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IntroductionThe current study evaluated the use of platelet-rich plasma (PRP), an autologous blood product with supraphysiologic concentrations of growth factors, in the treatment of prolonged coronavirus disease 2019 (COVID-19)-related smell loss.MethodsThis multi-institutional, randomized controlled trial recruited patients with COVID-19 who had objectively measured smell loss (University of Pennsylvania Smell Identification Test [UPSIT]≤33) between 6 and 12 months. Patients were randomized to three intranasal injections of either PRP or sterile saline into their olfactory clefts. The primary outcome measure was change in Sniffin' Sticks score (threshold, discrimination, and identification [TDI]) from baseline. The secondary end point measures included responder rate (achievement of a clinically significant improvement, ≥5.5 points TDI), change in individual TDI olfaction scores, and change in subjective olfaction via a visual analog scale.ResultsA total of 35 patients were recruited and 26 completed the study. PRP treatment resulted in a 3.67-point (95% CI: 0.05-7.29, p=0.047) greater improvement in olfaction compared with the placebo group at 3 months and a higher response rate (57.1% vs 8.3%, odds ratio 12.5 [95% exact bootstrap confidence interval, 2.2-116.7]). There was a greater improvement in smell discrimination following PRP treatment compared with placebo but no difference in smell identification or threshold. There was no difference in subjective scores between PRP and placebo. No adverse effects were reported.ConclusionOlfactory function following COVID-19 can improve spontaneously after 6 months and can improve to a greater extent with PRP injection. These data build on the promise of PRP to be a safe potential treatment option for patients with COVID-19-related smell loss, and larger-powered studies will help further assess its efficacy.

To evaluate the effect of olfactory dysfunction on the course and severity of COVID-19 and its prognostic and predictive significance for COVID-19.Prospective case-control study.Ondokuz Mayıs University School of Medicine.Reverse transcription polymerase chain reaction (PCR)-positive patients, patients with COVID-19-related symptoms who had a negative PCR result, and healthy controls were included in the study. Clinicodemographic characteristics, inflammatory markers, and computed tomography stages were recorded. Disease progression and intensive care unit admission were registered. The visual analog scale (0, worst; 10, best) was used to evaluate subjective olfactory, taste, and nasal breathing ability, and the Sniffin' Sticks identification (SS-ID) test was used for psychophysical olfactory assessment.Mean SS-ID scores were significantly lower in the positive group (8.77) than in the negative (10.43) and healthy control (12.17) groups. VAS-smell scores were significantly lower and anosmia was more prevalent in PCR-positive patients (Olfactory dysfunction was detected objectively and subjectively in the PCR-positive group, and no difference was found in terms of taste function and nasal breathing. The severity and prognosis of COVID-19 are not exclusively dependent on olfactory dysfunction. The degree of olfactory dysfunction can be useful in predicting PCR positivity.

Background Previous studies provided the first evidence that the importance of olfaction decreases with the duration of olfactory dysfunction (OD). Objective To evaluate differences in olfactory-related quality of life (QoL) between patients with new-onset and persistent smell loss (>4 weeks) during the coronavirus-19 (COVID-19) pandemic and patients with persistent postinfectious OD (PIOD) that were recruited before the pandemic. Methods This was a retrospective study that included 149 patients with self-reported OD. The olfactory-related QoL was measured using the questionnaire of OD (QOD). The QOD measures the degree to which patients (i) adjust and cope with smell loss (QOD-positive statement [QOD-PS]), (ii) suffer from distorted odor perceptions (QOD-parosmia [QOD-PAR]), and (iii) suffer from smell loss in general (QOD-negative statement [QOD-NS]). Self-perceived chemosensory function, demographics, olfactory function, and duration of smell loss were evaluated. Analyses of variance were used to depict differences in QoL-outcomes between different OD groups. Results All patients included during the COVID-19 pandemic reported an extensive loss of chemosensory functions of smell, taste, and flavor perception. Psychophysical retronasal screening testing showed olfactory impairments in more than half of these patients. One-way analysis of variance and posthoc tests revealed that the QOD-NS was significantly higher in the new-onset OD group than the PIOD group. At the same time, the QOD-PS score was significantly higher in the PIOD and the persistent COVID-19 OD group than in the new-onset OD group. Conclusion We showed that patients with persistent OD experienced better olfactory-related adjustment and lower QoL-impairment scores than those with recent-onset smell loss, suggesting that the olfactory-related QoL might change as a function of time after symptom onset.

Background: Smell disturbances are associated with wide range of viral infections. Viral upper respiratory tract infections may cause acute Smell loss due to viral damage to the olfactory epithelium or central nervous system involvement is a possible causes of smell disturbances but, the exact pathogenesis unknown. Aim of the study: assess the Covid 19 associated smell disturbances. Method: This is a prospective study consisted of 200 patients with a confirmed COVID-19 infection, who treated in Al-Diwanyah pandemic hospital in Al-Diwanyah city, Iraq, between July 2020 and May 2021.They were 115 males and 85 females. The age range from 20-80 years. The inclusion criteria were symptomatic patients with positive polymerase chain reaction (PCR) test for COVID-19 infection. Exclusion criteria were any physical, neurological or mental diseases preventing cooperation of the patients, use of central nervous system suppressing drugs. Results: We found that 36 % of patients developed smell disturbances. Most of those affected patients are above 60 years old and majority are females (58.3%). 33.3 % of patients present with isolated smell disturbances without any other features. The time for recovery of smell disturbances ranged from 7- 21 days, and the median time for recovery was 7 days. 8.3 % of patients develop persistent smell problems. Conclusion: Smell abnormalities are common symptoms in COVID-19 patients. It may be the only manifestation of COVID-19.

