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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (rs = 0.685; p < 0.001) and negatively associated with the time of recovery (rs = − 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. [ABSTRACT FROM AUTHOR]

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 (rs = 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. [ABSTRACT FROM AUTHOR]

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 (rs = 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. [ABSTRACT FROM AUTHOR]

Chemosensitive dysfunctions are now considered as frequent and early symptoms of coronavirus disease 2019 (COVID-19). In the last few weeks, researchers' greatest efforts have been focusing mainly on the analysis of olfactory disorders, neglecting taste dysfunctions. According to our psychophysical evaluations, it can be inferred that the pathogenesis of taste disorders in COVID-19 patients is largely smell-independent. Moreover, isolated gustatory disorders are highly specific of SARS-CoV-2 infection. For these reasons, it is essential that gustatory dysfunctions, like olfactory disorders, are included in the COVID-19 guidelines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 <.001). Smell disorders occurred before the other symptoms in 11.6% of patients and was not significantly associated with nasal obstruction or rhinorrhea. Interestingly, our statistical analysis did not show any significant difference, either for general symptoms or otorhinolaryngological features, between the clinical diagnosis group and the laboratory‐confirmed diagnosis (polymerase chain reaction) group. The structural equation model confirmed significant standardized paths (P <.05) between general symptoms, comorbidities, and general otorhinolaryngological complaints in the absence of a significant correlation between these elements and smell and taste alterations. The prevalence of smell and taste disorders in mild‐to‐moderate Italian COVID‐19 patients is significant both in suspected and laboratory‐confirmed cases and reveals a strong correlation between these clinical signs regardless of the presence of general or otorhinolaryngological symptoms, such as nasal obstruction or rhinorrhea. Highlights: This study evaluates the clinical features of mild‐to‐moderate COVID‐19 in a sample of adult Italian patients. The structural equation model (SEM) built to examine the clinical characteristics of the infection, confirms significant standardised paths between all the evaluated variables and underlines the absence of a significant correlation between smell and taste disorders and all the other variables. Furthermore, the study reveals a strong correlation between smell and taste alterations with a significant prevalence of these symptoms both in suspected (clinical diagnosis) and laboratory‐confirmed (pcr) cases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To investigate olfactory dysfunction (OD) in patients with mild coronavirus disease 2019 (COVID‐19) through patient‐reported outcome questionnaires and objective psychophysical testing. Methods: COVID‐19 patients with self‐reported sudden‐onset OD were recruited. Epidemiological and clinical data were collected. Nasal complaints were evaluated with the sinonasal outcome‐22. Subjective olfactory and gustatory status was evaluated with the National Health and Nutrition Examination Survey. Objective OD was evaluated using psychophysical tests. Results: Eighty‐six patients completed the study. The most common symptoms were fatigue (72.9%), headache (60.0%), nasal obstruction (58.6%), and postnasal drip (48.6%). Total loss of smell was self‐reported by 61.4% of patients. Objective olfactory testings identified 41 anosmic (47.7%), 12 hyposmic (14.0%), and 33 normosmic (38.3%) patients. There was no correlation between the objective test results and subjective reports of nasal obstruction or postnasal drip. Conclusion: A significant proportion of COVID‐19 patients reporting OD do not have OD on objective testing. [ABSTRACT FROM AUTHOR]

Keywords: anosmia; chest CT; coronavirus; COVID-19; hyposmia; olfactory; pneumonia; recovery; SARS-CoV-2; smell EN anosmia chest CT coronavirus COVID-19 hyposmia olfactory pneumonia recovery SARS-CoV-2 smell 103 107 5 12/31/21 20220101 NES 220101 INTRODUCTION The prognostic value of olfactory dysfunction (OD) in coronavirus disease 2019 (COVID-19) remains controversial, with conflicting reports of the association between OD and COVID-19 severity.1 Many of the prognostic studies published so far have important drawbacks that limit the reliability of the results; most are anamnestic studies that do not formally evaluate olfactory function with risk of recall bias, and use "need for hospitalization" alone to determine COVID-19 severity. Coronavirus, COVID-19, hyposmia, pneumonia, anosmia, chest CT, olfactory, recovery, SARS-CoV-2, smell At baseline, 35 patients (76.1%) had OD: 12 cases of anosmia (26.1%), severe hyposmia in 10 (21.7%), and moderate hyposmia in 13 cases (28.3%). [Extracted from the article]