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In this paper, we described technique of platelet rich plasma injection into the olfactory cleft in a 22-year-old female with 24-month post-COVID-19 anosmia. The technique starts with the blood extraction and the isolation of PRP through a 10-min centrifugation. The supernatant was injected in nasal regions after a local anesthesia through a 0° rigid optic. Several points of .2-.5 mL were performed in the nasal septum in regard of the head of the middle turbine and in the head of the middle turbine in both sides. The baseline threshold, discrimination, and identification scores were 1, 8, and 0, and the Olfactory Disorder Questionnaire score was 51, respectively. The injection of PRP in olfactory cleft was done without complication and mild pain. The patient perception of recovery of smell sense occurred at 3-week post-injection. From this time, the smell sense progressively improved to the 2-month consultation. At 2-month post-injection, the TDI scores reached 16, 16, and 16 (48), while the Olfactory Disorder Questionnaire was 73. The injection of PRP into the olfactory cleft appears to be a safe and easiness new approach that may improve the recovery of smell sense. Future controlled studies are needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Post-vaccine olfactory and gustatory disorders are very rare and were reported in patients who received influenza vaccines. In this article, we report 6 cases of post-coronavirus disease 2019 (COVID-19) vaccine olfactory and gustatory disorders in patients with negative nasal swabs. Precisely, olfactory and gustatory dysfunctions were reported in 5 and 1 patients, respectively. Sense disorders occurred after the first injection of AstraZeneca (n = 4) or the second injection of Pfizer (n = 2) vaccines. In 4 cases, the olfactory or gustatory disorder was confirmed with psychophysical evaluations. The duration of chemosensory dysfunction ranged from 4 to 42 days. None of the patient reported mid- or long-term olfactory or gustatory disorder. The occurrence of olfactory and gustatory dysfunctions in adults benefiting from COVID-19 vaccines is still rare but has to be known by otolaryngologists., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Olfactory dysfunction (OD) was one of the most common symptom of infection with the Wuhan strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and could persist for several months after symptom onset. The pathogenesis of prolonged OD remains poorly understood but probably involves sustained viral replication associated with limited mucosal immune response to the virus. This prospective study was conducted to investigate the potential relationship between nasal SARS-CoV-2 viral load and antibody levels in patients with loss of smell. One hundred and five patients were recruited 2 weeks after presenting with confirmed coronavirus disease 2019 associated OD. Based on the identification sniffing test performed at enrollment, 52 patients were still anosmic or hyposmic and 53 were normosmic. SARS-CoV-2 was detectable in nasal wash of about 50% of anosmic and normosmic patients. Higher viral load was detected in anosmic patients with lower levels of SARS-CoV-2 specific nasal immunoglobulins (Ig) IgG and IgA. This association was not observed in normosmic patients. No relationship between nasal viral load and antibodies to endemic coronaviruses was observed. SARS-CoV-2 replication in the nasal cavity may be promoted by defective mucosal antibody responses in patients with OD. Boosting mucosal immunity may limit nasal SARS-CoV-2 replication and thereby help in the control of persistent OD., (© 2024 Wiley Periodicals LLC.)

