Olfactory and taste disorders in COVID-19: a cross-sectional study in primary health care

SUMMARY OBJECTIVE: The objective of this study was to describe the occurrence of self-reported olfactory and taste disorders in non-hospitalized Brazilian adults who presented severe acute respiratory syndrome-related coronavirus 2 infection symptoms and attended primary health care. METHODS: This cross-sectional study was based on a routine standardized diagnostic screening questionnaire applied in a Brazilian primary care facility. The olfactory and taste disorder occurrence was compared between severe acute respiratory syndrome-related coronavirus 2-positive and severe acute respiratory syndrome-related coronavirus 2-negative cases and described by age and sex. RESULTS: Severe acute respiratory syndrome-related coronavirus 2-positive patients had a higher proportion of self-reported olfactory and taste disorders, as compared with severe acute respiratory syndrome-negative (50.7%, vs. 20.6%, p<0.0001). Of all individuals with self-reported olfactory and taste disorder cases, 69% presented both olfactory and taste impairments, 13% olfactory only, and 17% taste only. In severe acute respiratory syndrome-related coronavirus 2-positive cases, the frequency of olfactory and taste disorders was significantly higher among females as compared with males (71% vs. 34%). Additionally, people with olfactory and taste disorders were significantly younger in the severe acute respiratory syndrome-related coronavirus 2-positive group. CONCLUSION: Self-reported olfactory and taste disorders are highly common among non-hospitalized severe acute respiratory syndrome-related coronavirus 2-positive Brazilian people who attended the Family Health Care Unit. The co-occurrence of both self-reported olfactory and taste disorders was more frequent than self-reported olfactory or taste disorders alone.

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)

Research progress of olfactory dysfunction in Parkinson′s disease / 中国医师杂志

Parkinson′s disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly people. In addition to motor symptoms, PD also has many non motor symptoms, such as dysosmia, constipation, cognitive impairment, etc. Among them, dysosmia is a common non motor symptom of early Parkinson′s disease. Research has confirmed that olfactory dysfunction (OD) can appear before the typical clinical symptoms of PD, which is of great significance to the diagnosis and treatment of diseases. However, at present, the pathogenesis of OD is still unclear, and the inspection methods have not been unified, and there is no complete cure. This article reviews the latest research progress of dysosmia in Parkinson′s disease.

Adaptation of the Pediatric Smell WheelTM to evaluate olfactory function in Brazilian children

Abstract Objective: Olfaction influences nutrition, safety, and the cognitive development of children. Presently there are few olfactory tests for children, and normative reference values are generally lacking. In this study, we validate the Pediatric Smell WheelTM (PSW) to evaluate olfactory function in Brazilian children. Methods: We modified and validated the PSW, a test developed in the United States, for administration in Brazil, and established normative data for Brazilian children. The validation process consisted of five phases. First, we identified odorants familiar to Brazilian children. Second, we established the test-retest reliability of the Brazilian PSW test that employed these odorants. Third, we compared the test scores of healthy children to those microsmic from adenoid hypertrophy. Fourth, we examined the test's ability to detect improvement in olfactory function before and after adenoidectomy. Finally, we determined a normative 10th percentile cut point for defining microsmia in a sample of 169 healthy Brazilian children between 5 and 12 years of age. Results: Eleven odors were identified for inclusion in the test. The test-retest reliability was modest (r = 0.54, p < 0.001), although likely attenuated based on the inclusion of only data from children with normal function. The test clearly differentiated the olfactory function of children with adenoid hypertrophy from that of healthy children and demonstrated the return of function after adenoidectomy. An overall score <7 was found useful in defining hyposmia, although additional age-related cut-points were also defined. Conclusion: A Brazilian version of the PSW was developed and validated and found to be efficacious in detecting smell dysfunction in children ranging in age from 5 to 12 years. Level of evidence: 1b (Diagnosis).

Danish Validation of a Retronasal Olfactory Powder Test and Development of a Novel Quick Retronasal Olfactory Test

