A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss.

BACKGROUND: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. METHODS: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. RESULTS: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. CONCLUSIONS: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.

Configural memory of a blending aromatic mixture reflected in activation of the left orbital part of the inferior frontal gyrus.

Blending aromatic mixtures components naturally fuse to form a unique odor - a configuration- qualitatively different from each component's odor. Repeated exposure to the components either in the mixture or separately, favors respectively, configural and elemental processings. The neural bases of such processes are still unknown. We examined the brain correlates of the experienced-induced configural processing of a well-known model of binary blending odor mixture, the aromatic pineapple blending (AB, ethyl maltol + ethyl isobutyrate). Before fMRI recording, half of the participants were repeatedly exposed to the mixture (AB, group Gmix), with the other half exposed to its separate components (A and B; Gcomp). During the fMRI recording, all participants were stimulated with the mixture (AB) and the components (A and B). Finally, participants rated the number of odors perceived for each stimulus. Gmix perceived the AB mixture as less complex than did Gcomp. While Gcomp perceived the mixture as more complex than its components, Gmix did not. These results show the presence of experience-induced configural or elemental processing of the AB mixture in each group. Contrasting the brain activity of Gcomp and Gmix, when stimulated with AB, revealed higher activation in the left orbital part of the inferior frontal gyrus. This result sheds light on this area's function, commonly found activated in olfactory studies, and closely connected with the lateral orbitofrontal cortex. We discuss the role of this area as a mediator of configural percepts between temporal and orbitofrontal areas involved in configural memory processes.

Ham particle size influences saltiness perception in flans.

One major issue of the food industry is reducing sodium content while maintaining food acceptability and liking. Despite extensive research in this field, little has been published on real complex food products. The aim of this study was to investigate whether the size of particles, a parameter easily adjusted in food processing, could influence the salty taste of low-salt food product. We thus evaluated the effect of ham particle sizes (4 levels, including a zero level) on salt perception and the consumer liking of flans varying in their overall salt concentrations (low- and high-salt content). Two consumer panels, composed of 107 and 77 subjects, rated, respectively, the saltiness of and liking for the developed flans (8 samples). The outcomes of this study indicated first, that the addition of ham to flans increased the salty taste perception and second, that a decrease in ham particle size (ground ham) increased the perceived saltiness. Moreover, low- and high-salt flans were equally liked, demonstrating that food manufacturers could reduce the salt contents (here, by over 15%) while maintaining consumer acceptability through the manipulation of the size of the salt-providing particles.

Interactions of odorants with olfactory receptors and receptor neurons match the perceptual dynamics observed for woody and fruity odorant mixtures.

The present study aimed to create a direct bridge between observations on peripheral and central responses to odorant mixtures and their components. Three experiments were performed using mixtures of fruity (isoamyl acetate; ISO) and woody (whiskey lactone; WL) odorants known to contribute to some of the major notes in Burgundy red wine. These experiments consisted of (i) calcium imaging of human embryonic kidney cells (HEK293T) transfected with olfactory receptors (ORs); (ii) single-unit electrophysiological recordings from olfactory receptor neurons (ORNs) and analyses of electro-olfactogram (EOG) responses in the rat nose in vivo; and (iii) psychophysical measurements of the perceived intensity of the mixtures as rated by human subjects. The calcium imaging and electrophysiological results revealed that ISO and WL can act simultaneously on single ORs or ORNs and confirm that receptor responses to mixtures are not the result of a simple sum of the effects of the individual mixture compounds. The addition of WL to ISO principally suppressed the ORN activation induced by ISO alone and was found to enhance this activation in a subset of cases. In the human studies, the addition of high concentrations of WL to ISO decreased the perceived intensity of the ISO. In contrast, the addition of low concentrations of WL enhanced the perceived intensity of the fruity note (ISO) in this mixture, as it enhanced EOG responses in ORNs. Thus, both OR and ORN responses to ISO + WL mixtures faithfully reflected perceptual response changes, so the odour mixture information is set up after the peripheral stage of the olfactory system.

Perceptual blending in odor mixtures depends on the nature of odorants and human olfactory expertise.