Objective: To investigate the effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of coronavirus disease 2019 (COVID-19) patients with persistent olfactory dysfunction (OD)., Study Design: Controlled study., Setting: Multicenter study., Methods: From March 2022 to November 2022, COVID-19 patients with persistent OD were recruited from three European hospitals to undergo PRP injections into the olfactory clefts. Olfactory function was evaluated at baseline and 10 weeks postinjection with the Olfactory Disorder Questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test. Data were compared with a control group of untreated patients., Results: Eighty-one patients who underwent PRP injection and 78 controls were included. Sixty-five PRP patients (80.3%) experienced subjective smell improvement after a mean duration of 3.4 ± 1.9 weeks. The parosmia, life quality statement, and ODQ sub- and total scores significantly decreased from pre- to 10-week postinjection in the PRP group. The TDI sub- and total scores significantly increased 10 weeks postinjection. In controls, the ODQ score did not change over time, while the discrimination, identification, and total TDI scores significantly increase after 10 weeks of follow-up. The 10-week TDI and ODQ scores were significantly better in the PRP group compared with the controls., Conclusion: Patients who underwent PRP injection reported better 10-week subjective and objective smell outcomes than controls. Future randomized-controlled studies using saline injection into the olfactory cleft of controls are needed to determine the superiority of PRP over placebo., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objectives: To investigate the prevalence and the evolution of olfactory disorders (OD) related to coronavirus disease 2019 (COVID-19) in patients infected during the first and the second European waves., Methods: From March 2020 to October 2020, COVID-19 patients with OD were recruited and followed over the 12-month post-infection. The following data were collected: demographic, treatments, vaccination status, and olfactory function. Olfaction was assessed with the Olfactory Disorder Questionnaire (ODQ), and threshold, discrimination, and identification (TDI) test. Outcomes were compared between patients of the first wave (group 1: wild/D614G virus) and the second wave (group 2: B.1.1.7. Alpha variant) at 1-, 3- and 12-month post-infection., Results: Sixty patients completed the evaluations accounting for 33 and 27 patients in group 1 and 2, respectively. The 1-month TDI score (23.7 ± 5.3) was significantly lower in group 2 compared to group 1 (29.8 ± 8.7; p = 0.017). Proportion of normosmic patients at 1-month post-infection was significantly higher in group 1 compared to group 2 (p = 0.009). TDI scores only significantly increased from 1- to 3-month post-infection in anosmic and hyposmic patients. Focusing on There was a negative association between the 1-month ODQ and the 1-month TDI (r s  = - 0.493; p = 0.012). ODQ was a significant predictor of TDI scores at 3- and 12-month post-infection. The 12-month prevalence of parosmia was 60.6% in group 1 and 42.4% in group 2, respectively. There was no significant influence of oral corticosteroid treatment, adherence to an olfactory training and vaccination status on the olfactory outcomes., Conclusions: Patients of the second wave (Alpha B.1.1.7. variant) reported significant higher proportion of psychophysical test abnormalities at 1-month post-infection than patients infected during the first wave (D614G virus)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate safety, feasibility, and effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of COVID-19 patients with persistent olfactory dysfunction (OD)., Methods: From March 2022 to July 2022, COVID-19 patients with persistent OD were consecutively recruited to benefit from PRP injection into the olfactory clefts. Patient pain, annoyance, time of procedure, and adverse events were evaluated. Olfactory function was evaluated at baseline and 2-month post-injection with the olfactory disorder questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test., Results: Eighty-seven patients with anosmia (N = 30), hyposmia (N = 40), or parosmia (N = 17) with a mean OD duration of 15.7 months completed the evaluations. The PRP injection was successfully performed in all patients with a mean procedure time of 18.4 ± 3.4 min. The adverse events included transient epistaxis (N = 31), parosmia related to xylocaine spray (N = 10), and vasovagal episode (N = 2). The injection procedure was evaluated as somewhat or moderately painful by 41 (47%) and 22 (25%) patients, respectively. Thirty-seven patients were assessed after 2 months post-injection. The mean ODQ and TDI scores significantly improved from baseline to 2-month post-injection (p < 0.01). The olfactory improvement occurred after a mean of 3.6 ± 1.9 weeks., Conclusion: The injection of PRP into the olfactory clefts is safe and associated with adequate patient-reported outcomes. The findings of this preliminary study suggest possible efficacy on subjective and psychophysical evaluations, but future randomized controlled studies are needed to determine the superiority of PRP injection over placebo., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To investigate effectiveness of olfactory training (OT) in COVID-19 patients with persistent olfactory dysfunction (OD)., Methods: From March 2020 to March 2022, COVID-19 patients with OD were prospectively followed in three European medical centers for a period of 18 months. A standardized OT protocol were recommended to patients. Patient-reported outcome questionnaires and psychophysical evaluations were used to evaluate olfaction at baseline, 6, 12, and 18 months after the start of OT. The evolution of olfactory outcome was compared according to the adherence to the OT protocol., Results: Fifty-seven patients completed the evaluations. Thirty-two patients fully adhered to the OT, while 25 did not adhere. The psychophysical scores significantly improved from baseline to 6-month post-infection in both groups. In the OT group, the psychophysical scores continued to significantly improve from 6 to 12 months after the start of OT (p = 0.032). The mean duration of OT was 15.4 weeks. The mean delay of patient recovery perception was comparable between groups (27.4 weeks). The occurrence of cacosmia (35.1%) and parosmia (43.9%) throughout the follow-up period was comparable between groups. There proportion of phantosmia was higher in training (34.4%) compared with no-OT (16.0%; p = 0.007) group. The baseline Sniffin'Sticks tests was positively associated with the 6-month Sniffin'Sticks tests (r s  = 0.685; p < 0.001) and negatively associated with the time of recovery (r s  = - 0.369; p = 0.034)., Conclusions: The adherence to an OT protocol was associated with better mid-term improvement of psychophysical scores. Future large-cohort randomized-controlled studies are needed to confirm the effectiveness of OT in COVID-19 patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients 24 months after the infection., Methods: From 22 March 2020 to 5 June 2022, 251 COVID-19 patients were followed in three European medical centres. Olfactory function was assessed with subjective patient-reported outcome questionnaires and odour identification tests at baseline, 6, 12, 18 and 24 months postinfection. The predictive values of epidemiological and clinical data were investigated with multivariate analysis., Results: One hundred and seventy-one patients completed the evaluations. The odour identification test revealed that 123 patients (50.8%) had OD at baseline. The prevalence of persistent psychophysical abnormalities at 6, 12, 18 and 24 months post-COVID-19 was 24.2%, 17.9%, 5.8% and 2.9%, respectively (p = 0.001). Parosmia occurred in 40 patients (23.4%) and lasted 60 ± 119 days. At 2 years, 51 patients (29.8%) self reported that their olfaction was unnormalised. Older patients had better odour identification evaluations at baseline (p < 0.001) but those with OD reported lower odour identification test scores at the end of the follow-up. Parosmia occurred more frequently in young patients. The olfactory training was significantly associated with higher values of Sniffin' Sticks tests at 18 months postinfection (r s = 0.678; p < 0.001)., Conclusion: Two years post-COVID-19, 29.8% of patients reported persistent OD, but only 2.9% had abnormal identification psychophysical evaluations., (© 2022 The Association for the Publication of the Journal of Internal Medicine.)

