key: cord-0791190-ojfrvtuy authors: Bagheri, S. H. R.; Asghari, A. M.; Farhadi, M.; Shamshiri, A. R.; Kabir, A.; Kamrava, S. K.; Jalessi, M.; Mohebbi, A.; Alizadeh, R.; Honarmand, A. A.; Ghalehbaghi, B.; Salimi, A. title: Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak date: 2020-03-27 journal: nan DOI: 10.1101/2020.03.23.20041889 sha: 7c5f5cae848c60ea1b277a7f8117aae96314dab5 doc_id: 791190 cord_uid: ojfrvtuy Background Recent surge of olfactory dysfunction in patients who were referred to ENT clinics and concurrent COVID-19epidemic in Iran motivated us to evaluate anosmic/hyposmic patients to find any relation between these two events. Methods This is a cross-sectional study with an online checklist on voluntary cases in all provinces of Iran between the 12th and 17th March, 2020. Cases was defined as self-reported anosmia/hyposmia in responders fewer than 4 weeks later (from start the of COVID-19 epidemic in Iran). Variables consist of clinical presentations, related past medical history, family history of recent respiratory tract infection and hospitalization. Results In this study 10069 participants aged 32.5 +/- 8.6 (7-78) years, 71.13% female and 81.68% non-smoker completed online checklist. They reported 10.55% a history of a trip out of home town and 1.1% hospitalization due to respiratory problems recently. From family members 12.17% had a history of severe respiratory disease in recent days and 48.23% had anosmia/hyposmia. Correlation between the number of olfactory disorder and reported COVID-19 patients in all 31 provinces till 16th March 2020 was highly significant (Spearman correlation coefficient=0.87, p-Value<0.001). The onset of anosmia was sudden in 76.24% and till the time of filling the questionnaire in 60.90% of patients decreased sense of smell was constant. Also 83.38 of this patients had decreased taste sensation in association with anosmia. Conclusions It seems that we have a surge in outbreak of olfactory dysfunction happened in Iran during the COVID-19 epidemic. The exact mechanism of anosmia/hyposmia in COVID-19 patients needs further investigations. . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.23.20041889 doi: medRxiv preprint Abstract Background Recent surge of olfactory dysfunction in patients who were referred to ENT clinics and concurrent COVID-19epidemic in Iran motivated us to evaluate anosmic/hyposmic patients to find any relation between these two events. This is a cross-sectional study with an online checklist on voluntary cases in all provinces of Iran between the 12th and 17th March, 2020. Cases was defined as self-reported anosmia/hyposmia in responders fewer than 4 weeks later (from start the of COVID-19 epidemic in Iran). Variables consist of clinical presentations, related past medical history, family history of recent respiratory tract infection and hospitalization. In this study 10069 participants aged 32.5±8.6 (7-78) years, 71.13% female and 81.68% nonsmoker completed online checklist. They reported 10.55% a history of a trip out of home town and 1.1% hospitalization due to respiratory problems recently. From family members 12.17% had a history of severe respiratory disease in recent days and 48.23% had anosmia/hyposmia. Correlation between the number of olfactory disorder and reported COVID-19 patients in all 31 provinces till 16th March 2020 was highly significant (Spearman correlation coefficient=0.87, p-Value<0.001). The onset of anosmia was sudden in 76.24% and till the time of filling the . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint Olfactory dysfunction following the upper respiratory tract infections also named post-viral anosmia has been reported in previous studies 1, 2 . Epithelial damage and central nervous system involvement, have been presented as the probable causes, however, the exact pathogenesis remains unclear 2,3 . Generally, post-viral anosmia is more common in women and middle-aged or older individuals are more affected 4 . Whilst the olfactory impairment can be permanent, this is often not the case and this kind of anosmia has more favorable prognosis than the other different aspects of the disease will be released daily 6, 8 ; however, an update on its clinical and laboratory presentations has reported fever, respiratory symptoms, cough, fatigue, myalgia, arthralgia and breathing difficulties as the common presentations of the confirmed cases 9 . To our knowledge, in none of the updates after the COVID-19 outbreak, anosmia is mentioned as one of the most prominent symptoms. Islamic Republic of Iran is one of the countries which has reported 14991 laboratory-confirmed cases of COVID-19 with 853 total deaths up to March 16, 2020 7 . Since no published scientific evidence reported olfactory and taste disorders . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.23.20041889 doi: medRxiv preprint following the COVID-19 pandemic till now; the aim of present study is an assessment of the frequency of olfactory disorder and patients' characteristics in our country. This is a cross-sectional study on 10069 cases in all provinces of Iran between the 12th and 17th March, 2020. Participants were cases with problems in decreased sense of smell recently (the last month) invited to voluntarily respond to an online checklist, which was distributed in social The primary outcome of the study was anosmia-/-hyposmia of responders which measured by closed questions and scored by numerical scales at the commencement of their problem and its condition at the time of response to questionnaire. Secondary outcomes were clinical manifestations of participants such as flu or cold symptoms before anosmia, headache (which needed pain reliever drug), nasal stiffness, fever and chills, prominent cough, orbital (periorbital) pain, facial fullness and sinus pain, rhinorrhea, dyspnea, nasal irritation, parosmia, nasal pruritus, history of hypothyroidism, otalgia, sneezing (frequent), purulent nasal discharge, history of asthma, cheeks pain, , previous sinus surgery or septorhinoplasty, unilateral facial palsy and history of hypertension, diabetes mellitus and hyperthyroidism. To check about validity of data, questions cross-validated with each other. For example, if a person says that they have hyposmia but in semi-quantitative assessment by our numerical scale . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.23.20041889 doi: medRxiv preprint pointed out the zero score, he/she was deleted from the analysis. To prevent data duplication, personal information of responders was compared in the analysis phase and to exclude incomplete responses to questionnaire the records with more than 30% missing data were . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.23.20041889 doi: medRxiv preprint During this period the online questionnaire viewed by 15228 people from who 10249 have had anosmia/hyposmia and answered the questions. Some participants' information was excluded from analysis; 25 people who did not respond to more than 10 questions (out of 36 questions in the form), 155 records which were duplicated in personal information, 8 persons whose duration of disease was more than 30 days. So the final analysis is representative of 10069 responders. In demographic data; age distribution ranged from 7 to 78 years old (32.5±8.6), 71.13% were female and 81.68% non-smoker. Most responders were from Gilan (51.9%), Tehran (18.4%), Mazandaran (6.6%), Golestan . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.23.20041889 doi: medRxiv preprint During the last month (March 2020), concurrent with COVID-19 epidemic, the number of patients with olfactory dysfunction was increased in different provinces of Iran. So we decided to assess the prevalence of this olfactory disorder by an online questionnaire. Till now results indicate the widespread prevalence of anosmia/hyposmia around the country and a significant linear correlation between prevalence of COVID-19 and olfactory impairment. The recent great outbreak of olfactory dysfunction following flu like symptoms (75%), higher incidence in women (71%), and high incidence of anosmia in family members (48.23%) are suggestive of a post-viral epidemic olfactory dysfunction in Iran. Although our study could not confirm that COVID-19 is the definite cause of anosmia, but there is no other recent virus or flu epidemics in Iran except COVID-19. So, it seems that the recent anosmia outbreak in Iran is highly correlated to COVID-19. Common COVID-19 symptoms such as fever, cough and dyspnea were less common in the participants with anosmia / hyposmia compliant (87.9% vs 37.38%, 67.7% vs 18.98% and 18.6% vs 14.38% respectively) and only about 1.1% of study population were hospitalized due to respiratory problems recently. Studies of the prevalence of olfactory dysfunction in consecutive cases at olfactory clinics in the USA, Europe and Japan showed that the most common etiologies are: post-viral upper respiratory tract infections (18-45% of the clinical population) followed by nasal/sinus disease (7-56%), head trauma (8-20%), toxins/drugs (2-6%) and congenital loss (0-4%) 10 . By now, we found no studies to report a high frequency of olfactory disorder coincidence with COVID-19 virus epidemic and this study could be the first report of an epidemic of COVID-19 with simultaneous olfactory dysfunction. In the study of Mao et al. 2020 , detailed neurologic . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CNS findings were the significant form of neurological damage in patients with COVID-19 in their study 11 . The movement of the COVID-19 virus into the brain through the cribriform plate near to the olfactory bulb could be a route that would enable the virus to enter and influence the brain. Furthermore, the findings such as anosmia or hyposmia in an uncomplicated early stage COVID-19 patient should necessitate a thorough assessment for CNS involvement 17 . Our data is collected via an online self-reported questionnaire. The responders were part of the population who are literate and have access to the internet, personal computers or smart-phones. We announced the patients to answer this questionnaire via social networks so the participants are limited to those who use social networks. However, because of high prevalence of using . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.23.20041889 doi: medRxiv preprint smart phone even by housekeepers and people with education level lower than diploma, representativeness of the results does not seem to be affected by this bias. Another limitation of this study is that no definite test for COVID-19 infection was included. As this is an online survey, the main goal was to confirm the outbreak of anosmia during the COVID-19 epidemic. As the study was self-reported, we used some of questions to check others to increase the questionnaire response validity. Based on the findings of this study it seems that we have a surge in outbreak of olfactory dysfunction happened in Iran during the COVID-19 epidemic, that correlates with the number of patients infected with COVID-19 across the country. As olfactory dysfunction can affect the quality of life in affected patients, it needs to be assessed worldwide by further clinical studies to find out the exact correlation, pathogenesis, prognosis, and any correlation between disease severity and olfactory dysfunction. . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.23.20041889 doi: medRxiv preprint Re-establishment of olfactory and taste functions. 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