Patient Recruitment and Characteristics
A sample of 827 eligible patients were invited to complete the questionnaire, 743 agreed to participate, and 532 responses were received (response rate 64.3%). 34 responses were excluded due to either not meeting the inclusion criteria, duplicate responses, or inconsistent responses, while the remaining 498 responses were analysed.
Overall, the age of the patients ranged from 18 to 87 (median ± interquartile range [IQR]: 36 ± 24.25 years old). There were 279 males (56%) and 219 (44%) females. The largest ethnic group in our cohort were Malays (76.7%), followed by Chinese (10.0%) and Indians (1.8%), while the remaining (11.5%) included several ethnic groups native to East Malaysia (e.g., Kadazan, Dusun, and Murut) and foreign nationals (3%). 54.4% of patients had at least one comorbidity, the most common being hypertension (17.3%) and diabetes mellitus (13.9%). (Table 1).
Prevalence, Timing, and Severity of Smell and Taste Disorders
At time of COVID-19 testing, 206 patients (41.4%) reported either one of loss of smell and/or taste. Among them, 29.3% reported loss of both smell and taste, 7.4% reported loss of smell but not taste, and 5.0% reported loss of taste but not smell. Loss of smell and/or taste was the most common symptom besides fever (40.2%), ahead of cough (30.5%) and sore throat (25.5%) (Table 1). 34.6% of patients with smell loss reported experiencing this before other symptoms whereas 30.7% of patients with taste loss experienced this before other symptoms (Table 2). 7.7% and 3.0% of patients with smell and taste loss respectively experienced this as their only symptom.
In terms of symptom severity, 12.1% and 10.0% of patients with smell and taste loss respectively described their symptoms as “severe” to “as bad as it can be” in the preceding two weeks prior to diagnosis (Table 2). In the CATA question on the type of smell disorders, 73 patients (40.1%) reported complete loss of smell (anosmia) whereas 100 patients (55.5%) reported partial loss of smell (hyposmia). Of note, 17 patients (9.3%) reported fluctuating sense of smell (Table 2).
Factors Predictive of Smell and Taste Disorders
Loss of smell and/or taste were significantly associated with younger age group (< 50 years), female sex, and the presence of several other symptoms listed in Table 3 on univariate analyses. A multivariate logistic regression analysis was performed using these variables and found that the presence of blocked nose (p < 0.0001, OR 4.95, CI 2.41 – 10.15), loss of appetite (p < 0.0001, OR 4.16, CI 2.35 – 7.38), and gastrointestinal disturbances (p = 0.038, OR 2.17, CI 1.04 – 4.53) were independent predictors of loss of smell and/or taste (Table 3).
Quantitative Changes of Smell, Taste, Chemesthesis, and Nasal Obstruction during COVID-19
The distribution of patients’ self-ratings of smell, taste, and chemesthesis, and nasal obstruction before and during COVID-19 diagnosis are depicted in Figure 1. There were statistically significant changes in self-ratings of smell, taste, chemesthesis, and nasal blockage in the total patient cohort and the subgroups before and during COVID-19 diagnosis as measured by Wilcoxon matched pairs signed-rank test (Table 4).
We observed an increase in the percentage of patients with smell, taste, and chemesthesis ratings lower than a cut-off point of 4 compared to their baseline ratings prior to COVID-19 diagnosis (smell: 35.6% from 10.4%; taste: 34.2% from 10.0%; chemesthesis: 38.7% from 22.8%) (Figure 1). Subgroup analysis of only those who reported smell loss as their presenting complaint (n = 182) revealed a higher increase in the proportion of smell ratings lower than 4 from 19.6% to 86.7%. Similarly, those who reported taste loss as their presenting complaint (n = 169) had a greater increase in the proportion of taste and chemesthesis ratings below 4 (taste, 82.9% from 16.1%; chemesthesis: 71.1% from 26%).
In parallel, we observed a slight increase in perceived nasal obstruction related to COVID-19. At baseline, 21% of patients reported a nasal blockage rating of greater than 1, which increased to 27.7% when diagnosed with COVID-19. Subgroup analysis of only patients who reported smell loss as their presenting symptom (n = 182) found 47.8% reporting a nasal blockage rating of greater than 1, from 27.4% at baseline. This observation is concordant with findings of significant association of smell loss with nasal congestion on multivariate analysis.
Relationship between Self-Ratings of Smell, Taste, Chemesthesis, and Nasal Obstruction
To further characterise the relationship between changes in perceived nasal obstruction and changes in the three chemosensory modalities, we performed a principal component analysis of the changes in self-ratings of smell, taste, chemesthesis, and perceived nasal blockage (during minus before diagnosis of COVID-19) (Figure 2). This analytic approach was previously employed by Parma et al. 8 to determine whether changes in chemosensory function can be attributed to nasal obstruction. It leverages the orthogonal features of these principal components to evaluate the degree of statistical dependence between changes in chemosensory ability and perceived nasal obstruction. In our analysis, the two orthogonal principal components, Components 1 and 2, accounted for 59% and 22% of the total multidimensional variances respectively. Changes in self-ratings of smell, taste, and chemesthesis clustered together and correlated strongly with Component 1 (smell: r = 0.837, taste: r = 0.871, chemesthesis: r = 0.815), while showing negligible to weak positive correlation with the Component 2 (smell: r = 0.066, taste: 0.097, and chemesthesis: 0.333). In contrast, changes in self-ratings of nasal obstruction demonstrated only a moderate negative correlation with Component 1 (r = -0.474) but strong positive correlation (r = 0.873) with Component 2. The PCA loading vectors for changes in chemesthesis and nasal obstruction formed a right angle indicating that they were not correlated and statistically independent of each other, whereas vectors for smell and taste changes formed a small obtuse angle with the vector for nasal obstruction, indicating a weak negative correlation. These PCA findings suggest that nasal obstruction could only account for a small proportion of smell and taste changes, but not for chemesthesis.
Qualitative Changes of Smell and Taste during COVID-19
Qualitative changes in smell were uncommon among those who experienced smell disturbances – only 28 patients (15.3%) experienced parosmia and 19 patients (10.4%) experienced phantosmia. Among participants who reported gustatory changes, 33 patients (19.5%) reported impairment of a single taste quality and 106 patients (62.7%) reported impairment of 2 or more taste qualities in the CATA question. 30 patients (17.8 %) did not respond to this question (Table 2). Salty taste was the most frequently reported change (53.2%) followed by sweet (49.1%), sour (44.4%), bitter (42.6%), and umami/savoury (28.4%) taste.
Recovery of Smell and Taste Disorders
Among the patients with smell and/or taste disorders, 90.2% (n = 186) of them reported recovery of their symptoms at the time of answering the questionnaire. Self-ratings of sense of smell, taste, chemesthesis, and nasal congestion at this time-point returned to pre-COVID-19 baseline levels in all patients and in the subset of patients who reported the chemosensory disorders [Mean smell rating: all patients 4.66 ± 0.86 ; smell disturbance only 4.49 ± 0.93; Mean taste rating: all patients 4.74 ± 0.78; taste disturbance only 4.61 ± 0.82; Mean chemesthesis rating: all patients 4.16 ± 1.51; taste disturbance only 4.20 ± 1.36; Mean nasal congestion rating: all patients 0.54 ± 1.22; smell disturbance only 0.60 ± 1.23; mean ± SD ].