Loss or impaired sense of smell is a symptom of viral illnesses, including the common cold (Pellegrino et al., 2017) and SARS-CoV-2 (Gerkin et al., 2020; Pellegrino et al., 2020), sinonasal disease (Dalton, 2004), traumatic brain injury (Collet et al., 2009), drugs or toxins (Schiffman, 2018; Upadhyay & Holbrook, 2004), neurodegenerative diseases (Ponsen et al., 2009; Solomon, 1994), surgery (Deems et al., 1991), and chemotherapy (Amézaga et al., 2018), among others (Nordin & Brämerson, 2008). Prior to 2020, over 200,000 people sought treatment for olfactory impairment annually (Pellegrion et al., 2020), primarily caused by viral illnesses (Dalton, 2004). COVID-19 has increased the known prevalence for post-viral smell loss by ~30% (Hummel et al., 2016), and ~20% for all forms of smell loss (Hannum et al., 2020; Liu et al., 2016; Mullol et al., 2012). However, subjective measurements may underestimate the true prevalence of smell loss by about 26% (Hannum et al., 2020) in part due to general lack of awareness of chemosensory changes in the general population. Objective measurements can more accurately identify changes in smell function, but are not always feasible due to scaling, time or budget constraints (Parma et al., 2021). Yet they represent the best way to track recovery from smell loss. A quick recovery would minimize the negative effects associated with smell loss, such as a reduced quality of life (Boesveldt et al., 2017), depression (Rochet et al., 2018), malnutrition (Gopinath et al., 2016) and exposure to toxins such as smoke and natural gas (Pence et al., 2014). However, the time to recovery is variable: 85% of people recover from post-COVID smell loss within 3 weeks (Cecchetto et al., 2021; Chiesa-Estomba et al., 2020; Reiter et al., 2020; Vaira et al., 2020), while 15% of people do not recover and their smell loss persists long after the rest of their COVID-19 symptoms subside (Borsetto et al., 2020; Cecchetto et al., 2021; Chiesa-Estomba et al., 2020; Vaira et al., 2020). Others with post-viral smell loss have reportedly taken years to recover (Lee et al., 2014). Other etiologies of smell loss may also have longer or more permanent effects on smell loss, such as traumatic brain injury (Reden et al., 2006) or neurodegenerative diseases (Hummel et al., 2016; Whitcroft et al., 2017). Recovery may also differ depending on age and sex of the person (Amer et al., 2020; Lee et al., 2014; Mullol et al., 2012). There is currently no cure for smell loss, however some interventions have been effective in improving smell recovery, such as olfactory training (Sorokowska et al., 2017) and pharmacological interventions (Hummel et al., 2016; Yan et al., 2019). Due to the rapid influx of studies assessing smell loss from COVID-19, the time is mature for a metanalytic analysis to synthesize the factors influencing recovery from post-viral smell loss, and compare it recovery following smell loss due to other etiologies (e.g. post-traumatic, neurodegenerative, sinonasal, toxins, surgery, and chemotherapy). A comprehensive analysis of recovery from smell loss due to COVID-19 and how it compares to other etiologies of smell loss does not currently exist. The aim of the study is to determine the recovery prevalence and recovery time from smell loss based on the available literature. Etiology of smell loss, time since etiological event (for prevalence), type of test (subjective vs objective), presence/absence of an intervention, type of intervention, age, and sex will be used as moderators. With this literature search and analysis, we will answer the following experimental questions if data from 4 or more articles per condition can be included: 1. What is the prevalence (percent) of smell loss recovery overall (all etiologies with minimal intervention combined)? 2. What is the prevalence (percent) of smell loss recovery from post-COVID smell loss compared to other etiologies of smell loss (if 4 or more articles are available per etiology). 3. How does the prevalence (percent) of smell loss recovery differ among etiologies of smell loss (if 4 or more articles are available per etiology). ● Exploratory analysis: How does the prevalence (percent) of smell loss recovery differ among acute (12 weeks) cases of smell loss (if >4 of each case are available). 4. Does the prevalence (percent) of smell loss recovery differ based on type of assessment (objective vs. subjective)? 5. Do certain demographics (age and sex) have a higher prevalence (percent) of smell loss recovery than others? 6. Do interventions improve smell loss recovery prevalence (percent)? 7. What is the recovery time (days) from smell loss overall (all etiologies with minimal intervention combined)? 8. What is the recovery time (days) from post-COVID smell loss compared to other etiologies of smell loss (if 4 or more articles are available per etiology). 9. How does the recovery time (days) from smell loss differ among etiologies of smell loss (if 4 or more articles are available per etiology). ● Exploratory analysis: How does the recovery time (days) from smell loss differ among acute and chronic cases of smell loss (if >4 of each case are available). 10. How does the recovery time (days) from smell loss differ based on type of assessment (objective vs. subjective)? 11. Do certain demographics (age and sex) have a reduced recovery time (days) from smell loss than others? 12. What is the impact of interventions on recovery time (days) from smell loss? Recovery includes any reported improvement in smell function.

In recent months it has emerged that the novel coronavirus - responsible for the COVID-19 pandemic - causes reduction of smell and taste in a large fraction of patients. The chemosensory deficits are often the earliest, and sometimes the only signs in otherwise asymptomatic carriers of the SARS-CoV-2 virus. The reasons for the surprisingly early and specific chemosensory dysfunction in COVID-19 are now beginning to be elucidated. In this hypothesis review, we discuss implications of the recent finding that the prevalence of smell and taste dysfunction in COVID-19 patients differs between populations, possibly because of differences in the spike protein of different virus strains or because of differences in the host proteins that enable virus entry, thus modifying infectivity. We review recent progress in defining underlying cellular and molecular mechanisms of the virus-induced anosmia, with a focus on the emerging crucial role of sustentacular cells in the olfactory epithelium. We critically examine the current evidence whether and how the SARS-CoV-2 virus can follow a route from the olfactory epithelium in the nose to the brain to achieve brain infection, and we discuss the prospects for using the smell and taste dysfunctions seen in COVID-19 as an early and rapid diagnostic screening tool. Original article: Butowt R, von Bartheld CS. Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection. Neuroscientist.2020;1-22. DOI: 10.1177/1073858420956905 The article was translated into Russian and published under the terms of the Creative Commons Attribution 4.0 license.

The world has been facing a tremendous threat for more than 1 year by coronavirus disease 2019 (COVID-19) Because of the ongoing pandemic of COVID-19, it is necessary to be aware of the characteristics and symptoms of COVID-19 in order to prevent the COVID-19 spread Common symptoms of COVID-19 include fever, cough, shortness of breath, headache and various types of pneumonia Recently, smell loss has been extensively reported in COVID-19 patients They experience this before other general symptoms or smell loss can be their only symptom These types of patients may be neglected and a potential source for viral spread Thus, screening tests of COVID-19 should be considered if patients have smell loss without any other nasal symptoms Even though the recovery rate of smell loss in COVID-19 is relatively high, there are unmet needs for further studies including the mechanism of olfactory dysfunction, proper treatment and long-term recovery in COVID-19 © 2020 Korean Journal of Otorhinolaryngology-Head and Neck Surgery

Background Olfactory dysfunction (OD) has been reported to impact social interactions. However, the relationship between OD and loneliness has received little attention. The purpose of this study was to determine the association between OD and loneliness, controlling for patient factors. Methods Subjects without otolaryngic complaints were enrolled and olfactory function was assessed using: Sniffin’ Sticks test to measure threshold, discrimination and identification (TDI), Questionnaire of Olfactory Disorders Negative Statements (QOD-NS) and 9 – item Olfactory-Visual Analogue Scale (VAS). Loneliness was assessed using the De Jong Gierveld (DJG) and University of California Los Angeles (UCLA) loneliness scales. Bivariate analysis was performed followed by regression analysis, controlling for confounders. Results In total, 221 subjects were included with a mean age of 50.5 years (range 20 to 93), 133 (60.2%) females and 161 (72.9%) white. Mean TDI score was 29.3 (7.0) and 49.5% of the cohort was dysosmic. Using DJG, 36.4% of the cohort were classified as lonely, whereas 35.0% were lonely using UCLA. Olfactory measures were significantly associated with DJG, including TDI (β = −0.03, p = 0.050), olfactory discrimination (β = −0.111, p = 0.005), QOD-NS (β = 0.058, p Conclusions In this community-based sample of older adults, both OD and loneliness were common. Those subjects with worse olfactory function were more likely to report loneliness. Further research is necessary to establish causality, as well as explore the role of depression.

