Introduction: Olfactory dysfunction is a common symptom of COVID-19. However, subjective perception of olfactory function does not always correlate well with more objective measures. This study seeks to clarify associations between subjective and psychophysical measures of olfaction and gustation in patients with subjective chemosensory dysfunction following COVID-19. Methods: Adults with persistent COVID-19-associated chemosensory disturbance were recruited for a prospective, longitudinal cohort study at a tertiary care institution. Participants provided subjective measures of olfactory and gustatory function and underwent psychophysical assessment using Sniffin’ Sticks olfactory and Monell gustatory tests. Results: Data analysis (n = 65) showed a statistically significant association between subjective and psychophysical measures of olfaction (p < 0.001). For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.11 (95% CI: 0.06, 0.16; p < 0.001) point increase in TDI score while adjusting for age at baseline assessment, sex, and follow-up time. For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.04 (95% CI: 0.02, 0.06; p < 0.001) point and 0.05 (95% CI: 0.03, 0.07; p < 0.001) point increase in discrimination and identification scores, respectively, when adjusting for age at baseline assessment, sex, and follow-up time. Conclusion: Subjective olfaction shows a mild to moderate association with psychophysical measures, but it fails to comprehensively assess persistent COVID-19-associated chemosensory deficits. The lack of significant association between subjective olfaction and threshold limits the utility of subjective olfaction in tracking recovery. These findings support the push for more widespread psychophysical chemosensory testing.

COVID-19 causes both short-term and long-term morbidity across various organ systems [1‒3], with chemosensory dysfunction remaining a hallmark feature in both acute and chronic COVID-19 [4, 5]. Early reports associating olfactory loss with acute COVID-19 [6, 7] have evolved into tracking the prevalence of persistent olfactory dysfunction (OD) [8]. Although OD has a diagnostic role for acute COVID-19, studies have reported varying estimates of sensitivity and specificity [9‒12]. Diagnosis of persistent OD is limited by variability in individual perception of olfactory function, but patient-reported, or subjective, olfactory and gustatory function remains the mainstay of chemosensory evaluation. Subjective function is easy to assess, time-efficient, and cost effective with options ranging from clinical interview to formal survey. However, psychophysical assessment of olfaction typically requires considerable resources: more time, equipment, and person power [13, 14].

Individual perception of chemosensory function is multifactorial: though many individuals correctly report the degree of olfactory and gustatory dysfunction they experience, certain factors make predicting the true degree of dysfunction difficult, including older age and cold symptoms [15]. Additionally, impairment in olfaction can easily be misattributed to gustatory dysfunction due to the perception of retronasal olfaction as gustation [16, 17]. Among patients with COVID-induced OD, the method of olfactory assessment accounted for notable differences in prevalence, where studies using subjective measures of olfactory function suggested a 44.4% prevalence of olfactory loss and those using psychophysical measures suggested a 76.7% prevalence [18]. These data propose that isolated subjective assessment may underestimate the true prevalence of OD in COVID-19 patients. Further complicating estimation of the prevalence of persistent OD following COVID-19 are the different types of OD: quantitative dysfunction or alteration in perceived strength of an odor, and qualitative dysfunction or alteration in perception of odor character [19]. Options for assessing qualitative olfactory function remain largely limited to subjective assessments, which have been shown to be particularly useful in assessing this type of OD [20].

Utility of psychophysical testing, like Sniffin’ Sticks, largely depends on its ability to provide more objective assessment of olfaction than widely used subjective measures [21]. The objectivity of various olfactory assessments has been previously examined in the literature. Mori et al. [22] examined the association between the open essence scent identification test card and other conventional olfactory assessments widely used in Japan, including visual analog scale (VAS), and found a statistically significant correlation among the varying tests.

Though numerous studies have attempted to evaluate olfactory loss as a diagnostic indicator of COVID-19 infection [9, 10], few have examined the association of subjective and psychophysical measures of olfactory function over time in this patient population. This study seeks to clarify the association between subjective and psychophysical measures of olfaction and gustation among individuals with self-reported persistent OD after COVID-19 infection.

Participants and Study Design

Study participants were recruited by the CommonScents Research Group as part of an NIH-funded, prospective, longitudinal cohort study examining the relationship between chemosensation and neurocognition (NIH/NIDCD:K23DC019678-01). Participants entered the study following rhinology clinic referral on the basis of self-reported OD for more than 3 months, by volunteering through the online RecruitMe platform hosted by Columbia University Irving Medical Center (CUIMC), or by responding to posted flyers on the greater CUIMC campus. Informed consent was obtained from all participants. All recruitment and research practices were approved by the Institutional Review Board through the Human Research Protection Office at CUIMC (protocol AAAT6202).

This study included any adults with a personal history of COVID-19 confirmed by PCR testing or infection-specific serology. All participants had self-reported olfactory or gustatory dysfunction present for over 3 months. Participants with a history of preexisting OD, chronic rhinosinusitis, neurological disease, severe head trauma, a SNOT-22 rhinologic subdomain score of greater than 21, an answer of “severe” or worse for any SNOT-22 item, or an olfactory cleft endoscopy score (OCES) indicating probable rhinologic disease were excluded from this analysis [23].

Survey and Subjective Chemosensory Measures

Each participant completed a comprehensive survey, providing demographic information and sensory self-evaluation. Participants were asked to provide date of birth and sex assigned at birth. They were also asked to rate their senses of olfaction and gustation on a VAS from zero to 100 with zero as no sense of olfaction/gustation and 100 as an excellent sense of olfaction/gustation. Participants completed the survey portion of the study online utilizing the REDCap data management system prior to each in-person visit at zero and 1 year from initial intake, with select participants reporting for additional interval testing at 4 months (n = 36) and 8 months (n = 7) after baseline assessment. Sensory self-evaluation was completed prior to each round of in-person assessment.

