[Asociación entre rinitis alérgica e hiposmia].

Objective: To determine the association between AR and the frequency of hyposmia. Method: Cross-sectional, case-control, non-probabilistic census survey in subjects between 14 and 50 years of age. AR was identified by clinical symptoms and positive skin tests. Olfactory function was assessed with the Sniffin Sticks Screening Test. This research was approved by the Ethics and Research Committees of the ISSSTE Regional Hospital "Dr. Valentín Gómez Farías": ZAPOPAN ISSSTE/CEI/488/2020. Result: A total of 147 patients were included, 62 with AR and 85 controls. The average age was 33 years (35 years in AR and 31 years in controls). As a measure of association, the prevalence ratio was calculated, estimating that those with AR have 2.2 times more risk of having hyposmia than controls. Likewise, between them there was a calculated discrepancy of 12.5509 (expected discrepancy 3.84), and a statistical significance of 0.00039 (p=0.00039). Conclusion: AR represents a chronic systemic inflammatory process that leads to hyposmia. Its correlation has been reported from 23 to 48%.1 Likewise, it is important to consider the role that olfaction plays in recognizing and interacting with our environment, and consequently the impact on the quality of life of those who suffer from it. AR significantly increases the risk for suffering hyposmia.

Objetivo: Determinar la asociación entre la RA y la frecuencia de hiposmia. Método: Estudio transversal, casos y controles de carácter censal no probabilístico en sujetos entre 14 a 50 años. Se identificó RA mediante síntomas clínicos y pruebas cutáneas positivas. La función olfatoria fue evaluada con el Sniffin Sticks Screening Test. Esta investigación fue aprobada por los Comités de Ética e Investigación del Hospital Regional "Dr. Valentín Gómez Farías" del ISSSTE: ZAPOPAN ISSSTE/CEI/488/2020. Resultads: Se incluyeron 147 pacientes, 62 con RA y 85 controles. La edad promedio fue de 33 años (35 años en RA y 31 años en controles). Como medida de asociación se calculó la razón de prevalencia estimando que aquellos con RA tienen 2.2 veces más riesgo de tener hiposmia, que los controles. Asimismo, entre ellos hubo una discrepancia calculada de 12.5509 (discrepancia esperada 3.84), y una significancia de 0.00039 (p=0.00039). Conclusió: La RA representa un proceso inflamatorio sistémico crónico que condiciona a hiposmia. Su correlación se ha informado de 23 al 48%.1 A su vez, es importante considerar el papel que juega el olfato en el reconocimiento e interacción con nuestro entorno, y consecuentemente la afección a la calidad de vida de quien lo padece. La RA incrementa significativamente el riesgo de padecer hiposmia.

Are YouTube videos on smell dysfunction a good source of information for patients seeking a cure for their illness?

OBJECTIVE: To conduct unbiased research into the quality and reliability of videos published on YouTube on the subject of smell dysfunction and treatment through two Ear, Nose, and Throat (ENT) specialists using three different tools. METHODS: The videos were separated into two groups (reliable: Group 1; non-reliable: Group 2) according to whether or not the content was scientifically reliable, proven, accurate, and useful, as determined by two ENT specialist physicians. The DISCERN reliability tool, Global quality scale (GQS), and JAMA scoring system were used as video scoring tools in the evaluations. RESULTS: Group 1 included 173 videos, and Group 2, 16 videos. The GQS (First ENT specialist) points were 3 (2-5) and GQS (Second ENT specialist) points were 3 (2-5) in Group 1, and 2 (2-3) and 2 (1-3) in Group 2, respectively (p = 0.0001). The points in the DISCERN and JAMA scoring systems were found to be higher in Group 1 than in Group 2 (p = 0.0001). CONCLUSION: Although the majority of videos on YouTube related to smell dysfunction are reliable, the number of unreliable videos is not inconsiderable. When videos related to medical information are accepted onto YouTube, weighting should be given to videos which include scientifically proven evidence uploaded by specialist professionals and institutions.

OBJETIVO: realizar una investigación imparcial sobre la calidad y la confiabilidad de los videos publicados en YouTube sobre el tema de la disfunción y el tratamiento del olfato, a través de dos especialistas en oído, nariz y garganta que utilizan tres herramientas diferentes. MÉTODOS: Los videos se separaron en dos grupos (confiables: Grupo 1; no confiables: Grupo 2) según si el contenido era o no científicamente confiable, probado, preciso y útil, según lo determinado por dos médicos especialistas en Otorrinolaringología. La herramienta de confiabilidad DISCERN, la escala de calidad global (GQS) y el sistema de puntuación JAMA se utilizaron como herramientas de puntuación de video en las evaluaciones. RESULTADOS: el Grupo 1 incluyó 173 videos y el Grupo 2, 16 videos. Los puntos GQS (Primer especialista en ORL) fueron 3 (2-5) y los puntos GQS (Segundo especialista en ORL) fueron 3 (2-5) en el Grupo 1, y 2 (2-3) y 2 (1-3) en el Grupo 2, respectivamente (p= 0.0001). Se encontró que los puntos en los sistemas de puntuación DISCERN y JAMA eran más altos en el Grupo 1 que en el Grupo 2 (p= 0.0001). CONCLUSIÓN: aunque la mayoría de los videos en YouTube relacionados con la disfunción del olfato son confiables, la cantidad de videos poco confiables no es despreciable. Cuando se aceptan videos relacionados con información médica en YouTube, se debe dar peso a los videos que incluyen evidencia científicamente probada y subidos por instituciones y profesionales especialistas.