Objective Our study aimed to measure the percentage of reported olfactory or taste losses and their severity, recovery time, and association with other features in a large cohort of patients with COVID-19. Study Design Prospective survey. Setting Quaternary medical center and online survey. Methods The perceived chemosensory capacities of 655 patients with confirmed COVID-19 were assessed with 11-point category rating scales (0, no function; 10, normal function). Patients were contacted in hospital, by phone calls, or by internet regarding their ability to smell or taste, and 143 were interviewed by phone 1 to 4 months later to assess the recovery of their chemosensory abilities. Results The prevalence of self-reported olfactory, general taste, and taste quality–specific disturbances (sweet, sour, bitter, and salty) in the patients with COVID-19 were 82.4% (95% CI, 79.5%-85.3%), 76.2% (95% CI, 72.9%-79.4%), and 52.2% (95% CI, 48.3%-56.1%), respectively. The majority reported anosmia (42.9%). The presence of chemosensory symptoms was not associated with COVID-19 severity. At a median time >2 months after the onset of symptoms, rates of total and partial olfaction recovery were 53.8% and 44.7%, while complete or partial return to previous taste function was 68.3% and 27.6%. Less than 5% of the patients reported no chemosensory function improvement at all. Conclusion The prevalence of self-reported chemosensory dysfunction is high among patients with COVID-19. Almost all patients seem to recover a significant part of their smell and taste abilities in the first 4 months after the onset of symptoms.

The novel coronavirus SARS‐CoV‐2 is the causative agent of the global coronavirus disease 2019 (COVID‐19) outbreak. In addition to pneumonia, other COVID‐19‐associated symptoms have been reported, including loss of smell (anosmia). However, the connection between infection with coronavirus and anosmia remains enigmatic. It has been reported that defects in olfactory cilia lead to anosmia. In this Viewpoint, we summarize transmission electron microscopic studies of cilia in virus‐infected cells. In the human nasal epithelium, coronavirus infects the ciliated cells and causes deciliation. Research has shown that viruses such as influenza and Sendai attach to the ciliary membrane. The Sendai virus enters cilia by fusing its viral membrane with the ciliary membrane. A recent study on SARS‐CoV‐2–human protein–protein interactions revealed that the viral nonstructural protein Nsp13 interacts with the centrosome components, providing a potential molecular link. The mucociliary escalator removes inhaled pathogenic particles and functions as the first line of protection mechanism against viral infection in the human airway. Thus, future investigation into the virus–cilium interface will help further the battle against COVID‐19., The connection between coronavirus infection and anosmia remains enigmatic. Defects in olfactory cilia lead to anosmia. This viewpoint summarizes transmission electron microscopic studies of cilia in virus‐infected cells: Coronavirus infects the ciliated cells in human nasal epithelium and causes deciliation. Influenza viruses attach to the ciliary membrane, and Sendai virus enters cilia by fusing its viral membrane with the ciliary membrane.

Purpose Although the prevalence of olfactory dysfunction in children is thought to be lower compared to adults, little is known about the actual frequency of etiologies of smell dysfunction in children. Aim of the study was (i) to describe the epidemiology of olfactory dysfunction in a pediatric population and (ii) to compare the distribution of etiologies to adults. Material and methods Data of patients consulting a smell and taste clinic between 2000 and 2017 were retrospectively analyzed. Frequency of major causes of olfactory dysfunction was examined with a focus on the pediatric population. Results A total of 7153 patients (164 children) were included in the analysis. Most children presented with congenital olfactory dysfunction (67%), or head-trauma (12%). In contrast, the cumulative frequency of olfactory loss associated with sinonasal disorders or acute infections of the upper airways was 6%. The frequency of etiologies of olfactory dysfunction changed with age: While the frequency of patients with congenital anosmia decreased, the frequency of causes related to infections of the upper respiratory tract and idiopathic causes increased. Conclusion About 2/3 of olfactory dysfunction in children are congenital while 1/3 is acquired. The frequency of etiologies causing olfactory dysfunction change significantly from children to an adult population.

Author(s): Yan, Carol H; Mundy, David C; Patel, Zara M | Abstract: BackgroundOlfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia.MethodsSeven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months.ResultsAll patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI l 16) did not improve significantly. Five patients with hyposmia (TDI g 16 but l30) showed an improvement with 60% achieving normosmia (TDI g 30) at 3-month follow-up. On average, patients with baseline TDI g 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections.ConclusionPRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.Level of evidence 2b

Common symptoms of acute COVID-19 infection include fever, cough, headache, shortness of breath, and anosmia, i.e., partial, or complete loss of smell1 . Prior literature reported that COVID-19 patients (50%) developed sudden-onset anosmia prior to respiratory symptoms, thus making this an important symptom2 . The aim of this study sought to identify post-COVID-19 related olfactory dysfunction and recovery rates in children and adults in a community with a high incidence of COVID-19 infection.

IMPORTANCE: Olfactory dysfunction is a prodromal manifestation of many neurodegenerative disorders, including Alzheimer and Parkinson disease. However, its neuroanatomical basis is largely unknown. OBJECTIVE: To assess the association between olfactory brain structures and olfactory function in adults 30 years or older and to examine the extent to which olfactory bulb volume (OBV) mediates the association between central olfactory structures and olfactory function. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed baseline data from the first 639 participants with brain magnetic resonance imaging (MRI) in the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Participants were enrolled between March 7, 2016, and October 31, 2017, and underwent brain MRI and olfactory assessment. Data were analyzed from March 1, 2018, to June 30, 2021. EXPOSURE: Volumetric measures were derived from 3-T MRI T1-weighted brain scans, and OBV was manually segmented on T2-weighted images. The mean volumetric brain measures from the right and left sides were calculated, adjusted by head size, and normalized to all participants. MAIN OUTCOMES AND MEASURES: Performance on the 12-item smell identification test (SIT-12) was used as a proxy for olfactory function. RESULTS: A total of 541 participants with complete data on MRI-derived measures and SIT-12 scores were included. This population had a mean (SD) age of 53.6 (13.1) years and comprised 306 women (56.6%). Increasing age (difference in SIT-12 score, –0.04; 95% CI, –0.05 to –0.03), male sex (–0.26; 95% CI, –0.54 to 0.02), and nasal congestion (–0.28; 95% CI, –0.66 to 0.09) were associated with worse olfactory function (SIT-12 scores). Conversely, larger OBV was associated with better olfactory function (difference in SIT-12 score, 0.46; 95% CI, 0.29-0.64). Larger volumes of amygdala (difference in OBV, 0.12; 95% CI, 0.01-0.24), hippocampus (0.16; 95% CI, 0.04-0.28), insular cortex (0.12; 95% CI, 0.01-0.24), and medial orbitofrontal cortex (0.10; 95% CI, 0.00-0.20) were associated with larger OBV. Larger volumes of amygdala (volume × age interaction effect, 0.17; 95% CI, 0.03-0.30), parahippocampal cortex (0.17; 95% CI, 0.03-0.31), and hippocampus (0.21; 95% CI, 0.08-0.35) were associated with better olfactory function only in older age groups. The age-modified association between volumes of central olfactory structures and olfactory function was largely mediated through OBV. CONCLUSIONS AND RELEVANCE: This cross-sectional study found that olfactory bulb volume was independently associated with odor identification function and was a robust mediator of the age-dependent association between volumes of central olfactory structures and olfactory function. Thus, neurodegeneration-associated olfactory dysfunction may primarily originate from the pathology of peripheral olfactory structures, suggesting that OBV may serve as a preclinical marker for the identification of individuals who are at an increased risk of neurodegenerative diseases.

