Nature and human well-being: The olfactory pathway.

The world is undergoing massive atmospheric and ecological change, driving unprecedented challenges to human well-being. Olfaction is a key sensory system through which these impacts occur. The sense of smell influences quality of and satisfaction with life, emotion, emotion regulation, cognitive function, social interactions, dietary choices, stress, and depressive symptoms. Exposures via the olfactory pathway can also lead to (anti-)inflammatory outcomes. Increased understanding is needed regarding the ways in which odorants generated by nature (i.e., natural olfactory environments) affect human well-being. With perspectives from a range of health, social, and natural sciences, we provide an overview of this unique sensory system, four consensus statements regarding olfaction and the environment, and a conceptual framework that integrates the olfactory pathway into an understanding of the effects of natural environments on human well-being. We then discuss how this framework can contribute to better accounting of the impacts of policy and land-use decision-making on natural olfactory environments and, in turn, on planetary health.

Bilateral hypogeusia and food aversion due to lacunar infarct in the right dorsomedial pontine tegmentum.

A 70-year-old right-handed housewife suffered an acute loss of taste, an unpleasant change in the taste of foods and liquids, and a strong aversion to all kinds of food due to a small lacune in the right dorsomedial pontine tegmentum. Eating became so unpleasant that she lost 7 kg in three weeks. Olfaction and the sensibility of the tongue were spared. The right medial longitudinal fascicle, the central tegmental tract, or both, were injured by the tegmental lesion. A discrete right-sided lesion in the upper pontine tegmentum may cause a reversible syndrome consisting of bilateral hypogeusia which is more severe ipsilaterally.

Identification of the needs of individuals affected by COVID-19.

BACKGROUND: The optimal management of COVID-19 symptoms and their sequelae remains an important area of clinical research. Policy makers have little scientific data regarding the effects on the daily life of affected individuals and the identification of their needs. Such data are needed to inform effective care policy. METHODS: We studied 639 people with COVID-19 resident in France via an online questionnaire. They reported their symptoms, effects on daily life, and resulting needs, with particular focus on olfaction. RESULTS: The results indicate that a majority of participants viewed their symptoms as disabling, with symptoms affecting their physical and mental health, social and professional lives. 60% of the individuals reported having unmet medical, psychological and socio-professional support needs. Finally, affected individuals were concerned about the risk and invasiveness of possible treatments as shown by a preference for non-invasive intervention over surgery to cure anosmia. CONCLUSIONS: It is important that policy makers take these needs into consideration in order to assist affected individuals to regain a normal quality of life.

The impact of COVID-19 has been substantial, both on individuals' health and on society. Information is needed to understand the biological mechanisms underlying the illness and to provide appropriate support for people affected. This study uses data from an online questionnaire of adults diagnosed with COVID-19 to characterize symptoms, understand their impact on peoples' everyday lives, and determine the support that people need. Our over-arching analysis of symptoms experienced reveals that heart- and skin-related symptoms are linked to chronic illness, and symptoms related to the sense of smell may have a different underlying disease mechanism. Most respondents had a mild initial illness, but their symptoms were long-lasting and had a severe impact. Our findings show that sufferers need different kinds of support in order to regain a normal quality of life.

Allosteric Inhibition and Pharmacochaperoning of the Serotonin Transporter by the Antidepressant Drugs Trazodone and Nefazodone.

The antidepressants trazodone and nefazodone were approved some four and three decades ago, respectively. Their action is thought to be mediated - at least in part - by inhibition of the serotonin transporter (SERT/SLC6A4). Surprisingly, their mode of action on SERT has not been characterized. Here we show that - similar to the chemically related drug vilazodone - trazodone and nefazodone are allosteric ligands, which inhibit uptake by and transport-associated currents through SERT in a mixed-competitive and non-competitive manner, respectively. Contrary to noribogaine and its congeners, all three compounds preferentially interact with the Na+-bound outward-facing state of SERT. Nevertheless, they act as pharmacochaperones and rescue the folding-deficient variant SERT-P601A/G602A. The vast majority of disease-associated point mutations of SLC6 (solute carrier-6) family members impair folding of the encoded transporter proteins. Our findings indicate that their folding defect can be remedied by targeting allosteric sites on SLC6 transporters. Significance Statement The serotonin transporter is a member of the solute carrier 6 family and is the target of numerous antidepressants. Trazodone and nefazodone have long been used as antidepressants. Here we show that their inhibition of the serotonin transporter digressed from the competiti-ve mode seen with other antidepressants. Trazodone and nefazodone rescued a folding-deficient variant of the serotonin transporter. This finding demonstrates that folding defects of mutated solute carrier-6 family members can also be corrected by allosteric ligands.