OLFATO: forma más antigua de comunicación y sentido preciso que el otorrinolaringólogo debe conocer a profundidad / SMELL: oldest form of communication and precise sense that the otolaryngologist must know in depth

Introducción: el papel clave del olfato, antiguo sistema sensorial, es proporcionar información sobre las sustancias químicas en el medio ambiente. El olfato desempeña un papel en la detección de compuestos peligrosos, el mantenimiento de la nutrición, el comportamiento interpersonal, la salud neurológica y la sensación de placer, entre otras funciones. En consecuencia, la disfunción olfativa puede conducir a un riesgo de lesiones, desnutrición, aislamiento social y una mala calidad de vida. Materiales y métodos: se realizó una exploración bibliográfica y se identificaron artículos de acuerdo con los criterios de inclusión y exclusión definidos y se tomaron aquellos con calidad en la evidencia. Discusión: el sistema olfativo humano tiene diferencias anatómicas, fisiológicas y genéticas considerables con respecto al de otros mamíferos. Conclusiones: las destrezas olfativas varían con factores como la edad, el sexo, la etapa de desarrollo, ciertas enfermedades otorrinolaringológicas y enfermedades generales.

Introduction: The key role of the ancient olfactory sensory system is to provide information about chemicals in the environment. Smell plays a role in the detection of dangerous compounds, the maintenance of nutrition, interpersonal behavior, neurological health, and the sensation of pleasure, among other functions. Consequently, olfactory dysfunction can lead to a risk of injury, malnutrition, social isolation, and a poor quality of life. Materials and methods: A bibliographical exploration was carried out and articles were identified according to the inclusion and exclusion criteria defined and those with quality evidence were taken. Discussion: The human olfactory system has considerable anatomical, physiological, and genetic differences from that of other mammals. Conclusions: Olfactory skills vary with factors such as age, sex, stage of development, certain ear, nose and throat diseases and general diseases.

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.

Terapia de rehabilitación olfatoria en pacientes con síndrome pos-COVID-19 / Olfactory rehabilitation therapy in patients with post-COVID-19 syndrome

El olfato desempeña una función importante en el desarrollo diario de la vida de las personas. Sus alteraciones pueden ser cualitativas (disosmias, parosmias o fantosmias) y cuantitativas (hiposmia o anosmia). Estas alteraciones pueden deberse por enfermedades rinosinusales, neurodegenerativas o infecciones respiratorias como el resfriado común, la gripe y también el SARS-CoV-2, el agente causal del COVID-19. En relación a esta etiología, su fisiopatología no es del todo clara y la anosmia es poco distinguible clínicamente del resto de las infecciones virales, con una duración variable desde ocho días hasta más de cuatro semanas, en cuyo caso se denomina síndrome pos-COVID-19 o COVID prolongado. Este cuadro se caracteriza por la presencia de síntomas que se desarrollan durante la enfermedad aguda por COVID-19,y que persisten durante más de cuatro semanas, sin explicación por un diagnóstico alternativo. El autor de este artículo realiza una revisión de la literatura médica a partir de un caso clínico con el fin de identificar y resumir la evidencia disponible sobre la terapia de rehabilitación olfatoria. (AU)

Sense of smell plays an important role in the daily development of people's lives. Its alterations can be both qualitative (dysosmias, parosmias, or phantosmias) and quantitative (hyposmia or anosmia). These alterations may be due to rhinosi-nusal diseases, neurodegenerative diseases, and respiratory infections such as common cold, influenza, and SARS-CoV-2,causative agent of COVID-19. In relation to this etiology, its pathophysiology is not entirely clear, and anosmia is clinically indistinguishable from the rest of the viral infections, with a variable duration ranging from eight days to more than four weeks, in which case it would be called post COVID- 19 syndrome or prolonged COVID. This condition is characterized by the presence of symptoms that develop during acute COVID-19 illness and persist for more than four weeks without an explanation by an alternative diagnosis.The author of this article carries out a review of the medical literature based on a clinical case in order to identify and summarize the available evidence on olfactory rehabilitation therapy. (AU)

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti–IL-5 Biologics: A Real-Life Study

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug–exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. Objectives: The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non–N-ERD subgroups.Methods: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). Results: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non–N-ERD (35.7%) groups. Conclusions: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non–N-ERD groups (AU)

La rinosinusitis crónica con poliposis nasal (PN), caracterizada por la pérdida parcial o completa del olfato (hiposmia o anosmia, respectivamente), se asocia frecuentemente a asma y a enfermedad respiratoria exacerbada por ácido acetilsalicílico (EREA), lo cual implica una mayor gravedad y un deterioro adicional de la calidad de vida del paciente. Objetivos: El objetivo principal de este estudio fue determinar, en condiciones de vida real, si los tratamientos biológicos prescritos para asma grave mejoraban el olfato en aquellos pacientes que asociaban PN. Como objetivo secundario, se comparó la mejoría del olfato entre los subgrupos EREA y no EREA. Métodos: Se llevó a cabo un estudio multicéntrico, observacional, retrospectivo, que incluyó 206 pacientes con PN y asma grave en tratamiento con algún biológico (omalizumab, mepolizumab, benralizumab oreslizumab). Resultados: Se encontró mejoría del olfato con todos los biológicos: omalizumab (35,8%), mepolizumab (35,4%), reslizumab (35,7%) y benralizumab (39,1%), sin diferencias estadísticamente significativas entre ellos. Los pacientes con atopia, mayor uso de corticoides sistémicos y mayor tamaño de PN inicial, presentaron mayor mejoría. La proporción de pacientes que presentaron mejoría en el olfato fue similar entre el grupo EREA (37%) y no EREA (35,7%). Conclusiones: Se trata del primer estudio que compara, en condiciones de vida real, la mejoría del olfato en pacientes en tratamiento con omalizumab, mepolizumab, reslizumab o benralizumab indicados por asma grave que asociaban PN. Aproximadamente, 4 de cada 10 pacientes refirió mejoría subjetiva en el olfato (sin diferencias estadísticamente significativas entre los distintos biológicos). No se encontraron diferencias entre el grupo EREA y no EREA (AU)

Improvement in Smell Using Monoclonal Antibodies Among Patients With Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review