Our olfactory system is confronted with complex mixtures of odorants, often recognized as single entities due to odor blending (e.g., coffee). In contrast, we are also able to discriminate odors from complex mixtures (e.g., off-odors). Therefore, the olfactory system is able to engage either configural or elemental processes when confronted with mixtures. However, the rules that govern the involvement of these processes during odor perception remain poorly understood. In our first experiment, we examined whether simple odorant mixtures (binary/ternary) could elicit configural perception. Twenty untrained subjects were asked to evaluate the odor typicality of mixtures and their constituents. The results revealed a significant increase in odor typicality in some but not all mixtures as compared with the single components, which suggest that perceptual odor blending can occur only in specific mixtures (configural processing). In our second experiment, we tested the hypothesis that general olfactory expertise can improve elemental perception of mixtures. Thirty-two trained subjects evaluated the odor typicality of the stimuli presented during the first experiment, and their responses were compared with those obtained from the untrained panelists. The results support the idea that general training with odors increases the elemental perception of binary and ternary blending mixtures.

Just noticeable differences in component concentrations modify the odor quality of a blending mixture.

The odors we perceive are mainly the result of mixtures of odorants that, however, are commonly perceived as single undivided entities; nevertheless, the processes involved remain poorly explored. It has been recently reported that perceptual blending based on configural olfactory processing can cause odorant mixtures to give rise to an emergent odor not present in the components. The present study examined whether specific component proportions are required to elicit an emergent odor. Starting from the composition of a ternary target mixture in which an emergent pineapple odor was perceived, 4 concentration levels of each component were chosen to elicit just noticeable differences (JNDs). Each combination of levels was used to design sample mixtures. Fifteen subjects evaluated the intensity, typicality, and pleasantness of each sample mixture against the target mixture in a paired-comparison protocol. Statistical modeling showed that a variation of less than 1 JND in one of the components was sufficient to induce a significant decrease in pineapple odor typicality in the ternary mixture. This finding confirms previous findings on perceptual blending in simple odorant mixtures and underscores the human ability to discriminate between odor percepts induced by mixtures including very similar odorant proportions.

Odor and color of cosmetic products: correlations between subjective judgement and autonomous nervous system response.

The color and odor of cosmetics have been shown to be crucial for affective states and able to influence autonomic responses. We report an original procedure to measure the effect on subjects of the color and odor of cosmetic products, and to quantify the correlation between objective (psychophysiological recording) and subjective (psychophysics) responses. Several cosmetic products (lipsticks and nail varnishes) of different colors (white, brown, red, orange, and pink) and odors (two per product) were presented. In a first step, autonomous parameters (skin conductance (SC) and heart rate (HR)) were recorded, and in the second step, subjects rated their sensations on subjective scales (overall appreciation, pleasantness, and emotional arousal). Results indicated that certain color and odor additives in cosmetics act on relaxation, excitation, perceived pleasantness, and emotional arousal. It was also found that certain colors, perceived as pleasant, decreased HR, and that the perception of an 'arousing' perfume significantly increased SC.

Modelling the human olfactory stimulus-response function.

Two models, derived from the equations of Michaelis-Menten and Hill, were adapted to olfaction. Their ability to model human olfactory stimulus-response relationships was compared with that of the classical laws of Fechner and Stevens. First, these four models were systematically compared on data available in the literature concerning 20 pure odorous compounds. At the lower concentrations of the odorous compound, the model of Stevens was found to be as good as the model of Hill. However, when the concentration range was extended further and included the concentration at half the maximum intensity, the model of Hill was found to be better. Second, the four models were tested on different parts of a true stimulus-response sigmoid curve with 5% noise added. The comparison confirmed the results obtained when experimental data were used. Third, the hypothesis that the psychophysical response is the sum of sigmoidal responses generated at the more peripheral parts of the olfactory system was examined, assuming a binomial distribution of receptor affinities. Within a very large range of variation in their characteristics, the sums of several sigmoids are indeed correctly modelled by Hill equations with exponents reflecting the distribution of receptor affinities.