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Anosmia has been recognized as a prevalent and early symptom by many COVID-19 patients. However, most researchers have recorded smell dysfunction solely as present or absent and based on subjective evaluation by patients. We described the results of 57 consecutive COVID-19 patients seen at FIOCRUZ, Rio de Janeiro, Brazil, from April to May 2020. Data about the presence of smell loss, the onset of smell loss and other COVID-19 symptoms such as ageusia and nasal congestion or rhinorrhea were recorded. All patients at the initial consultation and 34 healthy controls underwent the Q-SIT, which is a quick disposable three-item smell identification test, by a trained physician. We compared three groups: healthy controls, COVID+ patients with reported smell loss (COVID w/ SL) and COVID+ patients without smell loss (COVID+ w/o SL). The mean age of patients was 41.4 years (SD ± 10.4), and 54.4% were women. Smell loss was reported by 40.4% of COVID-19 patients. We observed a gradual effect with higher Q-SIT scores in healthy controls, followed by COVID+ w/o SL and COVID+ w/ SL (medians = 3, 2 and 0; respectively, p, Highlights • Smell dysfunction is frequent in COVID-19 patients. • Subtle olfactory dysfunction is frequently not perceived by patients when inquired during medical visits. • Q-SIT is a quick and reliable screening test for the detection of smell dysfunction during the pandemics.

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.

Recent research shows that the human sense of smell seems to be more efficient than previously believed and to have a major impact on our health condition and quality of life. During the COVID-19 pandemic, an increased clinical interest has become evident for the SARS-CoV-2 related impact on olfactory function. This article highlights important aspects in the diagnosis and therapy of the chemical senses.Zunehmende Evidenz belegt, dass der menschliche Geruchssinn eine große Bedeutung für die Gesundheit und Lebensqualität einnimmt sowie eine besondere Leistungsfähigkeit aufweist. Durch die häufig auftretende Riechstörung im Rahmen der Infektion mit SARS-CoV‑2 rückt das klinische Interesse in der Behandlung von Patienten mit Verlust des Geruchs- und Geschmackssinnes in den Vordergrund. Der vorliegende Artikel beleuchtet wichtige Aspekte in der Diagnose und Therapie der chemischen Sinne.

Soon after the outbreak of COVID-19, reports that smell and taste are disrupted by the illness drew the attention of chemosensory scientists and clinicians throughout the world. While other upper respiratory viruses are known to produce such disruptions, their occurrence with the deadly and highly infectious SARS-CoV-2 virus raised new questions about the nature of the deficits, their cause, and whether they might serve as indicators of the onset of the disease. Published in the July and August 2020 issues of Chemical Senses are 2 innovative, large-scale survey studies that were quickly devised and launched by separate multinational groups to address these questions in olfaction, taste, and chemesthesis. The surveys, which took different approaches and had somewhat different goals, add significant new data on the incidence and severity of smell loss in COVID-19, and the potential for olfactory dysfunction to serve as an indicator of the spread and severity of the disease. Less definitive evidence of the frequency, characteristics, and magnitude of disruptions in taste and chemesthesis point to the need for future survey studies that combine and refine the strengths of the present ones, as well as clinical studies designed to selectively measure deficits in all 3 chemosensory systems.

Olfactory disorders have been increasingly reported in individuals infected with SARS‐CoV‐2, the virus causing the coronavirus disease 2019 (COVID‐19). Losing the sense of smell has a strong impact on the quality of life, since it may lead to malnutrition, weight loss, food poisoning, depression, and exposure to dangerous chemicals. Individuals who suffer from anosmia (inability to smell) also cannot sense the flavor of food, which is a combination of taste and smell. Interestingly, infected individuals have reported sudden loss of smell with no congested nose, as is frequently observed in common colds or other upper respiratory tract infections. These observations suggest that SARS‐CoV‐2 infection leads to olfactory loss through a distinct mechanism, which is still unclear. This article provides an overview of olfactory loss and the recent findings relating to COVID‐19. Possible mechanisms of SARS‐CoV‐2 induced olfactory loss are also discussed.