Background: Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation are also present. Therapeutic options include intranasal and systemic corticosteroids, surgery, and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP.Methods: We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. The inclusion criteria were as follows: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab, or reslizumab; and studies published in English reporting outcomes for sense of smell based on psychophysical and/or subjective tools. We excluded reports that did not assess CRSwNP, loss of smell evaluated with a method other than those accepted in the inclusion criteria, review articles, and expert opinions. No funding was received.Results: Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and in real life. Omalizumab improves smell at 24 weeks. This improvement is maintained in the long-term, although it is not clinically relevant. Mepolizumab and benralizumab improved smell in the long term based on a subjective scale. No studies examining the improvement in smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic for improving impaired sense of smell.Conclusion: Dupilumab seems to be more efficacious for improving the sense of smell than omalizumab, mepolizumab, and benralizumab. (AU)

Antecedentes: La pérdida de olfato de la rinosinusitis crónica se relaciona principalmente con el fenotipo que presenta poliposis nasal (RSCcPN), especialmente si asocia asma y/o EREA, e inflamación tipo 2. Los corticoides intranasales y sistémicos, la cirugía y, de forma más reciente, los fármacos biológicos, constituyen las principales estrategias terapéuticas. Este documento contiene una revisión sistemática del efecto de los fármacos biológicos en el olfato de pacientes con RSCcPN. Métodos: Se realizó una búsqueda sistemática en las bases de datos PubMed y Cochrane desde enero de 2001 hasta junio de 2022. Los criterios de inclusión fueron: pacientes adultos con RSC tratados con dupilumab, omalizumab, mepolizumab, benralizumab o reslizumab; estudios publicados en inglés, con datos sobre la mejoría del olfato utilizando test psicofísicos y/o subjetivos. Los criterios de exclusión fueron: publicaciones que no incluían pacientes con poliposis nasal, la pérdida del olfato evaluada con un método diferente de los criterios de inclusión mencionados, los artículos de revisión y la opinión de expertos. No se empleó ningún recurso de financiación. Resultados: Dupilumab ha demostrado una mejora del olfato rápida y mantenida a largo plazo en ensayos clínicos y en la práctica clínica habitual. Omalizumab mejora el olfato en la 24ª semana y lo mantiene a largo plazo, pero no alcanza una mejoría clínicamente relevante. Mepolizumab y benralizumab mejoran el olfato a largo plazo, evaluado mediante un test subjetivo. No se encontraron estudios respecto a la mejoría del olfato en pacientes con RSCcPN tratados con reslizumab. Las comparaciones indirectas mediante metaanálisis concluyen de forma consistente que dupilumab es el biológico más eficaz para mejorar el sentido del olfato. Conclusión: Dupilumab es el biológico más eficaz en la mejoría del olfato en RSCcPN, en comparación con omalizumab, mepolizumab y benralizumab. (AU)

Factores asociados a la anosmia y ageusia en pacientes COVID-19 de una provincia peruana

Objetivo: identificar la presentación clínica y los factores asociados a la anosmia y ageusia en pacientes con la COVID-19 en un centro de salud de una provincia del Perú en el período de 2020-2021. Métodos: estudio transversal analítico a través de los datos del programa COVID-19 del Policlínico Essalud de Jauja - Perú. Se detallaron características sociodemográficas, sintomatología y comorbilidades de los pacientes. A través de un análisis bivariado se identificó los factores asociados a la anosmia y ageusia. Resultados: se identificó a 356 pacientes: 53,1 % fueron mujeres, la edad media fue 48,7 años (±17,8) y 261 (73,3 %) con COVID-19 leve. Del total, el 22,2 % presentó anosmia y 19,9 % ageusia; de los cuales la mayoría fueron menores de 65 años y del sexo femenino. Presentaron síntomas asociados un 86,1 % de los pacientes con anosmia y un 83,1% con ageusia. Los principales factores asociados a la anosmia fueron: la edad menor a 65 años (p=0,027), tos (p<0,001), cefalea (p<0,001), disnea (p<0,001), congestión nasal (p<0,001) y fiebre (p<0,001); y a la ageusia: edad menor a 65 años (p=0,006), tos (p=0,001), cefalea (p<0,001), disnea (p<0,001), congestión nasal (p<0,001) y diarrea (p<0,001). Conclusiones: la anosmia y ageusia son síntomas frecuentes de la COVID-19. La mayoría de pacientes presentaron estos síntomas asociados a los síntomas comunes. Gran parte de los que presentaban anosmia presentaron congestión nasal por lo que es recomendable considerar diferenciarlos al momento de realizar el diagnóstico.

Summary Objective: To identify the clinical presentation and factors associated with anosmia and ageusia in patients with COVID-19 in a health center in a province of Peru for the period 2020-2021. Methods: Cross-sectional analytical study through data from the COVID-19 program of the Essalud Polyclinic in Jauja, Peru. Sociodemographic characteristics, symptoms and comorbidities of the patients were detailed. A bivariate analysis identified the factors associated with anosmia and ageusia. Results: 356 patients were identified: 53.1 % were women, mean age was 48.7 years (±17.8) and 261 (73.3%) with mild COVID-19. Of the total, 22.2% had anosmia and 19.9% ageusia; of which the majority were under 65 and female. Associated symptoms were found in 86.1% of patients with anosmia and 83.1% with ageusia. The main factors associated with anosmia were age younger than 65 years (p=0.027), cough (p<0.001), headache (p<0.001), dyspnea (p<0.001), nasal congestion (p<0.001) and fever (p<0.001); and ageusia: age younger than 65 years (p=0.006), cough (p=0.001), headache (p<0.001), dyspnea (p<0.001), nasal congestion (p<0.001) and diarrhea (p<0.001). Conclusion: Anosmia and ageusia are common symptoms of COVID-19. Most patients had these symptoms associated with common symptoms. Many of those who had anosmia had nasal congestion, so it is advisable to consider differentiating them when making the diagnosis.