We performed a review of the literature to identify studies that tested patients with flulike symptoms for SARS‐CoV‐2 infection by RT‐PCR and that reported data on the prevalence of loss of smell and/or taste. We identified a total of 6 studies (Fig. 1A).2, 4, 7‐10 Sensitivity and specificity were represented using forest plots, and pooled estimates were calculated using a random intercept logistic regression model. Publication bias was assessed by funnel plot. PPVs and NPVs were calculated as a function of prevalence of COVID‐19, ranging from 0% to 100%, using pooled sensitivity and specificity.

The association of smell and taste loss with COVID-19 has been well demonstrated with high prevalence rates. In certain cases, chemosensory loss may be the only symptom of COVID-19 and may linger while other symptoms have resolved. The significance of persistent smell and taste loss and its relationship to ongoing viral shedding has yet to be investigated. In this cross-sectional study, of the 316 laboratory test–confirmed COVID-19 cases at our institution, 46 had subsequent test-based confirmation of viral clearance with 2 consecutive negative RT-PCR test results (reverse transcriptase polymerase chain reaction). Olfactory dysfunction was reported by 50% of the patients (23 of 46), with 78% (18 of 23) having subjective persistent smell loss despite negative RT-PCR test results. These preliminary data demonstrate the persistence of self-reported smell loss despite otherwise clinical resolution and undetectable nasal viral RNA.

To date, most studies on the relationship between chemosensory performance and quality of life have focused on orthonasal measures of olfactory function. In the current investigation, we examined the predictive value of orthonasal and flavor identification indices of olfactory function on a wide spectrum of health and sociopsychological factors, including quality of life, life satisfaction, overall health, and depressive symptoms. Participants were 178 ENT patients (Mage = 58 ± 1), representing various causes of olfactory loss: idiopathic smell loss (n = 51; Mage = 63 ± 2), sinunasal disease (n = 27; Mage = 56 ± 3), head trauma (n = 33; Mage = 51 ± 2), and infections of the upper respiratory tract (n = 67; Mage = 59 ± 2). They completed self-report questionnaires and underwent olfactory testing using Sniffin’ Sticks (orthonasal olfactory testing) and “Taste Powder” (intraorally applied flavors for retronasal olfactory testing, additionally inducing taste sensation). Data were analyzed with hierarchical regression models wherein the first step included subjects’ sex, age, and orthonasal olfaction score. In the second step, we included the “Taste Powder” score. Tested models revealed that the first step was not significantly predicting variables of interest; however, there was an improvement of the model’s predictive value when the “Taste Powder” score was added. Results of this study suggest that flavor identification significantly improves predictions of health and sociopsychological functioning of ENT patients with various etiologies.

Introduction Hyposmia is a common non-motor symptom occurring in Parkinson’s disease (PD), and has been included in the diagnostic criteria. Although a version of the Brief Smell Identification Test (B-SIT) has been developed specifically for Chinese populations, there have been no reports of the utility of this test in the diagnosis of PD in China. Objective Considering the influence of cultural factors on olfactory test findings, we sought to investigate the utility and efficiency of the B-SIT in Chinese PD patients. Methods PD patients were recruited from the Movement Disorder Clinic of Xuanwu Hospital, and healthy controls were recruited from the Beijing Longitudinal Study on Aging Cohort II, between 2015 and 2016. The B-SIT was used for olfactory function testing in all subjects, and the familiarity of 59 odors questionnaire was performed for the investigation of familiarity of odors. Results A sample of 275 subjects participated in the study, including 112 healthy controls and 163 PD patients. The sensitivity (64.1%), specificity (83.9%), positive predictive value (83.5%) and negative predictive value (64.8%) for identifying PD were measured with the B-SIT. The consistency values between the results of self-reported smell loss and hyposmia identified by B-SIT in control and PD groups were 74.8% and 64.2%, respectively. Most of the odors in the B-SIT were familiar to people in the Chinese population, based on a survey of 3356 subjects using a familiarity questionnaire. Conclusions It is recommended to use the B-SIT olfactory test instead of self-reported smell loss for PD diagnosis for Chinese.

OBJECTIVES: This study investigated the relationship between viral load and the incidence of olfactory and gustatory dysfunction (OD and GD), the incidence of respiratory and gastrointestinal symptoms and the recovery of OD and GD in COVID-19 patients. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: This study was conducted on 599 outpatients' cases in Golestan province between February and June 2020. MAIN OUTCOME MEASURES: The incidence, severity (complete or partial) and recovery time of OD and GD and their associations with cycle threshold (CT) values of SARS-CoV-2 polymerase chain reaction were assessed. RESULTS: The mean age of patients was 38.27 ± 13.62 years. The incidence of general symptoms included myalgia 70.1%, headache 51.8%, fever 47.7% and dyspnoea 21.4%. 41.9% of patients had gastrointestinal symptoms, including abdominal pain 26.5%, diarrhoea 25.2%, nausea 20.5% and vomiting 12.9%. 12.2% of patients had comorbidity. The trimester recovery rates of OD and GD were 93.94% and 94.74% respectively. The mean recovery time of OD and GD was 14.56 ± 13.37 and 13.8 ± 3.77 days respectively. The mean CT value in all patients was 27.45 ± 4.55. There were significant associations between the mean of CT value with headache (p = 0.04), GD (p = 0.002) and OD (p = 0.001). CONCLUSIONS: The finding of this study indicates a possible association between viral load with incidence of OD and GD in COVID-19 patient's cases and assures the recovery of OD/GD in these patients.