Abstract Introduction Quality of life is closely linked to retronasal olfactory function. Familiarity with odors vary, so tests need validation. Testing can be time-consuming, so a quick test and a thorough test are needed for clinical and research settings. Objectives The objectives of this study were to validate the original retronasal powder olfactory test in a Danish population and to develop a novel quick retronasal test for easy application. Methods Ninety-seven participants were included in the study, 59 healthy controls and 38 patients with olfactory impairment. The retronasal test was modified by substituting unfamiliar odors and descriptors and validated with a criterion of correct identification rate of 50% in the original test and 90% in the quick test. Items with over 90% correct identification rate in the modified original test were included in the quick test, resulting in a 10-item test. Results The modified retronasal olfactory test achieved good test characteristics, with a 10th percentile cut-off value of 13: sensitivity was 88.9%, specificity 83.0%, positive predictive value 78%, negative predictive value 91.7%, and the receiver operating characteristics area under the curve (ROC-AUC) was 0.86. The quick test achieved acceptable test characteristics, with a 10th percentile cut-off value of 8.2: sensitivity was 72.2%, specificity 90.6%, positive predictive value 83.9%, negative predictive value was 82.8%, and ROC-AUC 0.81. Conclusion Validation of both tests demonstrated satisfactory accuracy. We recommend the quick test for screening purposes, and the modified original version for a thorough evaluation. The tests are easily implemented as they are easy to understand and very affordable.

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.

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.

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.

Olfactory dysfunction in COVID-19: a marker of good prognosis? / Disfunção de olfato na Covid-19: marcador de bom prognóstico?

Abstract Introduction In May 2020, the World Health Organization recognized olfactory dysfunction as a COVID-19 symptom. The presence of hyposmia/anosmia may be a marker of good prognosis in COVID-19. Objective To associate the presence of olfaction disorder to the clinical condition severity in patients with COVID-19. Methods Individuals with the flu syndrome caused by SARS-CoV-2, diagnosed from March to June 2020, were recruited. They were divided into three groups: mild flu syndrome, severe flu syndrome (admitted to hospital wards) and critical illness (admitted to the ICU). Inpatients were interviewed by telephone contact after hospital discharge and their medical records were also evaluated regarding complementary test results. Outpatients answered an electronic questionnaire containing only clinical information. Results A total of 261 patients participated in the study: 23.75% with mild flu syndrome, 57.85% with severe flu syndrome and 18.40% with critical illness. A total of 66.28% patients with COVID-19 had olfaction disorders. In approximately 56.58% of the individuals the smell alterations lasted between 9 days and 2 months. There was a significantly higher proportion of individuals with olfactory dysfunction in the group with mild flu syndrome than in the severe flu syndrome group (mild × severe - p< 0.001; Odds Ratio = 4.63; 95% CI [1.87-10.86]). This relationship was also maintained between patients with mild flu syndrome and critically-ill patients (mild × critical - p< 0.001; Odds Ratio = 9.28; 95% CI [3.52-25.53]). Conclusion Olfaction dysfunction was significantly more prevalent in patients with mild flu syndrome in COVID-19. It may be a predictor of a good prognosis for this infection. New population-based studies must be carried out to corroborate these findings.

Resumo Introdução Em maio de 2020, a Organização Mundial da Saúde reconheceu a disfunção do olfato como um sintoma da C-19. A presença de hiposmia/anosmia pode ser um marcador de bom prognóstico na Covid-19. Objetivos Relacionar a presença do transtorno do olfato à gravidade do quadro clínico nos pacientes com Covid-19. Método Foram recrutados indivíduos com síndrome gripal causada pelo SARS-CoV-2, diagnosticados de março a junho de 2020. Eles foram divididos em três grupos: síndrome gripal leve; síndrome gripal grave (internados em enfermarias) e doença crítica (internados em UTI). Os doentes internados foram entrevistados por ligação telefônica após alta hospitalar e também tiveram seus prontuários avaliados para registro de exames complementares; os ambulatoriais responderam a um questionário eletrônico com somente informações clínicas. Resultados Participaram do estudo 261 pacientes: 23,75% com síndrome gripal leve, 57,85% com síndrome gripal grave e 18,40% com doença crítica. Ocorreu alteração do olfato em 66,28% doentes com Covid-19. Dos indivíduos, 56,58% apresentaram duração da alteração do olfato entre 9 dias e 2 meses. Houve significativamente maior proporção de indivíduos com disfunção olfatória no grupo com síndrome gripal leve do que nos graves (leves × graves - p < 0,001; odds ratio = 4,63; 95% IC [1,87-10,86]). Essa relação também se manteve entre os doentes leves e críticos (leves × críticos - p < 0,001; odds ratio = 9,28; 95% IC [3,52-25,53]). Conclusão A disfunção do olfato foi significantemente mais prevalente nos doentes com síndrome gripal leve na Covid-19. Pode ser um preditor de bom prognóstico dessa infecção. Novos estudos populacionais devem ser feitos para corroborar esses achados.