Alteraciones olfativas y déficits en la capacidad del reconocimiento emocional en pacientes con trauma craneoencefálico

El presente estudio tuvo como objetivo general identificar la asociación entre las alteraciones olfativas y el reconocimiento emocional en un grupo de pacientes con diagnóstico de traumatismo craneoencefálico. Fue desarrollada bajo un enfoque cuantitativo con diseño no experimental, en donde fueron evaluados 10 pacientes con antecedente de trauma craneoencefálico moderado y severo junto a 10 participantes controles sin daño cerebral. Para las variables sexo, edad y escolaridad los resultados fueron muy similares entre los grupos, con edades promedio de 26 años; la población fue predominantemente masculina, y la mayoría tenía grado de educación superior. En las pruebas de reconocimiento emocional, el grupo control logró un desempeño superior al grupo de casos. Adicionalmente, el grupo control logró mejor capacidad en las pruebas olfativas que el grupo de casos. Se encontró una correlación estadísticamente significativa entre los resultados del reconocimiento emocional y la variable olfativa en el grupo de casos, lo que permite identificar el rol que estructuras del sistema cerebral topográfica y funcionalmente pueden estar participando del procesamiento; a su vez, abre perspectivas de estudios a futuro, en especial a modelos de intervención en los grupos clínicos con afectación por el traumatismo craneoencefálico.

The general objective of this study was to "identify the association between emotional recognition and olfactory alterations in a group of patients with SCD". It was developed under a quantitative approach with nonexperimental design, in which 10 patients with a history of moderate and severe cranioencephalic trauma were evaluated along with 10 control participants without brain damage. For the variables sex, age and schooling the results were very similar among the groups, with average ages of 26 years, the population was predominantly male and most had higher education. In the tests of emotional recognition the control group achieved a superior performance to the group of cases. In addition, the control group achieved better capacity in olfactory tests than the group of cases. A statistically significant correlation was found between the emotional recognition results and the olfactory variable in the group of cases, which allows the identification of the role that topographic and functional brain system structures may be involved in processing; In turn, it opens prospects for future studies especially to intervention models in clinical groups affected by head trauma.

Validation of the Connecticut olfactory test (CCCRC) adapted to Brazil / Validação do teste de olfato de Connecticut (CCCRC) adaptado para o Brasil

Abstract Introduction Olfactory changes are quite common in the population, causing a significant impact on the quality of life. Documentation of the olfactory function is essential for the diagnosis, treatment and follow-up of patients with inflammatory diseases of the upper airways, neurodegenerative diseases or viral infections. Among the different existing smell tests, the CCCRC is an inexpensive test, easy to apply, but it has not yet been evaluated on a large scale in the Brazilian population. Objective To validate the CCCRC smell test, after adaptation for the Brazilian population, evaluating the performance of healthy volunteers and the stability of the test in retests. Methods In this study, we carried out a cultural adaptation of the CCCRC test to Brazil. To validate and determine the normality scores, we applied the test to 334 healthy volunteers, aged >18 years of age. The retest was also carried out in up to four weeks on 34 additional volunteers to assess validity of the results. Results When evaluating the participants' performance, normosmia and mild hyposmia values were obtained in more than 95% of them. Women (58.4%) showed better accuracy than men (41.6%): p < 0.02, and individuals over 60 years of age showed worse performance (median: 6; 75th percentile: 6.5; 25th percentile). The test and retest of the 34 volunteers demonstrated that there was agreement (ICC, intraclass correlation coefficient) considered good in the left nostril (ICC = 0.65) and excellent in the right nostril (ICC = 0.77) in the combined score. Conclusion The CCCRC test adapted to Brazil showed normal values, similar to the originally-described test and validations in other countries, with a high reproducibility rate. Considering the highly favorable cost-benefit ratio, the adapted CCCRC is a very useful tool for measuring olfactory function in the Brazilian population.

Resumo Introdução Alterações olfativas são bastante comuns na população, causam significativo impacto na qualidade de vida. A documentação da função olfatória é fundamental para o diagnóstico, tratamento e seguimento de pacientes que cursam com doenças inflamatórias das vias aéreas superiores, neurodegenerativas ou infecções virais. Entre os diferentes testes de olfato existentes, o teste do Connecticut Chemosensory Clinical Research Center (CCCRC) é barato, de fácil aplicação, mas que ainda não foi avaliado em grande escala para a população brasileira. Objetivo Validar o teste de olfato CCCRC com adaptação para a população brasileira, avaliar o desempenho de voluntários saudáveis e a estabilidade do teste em retestes. Método Neste estudo fizemos adaptação cultural do teste CCCRC para o Brasil. Para validação e determinação dos escores de normalidade, aplicamos o teste em 334 voluntários saudáveis, com mais de 18 anos. O reteste foi ainda feito em até quatro semanas em 34 voluntários adicionais para avaliar concordância dos resultados. Resultados Avaliando o desempenho dos participantes, valores de normosmia e hiposmia leve foram obtidos em mais de 95% deles. Mulheres (58,4%) apresentaram melhor acurácia em relação aos homens (41,6%), p< 0,02; e indivíduos acima dos 60 anos apresentaram pior desempenho (mediana: 6; percentil 75: 6,5; percentil 25: 5). O teste e reteste dos 34 voluntários demonstrou que houve concordância (coeficiente de correlação intraclasse, CCI) considerada boa em narina esquerda (CCI = 0,65) e excelente em narina direita (CCI = 0,77) no escore combinado. Conclusão O teste CCCRC adaptado para o Brasil apresentou valores de normalidade semelhantes ao teste originalmente descrito e a validações em outros países, com alta taxa de reprodutibilidade. Considerando a relação custo-benefício altamente favorável, o CCCRC adaptado é uma ferramenta muito útil para mensuração da função olfatória na população brasileira.