Introduction: Olfactory dysfunction (OD) is a well know symptom of coronavirus disease 2019 (COVID-19), accounting for 48 to 85% of patients. In 1 to 10% of cases, patients develop a chronic olfactory dysfunction (COD), lasting more than 6 months. Recently, platelet-rich plasma (PRP) was used in patients with non-COVID-19 COD and authors reported encouraging results., Methods: In the present study, we investigated the usefulness and safety of PRP injection in 56 patients with COVID-19 COD by the Sniffing Stick test (TDI score) and a linker-scale from 0 (none) to 3 (strong) and we compare the result to a control group., Results: At 1 month post-PRP injection, the mean TDI scores significantly improved by 6.7 points in the PRP group (p < 0,001), the mean self-assessment of improvement in smell function was 1.8 (mild-to-moderate) in the PRP group, which was significantly higher than the score (0.3) in the control group (p < 0,001)., Conclusion: Our results showed that PRP in the olfactory cleft can increase the olfactory threshold 1 month after the injection. Moreover, our results suggest that timing of treatment may be an important factor and that PRP is a safe treatment, because no adverse effects were reported throughout the study., Trial Registration Number: NCT05226546., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The purpose of this multicenter case-control study was to evaluate a group of patients at least 1 year after coronavirus disease 2019 (COVID-19) with Sniffin' Sticks tests and to compare the results with a control population to quantify the potential bias introduced by the underlying prevalence of olfactory dysfunction (OD) in the general population. The study included 170 cases and 170 controls. In the COVID-19 group, 26.5% of cases had OD (anosmia in 4.7%, hyposmia in 21.8%) versus 3.5% in the control group (6 cases of hyposmia). The TDI score (threshold, discrimination, and identification) in the COVID-19 group was significantly lower than in the control group (32.5 [interquartile range, 29-36.5] vs 36.75 [34-39.5], P < .001). The prevalence of OD was significantly higher in the COVID-19 group, confirming that this result is not due to the underlying prevalence of OD in the general population.