Evaluation of olfactory function in patients undergoing endoscopic skull base surgery with nasoseptal flap / Avaliação da função olfatória nos pacientes submetidos à cirurgia endoscópica da base do crânio com realização de retalho nasosseptal

Abstract Introduction Endoscopic transnasal access to the skull base, both for treatment and reconstruction, can cause olfactory morbidity. Knowing the main consequences of this intervention is essential to have objective criteria for decision-making regarding the appropriate surgical technique. Objectives The aim of this study is to determine the impact on olfactory function of the endonasal endoscopic access to the skull base with the creation of the nasoseptal flap. Methods A prospective research was carried out in which 22 patients who underwent endoscopic transnasal surgery at the skull base, with the creation of a nasoseptal flap. The Connecticut Chemosensory Clinical Research Center test was applied before and at the 1st, 3rd and 6th postoperative months. Results The results showed that only in the first month of follow-up the mean patient classification was statistically worse than at the other evaluation moments (p < 0.05), but there was no mean difference in the Connecticut score classification between the other moments (p > 0.05); that is, patients showed worsening in the 1st month and returned to the preoperative mean after the 3rd month of follow-up. Conclusion The present study showed that the postoperative decrease in olfaction is transient, since the patient's sense of smell returns to pre-surgical values in the 3rd postoperative month.

Resumo Introdução O acesso transnasal endoscópico à base do crânio, tanto no tratamento quanto na reconstrução, pode ocasionar morbidade olfatória. Conhecer as principais consequências dessa intervenção é fundamental para se dispor de elementos objetivos para a decisão da técnica cirúrgica adequada. Objetivo Determinar o impacto na função olfatória do acesso endoscópico endonasal à base do crânio com confecção do retalho nasosseptal. Método Foi feita pesquisa prospectiva na qual foram incluídos 22 pacientes submetidos à cirurgia endoscópica transnasal à base do crânio com confecção de retalho nasosseptal. Foi aplicado o teste Connecticut chemosensory clinical research center antes e após o 1°, 3° e 6° meses da cirurgia. Resultados Os resultados evidenciaram que apenas no 1° mês de seguimento a classificação média dos pacientes foi estatisticamente pior do que nos demais momentos de avaliação (p < 0,05), mas entre os demais momentos não houve diferença média na classificação do escore de Connecticut (p >0,05), ou seja, os pacientes pioraram no 1° mês e voltaram à média pré-operatória a partir do 3° mês de seguimento. Conclusão No presente estudo, demonstramos que a diminuição do olfato pós-operatória é transitória, já que, no 3° mês depois da cirurgia, o olfato do paciente retorna aos valores pré-cirúrgicos.

Diagnóstico clínico y tratamiento de la disfunción olfatoria relacionada con COVID-19: revisión de la literatura / Clinical diagnosis and treatment of olfactory dysfunction related to COVID-19: A literature review

Introducción: la enfermedad por coronavirus 2019 (COVID-19) es una enfermedad pandémica, que ha causado más de seis millones de muertes en todo el mundo. El cuadro clínico de la infección puede variar en función de la gravedad de la enfermedad y suele incluir síntomas generales, otorrinolaringológicos y neurológicos. Objetivo: proporcionar una revisión narrativa de la literatura científica sobre el diagnóstico clínico y tratamiento de la disfunción olfatoria relacionada con COVID-19. Resultados: la disfunción olfatoria definida como la capacidad reducida o distorsionada de oler al inhalar (olfato ortonasal) o al comer (olfato retronasal), a menudo se informa en casos leves o incluso asintomáticos. La prevalencia de la disfunción olfatoria puede variar con respecto al entorno clínico, con tasas de pérdida total del olfato hasta del 70 % en pacientes con COVID-19 leve. Además, hasta la fecha existen pocos artículos que evalúen prospectivamente las tasas de recuperación de la disfunción olfatoria en pacientes con COVID-19. Conclusión: COVID-19 se asocia con disfunción olfatoria en diversos pacientes. Se requiere una investigación activa y colaborativa para delinear la historia natural y el manejo apropiado de la disfunción olfatoria en esta virulenta enfermedad. Mientras tanto, el diagnóstico y los tratamientos dirigidos como el entrenamiento olfatorio pueden ser útiles en la disfunción olfatoria relacionada con COVID-19.

