Effects of genetics on odor perception: Can a quick smell test effectively screen everyone?

SCENTinel®, a rapid smell test designed to screen for olfactory disorders, including anosmia (no ability to smell an odor) and parosmia (distorted sense of smell), measures four components of olfactory function: detection, intensity, identification, and pleasantness. Each test card contains one of nine odorant mixtures. Some people born with genetic insensitivities to specific odorants (i.e., specific anosmia) may fail the test if they cannot smell an odorant but otherwise have a normal sense of smell. However, using odorant mixtures has largely been found to prevent this from happening. To better understand whether genetic differences affect SCENTinel® test results, we asked genetically informative adult participants (twins or triplets, N=630; singletons, N=370) to complete the SCENTinel® test. A subset of twins (n=304) also provided a saliva sample for genotyping. We examined data for differences between the nine possible SCENTinel® odors; effects of age, sex, and race on SCENTinel® performance, test-retest variability; and heritability using both structured equation modeling and SNP-based statistical methods. None of these strategies provided evidence for specific anosmia for any of the odors, but ratings of pleasantness were, in part, genetically determined (h2=0.40) and were nominally associated with alleles of odorant receptors (e.g., OR2T33 and OR1G1; p<0.001). These results provide evidence that using odorant mixtures protected against effects of specific anosmia for ratings of intensity but that ratings of pleasantness showed effects of inheritance, possibly informed by olfactory receptor genotypes.

Taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

Low to moderate genetic influences on the rapid smell test SCENTinel™.

SCENTinel™ - a rapid, inexpensive smell test that measures odor detection, intensity, identification, and pleasantness - was developed for population-wide screening of smell function. SCENTinel™ was previously found to screen for multiple types of smell disorders. However, the effect of genetic variability on SCENTinel™ test performance is unknown, which could affect the test's validity. This study assessed performance of SCENTinel™ in a large group of individuals with a normal sense of smell to determine the test-retest reliability and the heritability of SCENTinel™ test performance. One thousand participants (36 [IQR 26-52] years old, 72% female, 80% white) completed a SCENTinel™ test at the 2021 and 2022 Twins Days Festivals in Twinsburg, OH, and 118 of those completed a SCENTinel™ test on each of the festival's two days. Participants comprised 55% percent monozygotic twins, 13% dizygotic twins, 0.4% triplets, and 36% singletons. We found that 97% of participants passed the SCENTinel™ test. Test-retest reliability ranged from 0.57 to 0.71 for SCENTinel™ subtests. Broad-sense heritability, based on 246 monozygotic and 62 dizygotic twin dyads, was low for odor intensity (r=0.03) and moderate for odor pleasantness (r=0.4). Together, this study suggests that SCENTinel™ is a reliable smell test with only moderate heritability effects, which further supports its utility for population-wide screening for smell function.

Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19-related olfactory disorders.

It is estimated that 20%-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

The Adaptive Olfactory Measure of Threshold (ArOMa-T): a rapid test of olfactory function.

Many widely used psychophysical olfactory tests have limitations that can create barriers to adoption. For example, tests that measure the ability to identify odors may confound sensory performance with memory recall, verbal ability, and prior experience with the odor. Conversely, classic threshold-based tests avoid these issues, but are labor intensive. Additionally, many commercially available tests are slow and may require a trained administrator, making them impractical for use in situations where time is at a premium or self-administration is required. We tested the performance of the Adaptive Olfactory Measure of Threshold (ArOMa-T)-a novel odor detection threshold test that employs an adaptive Bayesian algorithm paired with a disposable odorant delivery card-in a non-clinical sample of individuals (n = 534) at the 2021 Twins Day Festival in Twinsburg, OH. Participants successfully completed the test in under 3 min with a false alarm rate of 7.5% and a test-retest reliability of 0.61. Odor detection thresholds differed by sex (~3.2-fold lower for females) and age (~8.7-fold lower for the youngest versus the oldest age group), consistent with prior studies. In an exploratory analysis, we failed to observe evidence of detection threshold differences between participants who reported a history of COVID-19 and matched controls who did not. We also found evidence for broad-sense heritability of odor detection thresholds. Together, this study suggests the ArOMa-T can determine odor detection thresholds. Additional validation studies are needed to confirm the value of ArOMa-T in clinical or field settings where rapid and portable assessment of olfactory function is needed.

Capturing high and low levels of participant engagement in sensory and consumer evaluations via a known groups design and an implicit correlate.