Objective: The objective of this study was to appreciate the tolerance and convenience of a new FFP2 mask allowed the realization of nasal examination in period of pandemic., Methods: Fifty-one patients were prospectively recruited from two European hospitals to test the FFP2 mask prototype. The following outcomes were evaluated in patients after the clinical examination: fear about coronavirus disease 2019 (COVID-19) infection; easiness of mask placement; tolerability; reassurance; and overall satisfaction about the use of this kind of mask in a pandemic context. Seven otolaryngologists evaluated the mask acceptance and usefulness in patients through a standardized physician-reported outcome questionnaire., Results: Fifty patients completed the evaluation. There were 25 males and 25 females. The mean age of patients was 41 years. Ninety percent of patients considered that the use of the mask reduced the risk to be infected during the examination. Seventy percent of patients reported high or very high satisfaction and should recommend mask to other patients in pandemic period. The realization of nasal examination was easier with optic compared with flexible trans-nasal examination (p = 0.001), which significantly impacted the satisfaction level of physician (p = 0.001). The physician difficulty to perform the examination significantly impacted the satisfactory of patient (p = 0.033)., Conclusion: The new bioserenity FFP2 mask allows the realization of the trans-nasal endoscopic examination during a pandemic. The use of this mask requires little training period of physician. The use of this mask prototype is well received by patients who reported better perception of self-protection against the virus., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome., Methods: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models., Results: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region., Interpretation: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission., Competing Interests: TS is part of the Data Safety Monitoring Committee of a study to evaluate the safety and immunogenicity of a candidate Ebola Vaccine in children - the GSK3390107A (ChAd3 EBO-Z) vaccine; he is a panel member of Covid-19 Vaccine Benefit Risk Expert Working Group for the Medicines and Healthcare Regulatory Agency (UK); he is a member of COVID-19 Therapeutics Advisory Panel for the UK Department of Health & Social Care; he is the Chair/Co-Chair of the COVID-19 Rapid Response and Rolling Funding Initiatives, which supported the development of the Oxford-AstraZeneca Covid-19 vaccine. In addition, Dr. Solomon has a diagnostic test for bacterial meningitis, based on a blood test, filed for patent pending.

Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae, but little is known about the eventual persistence of this immune alteration. Herein, we evaluated TLR-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n = 97). In the acute phase, we observed impaired cytokine production by monocytes in the patients with the most severe COVID-19. This capacity was globally restored in convalescent patients. However, we observed increased responsiveness to TLR1/2 ligation in patients who recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. In patients with acute severe COVID-19, we identified a specific transcriptomic and epigenomic state in monocytes that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at activating protein 1 (AP1) and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes, during both the acute and the convalescent phases, in a completely distinct manner. This could have important implications for our understanding of short- and long-term COVID-19-related morbidity.

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 nondysphonic 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 nondysphonic 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 nondysphonic 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 nondysphonic individuals. Future studies are needed to investigate the relevance of dysphonia in the COVID-19 clinical presentation., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19) METHODS: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19., Results: Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups. In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7-18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (r s  = 0.182) and not significant (p = 0.12)., Conclusions: In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions., (© 2021. The Author(s).)

The aim of this study is to investigate the clinical profile of patients who developed coronavirus disease 2019 (COVID-19) after full vaccination. Demographic, epidemiological and clinical data were collected through medical records and online patient-reported outcome questionnaire from patients who developed symptomatic SARS-CoV-2 infection, confirmed by nasopharyngeal swab, at least 2 weeks after completion of vaccination. A total of 153 subjects were included. The most frequent symptoms were: asthenia (82.4%), chemosensory dysfunction (63.4%), headache (59.5%), runny nose (58.2%), muscle pain (54.9%), loss of appetite (54.3%), and nasal obstruction (51.6%). Particularly, 62.3% and 53.6% of subjects reported olfactory and gustatory dysfunction, respectively. Symptom severity was mild or moderate in almost all cases. Chemosensory dysfunctions have been observed to be a frequent symptom even in subjects who contracted the infection after full vaccination. For this reason, the sudden loss of smell and taste could continue to represent a useful and specific diagnostic marker to raise the suspicion of COVID-19 even in vaccinated subjects. In the future, it will be necessary to establish what the recovery rate is in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:419-421, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Competing Interests: We declare no competing interests. We thank Claire Hopkins for advice and collaboration.