Psychophysical Chemosensory Evaluation

After online intake, participants underwent in-person chemosensory psychophysical testing using Sniffin’ Sticks olfactory (Burghart Messtechnik GmbH, Holm, Germany) and Monell gustatory tests. Individuals attended initial baseline and follow-up visits at zero and 1 year from initial intake, with select participants reporting for additional interval testing at 4 months and 8 months after baseline assessment.

Participants underwent olfactory evaluation with Sniffin’ Sticks, a psychophysical clinical examination that assesses olfactory function via three distinct olfactory tests: threshold (T), discrimination (D), and identification (I) [13, 24]. Normosmia is defined as a total TDI score greater than 30.75 out of a total possible score of 48. Hyposmia is defined as less than or equal to 30.75 but greater than 16.25. Anosmia is any score less than or equal to 16 [25].

Gustatory evaluation was achieved with a brief gustation test developed at the Monell Chemical Sciences Center. Participants had to taste six different compounds twice for a total of 12 tastings and identify each via a forced-choice paradigm [14]. Performance was graded by the number of correct identifications out of a total possible score of 12.

Statistical Analysis

Descriptive statistics were summarized as frequencies and proportions for categorical variables and means and standard deviations for continuous variables. Generalized estimating equation (GEE) models with exchangeable covariance matrices were utilized to analyze the association between predictors and outcomes in order to account for the correlation between subjects’ repeated measurements. For modeling, both predictors and outcomes were treated as continuous, using the normal distribution and the identity link function. The distribution of the residuals for each model was used to identify any potential outliers and assess model fit. If initial outliers were found, analyses were rerun after censoring outliers by setting them to missing. Models were adjusted for time (i.e., follow-up visit), age at baseline assessment, and sex at birth. The beta coefficient and 95% confidence interval of the predictor’s main effect were reported from both unadjusted and adjusted models, while the main effect of time was reported from the adjusted models. The predictor-by-time interaction terms were also evaluated but not reported unless found to be statistically significant. Partial R2 values for the predictors were also evaluated for each model. Lastly, analyses of score components were also conducted if the overall score was found to be significant in the adjusted model. All analyses were carried out using SAS version 9.4. All statistical tests were two-sided and used a p < 0.05 to determine statistical significance.

Participant characteristics and demographics are shown in Table 1. The sample cohort (n = 65) is comprised predominantly of individuals experiencing persistent OD following COVID illness prior to vaccination availability and not requiring hospitalization during the initial phase of the pandemic in 2020. Timing of illness for this cohort closely follows emergence of the SARS-CoV-2 B-type virus and subsequent variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) [26, 27]. Baseline chemosensory measures for the cohort are summarized in Table 2. Beta estimates from GEE analysis demonstrated a statistically significant association between subjective and psychophysical measures of olfaction. For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.11 (95% CI: 0.06, 0.16; p < 0.001) point increase in TDI score while adjusting for age at baseline assessment, sex, and follow-up time. Additionally, subjectively-reported olfactory ability can explain 14% of the variance beyond that of time, age at baseline assessment, and sex assigned at birth for psychophysical olfactory score. Overall associations between subjective and psychophysical chemosensory measures are summarized in Table 3 and Figure 1. When looking at each individual component of the TDI score, there are statistically significant associations between both the discrimination and identification domains and subjectively-reported olfaction. For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.04 (95% CI: 0.02, 0.06; p < 0.001) point and 0.05 (95% CI: 0.03, 0.07; p < 0.001) point increase in discrimination and identification scores, respectively, when adjusting for age at baseline assessment, sex, and follow-up time. Associations between subjective olfaction and each component of the TDI score are detailed in Table 4 and Figures 2-4.

Table 1.