Background The mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after viral infection, which provides a research opportunity to evaluate the natural course of this neurological finding. Clinical trials and prospective and histological studies of new-onset post-viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples. Although data from neuropathological specimens are now available, neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge. Recent developments The active replication of SARS-CoV-2 within the brain parenchyma (ie, in neurons and glia) has not been proven. Nevertheless, post-viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID-19. Evidence is also sparse for a direct causal relation between SARS-CoV-2 infection and abnormal brain findings at autopsy, and for trans-synaptic spread of the virus from the olfactory epithelium to the olfactory bulb. Taken together, clinical, radiological, histological, ultrastructural, and molecular data implicate inflammation, with or without infection, in either the olfactory epithelium, the olfactory bulb, or both. This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has revealed localised inflammation in intracranial olfactory structures. To date, histopathological, ultrastructural, and molecular evidence does not suggest that SARS-CoV-2 is an obligate neuropathogen. Where next? The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate that, in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term. An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease. Persistent olfactory impairment with or without perceptual distortions (ie, parosmias or phantosmias) after SARS-CoV-2 infection could, therefore, serve as a marker to identify people with an increased long-term risk of neurological disease.

Corona virus (COVID-19) infection has been growing as a biggest threat to human society. World Health Organization (WHO) has already declared it as a pandemic for the whole world, with nearly six million positive cases. Highly contagious nature of the virus has challenged the medical facilities of all the developed and developing country health system. Early identification of the infection is very important to provide medical facilities and cease the chain of infection to new persons. The symptoms such as fever, dry cough, breathing issues generally show in patients not before 5-7 days. However, the patients feel the loss of smell or taste (anosmia) as early as second day onwards due to the presence of virus in nose and throat. Low-cost techniques such as SniffIn-sticks ® Smell Test and UPSIT etc. can be used to test anosmia along with medically approved olfactory test leading to identification of COVID-19 infections. With leading researchers findings anosmia test will be effective in breaking the chain infection of COVID-19 virus. In the exit ports, anosmia test kits may be added to thermal testing to identify the infected patients with low symptoms. Additionally, home test kits may be developed at low cost and supplied for large scale testing of the infection.

The molecular stimuli that trigger a parosmic response have been identified. Parosmia is a debilitating disease in which familiar smells become distorted and unpleasant. Often a result of post infectious smell loss, incidences are increasing as the number of COVID-19 cases escalates worldwide. Little is understood of its pathophysiology, but the prevailing hypothesis for the underlying mechanism is a mis-wiring of olfactory sensory neurons. We identified 15 different molecular triggers in coffee using GC-Olfactometry as a relatively rapid screening tool for assessment of both quantitative olfactory loss and parosmia. This provides evidence for peripheral causation, but places constraints on the mis-wiring theory.

BACKGROUND: This cross-sectional, multi-centric study aimed to investigate the differences in quality of life among patients with olfactory dysfunction (OD) of different origin, and to identify factors associated with olfactory-related quality of life (QOL). METHODS: Seven hundred sixty-three adults were recruited from 8 Smell & Taste clinics in Germany, Switzerland, and Austria. Olfactory-related QOL was assessed by the Questionnaire of Olfactory Disorders (QOD). Olfactory function was assessed with the “Sniffin’ Sticks” test; self-assessment was performed with visual analog scales. RESULTS: Patients with post-infectious and post-traumatic OD showed poorer olfactory-related QOL than patients with sinonasal and idiopathic OD. The olfactory-related QOL was positively associated with the Sniffin’ Sticks test score, self-assessed olfactory function, disease duration, and age, with younger olfactory dysfunction patients showing lower QOL. Female patients presented with poorer olfactory-related QOL. In addition, the results showed that self-assessment of olfactory function explained more of the variance in olfactory-related QOL than olfactory function evaluated by the Sniffin’ Sticks test. CONCLUSIONS: In addition to the psychophysical testing results, several factors such as disease cause, disease duration, sex, or self- assessed olfactory dysfunction should be taken into account when assessing the individual severity of the smell loss.

BackgroundCommercially available smell tests are primarily used in research or in-depth clinical evaluations, but are too costly and lengthy for population surveillance in health emergencies like COVID-19. We developed the SCENTinel 1.0 test which rapidly evaluates three olfactory functions (detection, intensity, and identification). We tested whether self-administering the SCENTinel 1.0 test discriminates between individuals with smell loss or average smell ability (normosmics), and provides comparable performance as the validated and standardized NIH Toolbox® Odor Identification Test in normosmics.MethodsUsing Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1.0 performance of a group of self-reported anosmics (N=111, 47±13yo, F=71%,) and normosmics (N=154, 47±14yo, F=74%), as well as individuals reporting other smell disorders (e.g., hyposmia, parosmia; N=42, 55±10yo, F=67%).ResultsNinety-four percent of normosmics met our SCENTinel 1.0 accuracy criteria, while only 10% of anosmics and 64% of individuals with other smell disorders did. Overall performance on SCENTinel 1.0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC=0.95, Sensitivity=0.72, Specificity=0.94). Odor intensity provided the best single-feature predictor to classify normosmics. Among normosmics, 92% met the accuracy criteria at both SCENTinel 1.0 and the NIH Toolbox® Odor Identification Test.ConclusionsSCENTinel 1.0 is a practical test able to discriminate individuals with smell loss and is likely to be useful in many clinical situations, including COVID-19 symptom screening.

Background Anosmia and hyposmia have many etiologies, including trauma, chronic sinusitis, neoplasms, and respiratory viral infections such as rhinovirus and SARS-CoV-2. We aimed to systematically review the literature on the diagnostic evaluation of anosmia/hyposmia. Methods PubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990 using terms combined with Medical Subject Headings (MeSH). We included articles evaluating diagnostic modalities for anosmia, written in the English language, used original data, and had two or more patients. Results A total of 2065 unique titles were returned upon the initial search. Of these, 226 abstracts were examined, yielding 27 full-text articles meeting inclusion criteria (Level of evidence ranging from 1 to 4; most level 2). The studies included a total of 13,577 patients. The most utilized diagnostic tools were orthonasal smell tests (such as the Sniffin’ Sticks and the UPSIT, along with validated abridged smell tests). Though various imaging modalities (including MRI and CT) were frequently mentioned in the workup of olfactory dysfunction, routine imaging was not used to primarily diagnose smell loss. Conclusion The literature includes several studies on validity and reliability for various smell tests in diagnosing anosmia. Along with a thorough history and physical, validated orthonasal smell tests should be part of the workup of the patient with suspected olfactory dysfunction. The most widely studied modality was MRI, but criteria for the timing and sequence of imaging modalities was heterogenous.

Objectives To evaluate a therapeutic role for omega-3 fatty acid supplementation in the treatment of olfactory dysfunction associated with COVID-19 infection Trial design Randomized, double-blinded, placebo-controlled trial Participants Eligible patients are adults with self-reported new-onset olfactory dysfunction of any duration associated with laboratory-confirmed or clinically suspected COVID-19 patients. Exclusion criteria include patients with pre-existing olfactory dysfunction, history of chronic rhinosinusitis or history of sinus surgery, current use of nasal steroid sprays or omega-3 supplementation, fish allergy, or inability to provide informed consent for any reason. The trial is conducted at Mount Sinai Hospital Intervention and comparator The intervention group will receive 2000 mg daily of omega-3 supplementation in the form of two “Fish Oil, Ultra Omega-3” capsules (product of Pharmavite®) daily. The comparator group will take 2 placebo capsules of identical size, shape, and odor daily for 6 weeks. Main outcomes Each subject will take a Brief Smell Identification Test at study enrolment and completion after 6 weeks. The primary outcome will be change in Brief Smell Identification Test over the 6-week period. Randomisation Patients will be randomized by the Investigational Drug Pharmacy at the Icahn School of Medicine at Sinai via a computer-generated sequence in a 1:1 allocation to treatment or control arms. Blinding (masking) Both participants and researchers will be blinded. Numbers to be randomised (sample size) There will be 88 participants randomized to each group. A total of 176 participants will be randomized. Trial Status Protocol Version 1, 8/3/2020 Recruitment is ongoing, started 8/5/2020 with estimated completion 11/30/2020. Trial registration The trial is registered on ClinicalTrials.gov with Protocol Identifier: NCT04495816. Trial registration: ClinicalTrials.gov, NCT04495816. Registered 3 August 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).

BackgroundAs evidence emerged that loss of taste and/or loss of smell is frequently triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we investigated whether Google searches volume for these two disease-specific symptoms could be associated with disease epidemiology in United States (US).Materials and MethodsWe performed an electronic search in Google Trends using the keywords “taste loss” and “smell loss” within the US. The Google searches volume was correlated with the number of new weekly cases of coronavirus disease 2019 (COVID-19) in the country.ResultsThe weekly Google searches for taste and smell loss exhibited a trend similar to that of new weekly SARS-CoV-2 infections in the US. A nearly perfect correlation was found between Google Trends scores of taste and smell loss (r=0.98; 95% CI, 0.97-0.99; pConclusionsThese findings suggest that Google searches numbers for olfactory and gustatory dysfunctions may help predicting the epidemiological trajectory of COVID-19 early before official reporting.

The association of smell and taste loss with COVID-19 has been well demonstrated with high prevalence rates. In certain cases, chemosensory loss may be the only symptom of COVID-19 and may linger while other symptoms have resolved. The significance of persistent smell and taste loss and its relationship to ongoing viral shedding has yet to be investigated. In this cross-sectional study, of the 316 laboratory test-confirmed COVID-19 cases at our institution, 46 had subsequent test-based confirmation of viral clearance with 2 consecutive negative RT-PCR test results (reverse transcriptase polymerase chain reaction). Olfactory dysfunction was reported by 50% of the patients (23 of 46), with 78% (18 of 23) having subjective persistent smell loss despite negative RT-PCR test results. These preliminary data demonstrate the persistence of self-reported smell loss despite otherwise clinical resolution and undetectable nasal viral RNA.

ObjectivesSudden loss of smell is a very common symptom of coronavirus disease 19 (COVID-19). This study characterizes the structural and metabolic cerebral correlates of dysosmia in patients with COVID-19.MethodsStructural brain magnetic resonance imaging (MRI) and positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) were prospectively acquired simultaneously on a hybrid PET-MR in twelve patients (2 males, 10 females, mean age: 42.6 years, age range: 23-60 years) with sudden dysosmia and positive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on nasopharyngeal swab specimens. FDG-PET data were analysed using a voxel-based approach and compared with that of a group of healthy subjects.ResultsBilateral blocking of the olfactory cleft was observed in six patients, while subtle olfactory bulb asymmetry was found in three patients. No MRI signal abnormality downstream of the olfactory tract was observed. Heterogeneous (decrease or increase) glucose metabolism abnormalities were observed in core olfactory and high-order neocortical areas. A modulation of regional cerebral glucose metabolism by the severity and the duration of COVID-19-related dysosmia was disclosed using correlation analyses.ConclusionsThis PET-MR study shows that sudden loss of smell in COVID-19 is not related to central involvement due to SARS-CoV-2 neuroinvasiveness. Loss of smell is associated with heterogeneous cerebral metabolic changes in core olfactory and high-order cortical areas likely related to combined processes of deafferentation and active functional reorganisation secondary to the lack of olfactory stimulation.

OBJECTIVE/HYPOTHESIS This study aims to determine the association between parosmia and clinically relevant recovery of olfactory function in patients with post-infectious olfactory dysfunction (PIOD) receiving olfactory training. STUDY DESIGN Retrospective cohort study. METHODS This was a retrospective cohort study of patients with PIOD that received olfactory training. Adult patients with the major complaint of quantitative smell loss were recruited and treated at several ENT clinics in German between 2008 and 2018. The outcome was based on the association between smell-loss related factors (including parosmia and phantosmia) and clinically relevant changes in overall and subdimension olfactory function of threshold, discrimination, and identification using binary logistic regression analysis. RESULTS A total of 153 participants with PIOD were included. Clinically relevant improvements in overall olfactory function were more likely in those that had lower baseline olfactory function. Relevant improvements in discrimination function were more likely in those that had lower baseline olfactory function and those that had parosmia at the initial visit. Similarly, relevant improvements in odor identification were more likely in those that had a lower baseline olfactory function and in those who had parosmia at the first visit. Clinically significant improvements in odor threshold were more likely in those who were older in age. CONCLUSIONS This study demonstrated that the presence of parosmia is associated with clinically relevant recovery in olfactory discrimination and identification function in patients with PIOD receiving olfactory training. LEVEL OF EVIDENCE 4 Laryngoscope, 131:618-623, 2021.

Background: Anosmia has been reported as an early presentation of coronavirus disease 2019 (COVID-19). However, the pathophysiological mechanism of olfactory dysfunction is still unclear.Aim: The aim of this study to evaluate the knowledge regarding common symptoms, anosmia, treatment options, and PPE among medical students in three different universities of Saudi Arabia.Methods: This cross-sectional survey conducted among medical students in Saudi Arabia. Google Forms was used to create the survey. The questionnaire included demographic information, knowledge of COVID-19 symptoms, sources of information, and the level of awareness of specific symptoms (loss of smell and taste).Results: A total of 494 students completed the questionnaire. The majority of the participants were aware of common COVID-19 symptoms like fever and cough (79.8 and 67.2%, respectively), but less than half were aware that smell or taste dysfunction might be a symptom of COVID-19 (44.3 and 30.2%, respectively). The present study revealed that the source of information also plays a critical role in medical students' awareness regarding the symptoms of COVID-19. Students using international organization's websites, medical databases, or published research had better knowledge of anosmia as a COVID-19 symptom compared to those who used WhatsApp, Google, or unofficial social media pages. In our study, a minority (11.9%) of the participants relied on unofficial social media pages as the main source of their information.Conclusion: Saudi medical students understand that smell or taste dysfunction can be a potential symptom of COVID-19, but this knowledge was not as widespread as the knowledge regarding the most common COVID-19 symptoms.