Biopsy of the olfactory epithelium from the superior nasal septum: is it possible to obtain neurons without damaging olfaction? / Biópsia do epitélio olfatório do septo nasal superior: é possível obter neurônios sem prejudicar o olfato?

Abstract Introduction Olfactory epithelium biopsy has been useful for studying diverse otorhinolaryngological and neurological diseases, including the potential to better understand the pathophysiology behind COVID-19 olfactory manifestations. However, the safety and efficacy of the technique for obtaining human olfactory epithelium are still not fully established. Objective This study aimed to determine the safety and efficacy of harvesting olfactory epithelium cells, nerve bundles, and olfactory epithelium proper for morphological analysis from the superior nasal septum. Methods During nasal surgery, 22 individuals without olfactory complaints underwent olfactory epithelium biopsies from the superior nasal septum. The efficacy of obtaining olfactory epithelium, verification of intact olfactory epithelium and the presence of nerve bundles in biopsies were assessed using immunofluorescence. Safety for the olfactory function was tested psychophysically using both unilateral and bilateral tests before and 1 month after the operative procedure. Results Olfactory epithelium was found in 59.1% of the subjects. Of the samples, 50% were of the quality necessary for morphological characterization and 90.9% had nerve bundles. There was no difference in the psychophysical scores obtained in the bilateral olfactory test (University of Pennsylvania Smell Identification Test [UPSIT®]) between means before biopsy: 32.3 vs. postoperative: 32.5, p= 0.81. Also, no significant decrease occurred in unilateral testing (mean unilateral test scores 6 vs. 6.2, p= 0.46). None out of the 56 different odorant identification significantly diminished (p> 0.05). Conclusion The technique depicted for olfactory epithelium biopsy is highly effective in obtaining neuronal olfactory tissue, but it has moderate efficacy in achieving samples useful for morphological analysis. Olfactory sensitivity remained intact.

Resumo Introdução A biópsia do epitélio olfatório tem sido útil para estudar diversas doenças otorrinolaringológicas e neurológicas, incluindo seu potencial para melhor compreender a fisiopatologia por trás das manifestações olfatórias na COVID‐19. No entanto, a segurança e eficácia da técnica de obtenção de epitélio olfatório humano ainda não estão totalmente estabelecidas. Objetivos Este estudo teve como objetivo determinar a segurança e eficácia da coleta de células do epitélio olfatório, feixes nervosos e epitélio olfatório adequados para análise morfológica, no septo nasal superior. Método Durante a cirurgia nasal, 22 indivíduos sem queixas olfatórias foram submetidos a biópsias de epitélio olfatório do septo nasal superior. A eficácia da obtenção de epitélio olfatório, a verificação de epitélio olfatório íntegro e a presença de feixes nervosos nas biópsias foram avaliadas por imunofluorescência. A segurança da função olfatória foi testada psicofisicamente usando testes unilaterais e bilaterais antes e um mês após o procedimento cirúrgico. Resultados Epitélio olfatório foi encontrado em 59,1% dos sujeitos. Das amostras, 50% apresentaram a qualidade necessária para a caracterização morfológica e 90,9% continham feixes nervosos. Não houve diferença nos escores psicofísicos obtidos no teste olfatório bilateral (University of Pennsylvania Smell Identification Test [UPSIT®]) entre as médias antes da biópsia: 32,3 vs. pós‐operatório: 32,5, p = 0,81. Além disso, nenhuma diminuição significante ocorreu no teste unilateral (escore médio do teste unilateral 6 vs. 6,2, p = 0,46). Não houve redução significante na identificação de nenhum dos 56 odorantes diferentes (p > 0,05). Conclusão A técnica descrita para biópsia de epitélio olfatório é altamente eficaz na obtenção de tecido olfatório neuronal, mas tem eficácia moderada na obtenção de amostras adequadas para análise morfológica. A capacidade olfativa permaneceu intacta.

Pathophysiological relationship between COVID-19 and olfactory dysfunction: A systematic review / Relação fisiopatológica entre Covid‐19 e disfunção olfativa: uma revisão sistemática

Abstract Introduction SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins secreted by sustentacular cells in order to be processed by olfactory receptor neurons. Olfactory disorder is one of the main manifestations of COVID-19, however, research is still required to clarify the mechanism involved in SARS-CoV-2 induced anosmia. Objective This article aims to analyze current scientific evidence intended to elucidate the pathophysiological relationship between COVID-19 and the cause of olfactory disorders. Methods Pubmed, Embase, Scopus and ScienceDirect were used to compose this article. The research was conducted on November 24th, 2020. Original articles with experimental studies in human, animal and in vitro, short communications, viewpoint, published in the English language and between 2019 and 2020 were included, all related to the pathophysiological relationship between olfactory disorders and COVID-19 infection. Results Both human cell receptors ACE2 and TMPRSS2 are essential for the SARS-CoV-2 entrance. These receptors are mostly present in the olfactory epithelium cells, therefore, the main hypothesis is that anosmia is caused due to damage to non-neuronal cells which, thereafter, affects the normal olfactory metabolism. Furthermore, magnetic resonance imaging studies exhibit a relationship between a reduction on the neuronal epithelium and the olfactory bulb atrophy. Damage to non-neuronal cells explains the average recovery lasting a few weeks. This injury can be exacerbated by an aggressive immune response, which leads to damage to neuronal cells and stem cells inducing a persistent anosmia. Conductive anosmia is not sufficient to explain most cases of COVID-19 induced anosmia. Conclusion Olfactory disorders such as anosmia and hyposmia can be caused by COVID-19, the main mechanism is associated with olfactory epithelium damage, targeting predominantly non-neuronal cells. However, neuronal cells can also be affected, worsening the condition of olfactory loss.