Correlation of Molecular Status with Preoperative Olfactory Function in Olfactory Groove Meningioma.

PURPOSE: The study aims to examine the possible correlation between genomic alterations and preoperative olfactory function in patients with olfactory groove meningioma (OGM), due to the frequent presence of olfactory impairment. METHODS: We utilised next-generation sequencing to analyse samples from 22 individuals with OGM in order to detect driver mutations. Tumour morphology was assessed using preoperative imaging, whereas olfactory function was examined using Sniffin' Sticks. RESULTS: In a study of 22 OGM patients, mutations were as follows: 10 with SMO/SUFU, 7 with AKT1, and 5 as wild type. Planum sphenoidale hyperostosis (PSH) was present in 75% of patients, showing significant variation by mutation (p = 0.048). Tumour volumes, averaging 25 cm3, significantly differed among groups. PSH negatively impacted olfaction, notably affecting odour threshold, discrimination, identification, and global olfactory performance score (TDI) (p values ranging from <0.001 to 0.003). Perifocal oedema was associated with lower TDI (p = 0.009) and altered threshold scores (p = 0.038). Age over 65 and female gender were linked to lower thresholds and discrimination scores (p = 0.037 and p = 0.019). CONCLUSION: The study highlights PSH and perifocal oedema's significant effect on olfactory function in OGM patients but finds no link between olfactory impairment and tumour mutations, possibly due to the small sample size. This suggests that age and gender affect olfactory impairment. Additional research with a larger group of participants is needed to explore the impact of OGM driver mutations on olfactory performance.

A practical test for retronasal odor identification based on aromatized tablets.

BACKGROUND: Olfactory perceptions elicited by odors originating from within the body (retronasal olfaction) play a crucial role in well-being and are often disrupted in various medical conditions. However, the assessment of retronasal olfaction in research and the clinical practice is impeded by the lack of commercially available tests and limited standardization of existing testing materials. NEW METHOD: The novel ThreeT retronasal odor identification test employs 20 flavored tablets that deliver a standardized amount of odorous stimuli. The items represent common food- and non-food-related odors. RESULTS: The ThreeT test effectively distinguishes patients with olfactory dysfunction from healthy controls, achieving a specificity of 86% and sensitivity of 73%. Its scores remain stable for up to 3 months (r=.79). COMPARISON WITH EXISTING METHOD: ThreeT test exhibits a strong correlation with "Tasteless powders" measure of retronasal olfaction (r=.78) and classifies people into healthy and patient groups with similar accuracy. Test-retest stability of ThreeT is slightly higher than the stability of "Tasteless powders" (r=.79 vs r=.74). CONCLUSIONS: ThreeT is suitable for integration into scientific research and clinical practice to monitor retronasal odor identification abilities.

A Study on the Impact of the COVID-19 Pandemic on the Aetiology of Paediatric Olfactory Dysfunction.

INTRODUCTION: Although previous studies have examined olfactory dysfunction in children, the novel coronavirus SARS-CoV-2 has certainly had an unprecedented effect on their olfaction, which could not be taken into consideration. The aim of this report was to present data on the epidemiology of olfactory dysfunction during the pandemic and compare this dataset with a pre-pandemic set. We hypothesized an increase in URTI-related olfactory dysfunction. METHODS: Data of paediatric patients consulting a smell and taste clinic between March 2020 and June 2022 were retrospectively analysed. The frequency of major causes of olfactory dysfunction was examined and compared with three subsets of an older dataset. RESULTS: A total of 52 patients were included in the analysis. Most children presented with olfactory dysfunction due to upper respiratory tract infection (URTI) (52%). Congenital olfactory dysfunction was present in 34% of cases. Sinonasal disorders and idiopathic cases accounted for 6 and 4%, respectively, whereas head trauma was the least common cause (2%). This was in contrast with the results of the older set. The frequency of URTI-related olfactory dysfunction increased significantly. The frequency of head-trauma-related or congenital olfactory dysfunction showed marked reductions. There were no significant differences regarding the other aetiologies between our patient cohort and the three subsets. CONCLUSION: The COVID-19 pandemic has resulted in differences regarding the prevalence of aetiologies between our dataset and the subsets of pre-pandemic times. The surge of the frequency of URTI-related olfactory dysfunction may be ascribed to a novel pathomechanism involving sustentacular cells in the olfactory epithelium.