Demographics

Overall, subjective smell dysfunction (n = 65)Semi-objective normosmia (n = 16)aSemi-objective hyposmia (n = 45)bSemi-objective anosmia (n = 4)c
Age at baseline assessment 
 Mean (SE) 42.78 (1.88) 38.39 (2.97) 43.31 (2.21) 54.41 (11.81) 
Sex assigned at birth, n (%) 
 Female 45 (69.2) 12 (75.0) 32 (71.1) 1 (25.0) 
 Male 20 (30.8) 4 (25.0) 13 (28.9) 3 (75.0) 
Race, n (%) 
 American Indian/Alaska Native 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 
 Asian 4 (6.2) 2 (12.5) 2 (4.4) 0 (0.0) 
 Native Hawaiian or other Pacific Islander 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 
 Black or African American 5 (7.7) 0 (0.0) 5 (11.1) 0 (0.0) 
 White 42 (64.6) 9 (56.3) 29 (64.4) 4 (100.0) 
 More than one race 10 (15.4) 3 (18.8) 7 (15.6) 0 (0.0) 
 Unknown or not reported 4 (6.2) 2 (12.5) 2 (4.4) 0 (0.0) 
Ethnicity, n (%) 
 Hispanic 16 (24.6) 3 (18.8) 13 (28.9) 0 (0.0) 
 Non-Hispanic or not reported 49 (75.4) 13 (81.2) 32 (71.1) 4 (100) 
Chronic health conditions, n (%) 
 Hypertension 6 (9.2) 1 (6.3) 4 (8.9) 1 (25.0) 
 Chronic lung disease 6 (9.2) 2 (12.5) 4 (8.9) 0 (0.0) 
 Other 11 (16.9) 1 (6.3) 9 (20.0) 1 (25.0) 
 None or not reported 42 (64.6) 12 (75.0) 28 (62.2) 2 (50.0) 
Tobacco use, n (%) 
 Active 2 (3.1) 1 (6.3) 1 (2.2) 0 (0.0) 
 Former 13 (20.0) 3 (18.7) 10 (22.2) 0 (0.0) 
 None or not reported 50 (76.9) 12 (75.0) 34 (75.6) 4 (100) 
Level of education, n (%) 
 Less than high school 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 
 High school 5 (7.7) 1 (6.3) 4 (8.9) 0 (0.0) 
 College 30 (46.2) 5 (31.2) 23 (51.1) 2 (50.0) 
 Advanced degree 29 (44.6) 9 (56.3) 18 (40.0) 2 (50.0) 
 Unknown or not reported 1 (1.5) 1 (6.3) 0 (0.0) 0 (0.0) 
Vaccinated at time of smell loss, n (%) 
 Yes 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 
 No 65 (100) 16 (100) 45 (100) 4 (100) 
Perceived COVID-19 severity, n (%) 
 Substantially less severe 26 (40.0) 6 (37.5) 18 (40.0) 2 (50.0) 
 Slightly less severe 12 (18.5) 5 (31.2) 7 (15.5) 0 (0.0) 
 Same as others 7 (10.8) 1 (6.3) 6 (13.3) 0 (0.0) 
 Slightly more severe 10 (15.4) 1 (6.3) 8 (17.8) 1 (25.0) 
 Substantially more severe 4 (6.1) 1 (6.3) 3 (6.7) 0 (0.0) 
 Unknown or not reported 6 (9.2) 2 (12.5) 3 (6.7) 1 (25.0) 
Hospitalization, n (%) 
 Yes 4 (6.2) 1 (6.3) 3 (6.7) 0 (0.0) 
 No or not reported 61 (93.8) 15 (93.7) 42 (93.3) 4 (100) 
Days of olfactory dysfunction 
 Mean (SE) 368.35 (19.71) 381.07 (31.75) 362.38 (24.88) 388.67 (119.42) 
Depression, n (%) 
 Yesd 22 (33.8) 6 (37.5) 15 (33.3) 1 (25.0) 
 No or not assessed 43 (66.2) 10 (62.5) 30 (66.7) 3 (75.0) 
Overall, subjective smell dysfunction (n = 65)Semi-objective normosmia (n = 16)aSemi-objective hyposmia (n = 45)bSemi-objective anosmia (n = 4)c
Age at baseline assessment 
 Mean (SE) 42.78 (1.88) 38.39 (2.97) 43.31 (2.21) 54.41 (11.81) 
Sex assigned at birth, n (%) 
 Female 45 (69.2) 12 (75.0) 32 (71.1) 1 (25.0) 
 Male 20 (30.8) 4 (25.0) 13 (28.9) 3 (75.0) 
Race, n (%) 
 American Indian/Alaska Native 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 
 Asian 4 (6.2) 2 (12.5) 2 (4.4) 0 (0.0) 
 Native Hawaiian or other Pacific Islander 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 
 Black or African American 5 (7.7) 0 (0.0) 5 (11.1) 0 (0.0) 
 White 42 (64.6) 9 (56.3) 29 (64.4) 4 (100.0) 
 More than one race 10 (15.4) 3 (18.8) 7 (15.6) 0 (0.0) 
 Unknown or not reported 4 (6.2) 2 (12.5) 2 (4.4) 0 (0.0) 
Ethnicity, n (%) 
 Hispanic 16 (24.6) 3 (18.8) 13 (28.9) 0 (0.0) 
 Non-Hispanic or not reported 49 (75.4) 13 (81.2) 32 (71.1) 4 (100) 
Chronic health conditions, n (%) 
 Hypertension 6 (9.2) 1 (6.3) 4 (8.9) 1 (25.0) 
 Chronic lung disease 6 (9.2) 2 (12.5) 4 (8.9) 0 (0.0) 
 Other 11 (16.9) 1 (6.3) 9 (20.0) 1 (25.0) 
 None or not reported 42 (64.6) 12 (75.0) 28 (62.2) 2 (50.0) 
Tobacco use, n (%) 
 Active 2 (3.1) 1 (6.3) 1 (2.2) 0 (0.0) 
 Former 13 (20.0) 3 (18.7) 10 (22.2) 0 (0.0) 
 None or not reported 50 (76.9) 12 (75.0) 34 (75.6) 4 (100) 
Level of education, n (%) 
 Less than high school 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 
 High school 5 (7.7) 1 (6.3) 4 (8.9) 0 (0.0) 
 College 30 (46.2) 5 (31.2) 23 (51.1) 2 (50.0) 
 Advanced degree 29 (44.6) 9 (56.3) 18 (40.0) 2 (50.0) 
 Unknown or not reported 1 (1.5) 1 (6.3) 0 (0.0) 0 (0.0) 
Vaccinated at time of smell loss, n (%) 
 Yes 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 
 No 65 (100) 16 (100) 45 (100) 4 (100) 
Perceived COVID-19 severity, n (%) 
 Substantially less severe 26 (40.0) 6 (37.5) 18 (40.0) 2 (50.0) 
 Slightly less severe 12 (18.5) 5 (31.2) 7 (15.5) 0 (0.0) 
 Same as others 7 (10.8) 1 (6.3) 6 (13.3) 0 (0.0) 
 Slightly more severe 10 (15.4) 1 (6.3) 8 (17.8) 1 (25.0) 
 Substantially more severe 4 (6.1) 1 (6.3) 3 (6.7) 0 (0.0) 
 Unknown or not reported 6 (9.2) 2 (12.5) 3 (6.7) 1 (25.0) 
Hospitalization, n (%) 
 Yes 4 (6.2) 1 (6.3) 3 (6.7) 0 (0.0) 
 No or not reported 61 (93.8) 15 (93.7) 42 (93.3) 4 (100) 
Days of olfactory dysfunction 
 Mean (SE) 368.35 (19.71) 381.07 (31.75) 362.38 (24.88) 388.67 (119.42) 
Depression, n (%) 
 Yesd 22 (33.8) 6 (37.5) 15 (33.3) 1 (25.0) 
 No or not assessed 43 (66.2) 10 (62.5) 30 (66.7) 3 (75.0) 

Psychophysical testing classification is as follows:

aNormosmia TDI >30.75.

bHyposmia 30.75 ≥ TDI >16.25.

cAnosmia TDI ≤16.25.

dPHQ-9: yes, for score >4.

Table 2.

