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International audience; To review the data regarding the expression of angiotensin converting enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2) in head and neck tissue. Scopus, Cochrane Library, Medrxiv, Google Scholar and PubMED/MEDLINE were searched by four independent investigators for studies investigating ACE2 or TMPRSS2 expressions in head and neck tissues. The following outcomes were considered: sample origin (animal versus human); detection method; anatomical location and cell types. PRISMA checklist and modified population, intervention, comparison, outcome, timing and setting (PICOTS) framework were used to perform the review. Of the 24 identified studies, 17 met our inclusion criteria. Thirteen studies were conducted during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. ACE2 and TMPRSS2 were expressed in oral, pharyngeal, sinusonasal human mucosa. The following cell types expressed ACE2: basal, apical, goblet, minor salivary, and endothelial cells. TMPRSS2 was found in goblet and apical respiratory cells. ACE2 and TMPRSS2 were found in the olfactory region, especially in sustentacular non-neural and neural stem cells. Animal studies suggested that ACE2 expression may vary regarding age. There was an important heterogeneity between studies in the methods used to detect ACE2 and TMPRSS2, leading to a potential identification bias. The SARS-CoV-2 receptors, ACE2 and TMPRSS2, are both expressed in many head and neck tissues, enabling the viral entry into the host organism.

International audience; Objective: To investigate prevalence and epidemiological and clinical factors associated with olfactory dysfunction (OD) and gustatory dysfunction (GD) in COVID-19 patients according to the disease severity. Study design: Cross-sectional study. Methods: A total of 2579 patients with a positive diagnosis of COVID-19 were identified between March 22 and June 3, 2020 from 18 European hospitals. Epidemiological and clinical data were extracted. Otolaryngological symptoms, including OD and GD, were collected through patient-reported outcome questionnaire and Sniffin’Sticks tests were carried out in a subset of patients. Results: A total of 2579 patients were included, including 2166 mild (84.0%), 144 moderate (5.6%) and 269 severe-to-critical (10.4%) patients. Mild patients presented an otolaryngological picture of the disease with OD, GD, nasal obstruction, rhinorrhea and sore throat as the most prevalent symptoms. The prevalence of subjective OD and GD was 73.7 and 46.8%, and decreases with the severity of the disease. Females had higher prevalence of subjective OD and GD compared with males. Diabetes was associated with a higher risk to develop GD. Among the subset of patients who benefited from psychophysical olfactory evaluations, there were 75 anosmic, 43 hyposmic and 113 normosmic patients. The prevalence of anosmia significantly decreased with the severity of the disease. Anosmia or hyposmia were not associated with any nasal disorder, according to SNOT-22. Conclusion: OD and GD are more prevalent in patients with mild COVID-19 compared with individuals with moderate, severe or critical diseases. Females might have a higher risk of developing OD and GD compared with males.

International audience; Objective: To investigate the clinical features of patients who had two demonstrated coronavirus disease 2019 (COVID-19) episodes. Methods: Data of patients with both COVID-19 episodes were recruited from 22 March to 27 December 2020. The following outcomes were studied: epidemiological, comorbidities, prevalence and severity of general and otolaryngological symptom, olfactory, aroma, and gustatory dysfunctions. A comparison between first and second episodes was performed. Results: Forty-five patients reported having two confirmed COVID-19 episodes. The majority of patients had mild infections in both episodes. The second clinical episode was significantly similar to the first. The symptom duration of the second episode was shorter than the first. The occurrence of loss of smell was unpredictable from the first to the second episode. Conclusion: The recurrence of COVID-19 symptoms is associated with a similar clinical picture than the first episode in patients with initial mild-to-moderate COVID episode. The pathophysiological mechanisms underlying the development of second episode remain uncertain and may involve either true reinfection or virus reactivation from sanctuaries.