Histochemical Evidence for Reduced Immune Response in Nasal Mucosa of Patients with COVID-19.

The primary entry point of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the nasal mucosa, where viral-induced inflammation occurs. When the immune response fails against SARS-CoV-2, understanding the altered response becomes crucial. This study aimed to compare SARS-CoV-2 immunological responses in the olfactory and respiratory mucosa by focusing on epithelia and nerves. Between 2020 and 2022, we obtained post mortem tissues from the olfactory cleft from 10 patients with histologically intact olfactory epithelia (OE) who died with or from COVID-19, along with four age-matched controls. These tissues were subjected to immunohistochemical reactions using antibodies against T cell antigens CD3, CD8, CD68, and SARS spike protein for viral evidence. Deceased patients with COVID-19 exhibited peripheral lymphopenia accompanied by a local decrease in CD3+ cells in the OE. However, SARS-CoV-2 spike protein was sparsely detectable in the OE. With regard to the involvement of nerve fibers, the present analysis suggested that SARS-CoV-2 did not significantly alter the immune response in olfactory or trigeminal fibers. On the other hand, SARS spike protein was detectable in both nerves. In summary, the post mortem investigation demonstrated a decreased T cell response in patients with COVID-19 and signs of SARS-CoV-2 presence in olfactory and trigeminal fibers.

Olfactory Loss in Rhinosinusitis: Mechanisms of Loss and Recovery.

Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.

Pronounced Olfactory Habituation with Age.

OBJECTIVES: Olfactory habituation is a transient decrease in olfactory sensitivity caused by prolonged odor exposure, aiding in the discernment of new olfactory stimuli against the background. We explored the impact of subclinical olfactory impairment on odor habituation using age as a proxy. METHODS: Before the actual experiment, the individual olfactory threshold for the rose-like odorant phenylethyl alcohol (PEA) was assessed separately for the left and right nostril using the "Sniffin' Sticks" test, and ratings for odor intensity and pleasantness were collected. After applying a nasal clip continuously delivering PEA odor to one nostril for 10 min and 2 h, respectively, threshold, intensity, and pleasantness were reassessed immediately after clip removal. RESULTS: In the group of 80 participants (younger adults-mean age 27.7 ± 4.5 years; older adults-mean age 61.5 ± 4.7 years), olfactory thresholds were already significantly elevated after just 10 min, and this habituation was even more pronounced after 2 h. This effect could be observed bilaterally even though significantly more distinct on the exposed side. Older participants generally exhibited a more pronounced habituation on the exposed side after 2 h compared to the younger participants. CONCLUSION: The results indicate that older people experience more notable habituation after extended exposure to odors. This is most likely due to the compromised olfactory function in age. Although older and younger subjects scored in the normosmic range when tested with standardized olfactory tests, the stress on the system after exposure to an odor clearly revealed the lower functionality of the aging sense of smell. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Olfactory function in diabetes mellitus.

