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.

Olfactory and taste disorders in COVID-19: a systematic review.

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.

[Screening diabetic retinopathy using a telediagnosis system. Results of the upper Rhine survey]. / Dépistage de la rétinopathie diabétique par télédiagnostic dans le Haut-Rhin.

INTRODUCTION: The aim of this study was to present the results of diabetic retinopathy screening using a nonmydriatic fundus camera in the upper Rhine (France). METHOD: The screening period took place from September 2004 to December 2007. Patients came to three referring medical centers (Altkirch, Mulhouse, Thann) and all had three fundus photographs on both eyes without pupillary dilatation. The data were stored on a website. The photographs were then analyzed by the team of experts from the Department of Ophthalmology of the Mulhouse General Hospital. The results were sent to the general practitioner with treatment guidelines. The campaign was evaluated at the end of the screening period using a questionnaire. RESULTS: In this study, 1050 diabetics patients were screened: 18% had diabetic retinopathy; of these 1.5% had proliferative or serious nonproliferative diabetic retinopathies and 74.2% mild nonproliferative forms. The mean value of hemoglobin A1C was 9.3% (+/-2.55), the patients' mean age of patients was 61.5 (+/-14.3) years, and the mean onset of diabetes was 16.6 (+/-7.9) years before screening. After screening, 70% of the patients consulted an ophthalmologist. Ninety percent of the referent practitioners received the results of the screening. CONCLUSION: The diabetic retinopathy screening campaign in the upper Rhine provided a real benefit in terms of public health and prevention of diabetic retinal complications.

[The study of the in vitro effect of selenium on formation of active oxygen species and lipid peroxidation in rat liver microsomes]. / Izuchenie vliianiia selena in vitro na obrazovanie aktivnykh form kisloroda i perekisnoe okislenie lipidov v mikrosomakh pecheni krys.

In vitro influence of sodium selenite on cytochrome P-450-dependent formation of active oxygen species on lipid peroxidation (LPO) in rat liver microsomes was studied. Sodium selenite (10(-6)-10(-3) M) did not influence rates of NADPH/Fe-induced formation of active oxygen species (O2.-, OH., H2O2) and NAPDH-dependent LPO. Only at 10(-3) M selenite caused significant decrease in production of hydrogen peroxide in microsomes. Data obtained suggest that sodium selenite at physiological concentrations does not influence formation of active oxygen species by cytochrome P-450 and the rate of enzymatic LPO in rat liver microsomes.

[Modification of drug oxidation in rat liver microsomal fractions by mitochondria]. / Modifikatsiia mitokhondriiami okisleniia lekarstvennykh veshchestv v mikrosomnoi fraktsii pecheni krys.

In order to establish possible interaction between mitochondrial membranes and endoplasmic reticulum, the effects of succinate, fumarate and malate (10(-6)--10(-2) M) on N-demethylation of ethylmorphine in liver homogenate, liver homogenate, enriched by mitochondria and in liver sections of newborn animals were studied. In experiments with liver homogenate and liver mitochondria-enriched homogenate the substrates exerted no effect. Addition of mitochondria decreased the homogenate activity by 50%, when NADPH was used as cosubstrate. Studies on liver sections showed the increase of activity only in case of succinate. The activity of liver sections from newborn rate was 30% of that from adult animals. The enzyme activity was suppressed by the Krebs cycle substrates.

[Sulfaphenazole binding by p-450 cytochrome of liver microsomes of rats and its effect of cytochrome-p-450-reductase]. / Sviazyvanie sul'fafenazola tsitokhromom P-450 mikrosom pecheni krys i ego vliianie na tsitokhrom-P-450-reduktazu

Tests set up "in vitro" on the rats' liver microsomes showed that sulfaphenazol, which in an inhibitor of the mixed type N-and O-demethylation, is bound as a substrate of the II type (aniline type). It attenuates spectral changes caused by aniline and vice versa. Sulfaphenazol inhibits the activity of the ADPH cytochrome-P-450-reductase.