Recently developed to characterize consumer engagement during sensory and consumer testing, the Engagement Questionnaire (EQ) can quantify differences in participant engagement; however, the limits of the scale to detect disengagement has not been established. We conducted a known-group experimental design to verify the EQ's ability to differentiate between an engaged and disengaged participant. Participants were randomly assigned to a more engaging (positive condition) and a less engaging sensory task (negative condition). In the positive condition, participants (N = 31) completed 20 tetrad tests; however, stimuli varied in type and difficulty. For the negative condition, participants (N = 28) completed 20 tetrads of the same sucrose concentration to promote a state of helplessness and encourage disengagement with the task. Facial expressions were collected through video recordings, using automatic facial emotion recognition software (FaceReader, Noldus Technology). Accounting for sex differences across the conditions, the EQ successfully discriminated between the positive and negative conditions. When in the positive condition, participants were more actively involved in the task (F1,59 = 23.99, p < 0.001), and experienced higher levels of purposeful intent (F1,59 = 11.10, p = 0.002) and affective value (F1,59 = 26.03, p < 0.001). Participants were more emotive in general, and experienced increased happiness (F1,42 = 22.24, p < 0.001), anger (F1,42 = 12.10, p = 0.001) and disgust (F1,42 = 4.33, p = 0.04) as well as lower levels of a neutral expression (F1,42 = 24.88, p < 0.001) in the positive condition. Now validated via known-groups analysis, the EQ can confidently differentiate a greater range of engagement. Such an instrument allows for a deeper understanding of participant engagement and its potential effect on data quality.

Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19 related olfactory disorders.

It is estimated that 20-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of four possible odors. Those who completed the test (N = 381) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder (anosmia or hyposmia, N = 135), qualitative olfactory disorder (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

The Adaptive Olfactory Measure of Threshold (ArOMa-T): A rapid test of olfactory function.

PURPOSE: Many widely-used psychophysical tests of olfaction have limitations that can create barriers to adoption outside research settings. For example, tests that measure the ability to identify odors may confound sensory performance with memory recall, verbal ability, and past experience with the odor. Conversely, threshold-based tests typically avoid these issues, but are labor intensive. Additionally, many commercially available olfactory tests are slow and may require a trained administrator, making them impractical for use in a short wellness visit or other broad clinical assessment. METHODS: We tested the performance of the Adaptive Olfactory Measure of Threshold (ArOMa-T) -- a novel odor detection threshold test that employs an adaptive Bayesian algorithm paired with a disposable odor-delivery card -- in a non-clinical sample of individuals (n=534) at the 2021 Twins Day Festival in Twinsburg, OH. RESULTS: Participants successfully completed the test in under 3 min with a false alarm rate of 9.6% and a test-retest reliability of 0.61. Odor detection thresholds differed by sex (~3.2-fold) and between the youngest and oldest age groups (~8.7-fold), consistent with prior work. In an exploratory analysis, we failed to observe evidence of detection threshold differences between participants who reported a history of COVID-19 and matched controls who did not. We also found evidence for broad-sense heritability of odor detection thresholds. CONCLUSION: Together, these data indicate the ArOMa-T can determine odor detection thresholds. The ArOMa-T may be particularly valuable in clinical or field settings where rapid and portable assessment of olfactory function is needed.

Taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 241 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,897 COVID-19-positive patients, 39.2% reported taste dysfunction (95% confidence interval: 35.34%-43.12%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 18) versus self-report (n = 223) methodologies (Q = 0.57, df = 1, P = 0.45). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

Taste loss as a distinct symptom of COVID-19: A systematic review and meta-analysis.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19, taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 241 meeting all inclusion criteria. Additionally, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct prevalence measures of taste loss would be the most valid because they avoid the taste/smell confusion of self-report. The meta-analysis showed that, among 138,897 COVID-19-positive patients, 39.2% reported taste dysfunction (95% CI: 35.34-43.12%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 18) versus self-report (n = 223) methodologies (Q = 0.57, df = 1, p = 0.45). Generally, males reported lower rates of taste loss than did females and taste loss was highest in middle-aged groups. Thus, taste loss is a bona fide symptom COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

The genetics of eating behaviors: research in the age of COVID-19.