Diabetes mellitus (DM) is an increasingly common disease in both children and adults. In addition to neuronal and/or vascular disorders, it can cause chemosensory abnormalities including olfactory deterioration. The purpose of this article is to summarize current knowledge on olfactory function in DM, highlighting the impact of co-morbidities, especially obesity, thyroid dysfunction, chronic kidney disease and COVID-19 on olfactory outcomes. Research to date mostly shows that olfactory impairment is more common in people with diabetes than in the general population. In addition, the presence of concomitant diseases is a factor increasing olfactory impairment. Such a correlation was shown for type 1 diabetes, type 2 diabetes and gestational diabetes. At the same time, not only chronic diseases, but also DM in acute conditions such as COVID-19 leads to a higher prevalence of olfactory disorders during infection. Analyzing the existing literature, it is important to be aware of the limitations of published studies. These include the small number of patients studied, the lack of uniformity in the methods used to assess the sense of smell, frequently relying on rated olfactory function only, and the simultaneous analysis of patients with different types of diabetes, often without a clear indication of diabetes type. In addition, the number of available publications is small. Certainly, further research in this area is needed. From a practical point of view decreased olfactory performance may be an indicator for central neuropathy and an indication for assessing the patient's nutritional status, examining cognitive function, especially in older patients and performing additional diagnostic tests, such as checking thyroid function, because all those changes were correlated with smell deterioration.

What do brain oscillations tell about the human sense of smell?

Brain activity may manifest itself as oscillations which are repetitive rhythms of neuronal firing. These local field potentials can be measured via intracranial electroencephalography (iEEG). This review focuses on iEEG used to map human brain structures involved in olfaction. After presenting the methodology of the review, a summary of the brain structures involved in olfaction is given, followed by a review of the literature on human olfactory oscillations in different contexts. A single case is provided as an illustration of the olfactory oscillations. Overall, the timing and sequence of oscillations found in the different structures of the olfactory system seem to play an important role for olfactory perception.

Home screening of taste and oral trigeminal function: a feasibility study.

PURPOSE: gustatory ability is a marker of health not routinely tested in the medical practice. The current study wants to assess whether taste strips can be useful to monitor taste function from home. METHODS: we performed simple sensory tests in lab setting vs. unassisted testing at home, and compared the results with self-reports ability to taste and smell. Using paper strips impregnated with sweet, bitter, salty, or sour tastants, and with two trigeminal stimuli (capsaicin, tannins) in high and low concentrations, we assessed gustatory and trigeminal function in 74 participants (47 women) in the lab, where paper strips were administered by an experimenter, and in 77 participants (59 women) at home, where they self-administered the test. RESULTS: we found that high (but not low) concentration taste strips are correctly identified by vast majority of participants. On average, taste identification, intensity and pleasantness scores did not differ for the 8 taste strips, while identification of capsaicin was significantly better in the lab. Taste identification scores correlated with intensity ratings in both settings (r = 0.56, in the lab, r = 0.48, at home, p < 0.005). Self-rated taste ability correlated with self-rated smell ability (r = 0.68, and r = 0.39, p ≤ 0.005), but not with scores in the strips test. CONCLUSION: home testing with impregnated taste strips is feasible, and can be used for telemedical purposes.

Comparison of Patient Characteristics and Olfactory Sensitivity for Trigger Odorants in Parosmia and Phantosmia.

OBJECTIVES: This study aimed to determine the characteristics of patients with qualitative olfactory dysfunction (qualOD) and whether individuals with parosmia exhibit increased olfactory sensitivity to previously reported odorous triggers of parosmia. METHODS: This study included individuals aged ≥18 years, divided into quantitative OD only, parosmia, and phantosmia groups. Data collected included: clinical-demographic data, "Sniffin' Sticks" scores, questionnaires (depression scale, importance of olfaction), and information about parosmia and phantosmia. A proportion of patients underwent trigger odor threshold testing for 2-Furfurylthiol [FFT] found in coffee and 2,6-nonadienal [Nonadienal] found in cucumber. RESULTS: Those with parosmia were typically younger women, with shorter OD duration due to post-viral OD (PVOD), hyposmic/normosmic, and experienced parosmia more severely. Parosmia was 3.5 times more likely in PVOD. Those with phantosmia were older, with longer OD duration due to idiopathic OD, hyposmic/anosmic, and experienced phantosmia less severely. There were no significant differences between FFT and Nonadienal threshold scores in patients with parosmia, phantosmia, or only quantitative OD, but all groups had significantly increased olfactory sensitivity for trigger odors compared to phenyl ethyl alcohol (PEA). CONCLUSION: Parosmia and phantosmia patients have distinct characteristics. This may provide clinicians with a better understanding of possible olfactory outcomes in these patients. The higher olfactory sensitivity of all groups to trigger odors compared to PEA raises interesting points about parosmia triggers and odors in the context of warning for danger, in relation to the pathophysiology of parosmia that may be worth exploring in future studies. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Patients with parosmia respond faster to unpleasant odors than patients with hyposmia: Insights from olfactory event-related potentials.

