key: cord-333698-e73d9lbu authors: Lechien, Jerome R.; Chiesa-Estomba, Carlos M.; Cabaraux, Pierre; Mat, Quentin; Huet, Kathy; Harmegnies, Bernard; Horoi, Mihaela; Bon, Serge D. Le; Rodriguez, Alexandra; Dequanter, Didier; Hans, Stéphane; Crevier-Buchman, Lise; Hochet, Baptiste; Distinguin, Lea; Chekkoury-Idrissi, Younes; Circiu, Marta; Afia, Fahd El; Barillari, Maria Rosaria; Cammaroto, Giovanni; Fakhry, Nicolas; Michel, Justin; Radulesco, Thomas; Martiny, Delphine; Lavigne, Philippe; Jouffe, Lionel; Descamps, Géraldine; Journe, Fabrice; Trecca, Eleonora M.C.; Hsieh, Julien; Delgado, Irene Lopez; Calvo-Henriquez, Christian; Vergez, Sebastien; Khalife, Mohamad; Molteni, Gabriele; Mannelli, Giuditta; Cantarella, Giovanna; Tucciarone, Manuel; Souchay, Christel; Leich, Pierre; Ayad, Tareck; Saussez, Sven title: Features of Mild-to-Moderate COVID-19 Patients with Dysphonia. date: 2020-06-04 journal: J Voice DOI: 10.1016/j.jvoice.2020.05.012 sha: doc_id: 333698 cord_uid: e73d9lbu INTRODUCTION: To explore the prevalence of dysphonia in European patients with mild-to-moderate COVID-19 and the clinical features of dysphonic patients. METHODS: The clinical and epidemiological data of 702 patients with mild-to-moderate COVID-19 were collected from 19 European Hospitals. The following data were extracted: age, sex, ethnicity, tobacco consumption, comorbidities, general and otolaryngological symptoms. Dysphonia and otolaryngological symptoms were self-assessed through a 4-point scale. The prevalence of dysphonia, as part of the COVID-19 symptoms, was assessed. The outcomes were compared between dysphonic and non-dysphonic patients. The association between dysphonia severity and outcomes was studied through Bayesian analysis. RESULTS: A total of 188 patients were dysphonic, accounting for 26.8% of cases. Females developed more frequently dysphonia than males (p=0.022). The proportion of smokers was significantly higher in the dysphonic group (p=0.042). The prevalence of the following symptoms was higher in dysphonic patients compared with non-dysphonic patients: cough, chest pain, sticky sputum, arthralgia, diarrhea, headache, fatigue, nausea and vomiting. The severity of dyspnea, dysphagia, ear pain, face pain, throat pain and nasal obstruction was higher in dysphonic group compared with non-dysphonic group. There were significant associations between the severity of dysphonia, dysphagia and cough. CONCLUSION: Dysphonia may be encountered in a quarter of patients with mild-to-moderate COVID-19 and should be considered as a symptom list of the infection. Dysphonic COVID-19 patients are more symptomatic than non-dysphonic individuals. Future studies are needed to investigate the relevance of dysphonia in the COVID-19 clinical presentation. Since the first reported cases from Wuhan, the coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. 1 As of April 25, a total of 2,719,897 individuals have been diagnosed through laboratory testing, with 187,705 corresponding deaths. 2 According to Asian studies, the clinical presentation of COVID-19 mainly includes fever, fatigue, cough, and anorexia. 3, 4 However, recent European epidemiological studies suggested that European mild-to-moderate COVID-19 patients could present a different clinical picture than Asian. 5 In Europe, the most prevalent symptoms are headache, total loss of smell, nasal obstruction and cough. 5, 6 Thus, the otolaryngological symptoms are more prevalent than previously presumed in Asia. Throughout a recent epidemiological study, 7 we observed the occurrence of dysphonia in some COVID-19 patients, with a minority reporting aphonia over the clinical course of the disease. The aim of this study was to investigate the occurrence of dysphonia in mild-to-moderate COVID-19 patients. Five European Ethics Committees approved the study protocol (HAP2020-011; CHUSP20032020; EpiCURA-2020-2303, CHUC,P20/30-24/03-B325-2020; J.Bordet Institute: CE3137). The patient informed consent was obtained electronically. From March 22 to April 24, 2020, the data of hospitalized or home-managed COVID-19 patients were collected by otolaryngologists and non-otolaryngologist physicians from 19 European Hospitals (Paris, Marseille, Milan, Verona, Naples, Genova, Florence, Foggia, Forli, Sevilla, Santiago de Compostela, San Sebastian, Mons, Brussels, Charleroi and Saint-Ghislain). The diagnosis of Covid-19 infection was based on the WHO interim guidance. 8 Precisely, nasal or throat swabs were collected in suspected patients and the virus was identified through reverse transcription polymerase chain reaction (RT-PCR) analysis. The details of the viral RNA extraction and analyses are available in a previous paper. 