Baseline olfaction and gustation scores

Baseline olfaction and gustation scores (possible range)Mean±SD (n = 65)
TDI (1–48) 26.2±6.1 
Threshold (1–16) 5.5±2.9 
Discrimination (0–16) 10.9±2.6 
Identification (0–16) 9.8±2.4 
Subjective olfaction (0–100) 44.8±18.0 
Subjective gustation (0–100) 47.6±24.5 
Taste Test (0–12) 10.0±1.9 
Baseline olfaction and gustation scores (possible range)Mean±SD (n = 65)
TDI (1–48) 26.2±6.1 
Threshold (1–16) 5.5±2.9 
Discrimination (0–16) 10.9±2.6 
Identification (0–16) 9.8±2.4 
Subjective olfaction (0–100) 44.8±18.0 
Subjective gustation (0–100) 47.6±24.5 
Taste Test (0–12) 10.0±1.9 
Table 3.

Beta estimates from generalized estimating equation (GEE) analyses examining the various associations between subjective & semi-objective olfaction and gustation

Predictor and outcomeMain effect of predictorMain effect of timeInteraction p valueb
unadjusted beta (95% CI)p valueadjusted beta (95% CI)ap valuepartial R2 for predictoradjusted beta (95% CI)ap value
Association between subjective olfaction and semi-objective olfaction 0.10 (0.05, 0.16) <0.001 0.11 (0.06, 0.16) <0.001 0.14 2.95 (1.00, 4.89) 0.003 0.281 
Association between subjective gustation and semi-objective gustation −0.0007 (−0.0126, 0.0111) 0.902 −0.0034 (−0.0178, 0.0111) 0.649 0.02 0.25 (−0.36, 0.86) 0.425 0.966 
Association between semi-objective olfaction and semi-objective gustation 0.0115 (−0.0558, 0.0789) 0.737 −0.0001 (−0.0751, 0.0749) 0.997 −0.00 0.22 (−0.38, 0.82) 0.475 0.481 
Association between subjective gustation and semi-objective olfaction 0.05 (0.00, 0.10) 0.034 0.04 (−0.01, 0.08) 0.119 0.01 2.62 (0.66, 4.58) 0.009 0.815 
Predictor and outcomeMain effect of predictorMain effect of timeInteraction p valueb
unadjusted beta (95% CI)p valueadjusted beta (95% CI)ap valuepartial R2 for predictoradjusted beta (95% CI)ap value
Association between subjective olfaction and semi-objective olfaction 0.10 (0.05, 0.16) <0.001 0.11 (0.06, 0.16) <0.001 0.14 2.95 (1.00, 4.89) 0.003 0.281 
Association between subjective gustation and semi-objective gustation −0.0007 (−0.0126, 0.0111) 0.902 −0.0034 (−0.0178, 0.0111) 0.649 0.02 0.25 (−0.36, 0.86) 0.425 0.966 
Association between semi-objective olfaction and semi-objective gustation 0.0115 (−0.0558, 0.0789) 0.737 −0.0001 (−0.0751, 0.0749) 0.997 −0.00 0.22 (−0.38, 0.82) 0.475 0.481 
Association between subjective gustation and semi-objective olfaction 0.05 (0.00, 0.10) 0.034 0.04 (−0.01, 0.08) 0.119 0.01 2.62 (0.66, 4.58) 0.009 0.815 

aModels were adjusted for age at baseline, sex, and follow-up time.

bInteraction p values are for the interaction between the main predictor of interest and time while still adjusting for age at baseline and sex.

Fig. 1.

Scatter plot, with regression line, for association between subjective olfaction and psychophysical olfaction (TDI score, p < 0.001).

Fig. 1.

Scatter plot, with regression line, for association between subjective olfaction and psychophysical olfaction (TDI score, p < 0.001).

Close modal
Table 4.

Beta estimates from generalized estimating equation (GEE) analyses examining the association between subjective olfaction & semi-objective olfaction (TDI total score) components

Response variableUnadjusted beta (95% CI)p valueAdjusted beta (95% CI)ap valueInteraction p valueb
Mean threshold 0.02 (−0.01, 0.05) 0.156 0.02 (−0.01, 0.06) 0.246 0.256 
Discrimination score 0.04 (0.01, 0.06) 0.006 0.04 (0.02, 0.06) <0.001 0.731 
Identification 0.05 (0.03, 0.07) <0.001 0.05 (0.03, 0.07) <0.001 0.390 
Response variableUnadjusted beta (95% CI)p valueAdjusted beta (95% CI)ap valueInteraction p valueb
Mean threshold 0.02 (−0.01, 0.05) 0.156 0.02 (−0.01, 0.06) 0.246 0.256 
Discrimination score 0.04 (0.01, 0.06) 0.006 0.04 (0.02, 0.06) <0.001 0.731 
Identification 0.05 (0.03, 0.07) <0.001 0.05 (0.03, 0.07) <0.001 0.390 

aModels were adjusted for baseline age, sex, and follow-up time.

bInteraction p values are for the interaction between the main predictor of interest and time while still adjusting for baseline age and sex.

Fig. 2.

Scatter plot, with regression line, for association between subjective olfaction and threshold score (not statistically significant).

Fig. 2.

Scatter plot, with regression line, for association between subjective olfaction and threshold score (not statistically significant).

Close modal
Fig. 3.

Scatter plot, with regression line, for association between subjective olfaction and discrimination score (p < 0.001).

Fig. 3.

Scatter plot, with regression line, for association between subjective olfaction and discrimination score (p < 0.001).

Close modal
Fig. 4.

Scatter plot, with regression line, for association between subjective olfaction and identification score (p < 0.001).

Fig. 4.

Scatter plot, with regression line, for association between subjective olfaction and identification score (p < 0.001).

Close modal

Additionally, the main effect of time was found to be statistically significant when modeling the association between subjectively-reported olfactory ability and psychophysical olfactory score (AEst = 2.95, 95% CI: 1.00, 4.89; p = 0.003), and when modeling the association between subjectively-reported gustation and psychophysical olfactory score (AEst = 2.62, 95% CI: 0.66, 4.58; p = 0.009). Analysis of the interaction between the main effect of the predictor and the main effect of time was not statistically significant for any of the associations listed in Table 3.