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.

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.

Coronavirus SARS-COV-2 infections continue to spread across the world, yet effective large-scale disease detection and prediction remain limited. COVID Control: A Johns Hopkins University Study, is a novel syndromic surveillance approach, which collects body temperature and COVID-like illness (CLI) symptoms across the US using a smartphone app and applies spatio-temporal clustering techniques and cross-correlation analysis to create maps of abnormal symptomatology incidence that are made publicly available. The results of the cross-correlation analysis identify optimal temporal lags between symptoms and a range of COVID-19 outcomes, with new taste/smell loss showing the highest correlations. We also identified temporal clusters of change in taste/smell entries and confirmed COVID-19 incidence in Baltimore City and County. Further, we utilized an extended simulated dataset to showcase our analytics in Maryland. The resulting clusters can serve as indicators of emerging COVID-19 outbreaks, and support syndromic surveillance as an early warning system for disease prevention and control.

BackgroundClinical diagnosis of COVID-19 poses an enormous challenge to early detection and prevention of COVID-19, which is of crucial importance for pandemic containment. Cases of COVID-19 may be hard to distinguish clinically from other acute viral diseases, resulting in an overwhelming load of laboratory screening. Sudden onset of taste and smell loss emerge as hallmark of COVID-19. The optimal ways for including these symptoms in the screening of suspected COVID-19 patients should now be established.MethodsWe performed a case-control study on patients that were PCR-tested for COVID-19 (112 positive and 112 negative participants), recruited during the first wave (March 2020 – May 2020) of COVID-19 pandemic in Israel. Patients were interviewed by phone regarding their symptoms and medical history and were asked to rate their olfactory and gustatory ability before and during their illness on a 1-10 scale. Prevalence and degrees of symptoms were calculated, and odds ratios were estimated. Symptoms-based logistic-regression classifiers were constructed and evaluated on a hold-out set.ResultsChanges in smell and taste occurred in 68% (95% CI 60%-76%) and 72% (64%-80%), of positive patients, with 24 (11-53 range) and 12 (6-23) respective odds ratios. The ability to smell was decreased by 0.5±1.5 in negatives, and by 4.5±3.6 in positives, and to taste by 0.4±1.5 and 4.9±3.8, respectively (mean ± SD). A penalized logistic regression classifier based on 5 symptoms (degree of smell change, muscle ache, lack of appetite, fever, and a negatively contributing sore throat), has 66% sensitivity, 97% specificity and an area under the ROC curve of 0.83 (AUC) on a hold-out set. A classifier based on degree of smell change only is almost as good, with 66% sensitivity, 97% specificity and 0.81 AUC. Under the assumption of 8% positives among those tested, the predictive positive value (PPV) of this classifier is 0.68 and negative predictive value (NPV) is 0.97.ConclusionsSelf-reported quantitative olfactory changes, either alone or combined with other symptoms, provide a specific and powerful tool for clinical diagnosis of COVID-19. The applicability of this tool for prioritizing COVID-19 laboratory testing is facilitated by a simple calculator presented here.

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.

The main neurological manifestation of COVID-19 is loss of smell or taste. The high incidence of smell loss without significant rhinorrhea or nasal congestion suggests that SARS-CoV-2 targets the chemical senses through mechanisms distinct from those used by endemic coronaviruses or other common cold-causing agents. Here we review recently developed hypotheses about how SARS-CoV-2 might alter the cells and circuits involved in chemosensory processing and thereby change perception. Given our limited understanding of SARS-CoV-2 pathogenesis, we propose future experiments to elucidate disease mechanisms and highlight the relevance of this ongoing work to understanding how the virus might alter brain function more broadly., Impairments of smell and taste perception are two of the main symptoms of COVID–19. In this issue of Neuron, Cooper et al. focus on these chemosensory symptoms and review recent hypotheses of the putative mechanisms mediating the loss of taste and smell through COVID–19.