How much pleasure we take in eating is more than just how much we enjoy the taste of food. Food involvement - the amount of time we spend on food beyond the immediate act of eating and tasting - is key to the human food experience. We took a biological approach to test whether food-related behaviors, together capturing food involvement, have genetic components and are partly due to inherited variation. We collected data via an internet survey from a genetically informative sample of 419 adult twins (114 monozygotic twin pairs, 31 dizygotic twin pairs, and 129 singletons). Because we conducted this research during the pandemic, we also ascertained how many participants had experienced COVID-19-associated loss of taste and smell. Since these respondents had previously participated in research in person, we measured their level of engagement to evaluate the quality of their online responses. Additive genetics explained 16-44% of the variation in some measures of food involvement, most prominently various aspects of cooking, suggesting some features of the human food experience may be inborn. Other features reflected shared (early) environment, captured by respondents' twin status. About 6% of participants had a history of COVID-19 infection, many with transitory taste and smell loss, but all but one had recovered before the survey. Overall, these results suggest that people may have inborn as well as learned variations in their involvement with food. We also learned to adapt to research during a pandemic by considering COVID-19 status and measuring engagement in online studies of human eating behavior.

Non-food odors and the duality of smell: Impact of odorant delivery pathway and labeling convention on olfactory perception.

The olfactory system encompasses two perceptual pathways (orthonasal and retronasal) that activate the same receptors in the olfactory epithelium yet are thought to elicit different perceptions. Presently, a novel matching paradigm was employed using a non-food flavor set with low retronasal familiarity (honeysuckle, lavender, rose, and jasmine) to evaluate the effect of odor type on the Duality of Smell. Additionally, the influence of cognitive strategies used by subjects was assessed by manipulating the naming convention seen by the subjects: familiar (Honeysuckle, Lavender, Rose, Jasmine), unfamiliar (Inodora, Pedunculata, Beggeriana, Didymum), and generic (A, B, C, D). Subjects were presented with a reference, either in a vial (orthonasal delivery, ON) or a 2 oz. cup (retronasal delivery, RN) and instructed to match the same aroma from four unknowns, evaluated either by the same delivery route (congruent, e.g., ON-ON, RN-RN) or different route (incongruent, e.g., ON-RN, RN-ON) than the reference evaluation. All possible combinations of orthonasal and retronasal delivery for the reference and unknowns (e.g. ON-ON, RN-RN, ON-RN, RN-ON) were assessed by all subjects. Matching performance and signal detection measures indicated that, on average, subjects performed significantly better in the congruent conditions than in the incongruent conditions. These results suggest perceptual quality of aromas is route dependent and extend the Duality of Smell hypothesis to samples with low retronasal familiarity such as non-food odors. Labeling convention also had an impact on performance but, surprisingly, not in the direction anticipated. Indeed, as the information contained in the label decreased from familiar to generic reference names, performance increased. Moreover, depending on the labeling convention used, certain aromas were easier to match than others. The present research suggests odorant matching is a function of stimulus quality, cognitive strategy, and labeling convention.

Application of the Engagement Questionnaire (EQ) to compare methodological differences in sensory and consumer testing.

Understanding the panelist experience in sensory and consumer testing is a critical step in methodological development that improves data reliability. Therefore, the Engagement Questionnaire (EQ) was recently developed to characterize consumer engagement during sensory and consumer testing and to provide a novel and translatable metric for researchers to compare methodologies. Presently, we assessed whether relatively minor methodological manipulations to common consumer testing paradigms impact panelist engagement. Specifically, panelist engagement was measured in three scenarios: over the course of a two-day consumer hedonic evaluation (Experiment 1), with differing Just-About-Right (JAR) questionnaire formats in an evaluation (Experiment 2), and with a time pressure element imposed during a consumer acceptability test (Experiment 3). In Experiment 1, subjects remained actively involved in the evaluation across both days of testing, however, they found more purpose and affective value in the task after the second day. In Experiment 2, changing the structure of JAR questions did not impact subject's level of active involvement with the task, yet certain JAR question structures did elicit higher purposeful intent and affective value in subjects. Surprisingly, in Experiment 3, subjects were less actively involved in the time-pressure condition; purposeful intent and affective value were consistent across both conditions. Overall, the EQ was able to resolve differences in panelists' perceived level of engagement across all the experimental manipulations, aiding in discussion regarding the effect even minor manipulations might have on consumer panelists. The EQ is a valuable asset to methodological development and enables comparisons of differing sensory and consumer methodologies.

SCENTinel 1.0: Development of a Rapid Test to Screen for Smell Loss.