Resumo Introdução SARS‐CoV‐2 é o patógeno da Covid‐19. O vírus é composto pela proteína spike (espigão), a membrana e o envelope. No olfato fisiológico, as substâncias odoríferas se ligam a proteínas secretadas pelas células sustentaculares para serem processadas pelos neurônios receptores olfativos. O distúrbio olfativo é uma das principais manifestações da Covid‐19; entretanto, pesquisas ainda são necessárias para esclarecer o mecanismo envolvido na anosmia induzida pela SARS‐CoV‐2. Objetivos Este artigo tem como objetivo analisar as evidências científicas atuais destinadas a elucidar a relação fisiopatológica entre a Covid‐19 e a causa dos distúrbios olfativos. Método As bases de dados Pubmed, Embase, Scopus e ScienceDirect foram usadas para compor este artigo. A pesquisa foi feita em 24 de novembro de 2020. Foram incluídos artigos originais com estudos experimentais em seres humanos, animais e estudos in vitro, comunicações breves, pontos de vista, publicados na língua inglesa e entre 2019 e 2020, todos relacionados à relação fisiopatológica entre distúrbios olfativos e infecção por Covid‐19. Resultados Ambos os receptores de células humanas ACE2 e TMPRSS2 são essenciais para a penetração do SARS‐CoV‐2. Esses receptores estão presentes principalmente nas células do epitélio olfativo; portanto, a principal hipótese é que a anosmia é causada por lesão de células não neuronais que, a partir daí, afeta o metabolismo olfativo normal. Além disso, estudos de ressonância magnética mostram uma relação entre a redução do epitélio neuronal e a atrofia do bulbo olfatório. Danos às células não neuronais explicam o tempo médio de recuperação, que demora algumas semanas. Essa lesão pode ser exacerbada por uma resposta imune agressiva, que leva a danos às células neuronais e células‐tronco, induz uma anosmia persistente. A anosmia condutiva não é suficiente para explicar a maioria dos casos de anosmia induzida por Covid‐19. Conclusão Distúrbios olfativos como anosmia e hiposmia podem ser causados pela Covid‐19 e o principal mecanismo está associado à lesão do epitélio olfativo, tem como alvo células predominantemente não neuronais. Porém, células neuronais também podem ser afetadas, o que piora o quadro de perda olfativa.

Evaluation of the complete Sniffin Sticks Test versus its subtests in differentiating Parkinson's disease patients from healthy controls / Avaliação do Sniffin Sticks Test completo versus seus subtestes na diferenciação de pacientes com doença de Parkinson de controles sem a doença

Abstract Background Hyposmia is one of the most common, as well as the first nonmotor condition in Parkinson disease (PD). The sniffin sticks test (SST) evaluates three different aspects of olfactory function: threshold (T), discrimination (D), and identification (I). The sum of the scores of these three subtests produce a global score of olfaction, the Threshold-Discrimination-Identification (TDI) score. Objective The aim of this study was to investigate if the TDI score or one of its subtests is better to discriminate PD patients from controls. Methods We recruited 27 PD patients and 17 healthy age-matched controls (HC) who were evaluated through a clinical interview, the Montreal Cognitive Assessment and Movement Disorders Society - Unified Parkinson Disease Rating Scale. The olfaction was assessed using the complete SST. Results The performance of PD patients on the olfactory test was significantly worse when compared with the HC (T: 3.0 vs. 6.5, p < 0.001; D: 8.1 vs. 11.2, p <0.001; I: 7.3 vs. 11.7, p < 0.001; TDI: 18.8 vs. 29.9, p < 0.001). The prevalence of olfaction impairment in our study (PD: 100%, and HC: 56%) was greater than that found in the literature. Cognition influenced the performance on TDI. The olfactory subtests were impaired proportionally between patients and controls. Furthermore, D and I were correlated, but only in PD patients. The TDI showed a tendency to better discriminate PD patients from HC, when compared with its subtests. Conclusions Although the complete olfactory evaluation is time consuming, it seems to be a superior tool to identify olfaction impairment in PD patients, when compared with the isolated subtests.

Resumo Antecendentes Hiposmia é um dos sintomas mais comuns da doença de Parkinson (DP), além de ser um de seus primeiros sintomas não-motores. O Sniffin Sticks Test avalia três diferentes aspectos da função olfatória: limiar (L), discriminação (D) e identificação (I). A soma dos escores desses três subtestes produz um escore global do olfato, o Threshold-Discrimination-Identification (TDI). Objetivo O objetivo deste estudo foi investigar se oTDI ou um de seus subtestes seria melhor em discriminar pacientes com DP de controles saudáveis. Métodos Foram recrutados 27 pacientes com DP e 17 controles saudáveis de mesma faixa etária, que foram avaliados através de uma entrevista clínica, a Montreal Cognitive Assessment e Movement Disorders Society - Unified Parkinson Disease Rating Scale. O olfato foi examinado através da bateria completa do Sniffin Sticks Test (SST). Resultados Os pacientes com DP tiveram pior performance no teste olfatório quando comparados com os controles (L: 3,0 vs. 6,5; p < 0,001; D: 8,1 vs. 11,2; p <0,001; I: 7,3 vs. 11,7; p <0,001; TDI: 18,8 vs. 29,9; p < 0,001). A prevalência de comprometimento olfatório no nosso estudo (DP: 100%, e controles: 56%) foi maior do que a reportada na literatura. A cognição influenciou a performance no TDI. Os subtestes olfatórios foram afetados proporcionalmente entre pacientes e controles. Além disso, D e I se correlacionaram, mas apenas em pacientes de DP. O TDI mostrou uma tendência em melhor discriminar pacientes de DP dos controles, quando comparado com os seus subtestes. Conclusões Embora a avaliação olfatória completa consuma tempo, ela parece ser superior aos subtestes isolados para identificar comprometimento olfatório em pacientes com DP.