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

Evidence of smell loss in COVID-19 is growing. Researchers and analysts have suggested to use Google searches on smell loss as indicators of COVID-19 cases. However, such searches may be due to interest elicited by media coverage of the COVID-19-related smell loss, rather than attempts to understand self-symptoms. We analyzed searches related to 4 senses: smell and taste (both recently shown to be impaired in some COVID-19 patients), vision and sight (senses not currently known to be impaired in COVID-19 patients), and an additional general control (“COVID-19 symptoms”). Focusing on two countries with a large number of cases, Italy and the United States, we have compared Google Trends results per region or state to the number of new cases prevalence in that region. The analysis was performed for each of the 8 weeks ranging from March 4th till April 28th.No correlation with vision loss or sight loss searches was identified, while taste and smell loss searches were correlated with new COVID-19 cases during a limited time window, that starts when the number of weekly new cases reached for the first time 21357 cases in Italy (11-17 March) and 47553 in the US (18-24 March).Media effect on the specific symptoms searches was also analyzed, establishing a different impact according to the country.Our results suggest that Google Trends for taste loss and smell loss searches captured a genuine connection between these symptoms and new COVID-19 cases prevalence in the population. However, due to variability in correlation from week to week, and overall decrease in correlation as taste and smell loss are becoming known COVID-19 symptoms, recognized now by CDC and World Health Organization, Google Trends is no longer a reliable marker for monitoring the disease spread. The “surprise rise” followed by decrease, probably attributable to knowledge saturation, should be kept in mind for future digital media analyses of potential new symptoms of COVID-19 or future pandemics.

Objective: We recently demonstrated efficacy of intranasal theophylline in treatment of hyposmia in a large, diverse group of patients who exhibited this abnormality over an extended time period. Because hyposmia is long lasting we wished to evaluate hyposmia severity among patients related to length of time they exhibited hyposmia prior to initial evaluation and to whether hyposmia length or severity influenced treatment efficacy. Methods: Ninety-four patients with hyposmia were studied. Thirty-two had hyposmia for < 12 months prior to treatment whereas 62 had hyposmia >12 months before treatment. Treatment was intranasal delivery of 20 µg theophylline twice into each nostril once daily for two-12 months. Subjective responses, olfactometry and gustometry were obtained before and after treatment. Results: Hyposmia was similar in severity degree in both patient groups whether they exhibited hyposmia < or > 12 months after hyposmia onset. However, treatment with intranasal theophylline resulted in greater improvement in patients with onset < 12 months. Conclusions: Whereas degree of hyposmia severity does not differ with respect to length of dysfunction prior to treatment, treatment with intranasal theophylline was more effective in patients who exhibited hyposmia for shorter time periods - the earlier the treatment the better the result.

Objective: We recently demonstrated efficacy of intranasal theophylline in treatment of hyposmia in a large, diverse group of patients who exhibited this abnormality over an extended time period. Because hyposmia is long lasting we wished to evaluate hyposmia severity among patients related to length of time they exhibited hyposmia prior to initial evaluation and to whether hyposmia length or severity influenced treatment efficacy. Methods: Ninety-four patients with hyposmia were studied. Thirty-two had hyposmia for < 12 months prior to treatment whereas 62 had hyposmia >12 months before treatment. Treatment was intranasal delivery of 20 µg theophylline twice into each nostril once daily for two-12 months. Subjective responses, olfactometry and gustometry were obtained before and after treatment. Results: Hyposmia was similar in severity degree in both patient groups whether they exhibited hyposmia < or > 12 months after hyposmia onset. However, treatment with intranasal theophylline resulted in greater improvement in patients with onset < 12 months. Conclusions: Whereas degree of hyposmia severity does not differ with respect to length of dysfunction prior to treatment, treatment with intranasal theophylline was more effective in patients who exhibited hyposmia for shorter time periods - the earlier the treatment the better the result.

Author(s): Yan, Carol H; Faraji, Farhoud; Prajapati, Divya P; Ostrander, Benjamin T; DeConde, Adam S | Abstract: 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.