Objective: To investigate prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients according to the disease severity. Methods: From 22 March to 3 June 2020, 2581 COVID-19 patients were identified from 18 European hospitals. Epidemiological and clinical data were extracted at baseline and within the 2-month post-infection. Results: The prevalence of OD was significantly higher in mild form (85.9%) compared with moderate-to-critical forms (4.5–6.9%; P = 0.001). Of the 1916 patients with OD, 1363 completed the evaluations (71.1%). A total of 328 patients (24.1%) did not subjectively recover olfaction 60 days after the onset of the dysfunction. The mean duration of self-reported OD was 21.6 ± 17.9 days. Objective olfactory evaluations identified hyposmia/anosmia in 54.7% and 36.6% of mild and moderate-to-critical forms, respectively (P = 0.001). At 60 days and 6 months, 15.3% and 4.7% of anosmic/hyposmic patients did not objectively recover olfaction, respectively. The higher baseline severity of objective olfactory evaluations was strongly predictive of persistent OD (P, SCOPUS: ar.j, info:eu-repo/semantics/published

Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From March 2020, several studies indicate that many subjects affected by mild-to-moderate COVID-19 presented olfactory/gustatory dysfunction (OD/GD) that appeared strongly correlated between them but not with the other symptoms suggestive of upper airway infectionIn order to evaluate patterns of gustatoy recovery, data from patients with confirmed COVID-19 were collected prospectively from 4 University Hospitals. At this relatively early point in the pandemic, the authors considered that subjective patterns of recovery of olfactory disfunction in COVID-19 patients are valuable for our patients, for hypothesis generation and treatment development.

International audience; Background: The clinical presentation of European patients with mild-to-moderate COVID-19 infection is still unknown. Objective: To study the clinical presentation of COVID-19 in Europe. Methods: Patients with positive diagnosis of COVID-19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analysing the relationship between outcomes. Results: A total of 1,420 patients completed the study (962 females, 30.7% of healthcare workers). The mean age of patients was 39.17 ± 12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by 45.4%. The mean duration of COVID-19 symptoms of mild-to-moderate cured patients was 11.5 ± 5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild-to-moderate COVID-19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. Conclusion: The clinical presentation of mild-to-moderate COVID-19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild-to-moderate COVID-19 that needs to be recognized as such by the WHO.

Objective: To investigate the coronavirus disease 2019 (COVID-19) status of patients with initial sudden olfactory anosmia (ISOA) through nasopharyngeal swabs for reverse transcription–polymerase chain reaction (RT-PCR) analysis and to explore their olfactory dysfunctions with psychophysical olfactory evaluation. Methods: A total of 78 ISOA patients were recruited from April 6, 2020, to April 10, 2020, through a public call of University of Mons (Mons, Belgium). Patients benefited from nasopharyngeal swabs and fulfilled the patient-reported outcome questionnaire. Among them, 46 patients performed psychophysical olfactory evaluation using olfactory identification testing. Based on the duration of the ISOA, 2 groups of patients were compared: patients with olfactory dysfunction duration ≤12 days (group 1) and those with duration >12 days (group 2). Results: In group 1, 42 patients (87.5%) had a positive viral load determined by RT-PCR and 6 patients (12.5%) were negative. In group 2, 7 patients (23%) had a positive viral load and 23 patients (77%) were negative. The psychophysical olfactory evaluation reported that anosmia and hyposmia occurred in 24 (52%) and 11 (24%) patients, respectively. Eleven patients were normosmic. The viral load was significantly higher in patients of group 1 compared with those of group 2. Conclusions: Coronavirus disease 2019 was detected in a high proportion of ISOA patients, especially over the first 12 days of olfactory dysfunction. Anosmia is an important symptom to consider in the detection of COVID-19 infection.