Commercially available smell tests are primarily used in research or in-depth clinical evaluations and are too costly and time-consuming for population surveillance in health emergencies like COVID-19. To address this need, we developed the SCENTinel 1.0 test, which rapidly evaluates 3 olfactory functions: detection, intensity, and identification. We tested whether self-administering the SCENTinel 1.0 test discriminates between individuals with self-reported smell loss and those with average smell ability (normosmic individuals) and provides performance comparable to the validated and standardized NIH Toolbox Odor Identification Test in normosmic individuals. Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1.0 performance of a group of self-reported anosmic individuals (N = 111, 47 ± 13 years old, F = 71%) and normosmic individuals (N = 154, 47 ± 14 years old, F = 74%) as well as individuals reporting other smell disorders (such as hyposmia or parosmia; N = 42, 55 ± 10 years old, F = 67%). Ninety-four percent of normosmic individuals met our SCENTinel 1.0 accuracy criteria compared with only 10% of anosmic individuals and 64% of individuals with other smell disorders. Overall performance on SCENTinel 1.0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC = 0.95, specificity = 0.94). Odor intensity provided the best single-feature predictor to classify normosmic individuals. Among normosmic individuals, 92% met the accuracy criteria at both SCENTinel 1.0 and the NIH Toolbox Odor Identification Test. SCENTinel 1.0 is a practical test able to discriminate individuals with smell loss and will likely be useful in many clinical situations, including COVID-19 symptom screening.

SCENTinel 1.0 : development of a rapid test to screen for smell loss.

BACKGROUND: Commercially available smell tests are primarily used in research or in-depth clinical evaluations, but are too costly and lengthy for population surveillance in health emergencies like COVID-19. We developed the SCENTinel 1 . 0 test which rapidly evaluates three olfactory functions (detection, intensity, and identification). We tested whether self-administering the SCENTinel 1 . 0 test discriminates between individuals with smell loss or average smell ability (normosmics), and provides comparable performance as the validated and standardized NIH Toolbox ® Odor Identification Test in normosmics. METHODS: Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1 . 0 performance of a group of self-reported anosmics (N=111, 47±13yo, F=71%,) and normosmics (N=154, 47±14yo, F=74%), as well as individuals reporting other smell disorders (e.g., hyposmia, parosmia; N=42, 55±10yo, F=67%). RESULTS: Ninety-four percent of normosmics met our SCENTinel 1 . 0 accuracy criteria, while only 10% of anosmics and 64% of individuals with other smell disorders did. Overall performance on SCENTinel 1 . 0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC=0.95, Sensitivity=0.72, Specificity=0.94). Odor intensity provided the best single-feature predictor to classify normosmics. Among normosmics, 92% met the accuracy criteria at both SCENTinel 1 . 0 and the NIH Toolbox ® Odor Identification Test. CONCLUSIONS: SCENTinel 1 . 0 is a practical test able to discriminate individuals with smell loss and is likely to be useful in many clinical situations, including COVID-19 symptom screening.

Objective Sensory Testing Methods Reveal a Higher Prevalence of Olfactory Loss in COVID-19-Positive Patients Compared to Subjective Methods: A Systematic Review and Meta-Analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify the causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords "COVID-19," "smell," and/or "olfaction." We included any study that quantified smell loss (anosmia and hyposmia) as a symptom of COVID-19. Studies were grouped and compared based on the type of method used to measure smell loss-subjective measures, such as self-reported smell loss, versus objective measures using rated stimuli-to determine if prevalence differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbances. We identified 34 articles quantifying anosmia as a symptom of COVID-19 (6 objective and 28 subjective), collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4-89.2%) and 44% with subjective measurements (95% CI of 32.2-57.0%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2; the use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss.

Objective sensory testing methods reveal a higher prevalence of olfactory loss in COVID-19-positive patients compared to subjective methods: A systematic review and meta-analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence, from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords "COVID-19," "smell," and/or "olfaction." We included any study that quantified olfactory loss as a symptom of COVID-19. Studies were grouped and compared based on the type of method used to measure smell loss-subjective measures such as self-reported smell loss versus objective measures using rated stimuli-to determine if prevalence rate differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbance rates. We identified 34 articles quantifying anosmia as a symptom of COVID-19, collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4-89.2%) and 45% with subjective measurements (95% CI of 31.1-58.5%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2; the use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss.