III clinical trial that investigated BCG revaccinating adults who were recently infected with SARS-CoV-2 virus. BCG and placebo recipients were sub-grouped based on regular occupational contact with patients into HCWs (48 BCG and 50 placebo) and non-HCWs (124 BCG and 134 placebo). Weekly COVID-19 symptom progression and injection site reactions were compared between subgroups on weeks one, two, three, and six follow-ups. RESULTS: HCWs were more likely to complain of itching on the injection site early after injection (OR = 2.5, p = 0.049). They developed peeling and crusting on the site of injection faster than non-HCWs (during the second week, p = 0.033 and 0.040, OR = 3.3 and 2.7, respectively). HCWs were also more likely to maintain their papule or develop a late onset pustule during later weeks (weeks four and six, p = 0.024 and 0.006, OR = 2.2 and 8.6, respectively). In terms of COVID-19 symptom progression, recovery from anosmia was more likely in the non-HCWs who received BCG (week six, pHolm's corrected = 0.002, OR = 3.3). CONCLUSION: HCWs' local reaction to BCG injection was slightly more rapid and more intense, possibly due to their occupational exposure. BCG may also ameliorate COVID-19 induced inflammation and anosmia in non-HCWs but not HCWs. Therefore, HCWs might be less likely to benefit from BCG vaccination. CLINICALTRIALS: gov register number NCT04369794.

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.

Persistence of SARS-CoV-2 Antigens in the Nasal Mucosa of Eight Patients with Inflammatory Rhinopathy for over 80 Days following Mild COVID-19 Diagnosis.

The nasal mucosa is the main gateway for entry, replication and elimination of the SARS-CoV-2 virus, the pathogen that causes severe acute respiratory syndrome (COVID-19). The presence of the virus in the epithelium causes damage to the nasal mucosa and compromises mucociliary clearance. The aim of this study was to investigate the presence of SARS-CoV-2 viral antigens in the nasal mucociliary mucosa of patients with a history of mild COVID-19 and persistent inflammatory rhinopathy. We evaluated eight adults without previous nasal diseases and with a history of COVID-19 and persistent olfactory dysfunction for more than 80 days after diagnosis of SARS-CoV-2 infection. Samples of the nasal mucosa were collected via brushing of the middle nasal concha. The detection of viral antigens was performed using immunofluorescence through confocal microscopy. Viral antigens were detected in the nasal mucosa of all patients. Persistent anosmia was observed in four patients. Our findings suggest that persistent SARS-CoV-2 antigens in the nasal mucosa of mild COVID-19 patients may lead to inflammatory rhinopathy and prolonged or relapsing anosmia. This study sheds light on the potential mechanisms underlying persistent symptoms of COVID-19 and highlights the importance of monitoring patients with persistent anosmia and nasal-related symptoms.

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.

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

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.

Postinfectious Olfactory Complaints: A Follow-up Study.

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.

Intensive Olfactory Training in Post-COVID-19 Patients: A Multicenter Randomized Clinical Trial.

BACKGROUND: Olfactory dysfunction (OD)-including anosmia and hyposmia-is a common symptom of COVID-19. Previous studies have identified olfactory training (OT) as an important treatment for postinfectious OD; however, little is known about its benefits and optimizations after SARS-CoV-2 infection. OBJECTIVE: This study aimed to assess whether olfactory training performance can be optimized using more fragrances over a shorter period of time in patients with persistent OD after COVID-19. In addition, we determined the presence of other variables related to OD and treatment response in this population. METHODS: This multicenter randomized clinical trial recruited 80 patients with persistent OD and prior COVID-19 infection for less than 3 months. The patients were divided into 2 groups receiving either 4 or 8 essences over 4 weeks. Subjective assessments and the University of Pennsylvania Smell Identification Test (UPSIT) were performed before and after the treatment. RESULTS: Significant olfactory improvement was measured subjectively and using the UPSIT in both groups; however, no significant differences between the groups were observed. Additionally, the presence of olfactory fluctuations was associated with higher UPSIT scores. CONCLUSION: These data suggest that training intensification by increasing the number of essences for 4 weeks does not show superiority over the classical method. Moreover, fluctuant olfaction seems to be related to a higher score on the UPSIT.