Voice disorders are a significant public health issue; their lifetime prevalence is as high as 30% in the general population but much higher in professional voice users.1,2 Severe dysphonia is a very fatiguing condition with a negative impact on the social and professional life. In the era of the coronavirus disease 2019 (COVID-19) pandemic, lock-down and social restrictions have caused an abrupt interruption of voice therapy programs. This lack of care may impact the possibility of reestablishing a socially acceptable voice in a reasonable time, having a possible negative impact on professional careers and emotional life. At the time of writing this paper, in Western Europe, we are facing a progressive reduction in the number of people infected by the novel coronavirus. Nevertheless, the projection of the virus circulation in the post-pandemic period is predicting the possibility of several future clusters.3 Therefore we cannot imagine that the most vulnerable patients would still be regularly coming into a busy office to undergo voice therapy sessions. Currently, telemedicine has made incredible progress in a matter of a few weeks and can be valuable not only for the health of patients, but also to help them build and strengthen their resilience in such a difficult time of isolation and loneliness. Previous studies found that telemedicine may be useful in voice therapy.4 Telemedicine can be practiced on several platforms easily accessed with an electronic device. Currently, in Italy and France, we are facing several impediments regarding the wide use of remote voice therapy. We identified four main obstacles. First, in most hospitals the basic equipment is still unavailable. Many departments have no high-quality camera or software allowing the use of Telemedicine. Second, some voice therapists do not feel confident with the new technologies. Third, elderly individuals or patients who have a low income may not have easy access to electronic devices. However, in Western Europe, most patients own at least a smartphone. Four, the social health system and private insurance companies in many European countries do not recognize remote voice therapy sessions as reimbursable procedures. This is the main barrier that explains why the procedure is still underused. Due to the COVID-19 outbreak, speech therapists should be aware that most voice rehabilitative exercises are aerosol-generating procedures, such as breathing exercises and the widely used “semi-occluded voice therapy exercises” (SOVTEs).5,6 They are based on narrowing of the cross-sectional area of the vocal tract obtained to improve voice resonance by enhancing the interaction between the vocal folds and the vocal tract.5 SOVTEs can generate an aerosol generated by the turbulent flow occurring at the site of vocal tract narrowing. The most popular SOVTEs include lip and tongue trills and phonation into a straw or a tube into the air or water.7 Spreading in the room of contaminated droplets may cause the risk of viral aerosol inhalation for both the voice therapist and for the patient when the therapist is demonstrating it. The voice therapist should use personal protective equipment, such as facemasks and shields, considering that any patient might be an asymptomatic carrier of the novel coronavirus. However, the availability of protective equipment is limited in Europe, which may hinder access to a regular daily supply for the voice therapist. Another important question is: “could a voice therapy session be effective if the therapist is wearing a mask?” The sound of him/her voice would be muffled and distorted, articulatory movements would be not visible, and the speech therapist could not demonstrate exercises such as phonating into a tube or a straw or doing lip or tongue trills. Moreover, the patient might be unable to perform vocal exercises if wearing any type of facemask, and the therapist might have trouble assuring that the exercises were being done correctly. A different way to perform voice therapy is highly desirable in the context of the COVID-19 pandemic, and its development may also be valuable for potential future pandemics as well as for future routine care. Telemedicine offers the opportunity for this change and may allow patients to receive care in their home, without exposure to risk of infection. The voice therapist may demonstrate the exercises being seen and heard on a screen and, at the same time, may check how the patient is performing the exercises. Virtual voice therapy offers a great opportunity for all patients to have easy access to rehabilitation and can be valuable for those affected by mobility impairment or living a long distance away from the facility. Furthermore, the ability to invite a guest or observer to the encounter is another valuable opportunity to offer further support to the patient, considering that, currently, the patient cannot be accompanied in the medical unit by anyone due to the risk of contamination and the distancing measures required by the governments. The COVID-19 pandemic may change some speech therapy practices for the better, and it is time to overcome resistance to new technologies. For this reason, both private insurance companies and public healthcare systems have to work to recognize the opportunities related to “telespeech therapy,” ensuring efficient and effective healthcare continuity.

Based on observations described in our letter, we can draw the following conclusions: (1) anosmia must imperatively be added to the list of specific symptoms of COVID-19 infection, (2) anosmia can serve as a free and specific diagnostic tool for developing countries currently affected by the pandemic, (3) the mechanisms of COVID-19 anosmia seem not to directly involve nasal obstruction but rather seem to be related to damage the olfactory neuroepithelium.

International audience; Objective: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. Methods: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). Results: A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). Conclusion: Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.

BackgroundOlfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated.Case reportThis report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2.ConclusionThe biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.

International audience; The purpose of this study was to evaluate the clinical features of mild-to-moderate coronavirus disease 2019 (COVID-19) in a sample of Italian patients and to investigate the occurrence of smell and taste disorders. Infected individuals with suspected (clinical diagnosis) or laboratory-confirmed COVID-19 infection were recruited. Patients completed a survey-based questionnaire with the aim of assessing their epidemiological and clinical characteristics, general otorhinolaryngological symptoms, and smell and taste disorders. A total of 294 patients with mild-to-moderate COVID-19 completed the survey (147 females). The most prevalent general symptoms included fever, myalgia, cough, and headache. A total of 70.4% and 59.2% of patients reported smell and taste disorders, respectively. A significant association between the two above-mentioned disorders was found (rs: 0.412; P