Background and Purpose: The aim was to evaluate potential predictive factors of smell recovery in a clinical series of 288 patients presenting olfactory dysfunction (OD) related to coronavirus disease 2019 (COVID-19). Potential correlations were sought between epidemiological, clinical and immunological characteristics of patients and the persistence of OD at 60 days., Methods: COVID-19 positive patients presenting OD were prospectively recruited from three European hospitals. Baseline clinical and olfactory evaluations were performed within the first 2 weeks after OD onset and repeated at 30 and 60 days. In a subgroup of patients, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were measured in serum, saliva and nasal secretions at 60 days., Results: A total of 288 COVID-19 patients with OD were included in the study. Two weeks after the onset of the loss of smell, 52.4% of patients had OD on psychophysical tests, including 113 cases (39.2%) of anosmia and 38 cases (13.2%) of hyposmia. At 60-day follow-up, 25.4% of the patients presented persistent OD. There was no significant correlation between sex, age, viral load on nasopharyngeal swab or COVID-19 severity and poor olfactory outcome. In a subgroup of 63 patients, it was demonstrated that patients with poor olfactory outcomes at 60 days had lower levels of salivary and nasal immunoglobulin G (IgG) and IgG1, but similar levels of antibodies in the serum., Conclusions: No clinical markers predicted the evolution of OD at 60 days. Patients with poor olfactory outcome at 60 days had lower saliva and nasal antibodies, suggesting a role for local immune responses in the persistence of COVID-19 related OD., (© 2021 European Academy of Neurology.)

Objectives/hypothesis: The aim of this study was to evaluate the correlations between the severity and duration of olfactory dysfunctions (OD), assessed with psychophysical tests, and the viral load on the rhino-pharyngeal swab determined with a direct method, in patients affected by coronavirus disease 2019 (COVID-19)., Study Design: Prospective cohort study., Methods: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and determination of the normalized viral load on nasopharyngeal swab within 10 days of the clinical onset of COVID-19., Results: Sixty COVID-19 patients were included in this study. On psychophysical testing, 12 patients (20% of the cohort) presented with anosmia, 11 (18.3%) severe hyposmia, 13 (18.3%) moderate hyposmia, and 10 (16.7%) mild hyposmia with an overall prevalence of OD of 76.7%. The overall median olfactory score was 50 (interquartile range [IQR] 30-72.5) with no significant differences between clinical severity subgroups. The median normalized viral load detected in the series was 2.56E+06 viral copies/10 6 copies of human beta-2microglobulin mRNA present in the sample (IQR 3.17E+04-1.58E+07) without any significant correlations with COVID-19 severity. The correlation between viral load and olfactory scores at baseline (R 2  = 0.0007; P = .844) and 60-day follow-up (R 2  = 0.0077; P = .519) was weak and not significant., Conclusions: The presence of OD does not seem to be useful in identifying subjects at risk for being super-spreaders or who is at risk of developing long-term OD. Similarly, the pathogenesis of OD is probably related to individual factors rather than to viral load and activity., Level of Evidence: 4 Laryngoscope, 131:2312-2318, 2021., (© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

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.