Introduction: Coronavirus disease 2019 is a pandemic disease that has caused more than six million deaths worldwide. The clinical picture of the infection can vary depending on the severity of the disease and usually includes general, ENT and neurological symptoms. Objective: To provide a narrative review of the scientific literature on the clinical diagnosis and treatment of olfactory dysfunction related to coronavirus disease 2019. Results: Olfactory dysfunction defined as the reduced or distorted ability to smell when inhaling (orthonasal smell) or when eating (postnasal smell), is often reported in mild or even asymptomatic cases. The prevalence of olfactory dysfunction can vary with respect to the clinical setting, with rates of total loss of smell as high as 70% in patients with mild coronavirus disease 2019. In addition, to date there is a paucity of articles prospectively evaluating recovery rates of olfactory dysfunction in patients with coronavirus disease 2019. Conclusion: Coronavirus disease 2019 is associated with olfactory dysfunction in various patients. Active and collaborative research is required to delineate the natural history and appropriate management of olfactory dysfunction in this virulent disease. In the meantime, diagnosis and targeted treatments such as olfactory training may be helpful in olfactory dysfunction related to coronavirus disease 2019.

Estudo transversal sobre o transtorno olfatório no COVID-19: características e fatores prognósticos / Cross-sectional study on olfactory disorder in COVID-19: characteristics and prognostic factors

Objetivo: Apresentar as características e os fatores prognósticos da anosmia e hiposmia em pacientes infectados com COVID-19 em uma cidade no Brasil. Métodos: Estudo transversal através de contato telefônico, foi realizada uma pesquisa com questionário pré-estabelecido em uma população de 80 pacientes. Resultados: Entre os 80 participantes da pesquisa, 66,3% eram do sexo feminino. 90% relataram anosmia e 10% relataram hiposmia. 5% dos entrevistados evoluíram o quadro com internação hospitalar. 5% dos pacientes realizaram tratamento, sendo ele a terapia olfatória. Destes pacientes, 75% consideraram a terapia olfatória como um tratamento efetivo. Conclusões: O maior número de disfunção olfatória foi encontrado na menor faixa etária e em mulheres, variáveis associadas a um melhor prognóstico. A perda olfatória está relacionada com um curso mais brando da doença e consequentemente a um menor número de hospitalizações. Evidências apontam a terapia olfatória como um tratamento promissor.

Objective: To present the characteristics and prognostic factors of anosmia and hyposmia in patients infected with COVID-19 in a city in Brazil. Methods: A cross-sectional study through telephone contact, a survey was carried out with a pre-established questionnaire in a population of 80 patients. Results: Among the 80 research participants, 66.3% were female. 90% reported anosmia and 10% reported hyposmia. 5% of the interviewees evolved the condition with hospitalization. 5% of patients underwent treatment, which was olfactory therapy. Of these patients, 75% considered olfactory therapy to be an effective treatment. Conclusions: The highest number of olfactory dysfunction was found in the lowest age group and in women, variables associated with a better prognosis. Olfactory loss is related to a milder course of the disease and, consequently, to a lower number of hospitalizations. Evidence points to olfactory therapy as a promising treatment.

Olfactory impairment and the risk of cognitive decline and dementia in older adults: a meta-analysis / Distúrbio olfativo e o risco de declínio cognitivo e demência em idosos: uma metanálise

Abstract Introduction The prediction of the impact of olfactory impairment on cognitive decline in older adults has been different among different age groups. Objective This meta-analysis sought to estimate the predictive power of olfactory impairment on cognitive decline during follow-up in older adults of different ages. Material and methods A medical literature search was carried out using these databases for eligible studies: MEDLINE, COCHRANE and EMBASE. Studies recording olfaction and cognition detection at the beginning and end of the follow-up were included in the preliminary screening. The medical records of older adults without cognitive impairment at the beginning of the follow-up were taken into account in this analysis. Raw data was extracted in order to estimate the relative risk and the corresponding 95% confidence interval (95% CI). Subgroup analysis of age was performed to eliminate the effect of age on the results. Statistical heterogeneity was measured using the I 2 index and Cochran's Q test. Results Eight studies were enrolled in this analysis (3237 events and 13165 participants), and the pooled relative risk for the 70-80 years old subgroup was 2.00 (95% CI = 1.79-2.23). Conclusion Relatively, there is a higher risk of cognitive impairment at the end of follow-up in younger adults with olfactory impairment at the beginning of follow-up. The length of follow-up has a little effect on the relative risk.