Univariable analysis also showed a statistically significant association between subjectively-reported gustation and psychophysical olfactory score, but this association was no longer present after adjusting for age at baseline assessment, sex, and follow-up time. There was no statistically significant association between subjectively-reported gustation and psychophysical gustatory score or between psychophysical measures of olfaction and gustation, which remained unchanged when re-running analyses after censoring outliers.

Olfaction

The results of our study suggest an association between subjective report of olfactory function and the cumulative score from psychophysical testing. Additionally, the general subjective rating of olfactory function is associated with the discrimination and identification subdomains of the psychophysical testing, but not with the threshold subdomain. These findings demonstrate the utility of including patients’ subjective olfactory function within an overall evaluation; however, the inability to accurately self-report threshold may limit the utility of trending subjective olfactory function for recovery.

Similar to our results, a study conducted before the COVID-19 pandemic found that the rating of olfactory function on a VAS among patients with OD secondary to chronic rhinosinusitis, infection, or prior head trauma tracked with significant correlation to total Sniffin’ Sticks score (TDI) [28]. However, it was found that subjective VAS scores were significantly associated with all subdomains of the Sniffin’ Sticks assessment. In our study, subjective olfactory function was significantly associated with discrimination and identification subdomains, but not threshold. In a separate study looking specifically at patients with olfactory loss related to COVID-19, Bordin et al. [29] also found a significant correlation between VAS scores and Sniffin’ Sticks TDI scores at 6 months after their COVID diagnosis. These studies, along with our findings, suggest that subjective olfactory loss may be a reliable measure to provide a rough estimate of a person’s overall olfactory function. However, our study highlights a potential shortcoming of subjective olfactory report. It is also important to note that many psychophysical tests are predicated on odor recognition but lack the ability to classify olfactory threshold, highlighting a need for thoughtful selection of olfactory testing methods [30].

Prajapati et al. [31] found a correlation between subjective olfactory function and identification scores using the BSIT, and Jang et al. [15] found that the majority of people in their study were able to accurately assess their sense of olfaction with assessment of identification only. Our results similarly demonstrated a significant relationship between identification and subjective olfactory function; but, by including comprehensive psychophysical testing in our study design, we are able to highlight a specific caveat: that threshold is not associated with a person’s subjective reporting of their olfactory function in our post-COVID-19 patient population. There have been mixed results in the previous literature regarding the association between subjective olfactory scores and psychophysical threshold scores. Philpott et al. [32] found no correlation between threshold and subjective olfactory scores among patients with subjectively normal olfaction. The results of our study and from the prior literature demonstrate the importance of conducting full psychophysical olfactory testing in order to adequately assess threshold.

The neurocognitive underpinnings of olfaction remain relatively understudied [33, 34]. Prior research has shown significant cognitive influence on discrimination and identification domains of olfaction but not on threshold [35]. These findings may provide insight into why participants’ subjective assessments of olfaction are significantly correlated with only discrimination and identification. More research is needed to understand the relationship between olfaction and neurocognition and how that relationship may affect other cognitive domains.

Gustation

The findings of this study showed no significant associations between subjective and psychophysical gustation, psychophysical olfaction and gustation, and subjective gustation and psychophysical olfaction. While patients often report new onset loss of olfaction and gustation with COVID-19 infection, the main chemosensory deficit may exist in the olfactory domain [36]. Olfaction and gustation are part of a collective chemosensory system that combines multimodal input into a unified perception of flavor, making it difficult for an individual to localize chemosensory loss to any one particular domain [37, 38]. Despite the lack of statistically significant findings in the current study while controlling for baseline age, sex, and follow-up time, there was a statistically significant association between subjective gustation and psychophysical olfaction when disregarding these covariates. It is possible that subjective gustatory loss can be explained by psychophysical OD; however, recent research suggests the presence of isolated gustatory deficits secondary to COVID-19 [39, 40]. Further work is needed to determine the relative contributions of the distinct chemosensory systems to the overall deficits in this population.

Chemosensory Dysfunction over Time

Studies examining the persistence of OD over time have shown mixed results: some studies suggest that over time individuals became less aware of their OD, while others suggest that subjective OD persists long beyond resolution of acute infection [29, 41‒43]. In this study, the main effect of time analysis suggests that individuals significantly improved in their psychophysical olfactory scores while adjusting for subjective olfactory scores, age at baseline, and sex. However, there were no statistically significant findings in analyzing the interaction between the predictor and the main effect of time as detailed in Table 3; thus, the results of this study cannot make any claims on whether the associations between subjective and psychophysical measures change over time. More research is needed to understand how insight into one’s psychophysical chemosensory scores may affect subsequent perception of olfactory loss, and what implications these factors have for future quality of life assessments. Although for recruitment purposes, inclusion criteria were set for individuals with at least 3 months of self-reported persistent OD, our population purposely skews toward a more chronic phenotype, as spontaneous recovery occurs at diminishing rates over the course of the initial year [8, 44].

Limitations and Future Directions

The present study has limitations. Many of the participants had OD after infection with the B-type SARS-CoV-2 strain and early stage variants. Frequency and severity of chemosensory dysfunction secondary to later variants may differ from these initial strains [45‒47], but chemosensory changes remain a substantial issue across recent variants and subvariants as well as after vaccination [48, 49]. Additionally, unavailability of baseline chemosensory function prior to COVID-19 limits the true evaluation of chemosensory function over time; however, all participants met strict criteria for participation, including antecedent subjective changes in chemosensation. Finally, due to limited sample size, analysis may fail to show underlying associations.

In pursuit of future work, research assessing chemosensation is particularly needed in a racially and ethnically diverse population. This population is particularly important given the disproportionate effect that the COVID-19 pandemic has had on ethnic and racial minorities [50]. Also, in order to inform clinical practice and future psychophysical testing design, further research is needed to elucidate specific factors that contribute to differences between subjective and psychophysical measures of chemosensation. Finally, commitment of chemosensation researchers to a standardization of terminology used to describe OD would be beneficial in streamlining the literature and providing a framework for future scoping and systematic reviews [51].