Background: From the start of the pandemic, many European otolaryngologists observed an unprecendented number of anosmic patients. Early reports proposed that anosmia could be the first or even the only symptom of COVID-19 infection, prompting calls for self-isolation in affected patients., Methods: In the present article, we review the COVID-19 anosmia literature and try to answer the following two questions: first, why is COVID-19 infection responsible for such a high incidence of anosmia? Second, in patients with more severe forms is anosmia really less prevalent and why?, Results: In terms of the etiology of olfactory dysfunction, several hypotheses were proposed at the outset of the pandemic; that olfactory cleft inflammation and obstruction caused a localized conductive loss, that there was injury to the sustentacular supporting cells in the olfactory epithelium or, given the known neurotropic potential of coronavirus, that the virus could invade and damage the olfactory bulb. Olfactory cleft obstruction may contribute to the olfactory dysfunction in some patients, perhaps most likely in those that show very early resolution, it cannot account for the loss in all patients. Moreover, disordered regrowth and a predominance of immature neurons have been shown to be associated with parosmia, which is a common finding amongst patients with Covid-related anosmia. A central mechanism therefore certainly seems to be consistent with the group of patients with more prolonged olfactory deficits. Sustentacular cells showing ACE-2 immunohistochemical expression 200 to 700 times greater than nasal or tracheal epithelia seem to be the main SARS-CoV-2 gateway. As the pathophysiology of COVID-19 anosmia seems to be better understood, the question of why patients with a moderate to severe form of COVID-19 infection have less olfactory involvement remains unresolved. Different potential explanations are discussed in this review., Conclusions: The last 5 months have benefited from great international collaborative research, first highlighting and then proving the value of loss of smell and taste as a symptom of COVID-19. Adoption of loss of smell into the case definition by international public health bodies will facilitate control of disease transmission.

Post-vaccine olfactory and gustatory disorders are very rare and were reported in patients who received influenza vaccines. In this article, we report 6 cases of post-coronavirus disease 2019 (COVID-19) vaccine olfactory and gustatory disorders in patients with negative nasal swabs. Precisely, olfactory and gustatory dysfunctions were reported in 5 and 1 patients, respectively. Sense disorders occurred after the first injection of AstraZeneca (n = 4) or the second injection of Pfizer (n = 2) vaccines. In 4 cases, the olfactory or gustatory disorder was confirmed with psychophysical evaluations. The duration of chemosensory dysfunction ranged from 4 to 42 days. None of the patient reported mid- or long-term olfactory or gustatory disorder. The occurrence of olfactory and gustatory dysfunctions in adults benefiting from COVID-19 vaccines is still rare but has to be known by otolaryngologists. [ABSTRACT FROM AUTHOR]

10.4193/Rhin21.378 40 Lechien J.R., Le Bon S.D., Saussez S. Platelet-rich plasma injection in the olfactory clefts of COVID-19 patients with long-term olfactory dysfunction. At the beginning of 2021, the scientific community realized the burden of COVID-19-related persistent olfactory disorders (ODs). 10.1007/s12070-021-02749-9. 34277384 26 Kasiri H., Rouhani N., Salehifar E., Ghazaeian M., Fallah S. Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial. This will no longer be possible now that COVID-19 has shed light on this type of disabling dysfunction, raising awareness among patients who will not accept being offered no therapy. [Extracted from the article]

10.4193/Rhin21.249 11 Lechien J.R., Vaira L.A., Saussez S. Prevalence and 24-month recovery of olfactory dysfunction in COVID-19 patients: A multicentre prospective study. It has now been two years since the publication in I Pathogens i of our European multicenter study on the prevalence of olfactory dysfunctions (OD) during COVID-19 [[1]]. 10.3390/pathogens10060698 30 Lechien J.R., Vaira L.A., Saussez S. Effectiveness of olfactory training in COVID-19 patients with olfactory dysfunction: A prospective study. 33445604 2 Saniasiaya J., Islam M.A., Abdullah B. Prevalence of olfactory dysfunction in coronavirus disease 2019 (COVID-19): A meta-analysis of 27,492 patients. [Extracted from the article]

The article proposes a potential hypothesis about the pathophysiological mechanism of olfactory dysfunction (OD) based on some clinical observations. Topics include observation on some patients with persistent COVID-19 OD since the development of vaccination in Western countries, observation on olfactory region abnormalities in imaging study several months after the onset of OD, and analysis of the persistence of OD in COVID-19 patients.

The article discusses two cases of patients who experienced episodes of olfactory and gustatory dysfunctions after COVID-19 reinfection. Topics mentioned include the prevalence of loss of smell and taste senses in COVID-19 patients, the impact of COVID-19 on the quality of life, the definition of gustatory function, and other symptoms of COVID-19.

(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up. [ABSTRACT FROM AUTHOR]

In the original publication of the article, one of the co-author's name was published incorrectly as "Liugi A. Varia". The correct name should read as "Luigi A. Vaira". [ABSTRACT FROM AUTHOR]