Resumo Introdução A previsão do impacto do comprometimento olfativo no declínio cognitivo em idosos tem sido distinta entre diferentes faixas etárias. Objetivo Esta metanálise buscou estimar o poder preditivo do comprometimento olfativo no declínio cognitivo durante o seguimento em idosos de diferentes idades. Material e métodos Foi feita uma pesquisa na literatura médica nos seguintes bancos de dados para estudos elegíveis: Medline, Cochrane e Embase. Os estudos que registraram olfação e detecção de cognição no início e no fim do seguimento foram incluídos na triagem preliminar. Os prontuários médicos de idosos sem comprometimento cognitivo no início do seguimento foram considerados nessa análise. Os dados brutos foram extraídos para estimar o risco relativo e o intervalo de confiança de 95% (IC95%) correspondente. A análise de subgrupos da idade foi feita para eliminar o efeito da idade nos resultados. A heterogeneidade estatística foi medida utilizando o índice I2 e o teste Q de Cochran. Resultados Oito estudos foram incluídos nesta análise (3.237 eventos e 13.165 participantes) e o risco relativo combinado para o subgrupo de 70 a 80 anos foi de 2,00 (IC95% = 1,79-2,23). Conclusão Relativamente, existe um risco maior de comprometimento cognitivo no fim do seguimento em adultos mais jovens que se se apresentam com comprometimento olfativo no início do seguimento. A duração do seguimento tem um pequeno efeito no risco relativo.

Olfactory dysfunction in the scenario of COVID-19 pandemic in patients screened by the telemonitoring / Distúrbio do olfato no cenário da pandemia de COVID-19 em pacientes triados por telemonitoramento

ABSTRACT Objective To assess the clinical and epidemiological profile of patients with olfactory dysfunction in the scenario of COVID-19 pandemic. Methods The study selected patients with loss of smell, previously screened by telemonitoring system of the Municipal Health Department of Goiânia (GO), Brazil, who agreed to answer a questionnaire about COVID-19 symptoms and findings of exams. The interviews were conducted by six otolaryngologists, who applied the specific questionnaire, over the phone. Results A total of 13,910 patients underwent telemonitoring, and 627 (4.51%) had olfactory loss complaints. Out of them, 330 were included in the survey. We observed a higher prevalence of altered smell in women (67%), and in patients aged under 50 years (86%). In most cases the manifestations had a sudden onset (70%), and in the first 5 days of illness (80%). The most prevalent associated symptom was a change in taste (89%), and only 2.7% of interviewed patients required hospitalization. Conclusion Anosmia in COVID-19 is more prevalent in females and individuals aged under 50 years. It is a relevant initial symptom predictive of the disease, together with dysgeusia.

RESUMO Objetivo Avaliar o perfil clínico-epidemiológico dos pacientes com distúrbios olfatórios no cenário de pandemia da COVID-19. Métodos Foram selecionados pacientes com queixa de perda de olfato, previamente triados pelo sistema de telemonitoramento da Secretaria Municipal de Saúde de Goiânia (GO), Brasil, que concordaram em responder um questionário sobre sintomas e achados de exame em relação à COVID-19. As entrevistas foram realizadas por seis médicos otorrinolaringologistas que, via telefonema, submeteram os participantes a questionário específico. Resultados Dos 13.910 pacientes em telemonitoramento, 627 (4,51%) apresentavam queixas de alteração do olfato, e, destes, 330 foram incluídos na pesquisa. A maior prevalência de alteração do olfato se deu em mulheres (67%), e em pacientes com menos de 50 anos (86%). Na maioria dos casos, as manifestações ocorreram de forma súbita (70%), e nos primeiros 5 dias de doença (80%). O sintoma associado mais prevalente foi alteração do paladar (89%), e houve necessidade de internação hospitalar somente em 2,7% dos pacientes entrevistados. Conclusão A anosmia na COVID-19 é mais prevalente no sexo feminino e em pacientes com menos de 50 anos. Juntamente da disgeusia, trata-se de importante sintoma inicial preditivo da doença.

Olfactory and taste disorders in COVID-19: a systematic review / Desordens olfativas e gustativas na COVID-19: uma revisão sistemática

Abstract Introduction: The SARS-CoV-2 virus causes COVID-19, and it is responsible for the largest pandemic since the 1918 H1N1 influenza outbreak. The classic symptoms of the disease have been well defined by the World Health Organization; however, olfactory/gustatory disorders have been reported in some studies, but there are still several missing points in the understanding and in the consensus about the clinical management of these cases. Objective: To identify evidence in the scientific literature about olfactory/gustatory disorders, their clinical presentation, prevalence and possible specific treatments associated with COVID-19. Methods: A systematic review of articles published up to April 25, 2020 was performed in Medline, Cochrane Clinical Trials, ScienceDirect, Lilacs, Scopus and Google Schoolar, OpenGrey.eu, DissOnline, The New York Academy of Medicine and Reasearch Gate. Inclusion criteria: (1) Studies on patients with COVID-19; (2) Records of COVID-19 signs/symptoms, and olfactory/gustatory functions. Exclusion criteria: (1) Studies on non-human coronavirus; (2) Review articles; (3) Experimental studies (in animals or in vitro); (4) Olfactory/gustatory disorders initiated prior to SARS-CoV-2 infection. The risk assessment of bias of the selected studies was performed using the Newcastle-Ottawa scale. Results: Six articles from the 1788 records met the inclusion criteria and were analyzed. A total of 1457 patients of different ethnicities were assessed; of them, 885 (60.7%) and 822 (56.4%) had smell and taste disorders, respectively, with women being most often affected. There were olfactory/gustatory disorders even without nasal obstruction/rhinorrhea and beginning even before the signs/symptoms of COVID-19; the recovery of smell/taste, when it occurs, usually happened in the first two weeks after COVID-19 resolution. There is evidence that olfactory/gustatory disorders are strong predictors of infection by SARS-CoV-2, and it is possible to recommend patient isolation, as early as of the medical consultation, preventing the spread of the virus. No scientific evidence has been identified for effective treatments for any of the disorders. Conclusion: Olfactory/gustatory disorders may occur at varying intensities and prior to the general symptoms of COVID-19 and should be considered as part of the clinical features of COVID-19, even in mild cases. There is still no scientific evidence of specific treatments for such disorders in COVID-19 disease.