This study supports the overall association between subjective perception of chemosensory functioning and more comprehensive psychophysical testing results. Utilizing psychophysical chemosensory testing inclusive of threshold assessment is necessary to facilitate recovery trending and for the assessment of true chemosensory function in patients with COVID-19-associated chemosensory dysfunction.

We would like to thank the NIDCD for supporting this research. Study data were collected and managed using REDCap electronic data capture tools hosted at Columbia University [52, 53]. REDCap (Research Electronic Data Capture) is a secure, web-based software platform designed to support data capture for research studies, providing (1) an intuitive interface for validated data capture; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for data integration and interoperability with external sources.

This study protocol was reviewed and approved by the Institutional Review Board through the Human Research Protection Office at CUIMC, protocol number AAAT6202. Written informed consent was obtained from participants through REDCap [54].

The authors have no conflicts of interest to declare.

This project was funded by the NIDCD of the National Institutes of Health under grant K23DC019678-01. This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

B.J.V. and P.T.J. coordinated the study, performed data collection, and wrote the manuscript. C.J.S. and T.-H.C. performed statistical analyses and wrote the statistical methods. L.W.G., F.F.C., J.P.T., and J.B.G. conceptualized the project, led initial data collection, and reviewed the manuscript. T.M.S. continued data collection and reviewed the manuscript. D.A.G. and P.V.J. reviewed and revised the manuscript. T.E.G. and D.P.D. developed methodology, oversaw the project, and reviewed the manuscript. J.B.O. led, managed, and coordinated the project and wrote the manuscript.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