Avaliação da Disfunção Endotelial em Casos de COVID-19 com Dilatação Fluxo-Mediada / Evaluation of Endothelial Dysfunction in COVID-19 With Flow-Mediated Dilatation

Resumo Fundamento: Sabe-se que a inflamação desempenha um papel crucial em muitas doenças, incluindo a COVID-19. Objetivo: Utilizando a dilatação fluxo-mediada (DFM), objetivou-se avaliar os efeitos da inflamação na função endotelial de pacientes com COVID-19. Métodos: Este estudo foi realizado com um total de 161 indivíduos, dos quais 80 foram diagnosticados com COVID-19 nos últimos seis meses (48 mulheres e 32 homens com idade média de 32,10±5,87 anos) e 81 eram controles saudáveis (45 mulheres e 36 homens com idade média de 30,51±7,33 anos). Os achados do ecocardiograma transtorácico e da DFM foram analisados em todos os indivíduos. Resultados com p<0,05 foram considerados estatisticamente significantes. Resultados: O ecocardiograma e a DFM do grupo COVID-19 foram realizados 35 dias (intervalo: 25-178) após o diagnóstico. Não houve diferença estatisticamente significativa nos parâmetros ecocardiográficos. Em contraste, a DFM (%) foi significativamente maior no grupo controle (9,52±5,98 versus 12,01±6,18; p=0,01). Na análise multivariada com o modelo stepwise progressivo, a DFM foi significativamente diferente no grupo controle em relação ao grupo COVID-19 (1,086 (1,026-1,149), p=0,04). O teste de correlação de Spearman indicou que a DFM (r=0,27; p=0,006) apresentou correlação positiva fraca com a presença de COVID-19. Conclusão: Os achados deste estudo apontam para disfunção endotelial induzida por COVID-19, avaliada por DFM, na fase inicial de recuperação.

Abstract Background: Inflammation is known to play a crucial role in many diseases, including COVID-19. Objective: Using flow-mediated dilatation (FMD), we aimed to assess the effects of inflammation on endothelial function in COVID-19 patients. Methods: This study was conducted with a total of 161 subjects, of whom 80 were diagnosed with COVID-19 within the last six months (comprising 48 women and 32 men with a mean age of 32.10 ± 5.87 years) and 81 were healthy controls (comprising 45 women and 36 men with a mean age of 30.51 ± 7.33 years). We analyzed the findings of transthoracic echocardiography and FMD in all subjects. All results were considered statistically significant at the level of p < 0.05. Results: The echocardiography and FMD of the COVID-19 group were performed 35 days (range: 25-178) after diagnosis. There was no statistically significant difference in echocardiographic parameters. Differently, FMD (%) was significantly higher in the control group (9.52 ± 5.98 vs. 12.01 ± 6.18, p=0.01). In multivariate analysis with the forward stepwise model, FMD was significantly different in the control group compared to the COVID-19 group (1.086 (1.026 - 1.149), p=0.04). A Spearman's correlation test indicated that FMD (r=0.27, p=0.006) had a weak positive correlation with the presence of COVID-19. Conclusion: Our findings point to COVID-19-induced endothelial dysfunction, as assessed by FMD, in the early recovery phase.

Psicología y olfato hacia un abordaje interdisciplinar frente a la COVID-19 / Psychology and smell towards an interdisciplinary approach against Covid-19 / Psicologia e cheiro por uma abordagem interdisciplinar contra o Covid-19

La psicología frente al olfato puede constituirse en una alternativa para mejorar la calidad de vida de las personas que han sufrido trastornos olfativos a causa de la pandemia de la Covid-19, en tal sentido a nivel mundial se van conformando equipos interdisciplinares para brindar alternativas científicas globales con diferentes perspectivas profesionales, es así que esta disciplina tiene la oportunidad y el reto de vincularse a estos equipos de alto nivel, fortaleciendo la perspectiva del entrenamiento olfativo clásico del área médica, y matizarlo con los criterios técnicos de la psicología del tercer milenio, y así tratar de disminuir las secuelas de esta enfermedad y ampliar las esperanzas de las personas de cualquier parte del mundo que sufren estos deterioros sensoriales.

Psychology against smell can become an alternative to improve the quality of life of people who have suffered olfactory disorders due to the Covid-19 pandemic, in this sense, interdisciplinary teams are being formed worldwide to provide scientific alternatives groups with different professional perspectives, so this discipline has the opportunity and the challenge of being linked to these high-level teams, strengthening the perspective of classical olfactory training in the medical area, and qualifying it with the technical criteria of the psychology of the third millennium, and thus try to reduce the consequences of this disease and expand the hopes of people from any part of the world who suffer from these sensory impairments.

A psicologia contra o olfato pode se tornar uma alternativa para melhorar a qualidade de vida de pessoas que sofreram distúrbios olfativos devido à pandemia de Covid-19, nesse sentido, equipes interdisciplinares estão sendo formadas em todo o mundo para fornecer alternativas científicas a grupos com diferentes perspectivas profissionais. disciplina tem a oportunidade e o desafio de estar vinculada a essas equipes de alto nível, fortalecendo a perspectiva da formação olfativa clássica na área médica, e qualificando-a com os critérios técnicos da psicologia do terceiro milênio, e assim tentar reduzir o consequências desta doença e ampliar as esperanças de pessoas de qualquer parte do mundo que sofrem com essas deficiências sensoriais.