Resumo Introdução: O vírus SARS-CoV-2 causa a COVID-19 e é responsável pela maior pandemia desde o surto de influenza H1N1 de 1918. Os sintomas clássicos da doença já foram bem definidos pela Organização Mundial da Saúde; entretanto, distúrbios olfativo-gustativos têm sido relatados em alguns estudos, mas ainda com várias lacunas no entendimento e no consenso sobre a condução clínica desses casos. Objetivo: Identificar evidências na literatura científica sobre os distúrbios olfativo-gustativos acerca da apresentação clínica, prevalência e possíveis tratamentos específicos associados à COVID-19. Método: Revisão sistemática de artigos publicados até 25 de abril de 2020 nas bases de dados: Medline, Cochrane Clinical Trials, ScienceDirect, Lilacs, Scopus e Google Schoolar, OpenGrey.eu, DissOnline, The New York Academy of Medicine e Research Gate. Foram critérios de inclusão: 1) Estudos com indivíduos com COVID-19; 2) Registro dos sinais/sintomas da COVID-19 e das funções olfativo-gustativa. Foram critérios de exclusão: 1) Estudos sobre coronavírus não humano; 2) Artigos de revisão; 3) Estudos experimentais (em animais ou in vitro); 4) Distúrbios olfativos-gustativos iniciados previamente à infecção pelo SARS-CoV-2. A avaliação de risco de viés dos estudos selecionados foi feita por meio da escala de Newcastle-Ottawa. Resultados: Seis artigos dos 1.788 registros foram selecionados. Um total de 1.457 pacientes de diversas etnias foi avaliado; desses, 885 (60,7%) apresentaram perda do olfato e 822 (56,4%) perda do paladar, sendo as mulheres as mais afetadas. Os distúrbios olfativo-gustativos estiveram presentes mesmo sem obstrução nasal/rinorreia e com início mesmo antes dos sinais/sintomas clínicos da COVID-19; a recuperação do olfato/paladar, quando ocorre, geralmente se dá nas duas primeiras semanas após a resolução da doença. Há evidências de que os distúrbios olfativo-gustativos sejam fortes preditores de infecção pelo SARS-CoV-2, podendo-se recomendar o isolamento do paciente, já a partir da consulta médica, para evitar a disseminação do vírus. Não foram identificadas evidências científicas para tratamentos eficazes para qualquer dos distúrbios. Conclusão: Podem ocorrer distúrbios olfativo-gustativos em intensidades variáveis e prévios aos sintomas gerais da COVID-19, devem ser considerados como parte dos sintomas da doença, mesmo em quadros leves. Não há ainda evidências científicas de tratamentos específicos para tais distúrbios na COVID-19.

Síntomas atípicos en enfermedad por COVID-19: reporte de caso / Atypical symptoms in COVID-19 disease: case report

The infection caused by the SARS-CoV-2 virus, recently described in Wuhan, China, has put numerous health systems around the world in check. Given its high contagiousness and the exponential growth of cases, it was declared a pandemic by the world health organization. Although the majority of those infected will present mild symptoms, a smaller percentage will present severe manifestations of the disease, such as acute respiratory distress syndrome, requiring ventilator support measures and stays in intensive care units. The main symptoms described in SARS-CoV-2 infection are fever, fatigue, dry cough and myalgia. Despite this, there is a not insignificant number of patients who present with atypical symptoms of the disease, some described are anosmia, ageusia, gastrointestinal symptoms like diarrhea, dermatological manifestations, among others. In these patients it is particularly where the diagnosis is made late, delaying isolation and prevention measures, thus increasing the risk of contagion within the population.