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

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

Objective With the advent of new treatment options for Chronic Rhinosinusitis (CRS) comes the ability for physicians to provide more individualized patient care. Physicians are now tasked with identifying who may be the best candidate for a particular therapy. In this review, existing biomarkers and potentially new methods that could guide treatment choices in CRS patients will be discussed. Data Sources Published literature obtained through PubMed searches. Study Selection Studies relevant to inflammatory endotypes, phenotypes, and biomarkers in CRS were included. Results Currently, there are no clinically validated tools that determine the best therapeutic modality for CRS patients with or without nasal polyps (CRSwNP or CRSsNP). Patients with CRS can be classified into three endotypes based on the presence of type 1, type 2, or type 3 inflammation. CRS endotypes can be influenced by age and geographic location. Clinical application however may be limited since endotyping current requires basic research laboratory support. Clinical symptoms may also predict inflammatory endotypes with smell loss being indicative of type 2 inflammation. Numbers of tissue and/or peripheral eosinophils as well as levels of IgE may predict disease severity in CRSwNP but not necessarily treatment responses. Unique clinical phenotypes or biomarkers are especially lacking that predict type 1 or type 3 inflammation in CRSwNP or type 1, type 2, or type 3 inflammation in CRSsNP. Conclusion While significant progress has been made in characterizing endotypes, phenotypes, and biomarkers in CRS, additional studies are needed to determine if and how these factors could assist physicians in providing more individualized clinical care.

Olfaction plays a major role in food intake regulation. Losing the sense of smell might therefore affect eating behavior. This study investigated food preferences and intake in individuals suffering from self-reported smell loss with an online survey. Members of the Dutch Anosmia Foundation (DAF) performed the Macronutrient and Taste Preference Ranking Task (n = 71) to measure preference for foods high in fat, carbohydrates or protein and low energy foods, and for sweet and savory tastes. To assess dietary intake, adherence to the Dutch Dietary Guidelines for consumption of vegetables, fruit, fiber, fish, saturated fat, trans fatty acids, salt and alcohol was measured (n = 105). Results of the DAF participants were compared to local cohort groups. Both the control and DAF participants showed the lowest preference for carbohydrate-rich foods and highest preference for low-energy foods. Participants suffering from congenital smell loss showed an aberrant pattern, with a higher preference for fat. The total adherence score to the Dutch Dietary Guidelines was similar for the control and DAF group, but adherence scores for fiber, trans fatty acids and alcohol were lower in DAF participants. Overall, no major significant differences in food preferences and intake were found for participants who lost their sense of smell during life. Participants suffering from congenital smell loss did show changes in food preferences, suggesting they are potentially more taste-oriented during eating. Together these results show the importance of tailored advice on dietary intake for this patient group.

Introduction: Olfactory dysfunction could be the sign of acquired or degenerative diseases. The loss of the sense can be caused by a damage in the nasal structure (olfactory epithelium) or a neuro inflammation/degeneration in the superior olfactory pathway. The understanding of the origin of the smell alteration would be desirable for appropriate management of the problem. Unfortunately, clinical investigations do not always allow to define the exact cause., Areas Covered: This review discusses the treatments available and their mechanism of action based on the administration methods; in fact, just looking at the results obtained by the researcher using topic versus systemic treatment, might be possible to speculate about the peripheral or central origin of the olfactory disorder., Expert Opinion: Because COVID-19 causes olfactory loss and several treatments (topical and systemic) have been tested in this disease, we have decided to use this model of acquired olfactory loss to discuss the different therapeutical option. The authors believe these treatments might be an option also for treating olfactory disease related to neurodegeneration.

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.