1.
Sudre
CH
,
Murray
B
,
Varsavsky
T
,
Graham
MS
,
Penfold
RS
,
Bowyer
RC
, et al
.
Attributes and predictors of long COVID
.
Nat Med
.
2021
;
27
(
4
):
626
31
.
2.
Lopez-Leon
S
,
Wegman-Ostrosky
T
,
Perelman
C
,
Sepulveda
R
,
Rebolledo
PA
,
Cuapio
A
, et al
.
More than 50 long-term effects of COVID-19: a systematic review and meta-analysis
.
Sci Rep
.
2021
;
11
(
1
):
16144
.
3.
Soriano
JB
,
Murthy
S
,
Marshall
JC
,
Relan
P
,
Diaz
JV
;
WHO Clinical Case Definition Working Group on Post-COVID-19 Condition
.
A clinical case definition of post-COVID-19 condition by a Delphi consensus
.
Lancet Infect Dis
.
2022
;
22
(
4
):
e102
7
.
4.
Ohla
K
,
Veldhuizen
MG
,
Green
T
,
Hannum
ME
,
Bakke
AJ
,
Moein
ST
, et al
.
A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss
.
Rhinology
.
2022
;
60
(
3
):
207
17
.
5.
Parma
V
,
Ohla
K
,
Veldhuizen
MG
,
Niv
MY
,
Kelly
CE
,
Bakke
AJ
, et al
.
More than smell-COVID-19 is associated with severe impairment of smell, taste, and chemesthesis
.
Chem Senses
.
2020
;
45
(
7
):
609
22
.
6.
Izquierdo-Dominguez
A
,
Rojas-Lechuga
MJ
,
Mullol
J
,
Alobid
I
.
Olfactory dysfunction in the covid-19 outbreak
.
J Investig Allergol Clin Immunol
.
2020
;
30
(
5
):
317
26
.
7.
Yan
CH
,
Faraji
F
,
Prajapati
DP
,
Boone
CE
,
DeConde
AS
.
Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms
.
Int Forum Allergy Rhinol
.
2020
;
10
(
7
):
806
13
.
8.
Tan
BKJ
,
Han
R
,
Zhao
JJ
,
Tan
NKW
,
Quah
ESH
,
Tan
CJW
, et al
.
Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves
.
BMJ
.
2022
;
378
:
e069503
.
9.
Haehner
A
,
Draf
J
,
Dräger
S
,
de With
K
,
Hummel
T
.
Predictive value of sudden olfactory loss in the diagnosis of COVID-19
.
ORL J Otorhinolaryngol Relat Spec
.
2020
;
82
(
4
):
175
80
.
10.
Roland
LT
,
Gurrola
JG
,
Loftus
PA
,
Cheung
SW
,
Chang
JL
.
Smell and taste symptom-based predictive model for COVID-19 diagnosis
.
Int Forum Allergy Rhinol
.
2020
;
10
(
7
):
832
8
.
11.
Gerkin
RC
,
Ohla
K
,
Veldhuizen
MG
,
Joseph
PV
,
Kelly
CE
,
Bakke
AJ
, et al
.
Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms
.
Chem Senses
.
2021
;
46
:
bjaa081
.
12.
El Ghiadi
A
,
Eddali
O
,
Ashur
S
,
Sabei
L
.
Could self-reported symptoms be predictors of RT-PCR positivity in suspected COVID-19 cases? The Libya experience
.
East Mediterr Health J
.
2022
;
28
(
9
):
664
72
.
13.
Hummel
T
,
Sekinger
B
,
Wolf
SR
,
Pauli
E
,
Kobal
G
.
“Sniffin” sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold
.
Chem Senses
.
1997
;
22
(
1
):
39
52
.
14.
Douglas
JE
,
Mansfield
CJ
,
Arayata
CJ
,
Cowart
BJ
,
Colquitt
LR
,
Maina
IW
, et al
.
Taste exam: a brief and validated test
.
J Vis Exp
.
2018
;
138
:
56705
.
15.
Jang
SS
,
Choi
JS
,
Kim
JH
,
Kim
N
,
Ference
EH
.
Discordance between subjective and objective measures of smell and taste in US adults
.
Otolaryngol Head Neck Surg
.
2022
;
166
(
3
):
572
9
.
16.
Hintschich
CA
,
Niv
MY
,
Hummel
T
.
The taste of the pandemic–contemporary review on the current state of research on gustation in coronavirus disease 2019 (COVID-19)
.
Int Forum Allergy Rhinol
.
2022
;
12
(
2
):
210
6
.
17.
Favero
R
,
Hajrulla
S
,
Bordin
A
,
Mucignat-Caretta
C
,
Gaudioso
P
,
Scarpa
B
, et al
.
Olfactory dysfunction in COVID-19 patients who do not report olfactory symptoms: a pilot study with some suggestions for dentists
.
Int J Environ Res Public Health
.
2022
;
19
(
3
):
1036
.
18.
Hannum
ME
,
Ramirez
VA
,
Lipson
SJ
,
Herriman
RD
,
Toskala
AK
,
Lin
C
, et al
.
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
.
Chem Senses
.
2020
;
45
(
9
):
865
74
.
19.
Gary
JB
,
Gallagher
L
,
Joseph
PV
,
Reed
D
,
Gudis
DA
,
Overdevest
JB
.
Qualitative olfactory dysfunction and COVID-19: an evidence-based review with recommendations for the clinician
.
Am J Rhinol Allergy
.
2023
;
37
(
1
):
95
101
.
20.
Cancellieri
E
,
Hernandez
AK
,
Degkwitz
H
,
Kahre
E
,
Blankenburg
J
,
Horst
TS
, et al
.
Subjective perception of recovery and measured olfactory function in COVID-19 patients
.
Viruses
.
2023
;
15
(
7
):
1418
.
21.
Hummel
T
,
Sekinger
B
,
Wolf
SR
,
Pauli
E
,
Kobal
G
.
“Sniffin” sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold
.
Chem Senses
.
1997
;
22
(
1
):
39
52
.
22.
Mori
E
,
Matsuwaki
Y
,
Mitsuyama
C
,
Yamazaki
M
,
Okushi
T
,
Moriyama
H
.
Comparison of open essence scent identification test card and conventional olfaction tests
.
Nihon Jibiinkoka Gakkai Kaiho
.
2011
;
114
(
12
):
917
23
.
23.
Schlosser
RJ
,
Smith
TL
,
Mace
JC
,
Alt
JA
,
Beswick
DM
,
Mattos
JL
, et al
.
The Olfactory Cleft Endoscopy Scale: a multi-institutional validation study in chronic rhinosinusitis
.
Rhinology
.
2020
;
59
(
2
):
181
90
.
24.
Rumeau
C
,
Nguyen
DT
,
Jankowski
R
.
How to assess olfactory performance with the Sniffin’ Sticks test(®)
.
Eur Ann Otorhinolaryngol Head Neck Dis
.
2016
;
133
(
3
):
203
6
.
25.
Oleszkiewicz
A
,
Schriever
VA
,
Croy
I
,
Hähner
A
,
Hummel
T
.
Updated Sniffin’ Sticks normative data based on an extended sample of 9139 subjects
.
Eur Arch Oto-Rhino-Laryngol
.
2019
;
276
(
3
):
719
28
.
26.
Gonzalez-Reiche
AS
,
Hernandez
MM
,
Sullivan
MJ
,
Ciferri
B
,
Alshammary
H
,
Obla
A
, et al
.
Introductions and early spread of SARS-CoV-2 in the New York City area
.
Science
.
2020
;
369
(
6501
):
297
301
.
27.
Centers for Disease Control and Prevention [Internet]
.
SARS-CoV-2 variant classifications and definitions
. [cited 2023 Jan 20]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html
28.
Haxel
BR
,
Bertz-Duffy
S
,
Fruth
K
,
Letzel
S
,
Mann
WJ
,
Muttray
A
.
Comparison of subjective olfaction ratings in patients with and without olfactory disorders
.
J Laryngol Otol
.
2012
;
126
(
7
):
692
7
.
29.
Bordin
A
,
Mucignat-Caretta
C
,
Gaudioso
P
,
Pendolino
AL
,
Leoni
D
,
Scarpa
B
, et al
.