Clinical effects of two combinations of olfactory agents on olfactory dysfunction after upper respiratory tract infection during olfactory training

SUMMARY OBJECTIVE To compare two combinations of olfactory agents for olfactory training therapy of olfactory dysfunction after upper respiratory tract infection (URTI) and investigate the influencing factors on clinical effects. METHODS 125 patients with olfactory dysfunction were randomly divided into two groups: test and control. During the olfactory training, four odors were used in both groups. The olfactory training lasted for 24 weeks. Then, participants were tested using Sniffin' Sticks and threshold-discrimination-identification (TDI) composite scoring before treatment and at 1, 3, and 6 months after treatment. The TDI scores were compared at different time points between the groups and within them, and influence factors were analyzed. RESULTS There was no significant difference in TDI scores between both groups. Furthermore, TDI scores did not significantly change after one month of treatment in either of the groups. After 3 and 6 months of treatment, TDI scores both significantly increased, and the odor discrimination and identification abilities significantly strengthened in both groups; however, the odor thresholds did not improve. The course of the disease was a significant influencing factor on the therapeutic effect of olfactory training for both groups. CONCLUSION The combination of essential balm, vinegar, alcohol, and rose perfume for olfactory training, which are scents commonly found in daily life, can effectively cure URTI-induced olfactory dysfunction, and significantly improve the odor discrimination and identification abilities. Furthermore, prolonging the treatment time can help with the recovery of olfactory functions, and earlier olfactory training can improve the therapeutic effect.

RESUMO OBJETIVO Comparar duas combinações de agentes olfativos para uso em terapia de treinamento olfativo no tratamento de disfunção olfatória após infecção do trato respiratório superior (ITRS) e investigar os fatores que influenciam os efeitos clínicos. METODOLOGIA 125 pacientes com disfunção olfativa foram divididos aleatoriamente em dois grupos: teste e controle. Durante o treinamento olfativo, quatro odores foram utilizados em ambos os grupos. O treinamento olfativo durou 24 semanas. Em seguida, os participantes foram testados usando Sniffin' Sticks e o escore de discriminação, limiar e identificação (TDI) antes do tratamento e 1, 3 e 6 meses após o ele. Os escores de TDI foram comparados em momentos diferentes, entre os grupos e dentro deles, e os fatores de influência foram analisados. RESULTADOS Não houve diferença significativa nos escores de TDI entre os dois grupos. Além disso, os escores de TDI não demonstração nenhuma alteração significa após um mês de tratamento em ambos os grupos. Após 3 e 6 meses de tratamento, ambos os escores de TDI aumentaram significativamente, e as habilidades de identificação e discriminação de odores melhoraram significativamente em ambos os grupos; contudo, os limiares de odor não demonstraram melhora. O curso da doença foi um importante fator de influência no efeito terapêutico do treinamento olfativo em ambos os grupos. CONCLUSÃO A combinação de bálsamo essencial, vinagre, álcool, e perfume de rosas no treinamento olfativo, todos aromas comumente encontrados na vida cotidiana, podem efetivamente curar disfunção olfativa induzida por ITRS e melhorar significativamente as habilidades de discriminação e identificação de odores. Além disso, a prolongamento do tempo de tratamento pode ajudar na recuperação das funções olfativas, e o início antecipado do treinamento olfativo pode melhorar o efeito terapêutico.

Alteraciones en el olfato y el gusto asociadas con la infección por SARS-CoV-2: una revisión / Olfactory and taste disorders associated with SARS-CoV-2 infection: a review

Los sentidos químicos, como el olfato y el gusto, son determinantes en la calidad de vida y el desempeño de algunas labores de la vida diaria, ya que desempeñan un papel fundamental tanto en la rutina como en las relaciones interpersonales. Existen múltiples patologías que alteran estos sentidos, entre estas las enfermedades por infección viral. A través de los últimos meses, se ha demostrado que el virus responsable de la pandemia actual (SARS-CoV-2) puede generar cambios en el olfato y en el gusto secundarios a la infección por este, siendo estas alteraciones, en ocasiones, las primeras manifestaciones. En esta revisión se busca recopilar la información encontrada en la literatura médica y resaltar la importancia de tener en cuenta estas alteraciones al momento de examinar a un paciente y generar una alerta en cuanto a las posibles medidas de aislamiento y/o tratamiento de estos pacientes.