7 The mild-to-moderate COVID-19 patients were identified through different ways. First, the database of the laboratories of the hospitals provided a list of hospitalized or home-managed patients. Second, many patients were referred by the family physician or specialists from hospital departments (e.g. Emergency, Internal Medicine or Otolaryngology Departments). A public call of University of Mons allowed an increase in the recruitment of patients. Third, many infected health care workers were included. Patients who were hospitalized in intensive care units were not included due to their health status and the inability to answer to the questions. Patients who reported dysphonia prior to the infection were not included in the present analysis. Patients with a history of head & neck trauma, (chemo)radiotherapy, benign or malignant laryngeal lesions, or head and neck cancer surgery were identified through the epidemiological questionnaire and carefully excluded. Regarding the inclusion and exclusion criteria, the patients included in the present study were defined as mild-to-moderate COVID-19 patients. Due to the sanitary situation, the data were collected through an electronic patient-reported outcome questionnaire. Home-managed patients were contacted over the phone. Physicians completed the questionnaire in the patient's room for hospitalized patients through an electronic device. For these patients, physicians had access to the patient medical records to complete some data. The professional Survey Monkey (San Mateo, California, USA) was used for the patient reported outcome questionnaire. The following epidemiological and clinical data were considered: age, sex, ethnicity, tobacco consumption, comorbidities, general and otolaryngological symptoms. The general symptoms included headache, asthenia, myalgia, arthralgia, cough, loss of appetite, dyspnea, fever, diarrhea, nausea/vomiting, abdominal pain and chest pain. The otolaryngological symptoms included nasal obstruction, rhinorrhea, postnasal drip, sore throat, face pain, dysphonia, ear pain, dysphagia and sticky throat mucus. Otolaryngological symptoms were assessed through a 4-point scale, ranging from 0 (=no symptom) to 4 (=very severe symptom). The prevalence rates of total or partial loss of smell and dysgeusia were evaluated through questions from the smell and taste component of the National Health and Nutrition Examination Survey (NHNES). 8 NHNES is a population survey that monitors the health of U.S. citizens through a nationally representative sample of 5,000 persons on a yearly basis. 8 The statistical analysis was realized through Bayesian networks. The details about the qualitative and quantitative models of the network analysis were reported in a previous study. 7 The outcomes were compared between dysphonic and non-dysphonic patients. The relationships between dysphonia, epidemiological data and general and otolaryngological symptoms were studied. A p-value <0.05 was considered as significant. The data of 702 patients were collected. Among them, 188 reported dysphonia (26.8%) as a COVID-19 symptom while 514 patients did not report dysphonia during the clinical course of the disease. Seven dysphonic patients reported aphonia throughout the clinical course of the disease (3.7%). The characteristics of patient groups are described in Table 1 . There were 70.8% of females, the proportion of females reaching 76.6% in the dysphonic group. The female proportion was significantly higher in the dysphonic group compared to the nondysphonic group (p=0.022). The majority of patients were Caucasian. The percentage of smokers was significantly higher in dysphonic group compared with non-dysphonic group (p=0.042). The proportion of allergic patients was similar in both groups. The most prevalent comorbidities were allergic rhinitis, hypertension and gastroesophageal reflux disease. The prevalence of general symptoms in both groups is available in Table 2 . Patients with dysphonia had a higher proportion of systemic symptoms compared with non-dysphonic patients, including cough, chest pain, sticky sputum, arthralgia, diarrhea, headache, fatigue, nausea and vomiting ( Figure 1 ). Table 3 . According to NHNES questions, the total and partial losses of smell concerned 128 (68.1%) and 20 (10.6%) dysphonic patients, respectively. In the group of non-dysphonic patients, there were 369 (71.8%) and 66 (12.8%) individuals with total and partial losses of smell, respectively. As reported in Table 3 , dysphonic patients had higher proportions of dyspnea, dysphagia, ear pain, face pain, throat pain and nasal obstruction compared with non-dysphonic individuals. The severity of dysphonia was significantly associated with the severity of dysphagia. A significant positive association was found between dysphonia and cough. The spread of COVID-19 in Europe led to the emergence of an otolaryngological clinical picture of the infection, which is mainly associated with loss of smell and taste. However, many other otolaryngological symptoms could be prevalent in COVID-19. The self-reported dysphonia could concern a quarter of COVID-19 patients. Dysphonia is encountered in less than 20% of common viral infections such as common cold or flu. 9 13 it could be conceivable that muscle or lung virus-related impairments may lead to dysphonia. As for the ACE2 expression in laryngeal tissue, this hypothesis has to be investigated in future studies. Another issue that could be studied concerns the impact of gender in the voice-related presentation of COVID-19. Indeed, female could be most at risk of dysphonia in COVID-19, which could involve gender-related difference in the inflammatory process. 14 The future studies have to be conducted in the context of potential hormonal and gender differences in the expression of ACE2, in the inflammatory process and, therefore, the clinical presentation of the disease. 7, 15 This study is a preliminary epidemiological study investigating potential association between Table 3 footnotes: The patients assessed their symptom severity through a 5-point scale (0 to 4). 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