Introduction Individuals with unexplained smell loss constitute an at-risk population for the development of Parkinson's disease (PD). Currently, no specific MRI patterns are known for early PD diagnosis. In this study, we measured the fractional anisotropy (FA) in the substantia nigra (SN) in PD patients, in patients with idiopathic smell loss, and in healthy controls. Methods All subjects underwent extensive olfactory testing and MR imaging data were obtained to explore SN diffusion characteristics. The SN regions were manually identified by two independent raters on the individual imaging data. Results FA measurements in the SN revealed significant group differences, with reduced values clearly distinguishing PD patients and patients with idiopathic smell loss from healthy controls. Conclusion These findings indicate a reduced intrinsic integrity of the SN in PD at-risk subjects and support the risk status of patients with idiopathic smell loss.

The loss of smell and taste is one of the most consistent symptoms of covid-19, so what can that tell us about the condition, asks Kayt Sukel

Post-COVID syndrome can be defined as symptoms of COVID-19 that persist for longer than 12 weeks, with several studies reporting persistent symptoms relating to the sensory organs (eyes, ears, and nose). The aim of this systematic review was to examine the prevalence of persistent anosmia, hyposmia, ageusia, and hypogeusia, as well as eye/vision and ear/hearing related long-COVID symptoms. Authors searched the electronic databases from inception to November 2021. Search terms included words related to long-COVID, smell, taste, eyes/vision, and ears/hearing, with all observational study designs being included. A random effects meta-analysis was undertaken, calculating the prevalence proportions of anosmia, hyposmia, ageusia, and hypogeusia, respectively. From the initial pool, 21 studies met the inclusion criteria (total n 4,707; median n per study 125; median age = 49.8; median percentage female = 59.2%) and 14 were included in the meta-analysis The prevalence of anosmia was 12.2% (95% CI 7.7-16.6%), hyposmia 29.9% (95% CI 19.9-40%), ageusia 11.7% (95% CI 6.1-17.3%), and hypogeusia 31.2% (95% 16.4-46.1%). Several eye/vision and ear/hearing symptoms were also reported. Considering that changes in the sensory organs are associated with decreases in quality of life, future research should examine the etiology behind the persistent symptoms., Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021292804]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Trott, Driscoll and Pardhan.)

To determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period.Prospective cohort study.Betula Study, Umeå, Sweden.A population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).Olfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.Within the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P.001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction.Poor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.

It has been suggested that systemic pentoxifylline may be beneficial in the treatment of olfactory dysfunction. The postulated mechanism of action involves nonselective competitive phosphodiesterase inhibition, leading to increased intracellular cyclic adenosine monophosphate and consequent increased olfactory neuron activity. This should in theory lead to improved olfactory function. We describe a pilot case series from our tertiary referral center of patients treated with oral pentoxifylline for olfactory dysfunction. Six patients with post-traumatic impairment who were treated with systemic pentoxifylline were included. Patients were treated with 200 mg of oral prolonged release pentoxifylline, 3 times a day for 21 days. Olfactory function was tested pre and post-treatment for odor threshold (T), discrimination (D), identification (I) and composite 'TDI' score using a psychophysical test battery, the “Sniffin’ Sticks.” Oral pentoxifylline was well tolerated and all patients completed the treatment period. There was a small improvement in odor threshold and identification scores, but these did not reach statistical or clinical significance. There were deteriorations in discrimination and composite TDI score, which did not reach significance. While our case series was small, systemic pentoxifylline did not appear to be beneficial in the treatment of hyposmia in this patient group.

There seems to be a correlation between soluble amyloid beta protein (Aβ) accumulation in the main olfactory bulb (OB) and smell deterioration in both Alzheimer’s disease (AD) patients and animal models. Moreover, this loss of smell appears to be related to alterations in neural network activity in several olfactory-related circuits, including the OB, as has been observed in anesthetized animals and brain slices. It is possible that there is a correlation between these two pathological phenomena, but a direct and simultaneous evaluation of the acute and direct effect of Aβon OB activity while animals are actually smelling has not been performed. Thus, here, we tested the effects of acute intrabulbar injection of Aβat a low dose (200 pmol) on the OB local field potential before and during the presence of a hidden piece of smelly food. Our results show that Aβdecreases the power of OB network activity while impairing the animal’s ability to reach the hidden food. We found a strong relationship between the power of the OB oscillations and the correlation between OBs and the olfactory detection test scores. These findings provide a direct link between Aβ-induced OB network dysfunction and smell loss in rodents, which could be extrapolated to AD patients.