Evaluación del olfato en pacientes operados por adenoma hipofisario con acceso transesfenoidal en el Instituto de Neurocirugía Dr. Asenjo / Olfactory evaluation in patients operated for pituitary adenoma with transsphenoidal access at the Instituto de Neurocirugía Dr. Asenjo

Introducción: El olfato tiene una gran importancia en la calidad de vida. Los accesos quirúrgicos selares pueden realizarse por vía transcraneal, transeptal y transnasal, y pueden generar hiposmia al incluir resecciones que afectan a la mucosa olfatoria. Objetivo: Determinar la existencia de alteración persistente en el olfato ocasionado por los accesos quirúrgicos transeptal y transnasal en pacientes operados por adenoma hipofisiario en el Instituto de Neurocirugía Dr. Asenjo. Material y Método: Estudio prospectivo de cohorte con comparación de resultados olfatorios ("sniffin' sticks" versión extendida) y encuesta SNOT-22 pre y poscirugía por adenoma hipofisiario por vía transeptal o transnasal. Se utilizaron medidas estadísticas de comparación de pruebas pareadas paramétricas y no paramétricas según las características de las variables evaluadas. Resultados: Se reclutaron 60 pacientes, completando el seguimiento 39. En 21 se realizó acceso transeptal y en 18 transnasal. Al analizar el total de pacientes y por cada técnica quirúrgica, no hubo diferencias significativas en los puntajes del "sniffin' sticks" versión extendida y tampoco en SNOT-22. Conclusión: La literatura describe incidencia de hiposmia posoperatoria muy variable, entre 0% y 88%, con mediciones subjetivas y objetivas. Existe una predilección por la técnica endoscópica a nivel internacional, por lo que cuenta con estudios de mejor calidad. A nivel nacional existen dos estudios previos que han encontrado tasas de hiposmia posoperatoria de 10% y 14%. En este estudio no hubo diferencias significativas en los puntajes obtenidos en la prueba de olfato entre el pre y posoperatorio.

Introduction: Olfaction is of great importance in quality of life. Surgical accesses to the sellar region can be performed by transcranial, transseptal, and transnasal routes, which can generate hyposmia when including resections that affect the olfactory mucosa. Aim: To determine the existence of persistent alteration in olfaction caused by transseptal and transnasal surgical accesses in patients operated for pituitary adenoma at the Instituto de Neurocirugía Dr. Asenjo. Material and Method: Prospective cohort study with comparison of olfactory results ("sniffin' sticks" extended version) and SNOT-22 survey pre and post transseptal or transnasal surgery for pituitary adenoma. Parametric and non-parametric paired test comparison statistics were used according to the characteristics of the variables evaluated. Results: 60 patients were recruited and 39 completed follow-up. 21 patients underwent transseptal access and 18 underwent transnasal access. When analyzing the total number of patients and for each surgical technique, there were no significant differences in the scores obtained in the "sniffin' sticks" extended version and neither for the SNOT-22. Conclusion: The literature describes a highly variable incidence of postoperative hyposmia, between 0% and 88%, with subjective and objective measurements. There is a predilection for the endoscopic technique at an international level, which is why it has better quality studies. At the national level there are two previous studies that have found postoperative hyposmia rates of 10% and 14%. In this study there were no significant differences in the scores obtained between pre and postoperative olfaction test.

Subjective assessment of taste and smell disfunction in patients with COVID-19 in Paraguay / Evaluación subjetiva de las alteraciones del sentido del gusto y del olfato en pacientes con COVID-19 en Paraguay

The alteration of the senses of taste and smell in relation to COVID-19 is a widely known phenomenon; however, this alteration has not been exhaustively characterized in the international literature. The following study is proposed with the aim of describing the alterations in the senses of taste and smell in relation to COVID-19 by means of their subjective evaluation. The nature of the study is observational, descriptive and cross-sectional, and was applied to patients who sought medical attention via remote consultations carried out on virtual platforms of the Service of Otorhinolaryngology and Head and Neck Surgery of the Clínicas Hospital, San Lorenzo, between the months of March and October of 2021. We included 440 patients aged 31.3 ± 9.9 years (18 to 60 years), 308 (70%) female, 388 (88%) from urban areas, with evidence of infection by SARS-CoV-2 by RT-PCR in 260 (59%), predominantly without comorbidities 232 (53%), with fever as the most frequently reported symptom 352 (80%), treated more frequently with NSAIDs 208 (47%) and/or Paracetamol 216 (49%). Both taste and smell alterations in patients who have had COVID-19 have been shown to appear more frequently 1 to 7 days after the onset of symptoms (207 for smell, 184 for taste), occurring more frequently with a total decrease of both senses (anosmia 302 and ageusia 216), recovering completely in most cases (214 and 216) and within a period of 1 to 4 weeks (140 and 130).

La alteración de los sentidos del gusto y del olfato en relación con el COVID-19 es un fenómeno ampliamente conocido, sin embargo, esta alteración no ha sido caracterizada de forma exhaustiva en la literatura internacional. Se plantea el siguiente estudio con el objetivo de describir las alteraciones del sentido del gusto y del olfato en relación con el COVID-19 a través de la evaluación subjetiva del mismo. El mismo es observacional, descriptivo, de corte transversal, aplicado a pacientes que consultaron a través de teleconsultas realizadas sobre plataformas virtuales de la Cátedra y Servicio de Otorrinolaringología y Cirugía de Cabeza y Cuello del Hospital de Clínicas, de San Lorenzo, durante los meses de marzo a octubre del 2021. Fueron incluidos 440 pacientes de 31,3 ± 9,9 años (18 a 60 años), 308 (70%) de sexo femenino, 388 (88%) provenientes de zona urbana, con evidencia de infección por SARS-CoV-2 por RT-PCR en 260 (59%), predominantemente sin comorbilidades 232 (53%), con fiebre como síntoma asociado al COVID-19 más frecuentemente reportado 352 (80%), tratados más frecuentemente con AINES 208 (47%) y/o Paracetamol 216 (49%). Tanto la alteración del gusto como del olfato en pacientes que han cursado con COVID-19 ha demostrado ser aparecer más frecuentemente en 1 a 7 días del inicio del cuadro (207 para el olfato. 184 para el gusto), cursando más frecuentemente con disminución total de ambos sentidos (anosmia 302 y ageusia 216), recuperándose más frecuentemente de forma total (214 y 216) y en un plazo de 1 a 4 semanas (140 y 130).