BACKGROUND: Diagnosing parosmia is a challenge. The present study aimed to explore the distinctions between hyposmic patients with and without parosmia utilizing electroencephalography-derived olfactory event-related potentials (ERP). METHODS: Forty-four patients with hyposmia were enrolled and divided into a group with parosmia (n = 23, mean age ± standard deviation = 48 ± 14 years, seven men) and a group without parosmia (n = 21, age = 52 ± 12 years, seven men) based on the clinical interview. Additionally, 21 healthy controls (mean age = 45 ± 14 years, six men) were included. Various measurements were obtained, including the Sniffin' Stick test, threshold tests for the odorants furfural mercaptan and 2,6-nonadienal, a modified Sniffin' Stick parosmia test, and well-being ratings. Chemosensory ERPs were recorded separately for each nostril using high-precision, computer-controlled air-dilution olfactometry. RESULTS: Patients with parosmia had a decreased olfactory function similar to that observed in patients with hyposmia, although the odor sensitivity of patients with severe parosmia remained relatively unaffected. Patients with parosmia reported a decrease in well-being compared to controls. The severity of parosmia was positively correlated with odor sensitivity. Furthermore, patients with severe parosmia exhibited faster responses to unpleasant odors than patients without parosmia. CONCLUSION: Overall, the present findings support the idea that parosmia predominantly occurs during olfactory recovery, significantly disturbing patients and warranting the development of effective treatments. Notably, the relatively faster responses of hyposmic patients with severe parosmia suggest that the generation of distorted olfactory responses may involve early stages of the processing of olfactory information.

Differential connectivity of the posterior piriform cortex in Parkinson's disease and postviral olfactory dysfunction: an fMRI study.

Olfactory dysfunction is a common feature of both postviral upper respiratory tract infections (PV) and idiopathic Parkinson's disease (PD). Our aim was to investigate potential differences in the connectivity of the posterior piriform cortex, a major component of the olfactory cortex, between PV and PD patients. Fifteen healthy controls (median age 66 years, 9 men), 15 PV (median age 63 years, 7 men) and 14 PD patients (median age 70 years, 9 men) were examined with task-based olfactory fMRI, including two odors: peach and fish. fMRI data were analyzed with the co-activation pattern (CAP) toolbox, which allows a dynamic temporal assessment of posterior piriform cortex (PPC) connectivity. CAP analysis revealed 2 distinct brain networks interacting with the PPC. The first network included regions related to emotion recognition and attention, such as the anterior cingulate and the middle frontal gyri. The occurrences of this network were significantly fewer in PD patients compared to healthy controls (p = 0.023), with no significant differences among PV patients and the other groups. The second network revealed a dissociation between the olfactory cortex (piriform and entorhinal cortices), the anterior cingulate gyrus and the middle frontal gyri. This second network was significantly more active during the latter part of the stimulation, across all groups, possibly due to habituation. Our study shows how the PPC interacts with areas that regulate higher order processing and how this network is substantially affected in PD. Our findings also suggest that olfactory habituation is independent of disease.

Lateralisation of nasal cycle is not reflected in the olfactory bulb volumes and cerebral activations.

Nasal cycle (NC) is a rhythmic change of lateralised nasal airflow mediated by the autonomous nervous system. Previous studies reported the dependence of NC dominance or more patent side on handedness and hemispheric cerebral activity. We aimed to investigate firstly the possible lateralised effect of NC on olfactory bulb volume and secondly the association of NC with the lateralised cerebral dominance in terms of olfactory processing. Thirty-five subjects (22 women and 13 men, mean age 26 ± 3 years) participated in the study. NC was ascertained using a portable rhino-flowmeter. Structural and functional brain measurements were assessed using a 3T MR scanner. Vanillin odorant was presented during functional scans using a computer-controlled olfactometer. NC was found to be independent of the olfactory bulb volumes. Also, cerebral activations were found independent of the NC during odorant perception. NC potency is not associated with lateralised structural or functional differences in the cerebral olfactory system.