Background: Olfactory dysfunction (OD) in COVID-19 presents as a sudden onset smell loss commonly seen in mild symptomatic cases with or without rhinitis but can occur as an isolated symptom. The reported prevalence of OD among COVID-19 patients ranged from 5% to 98%. Although numerous studies have been conducted about their association, these were mainly based on self-reported cases and subjective questionnaires. Objective: This study investigates whether there is a significant difference in the prevalence of olfactory dysfunction between self-reported and objective testing using validated objective olfactory tests among RT-PCR confirmed COVID-19 patients. Methods: PubMed (MEDLINE), Cochrane, Web of Science, and Google Scholar were searched for studies investigating the prevalence of OD by using objective olfactory tests among patients who self-reported OD (November 1, 2019 to July 31, 2020). All studies were assessed for quality and bias using the Cochrane bias tool. Patient demographics, type of objective olfactory test, and results of self-reported OD and objective testing were reported. Results: Nine studies encompassing 673 patients met the inclusion criteria. Validated objective olfactory tests used in the included studies were CCCRC, SST and SIT. Overall prevalence of OD among patients who self-reported was higher after objective testing (71% versus 81%). This was also seen in when we performed subgroup analysis based on the objective tests that were used. However, meta-analysis using random effects model showed no significant difference in the overall prevalence of OD (p value=.479, 95% CI 56.6 to 84.0 versus 71.2 to 89.8) as well as in the subgroups. Conclusion: To the best of our knowledge, this is the first meta-analysis that statistically reviewed articles that evaluated the difference between self-reported and objective tests done on the same patients. Results showing that self-reporting OD approximates the results of the objective tests among COVID-19 positive patients may imply that self-reporting can be sufficient in contact tracing and triggering swabbing and self quarantine during the time of COVID-19 and objective tests can be used as an adjunct in the diagnosis particularly in research. However, this study was limited by small sample size and articles done in European countries hence, interpretation and application of the results of this study must be approached with care. Further studies documenting the difference between self-reporting and objective test in large scale setting involving different countries may be helpful in establishing a definitive consensus.

Objectives: Besides the common symptoms of the coronavirus disease 2019 (COVID-19) including fever, shortness of breath, and cough, a “sudden loss of smell” has recently been added as a diagnostic symptom. The relationship between paranasal sinus computed tomography (PNS CT) and sudden loss of smell in COVID-19 was examined. Materials and Methods: Two groups were selected for the study, the COVID-19 and the control groups. The control group consisted of 40 patients who applied to our clinic with headache and therefore underwent PNS CT. The other group consisted of 40 patients with COVID-19 who were diagnosed with sudden loss of smell with the Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test. Clinical and demographic characteristics, tomography results, and olfactory test scores of patients with COVID-19 loss of smell and control group patients were recorded. The relationship between CT changes in the olfactory cleft and the degree of loss of smell was evaluated. The “Opacification in the olfactory cleft” was accepted as a positive CT finding. Results: Comparison of patients with COVID-19 who had a loss of smell and the control group indicated that a significant difference was observed in terms of CT findings ( P = .022). When we evaluated the paranasal CTs obtained from our patients with loss of smell, the CT of 13 patients showed pathological findings ( P < .05). As the COVID-19 progressed (pneumonia and respiratory failure), the degree of loss of smell increased ( P < .05). A statistically significant relationship was found between the CCCRC score and the presence of PNS CT findings ( P = .0012). Conclusion: The PNS CT findings are significant in patients with COVID-19 with a loss of smell and were significantly associated with the degree of loss of smell. In patients with olfactory loss due to COVID-19, PNS CT can help in diagnosis. However, for this imaging to be diagnostic, a larger patient series is needed.

Introduction Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW. Methods and findings We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV-2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01). Conclusions In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.