Association between olfactory dysfunction and COVID-19 severity: A prospective study in a highly complex hospital in Peru.

INTRODUCTION: Olfactory dysfunction has been included among the early symptoms of coronavirus disease (COVID-19). Evidence suggests that a relationship exists between the duration of olfaction disorders and the probability of developing severe COVID-19. Given the scope of the COVID-19 pandemic, this study aimed to determine the frequency of smell alteration and its association with the severity of COVID-19 in a referral hospital in Peru, which is one of the most affected countries in the Latin American region. MATERIALS AND METHODS: This study was an observational, prospective cohort study that included patients with COVID-19 who were treated at the Hospital Nacional Edgardo Rebagliati Martins from August to November 2020. To assess the association, the chi-square test of independence or Fisher's exact test was performed. The outcome variable was COVID-19 severity, and the exposure variable was olfactory dysfunction. The first data collection was in the emergency department and the follow-up was via telephone. RESULTS: A total of 179 patients were included. The mean age was 61.6 ± 15.5 years, and 129 patients (72.1%) were male. Olfactory dysfunction was observed in 43 patients (24%). An inverse association was found between age and olfactory dysfunction (P = .002). No significant association was found between COVID-19 severity level and olfactory alteration (P = .056). However, a direct association was found between COVID-19 severity and age (P = .003), cough (P < .001), and respiratory distress (P = .003). CONCLUSION: This study did not find any association between the severity of COVID-19 and olfactory dysfunction. It showed a low incidence rate of smell alteration compared with studies from other regions. Moreover, smell alteration was associated with younger age.

Smell tests can discriminate Parkinson's disease patients from healthy individuals: A meta-analysis.

BACKGROUND: Olfactory impairment is common in Parkinson's disease (PD). The authors aimed to identify the clinical tests used to assess olfactory function and examine their ability to distinguish PD with different disease duration from healthy individuals with physiological aging. METHODS: Cross-sectional studies published until May 2020 that assessed the olfaction of individuals with PD using search terms related to PD, olfactory function, and assessment were searched on PubMed, PsycInfo, Cinahl, and Web of Science databases. RESULTS: Twelve smell tests were identified from the reviewed studies (n = 125) that assessed 8776 individuals with PD. Data of 6593 individuals with PD and 8731 healthy individuals were included in the meta-analyses. Individuals with PD presented worse performance than healthy individuals, regardless of the smell test used. The University of Pennsylvania Smell Identification Test (UPSIT) was used by most studies (n = 2310 individuals with PD) and presented smaller heterogeneity. When the studies were subclassified according to the years of PD duration, there were no significant differences. CONCLUSION: All smell tests were able to discriminate the olfactory function of PD from that of healthy individuals, although the UPSIT was widely used. The abnormal olfaction was not related to the disease duration. Systematic review protocol registration (PROSPERO/2020-CRD42020160878).

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.

Frequency of olfactory dysfunction in pregnant women with SARS-CoV-2 infection.

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 at 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.

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.

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.

Protective effects of intracerebroventricular adiponectin against olfactory impairments in an amyloid ß1-42 rat model.

BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive impairment that eventually develops into dementia. Amyloid-beta (Aß) accumulation is a widely described hallmark in AD, and has been reported to cause olfactory dysfunction, a condition considered an early marker of the disease associated with injuries in the olfactory bulb (OB), the hippocampus (HIPP) and other odor-related cortexes. Adiponectin (APN) is an adipokine with neuroprotective effects. Studies have demonstrated that APN administration decreases Aß neurotoxicity and Tau hyperphosphorylation in the HIPP, reducing cognitive impairment. However, there are no studies regarding the neuroprotective effects of APN in the olfactory dysfunction observed in the Aß rat model. The aim of the present study is to determine whether the intracerebroventricular (i.c.v) administration of APN prevents the early olfactory dysfunction in an i.c.v Amyloid-beta1-42 (Aß1-42) rat model. Hence, we evaluated olfactory function by using a battery of olfactory tests aimed to assess olfactory memory, discrimination and detection in the Aß rat model treated with APN. In addition, we determined the number of cells expressing the neuronal nuclei (NeuN), as well as the number of microglial cells by using the ionized calcium-binding adapter molecule 1 (Iba-1) marker in the OB and, CA1, CA3, hilus and dentate gyrus (DG) in the HIPP. Finally, we determined Arginase-1 expression in both nuclei through Western blot. RESULTS: We observed that the i.c.v injection of Aß decreased olfactory function, which was prevented by the i.c.v administration of APN. In accordance with the olfactory impairment observed in i.c.v Aß-treated rats, we observed a decrease in NeuN expressing cells in the glomerular layer of the OB, which was also prevented with the i.c.v APN. Furthermore, we observed an increase of Iba-1 cells in CA1, and DG in the HIPP of the Aß rats, which was prevented by the APN treatment. CONCLUSION: The present study describes the olfactory impairment of Aß treated rats and evidences the protective role that APN plays in the brain, by preventing the olfactory impairment induced by Aß1-42. These results may lead to APN-based pharmacological therapies aimed to ameliorate AD neurotoxic effects.

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

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; I 2 = 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.

Chronic intermittent hypoxia alters main olfactory bulb activity and olfaction.

Olfactory dysfunction is commonly observed in patients with obstructive sleep apnea (OSA), which is related to chronic intermittent hypoxia (CIH). OSA patients exhibit alterations in discrimination, identification and odor detection threshold. These olfactory functions strongly rely on neuronal processing within the main olfactory bulb (MOB). However, a direct evaluation of the effects of controlled CIH on olfaction and MOB network activity has not been performed. Here, we used electrophysiological field recordings in vivo to evaluate the effects of 21-day-long CIH on MOB network activity and its response to odors. In addition, we assessed animals´ olfaction with the buried food and habituation/dishabituation tests. We found that mice exposed to CIH show alterations in MOB spontaneous activity in vivo, consisting of a reduction in beta and gamma frequency bands power along with an increase in the theta band power. Likewise, the MOB was less responsive to odor stimulation, since the proportional increase of the power of its population activity in response to four different odorants was smaller than the one observed in control animals. These CIH-induced MOB functional alterations correlate with a reduction in the ability to detect, habituate and discriminate olfactory stimuli. Our findings indicate that CIH generates alterations in the MOB neural network, which could be involved in the olfactory deterioration in patients with OSA.

Smell tests to distinguish Parkinson's disease from other neurological disorders: a systematic review and meta-analysis.

Introduction: Olfactory impairment has been considered for differential diagnosis in Parkinson's disease (PD) patients. The authors aimed to identify the tests used to assess the olfactory function in PD patients and examine these tests' ability to distinguish them from other neurological disorders.Areas covered: Cross-sectional studies published until May 2020 comparing the olfactory function of PD patients to other neurological disorders were searched on PubMed, PsycInfo, Cinahl, and Web of Science databases using search terms related to PD, olfactory function, and assessment. Five thousand three hundred and four studies were screened, and 35 were included in the systematic review. Six smell tests that evaluated a total of 1,544 PD patients were identified. Data of 1,144 patients included in the meta-analyses revealed worse smell performance than individuals with other neurological disorders, such as progressive supranuclear palsy and essential tremor, but not with idiopathic rapid eye movement sleep behavior disorder.Expert opinion: The University of Pennsylvania Smell Identification Test was the most used test to assess the olfactory function of PD. Smell loss was worse in PD than in some neurological disorders. The smell tests' ability in differentiating PD from other neurological disorders still deserves more attention in future studies. Protocol register (PROSPERO/2018-CRD42018107009).