Background The coronavirus disease 2019 (COVID-19) pandemic has caused recurring and major outbreaks in multiple human populations around the world. The plethora of clinical presentations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been described extensively, of which olfactory dysfunction (OD) was established as an important and common extrapulmonary manifestation of COVID-19 infection. The aim of this protocol is to conduct a systematic review and meta-analysis on peer-reviewed articles which described clinical data of OD in COVID-19 patients. Methods This research protocol has been prospectively registered with the Prospective Register of Systematic Reviews (PROSPERO; CRD42020196202). CINAHL, ClinicalTrials.gov, Cochrane Central, EMBASE, MEDLINE and PubMed, as well as Chinese medical databases China National Knowledge Infrastructure (CNKI), VIP and WANFANG, will be searched using keywords including ‘COVID-19’, ‘coronavirus disease’, ‘2019-nCoV’, ‘SARS-CoV-2’, ‘novel coronavirus’, ‘anosmia’, ‘hyposmia’, ‘loss of smell’, and ‘olfactory dysfunction’. Systematic review and meta-analysis will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines. Articles will be screened according to pre-specified inclusion and exclusion criteria to extract studies that include new clinical data investigating the effect of COVID-19 on olfactory dysfunction. Included articles will be reviewed in full; data including patient demographics, clinical characteristics of COVID-19-related OD, methods of olfactory assessment and relevant clinical outcomes will be extracted. Statistical analyses will be performed using the Comprehensive Meta-Analysis version 3. Discussion This systematic review and meta-analysis protocol will aim to collate and synthesise all available clinical evidence regarding COVID-19-related OD as an important neurosensory dysfunction of COVID-19 infection. A comprehensive search strategy and screening process will be conducted to incorporate broad clinical data for robust statistical analyses and representation. The outcome of the systematic review and meta-analysis will aim to improve our understanding of the symptomatology and clinical characteristics of COVID-19-related OD and identify knowledge gaps in its disease process, which will guide future research in this specific neurosensory defect. Systematic review registration PROSPERO registration number: CRD42020196202.

Background Emerging reports suggest that new onset of smell or taste loss are potential early clinical markers of SARS-CoV-2 infection, but it remains unclear as to what extent. Therefore, the purpose of this study is to systematically assess the prevalence of self-reported altered sense of smell or taste in patients with confirmed SARS-CoV-2 infection, overcoming the limitations of individual studies by meta-analysis of pooled data. Methods The databases Medline, Embase, Web of Science, Scopus and MedRxiv's set were searched from inception to the 4th May 2020. This study was conducted following the PRISMA checklist. Results 18 studies met the eligibility criteria out of the 171 initially screened citations. The overall prevalence of alteration of the sense of smell or taste was 47% , but estimates were 31% and 67% in severe and mild-to-moderate symptomatic patients, respec- tively. The loss of smell and taste preceded other symptoms in 20% of cases and it was concomitant in 28%. Conclusions Based on this meta-analysis, we recommend self-isolation and testing, where possible, for patients complaining smell or taste impairment during COVID-19 pandemic in order to prevent spread of disease and propose the inclusion of loss of smell and taste as recognized symptoms of SARS-CoV-2 in the World Health Organization and other relevant regulatory body's lists.

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases.MethodsA single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity.ResultsA total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness.ConclusionIn ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus has left many health systems around the world overwhelmed, forcing triaging of scarce medical resources. Identifying indicators of hospital admission for coronavirus disease 2019 (COVID-19) patients early in the disease course could aid the efficient allocation of medical interventions. Self-reported olfactory impairment has recently been recognized as a hallmark of COVID-19 and may be an important predictor of clinical outcome.MethodsA retrospective review of all patients presenting to a San Diego Hospital system with laboratory-confirmed positive COVID-19 infection was conducted with evaluation of olfactory and gustatory function and clinical disease course. Univariable and multivariable logistic regression were performed to identify risk factors for hospital admission and anosmia.ResultsA total of 169 patients tested positive for COVID-19 disease between March 3 and April 8, 2020. Olfactory and gustatory data were obtained for 128 (75.7%) of 169 subjects, of which 26 (20.1%) of 128 required hospitalization. Admission for COVID-19 was associated with intact sense of smell and taste, increased age, diabetes, and subjective and objective parameters associated with respiratory failure. On adjusted analysis, anosmia was strongly and independently associated with outpatient care (adjusted odds ratio [aOR] 0.09; 95% CI, 0.01-0.74), whereas positive findings of pulmonary infiltrates and/or pleural effusion on chest radiograph (aOR 8.01; 95% CI, 1.12-57.49) was strongly and independently associated with admission.ConclusionNormosmia is an independent predictor of admission in COVID-19 cases. Smell loss in COVID-19 may be associated with a milder clinical course.

Purpose To determine prevalence, severity, duration, and time from onset to diagnosis of general and Otorhinolaryngologic symptoms related to COVID-19 in whole disease spectrum: from mild to critical patients. Methods All adult patients with positive SARS-CoV-2 RNA found in nasopharyngeal and oropharyngeal swabs between March 10 and April 21, 2020 were surveyed by the authors for new onset symptoms during disease course. Demographic features, general symptoms, and Otorhinolaryngological symptoms were evaluated and compared by disease severity. Results Of 223 included patients, 18.4% had mild, 61.4%; moderate, 14.3%; severe, and 5.8%; critical disease. Median age was 51 (range 20–93), 113 (50.7%) were male and 110 (49.3%) were female. The most common general symptoms were fatigue, cough, and fever with respective frequencies of 71.3%, 54.3%, and 50.7%. The most common Otorhinolaryngologic symptoms were taste loss, smell loss, and sore throat with respective frequencies of 34.5%, 31.8%, and 26%. Fatigue, fever, and dyspnea were more common in severe-critical patients compared to mild–moderate patients (p = 0.029, p = 0.016, and p

Objectives This study aims to determine the association between parosmia and clinically relevant recovery in olfactory function in patients with smell loss receiving olfactory training. Design and setting This was a retrospective cohort study of patients that received olfactory training. Adult patients with the major complaint of quantitative smell loss were recruited and treated at several ENT clinics in German between 2008 and 2018. Participants A total of 243 participants were included. Main outcome measures Changes in olfactory function after olfactory training. Age, gender, baseline olfactory function, etiology and duration of smell loss, duration of training, and presence of parosmia and phantosmia were assessed for their impact on clinically relevant changes in overall and subdimension olfactory function using binary logistic regression analysis. Results Relevant improvements in discrimination function were more likely in those that had lower baseline olfactory function, postinfectious reasons compared to posttraumatic or idiopathic causes and those that had parosmia at initial visit. Relevant improvements in odour identification were more likely in those that had a lower baseline olfactory function, female gender, and in those who had parosmia at the first visit. Clinically significant improvements in odour threshold were more likely in postinfectious causes compared to posttraumatic reasons and those who were older in age. Conclusions This study demonstrated that the presence of parosmia is associated with clinically relevant recovery in olfactory function in patients with smell loss receiving olfactory training.