Chemical senses such as smell and taste are decisive in the quality of life and performance of some tasks of daily life. They are senses that play a fundamental role in everyday life and in interpersonal relationships. There are multiple pathologies that alter these senses, including viral infection diseases. Over the last few months, it has been shown that the virus responsible for the current pandemic (SARS-CoV-2) can generate changes in smell and taste secondary to its infection, these alterations being sometimes the first demonstrations. This review seeks to compile the information found in the medical literature and conclude the importance of taking these alterations into account when examining a patient and generating an alert regarding the possible isolation and / or treatment measures for these patients.

Reversal of Olfactory Disturbance in Allergic Rhinitis Related to OMP Suppression by Intranasal Budesonide Treatment

PURPOSE: We evaluated the severity of olfactory disturbance (OD) in the murine model of allergic rhinitis (AR) and local allergic rhinitis (LAR) in mice. We also investigated the therapeutic effect of an intranasal steroid on OD. METHODS: Forty BALB/c mice were divided into 5 groups (n = 8 for each). The control group was sensitized intraperitoneally (i.p.) and challenged intranasally (i.n.) with saline. Mice in the AR group got i.p. and i.n. ovalbumin (OVA) administration for AR induction. The LAR group was challenged i.n. with 1% OVA for inducing local nasal allergic inflammation, without inducing the systemic allergy. The OD group got an i.p. methimazole administration (75 mg/kg) to induce total destruction of olfactory mucosa. Mice in the intranasal budesonide group received i.n. budesonide (12.8 μg per time, 30 minutes after the i.n. OVA challenge) while using OVA to cause systemic allergies. We conducted a buried-food pellet test to functionally assess the degree of OD in each group by measuring the time taken until finding hidden food. We evaluated the damage to olfactory epithelium using histopathologic evaluation and compared the degree of olfactory marker protein (OMP) expression in olfactory epithelium using immunofluorescent staining. RESULTS: Mice of the AR (81.3 ± 19.8 seconds) and LAR groups (66.2 ± 12.7 seconds) spent significantly more time to detect the pellets than the control group (35.6 ± 12.2 seconds, P < 0.01). After treatment, the intranasal budesonide group exhibited significantly better results (35.8 ± 11.9 seconds) compared with the AR and LAR groups (P < 0.01). The AR and LAR groups showed considerable olfactory epithelial damage and suppression of OMP expression compared with the control group. In the intranasal budesonide group, the olfactory lesions and OMP expression had improved substantially. CONCLUSIONS: OD may be caused by olfactory epithelial damage and suppression of OMP expression in nasal allergic inflammation and could be reversed using an intranasal steroid.

Efectos físicos de la contaminación atmosférica percibidos de manera inconsciente por la ciudadanía, en el área metropolitana de la ciudad de Monterrey, Nuevo León, México / Physical effects of atmospheric pollution unconsciously perceived by citizenship, in the metropolitan area of Monterrey city, Nuevo León, Mexico

RESUMEN Objetivo Percibir la contaminación atmosférica por partículas finas (PM25) en el organismo humano en la zona urbana del Área Metropolitana de Monterrey [AMM], Nuevo León; considerando sus efectos y capacidad de detección sensorial a razón y percepción de cada sujeto. Materiales y Métodos Se realizó una investigación con 504 sujetos participantes de los efectos producidos por dicha exposición de contaminantes en el AMM, Nuevo León, teniendo en cuenta en el diseño los antecedentes del sujeto y su percepción inconsciente, con motivo de evitar el posible sesgo en el resultado. Resultados Se encontró que los niveles de contaminación presentes en el ambiente por partículas finas afectaron de manera distinta a los sujetos participantes sanos que a los reportados con alguna susceptibilidad o enfermedad visual y/o respiratoria. Discusión Se determinó que los niveles prevalecientes de contaminación atmosférica en el AMM han alcanzado grados de afectación en organismos de personas con susceptibilidad o problemas, ya sea visuales o respiratorios, cuando realizan sus actividades en ambientes exteriores.(AU)

ABSTRACT Objective Perceive the air pollution atmospheric by fine particles (PM25) in the human organism on the Metropolitan Urban Area of Monterrey [MUAM], Nuevo León; considering its effects and the sensorial detection capability by each subject's perception. Materials and Methods This research was made with 504 participating subjects exposed to the effects of the contaminants mentioned on the MUAM, Nuevo León, considering the background of each subject and their unconscious perception, in order to avoid the possible bias in the result. Results It was found that the present levels of environment pollution by fine particles affected on different ways the healthy participant subjects than the ones reported with any susceptibility or visual affection and/or respiratory illness. Discussion It was determined that the current levels of environment contaminants in the MUAM have reached degrees of affectation in organisms of people with susceptibility or problems either visual or respiratory, when they carry out their activities in external environments.(AU)