Comparison of self-reported symptoms and psychophysical tests in coronavirus disease 2019 (COVID-19) subjects experiencing long-term olfactory dysfunction: a 6-month follow-up study
.
Int Forum Allergy Rhinol
.
2021
;
11
(
11
):
1592
5
.
30.
Hummel
T
,
Podlesek
D
.
Clinical assessment of olfactory function
.
Chem Senses
.
2021
;
46
:
bjab053
.
31.
Prajapati
DP
,
Shahrvini
B
,
MacDonald
BV
,
Crawford
KL
,
Lechner
M
,
DeConde
AS
, et al
.
Association of subjective olfactory dysfunction and 12-item odor identification testing in ambulatory COVID-19 patients
.
Int Forum Allergy Rhinol
.
2020
;
10
(
11
):
1209
17
.
32.
Philpott
C
,
Wolstenholme
C
,
Goodenough
P
,
Clark
A
,
Murty
G
.
Comparison of subjective perception with objective measurement of olfaction
.
Otolaryngol Head Neck Surg
.
2006
;
134
(
3
):
488
90
.
33.
Dulay
MF
,
Gesteland
RC
,
Shear
PK
,
Ritchey
PN
,
Frank
RA
.
Assessment of the influence of cognition and cognitive processing speed on three tests of olfaction
.
J Clin Exp Neuropsychol
.
2008
;
30
(
3
):
327
37
.
34.
Larsson
M
,
Nilsson
L
,
Olofsson
JK
,
Nordin
S
.
Demographic and cognitive predictors of cued odor identification: evidence from a population-based study
.
Chem Senses
.
2004
;
29
(
6
):
547
54
.
35.
Hedner
M
,
Larsson
M
,
Arnold
N
,
Zucco
GM
,
Hummel
T
.
Cognitive factors in odor detection, odor discrimination, and odor identification tasks
.
J Clin Exp Neuropsychol
.
2010
;
32
(
10
):
1062
7
.
36.
Whitcroft
KL
,
Hummel
T
.
Olfactory dysfunction in COVID-19: diagnosis and management
.
JAMA
.
2020
;
323
(
24
):
2512
4
.
37.
Dalton
P
,
Doolittle
N
,
Nagata
H
,
Breslin
PAS
.
The merging of the senses: integration of subthreshold taste and smell
.
Nat Neurosci
.
2000
;
3
(
5
):
431
2
.
38.
Lundström
JN
,
Boesveldt
S
,
Albrecht
J
.
Central processing of the chemical senses: an overview
.
ACS Chem Neurosci
.
2011
;
2
(
1
):
5
16
.
39.
Nguyen
H
,
Albayay
J
,
Höchenberger
R
,
Bhutani
S
,
Boesveldt
S
,
Busch
NA
, et al
.
Covid-19 affects taste independent of taste-smell confusions: results from a combined chemosensory home test and online survey from a large global cohort
.
Chem Senses
.
2023
;
48
:
bjad020
.
40.
Doyle
ME
,
Appleton
A
,
Liu
QR
,
Yao
Q
,
Mazucanti
CH
,
Egan
JM
.
Human type II taste cells express angiotensin-converting enzyme 2 and are infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
.
Am J Pathol
.
2021
;
191
(
9
):
1511
9
.
41.
Ciofalo
A
,
Cavaliere
C
,
Masieri
S
,
Di Chicco
A
,
Fatuzzo
I
,
Lo Re
F
, et al
.
Long-term subjective and objective assessment of smell and taste in COVID-19
.
Cells
.
2022
;
11
(
5
):
788
.
42.
Jensen
MM
,
Larsen
KD
,
Homøe
AS
,
Simonsen
AL
,
Arndal
E
,
Koch
A
, et al
.
Subjective and psychophysical olfactory and gustatory dysfunction among COVID-19 outpatients; short- and long-term results
.
PLoS One
.
2022
;
17
(
10
):
e0275518
.
43.
Winkelmann
S
,
Korth
A
,
Voss
B
,
Nasr
MA
,
Behrend
N
,
Pudszuhn
A
, et al
.
Persisting chemosensory dysfunction in COVID-19 - a cross-sectional population-based survey
.
Rhinology
.
2022
;
61
(
1
):
12
23
.
44.
Vaira
LA
,
De Riu
G
,
Salzano
G
,
Maglitto
F
,
Boscolo-Rizzo
P
,
Lechien
JR
.
The rate of persistent COVID-19-related chemosensory dysfunctions can be established only after one year
.
Oral Dis
.
2022
;
28
(
Suppl 2
):
2630
1
.
45.
Coelho
DH
,
Reiter
ER
,
French
E
,
Costanzo
RM
.
Decreasing incidence of chemosensory changes by COVID-19 variant
.
Otolaryngol Head Neck Surg
.
2022
;
168
(
4
):
704
6
.
46.
Vaira
LA
,
Lechien
JR
,
Deiana
G
,
Salzano
G
,
Maglitto
F
,
Piombino
P
, et al
.
Prevalence of olfactory dysfunction in D614G, alpha, delta and omicron waves: a psychophysical case-control study
.
Rhinology
.
2022
;
61
(
1
):
32
8
.
47.
Klimek
L
,
Hagemann
J
,
Hummel
T
,
Altundag
A
,
Hintschich
C
,
Stielow
S
, et al
.
Olfactory dysfunction is more severe in wild-type SARS-CoV-2 infection than in the Delta variant (B.1.617.2)
.
World Allergy Organ J
.
2022
;
15
(
6
):
100653
.
48.
Boscolo-Rizzo
P
,
Tirelli
G
,
Meloni
P
,
Hopkins
C
,
Madeddu
G
,
De Vito
A
, et al
.
Coronavirus disease 2019 (COVID-19)–related smell and taste impairment with widespread diffusion of severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2) Omicron variant
.
Int Forum Allergy Rhinol
.
2022
;
12
(
10
):
1273
81
.
49.
Vaira
LA
,
De Vito
A
,
Lechien
JR
,
Chiesa-Estomba
CM
,
Mayo-Yàñez
M
,
Calvo-Henrìquez
C
, et al
.
New onset of smell and taste loss are common findings also in patients with symptomatic COVID-19 after complete vaccination
.
Laryngoscope
.
2022
;
132
(
2
):
419
21
.
50.
Magesh
S
,
John
D
,
Li
WT
,
Li
Y
,
Mattingly-app
A
,
Jain
S
, et al
.
Disparities in COVID-19 outcomes by race, ethnicity, and socioeconomic status: a systematic-review and meta-analysis
.
JAMA Netw Open
.
2021
;
4
(
11
):
e2134147
.
51.
Hernandez
AK
,
Landis
BN
,
Altundag
A
,
Fjaeldstad
AW
,
Gane
S
,
Holbrook
EH
, et al
.
Olfactory nomenclature: an orchestrated effort to clarify terms and definitions of dysosmia, anosmia, hyposmia, normosmia, hyperosmia, olfactory intolerance, parosmia, and phantosmia/olfactory hallucination
.
ORL J Otorhinolaryngol Relat Spec
.
2023
;
85
(
6
):
312
20
.
52.
Harris
PA
,
Taylor
R
,
Thielke
R
,
Payne
J
,
Gonzalez
N
,
Conde
JG
.
Research electronic data capture (REDCap) – a metadata-driven methodology and workflow process for providing translational research informatics support
.
J Biomed Inform
.
2009
;
42
(
2
):
377
81
.
53.
Harris
PA
,
Taylor
R
,
Minor
BL
,
Elliott
V
,
Fernandez
M
,
O’Neal
L
, et al
.
The REDCap consortium: building an international community of software platform partners
.
J Biomed Inform
.
2019
;
95
:
103208
.
54.
Lawrence
CE
,
Dunkel
L
,
McEver
M
,
Israel
T
,
Taylor
R
,
Chiriboga
G
, et al
.
A REDCap-based model for electronic consent (eConsent): moving toward a more personalized consent
.
J Clin Transl Sci
.
2020
;
4
(
4
):
345
53
.