Background: Numerous diseases are mediated by autoimmune mechanisms some of which have been shown to be associated with reduced olfactory function, e.g. systemic lupus erythematosus, Sjögren syndrome, psoriasis vulgaris. Postinfectious smell loss is a frequent cause of olfactory dysfunction. However, its nature is not fully understood, but connections to immune mediated processes might be possible. The primary aim of the present study was therefore to investigate the possible relation of postinfectious smell loss with autoimmune processes. Methods: Fifty-two patients (35 female, 17 male; mean age 57 years ± 12 years) with postinfectious smell loss and 56 controls (21 female, 35 male; mean age 58 years ± 13 years), with olfactory dysfunction of other causes (sinunasal, posttraumatic or idiopathic) were included in the present study. The patients’ olfactory function was measured using the extended test battery of the "Sniffin’ Sticks“. Furthermore venous blood samples were taken and analyzed for antinuclear autoantibodies. Results: Patients showed anti-nuclear antibodies (ANA) significantly more frequently compared to controls, although ANAs were typically only present at cut off levels of 1:100. In addition, there was a significant association between the presence of ANAs and odor thresholds. Conclusions: Results from this study indicate that postinfectious olfactory dysfunction may be associated with autoimmune processes, as they show significantly more ANAs – although not at a clincially significant level - compared to patients with olfactory deficits of other origin.

Early reports have suggested that smell loss may be an early symptom associated with the pandemic known as COVID‐19. The possibility that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) might cause olfactory dysfunction is certainly plausible. Patients presenting to specialized smell clinics are commonly diagnosed with upper respiratory infection (URI)‐associated olfactory loss and most are presumed to be viral related. In acute phases of infection, it is common to experience some smell loss as a result of nasal inflammation, mucosal edema, and obstruction of airflow into the olfactory cleft. In most cases, these episodes of smell loss are self‐limiting and coincide with resolution of URI symptoms. However, in some cases the smell loss persists for months to years and this is presumed to occur through a more direct olfactory insult by the virus. It remains too early to know whether infection with SARS‐CoV‐2 causes persistent olfactory dysfunction. However, given the scale of this pandemic, if SARS‐CoV‐2 does cause chronic olfactory loss in even a small portion of those infected, then the overall population prevalence could be quite large. This review provides a brief, practical overview of viral‐associated olfactory loss, realizing that evidence related to COVID‐19 will likely not be clear for some time. Our goal is to highlight the existence and importance of this condition and provide information geared for both providers and patients. Practical suggestions regarding evaluation and treatment will be provided, realizing that there may be constraints on medical resources and the nature of this pandemic remains dynamic. This article is protected by copyright. All rights reserved

BackgroundOlfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia.MethodsSeven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months.ResultsAll patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI 16 but 30) at 3-month follow-up. On average, patients with baseline TDI > 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections.ConclusionPRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.Level of evidence 2b

Background Initial reports describing COVID‐19 were dominated by the presence of cough, breathlessness, and fever, anecdotal reports suggested anosmia may also be a manifestation. We sought to use Google Trends (GT) to investigate whether there was a surge in individuals searching for information related to smell loss during the COVID‐19 epidemic in the Italy, Spain, UK, USA, Germany, France, Iran and Netherlands. Methods GT was used to explore Internet activity related to loss of smell in Italy, Spain, UK, USA, Germany, France, Iran and Netherlands. Spearman rank analysis was performed to correlate loss of smell relative search volumes (RSV) with the increases of daily confirmed cases of COVID‐19 and deaths attributed to disease. As a control event, we also performed analysis of smell‐related searches during the last UK Influenza epidemic of 2009. Results In all three countries, we observed strong correlations between daily RSVs related to loss of smell, increases of daily COVID‐19+ cases and deaths ranging from 0.633 to 0.952. All correlations were statistically significant (p

Traumatic Brain Injury (TBI) can be associated with partial or total smell loss. Recent studies have suggested that olfactory outcome can be positively modulated after olfactory training (OT). This study's aim was to investigate OT's potential role in smell recovery after TBI-induced olfactory loss. A prospective, randomized, and controlled study was developed. Patients with TBI-induced olfactory dysfunction (n = 42) were randomized into an experimental group with OT and a control group without (nOT). OT was performed twice daily with a six odor training set during 12 weeks. Olfactory loss was assessed using subjective olfactometry (Barcelona Smell Test [BAST] 24), a visual analogue scale (VAS), and n-butanol threshold (n-BTt) at baseline at 4, 12, and 24 weeks. Additionally, patients underwent MRI of the olfactory brain and olfactory bulbs (OB). Based on the MRI results, an overall score (0-16) was developed to associate the structural neurological damage with olfactory outcomes. The primary outcome was the change in olfactory measurements (VAS and BAST-24) between baseline and 12 weeks. The secondary outcome was the association of the MRI score with olfactory outcomes at baseline, and the impact on quality of life (QoL). After 12 weeks of training, OT patients showed a significant improvement in n-BTt (0.6 ± 1.7 OT vs. -0.6 ± 1.8 nOT, p 0.05), but not in the smell VAS and BAST-24 scores. Olfactory outcomes (VAS, BAST-24, and n-BTt) were significantly associated with MRI structural findings (p 0.001), but not with the OB volume or olfactory sulcus length. The present study suggests that 12 weeks of OT mildly improves the olfactory threshold in TBI, whereas the overall MRI score may be used as an imaging marker of olfactory dysfunction and disease severity in TBI patients.

Background In this study, we employed a novel children's olfactory test in order to more accurately assess the relationship between nasopharyngeal obstruction and odor identification ability. We quantified the impact of adenoidectomy on olfactory function, established whether the influences of the operation were related to the preoperative amount of nasopharyngeal obstruction, and determined whether sex influenced the olfactory measures. Methods Fifty-three boys and 23 girls were administered a standardized children's olfactory test, the Pediatric Smell Wheel™, before and 45 days after adenoidectomy. They ranged in age from 5 to 12 years and exhibited varying degrees of adenotonsillar hypertrophy and histories of recurrent adenotonsillitis. Radiographs of the nasopharynx were used to grade the degree of nasopharyngeal obstruction. Results Significant postoperative improvement in smell function occurred more frequently in children with >50% preoperative obstruction of the nasopharynx. In this group, average function improved 50.8% after surgery (95% confidence interval [CI], 39.1% to 64%). Improvement on 9 of the 11 odors was present, with significant differences occurring for the odors of bubble gum, baby powder, mint, and cinnamon. No sex differences were evident. Conclusion Olfactory dysfunction occurs primarily in children whose nasopharyngeal obstruction is >50%. Removal of the hypertrophied adenoids returned smell function back to normal in these cases. This study suggests that smell loss may be of value in decisions regarding whether or not to perform adenoidectomy in children with nasopharyngeal obstruction.