Odor dilution sorting as a clinical test of olfactory function: normative values and reliability data.

Clinical assessment of an individual's sense of smell has gained prominence, but its resource-intensive nature necessitates the exploration of self-administered methods. In this study, a cohort of 68 patients with olfactory loss and 55 controls were assessed using a recently introduced olfactory test. This test involves sorting 2 odorants (eugenol and phenylethyl alcohol) in 5 dilutions according to odor intensity, with an average application time of 3.5 min. The sorting task score, calculated as the mean of Kendall's Tau between the assigned and true dilution orders and normalized to [0,1], identified a cutoff for anosmia at a score ≤ 0.7. This cutoff, which marks the 90th percentile of scores obtained with randomly ordered dilutions, had a balanced accuracy of 89% (78% to 97%) for detecting anosmia, comparable to traditional odor threshold assessments. Retest evaluations suggested a score difference of ±0.15 as a cutoff for clinically significant changes in olfactory function. In conclusion, the olfactory sorting test represents a simple, self-administered approach to the detection of anosmia or preserved olfactory function. With balanced accuracy similar to existing brief olfactory tests, this method offers a practical and user-friendly alternative for screening anosmia, addressing the need for resource-efficient assessments in clinical settings.

Time-frequency analysis of gustatory event related potentials (gERP) in taste disorders.

In taste disorders, the key to a correct diagnosis and an adequate treatment is an objective assessment. Compared to psychophysical tests, EEG-derived gustatory event-related potentials (gERP) could be used as a less biased measure. However, the responses identified using conventional time-domain averaging show a low signal-to-noise ratio. This study included 44 patients with dysgeusia and 59 healthy participants, who underwent a comprehensive clinical examination of gustatory function. gERPs were recorded in response to stimulation with two concentrations of salty solutions, which were applied with a high precision gustometer. Group differences were examined using gERP analyzed in the canonical time domain and with Time-Frequency Analyses (TFA). Dysgeusic patients showed significantly lower scores for gustatory chemical and electrical stimuli. gERPs failed to show significant differences in amplitudes or latencies between groups. However, TFA showed that gustatory activations were characterized by a stronger power in controls than in patients in the low frequencies (0.1-4 Hz), and a higher desynchronization in the alpha-band (8-12 Hz). Hence, gERPs reflect the altered taste sensation in patients with dysgeusia. TFA appears to enhance the signal-to-noise ratio commonly present when using conventional time-domain averaging, and might be of assistance for the diagnosis of dysgeusia.

Diagnosed and subjectively perceived long-term effects of COVID-19 infection on olfactory function assessed by supervised machine learning.

Loss of olfactory function is a typical acute coronavirus disease 2019 (COVID-19) symptom, at least in early variants of SARS-CoV2. The time that has elapsed since the emergence of COVID-19 now allows for assessing the long-term prognosis of its olfactory impact. Participants (n = 722) of whom n = 464 reported having had COVID-19 dating back with a mode of 174 days were approached in a museum as a relatively unbiased environment. Olfactory function was diagnosed by assessing odor threshold and odor identification performance. Subjects also rated their actual olfactory function on an 11-point numerical scale [0,…10]. Neither the frequency of olfactory diagnostic categories nor olfactory test scores showed any COVID-19-related effects. Olfactory diagnostic categories (anosmia, hyposmia, or normosmia) were similarly distributed among former patients and controls (0.86%, 18.97%, and 80.17% for former patients and 1.17%, 17.51%, and 81.32% for controls). Former COVID-19 patients, however, showed differences in their subjective perception of their own olfactory function. The impact of this effect was substantial enough that supervised machine learning algorithms detected past COVID-19 infections in new subjects, based on reduced self-awareness of olfactory performance and parosmia, while the diagnosed olfactory function did not contribute any relevant information in this context. Based on diagnosed olfactory function, results suggest a positive prognosis for COVID-19-related olfactory loss in the long term. Traces of former infection are found in self-perceptions of olfaction, highlighting the importance of investigating the long-term effects of COVID-19 using reliable and validated diagnostic measures in olfactory testing.