Prevalence and reversibility of smell dysfunction measured psychophysically in a cohort of COVID-19 patients

Abstract

Background: Considerable evidence suggests that smell dysfunction is common in coronavirus disease-2019 (COVID-19). Unfortunately, extant data on prevalence and reversibility over time are highly variable, coming mainly from self-report surveys prone to multiple biases. Thus, validated psychophysical olfactory testing is sorely needed to establish such parameters.

Methods: One hundred severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-positive patients were administered the 40-item University of Pennsylvania Smell Identification Test (UPSIT) in the hospital near the end of the acute phase of the disease. Eighty-two were retested 1 or 4 weeks later at home. The data were analyzed using analysis of variance and mixed-effect regression models.

Results: Initial UPSIT scores were indicative of severe microsmia, with 96% exhibiting measurable dysfunction; 18% were anosmic. The scores improved upon retest (initial test: mean, 21.97; 95% confidence interval [CI], 20.84-23.09; retest: mean, 31.13; 95% CI, 30.16-32.10; p < 0.0001); no patient remained anosmic. After 5 weeks from COVID-19 symptom onset, the test scores of 63% of the retested patients were normal. However, the mean UPSIT score at that time continued to remain below that of age- and sex-matched healthy controls (p < 0.001). Such scores were related to time since symptom onset, sex, and age.

Conclusion: Smell loss was extremely common in the acute phase of a cohort of 100 COVID-19 patients when objectively measured. About one third of cases continued to exhibit dysfunction 6 to 8 weeks after symptom onset. These findings have direct implications for the use of olfactory testing in identifying SARS-CoV-2 carriers and for counseling such individuals with regard to their smell dysfunction and its reversibility.

Keywords: COVID-19; SARS-CoV-2; UPSIT; anosmia; hyposmia; odor identification; olfaction; virus.

FIGURE 1

UPSIT scores of the COVID‐19 patients for the initial (Test 1) and follow‐up (Test 2) periods. The distribution of the subjects' scores in each group is depicted in a violin plot. White circles: medians; vertical dark lines: interquartile ranges. COVID‐19 = coronavirus disease‐2019; UPSIT = University of Pennsylvania Smell Identification Test.

FIGURE 2

Test and retest UPSIT scores as a function of days from the onset of COVID‐19 symptoms. The intertest intervals were 1 and 4 weeks. Repeat test scores to the right of the vertical dashed line represent the data that were compared with those of the healthy matched controls. The inset shows mean (95% confidence interval) differences between the initial and retest scores for the 1‐ and 4‐week intervals. COVID‐19 = coronavirus disease‐2019; UPSIT = University of Pennsylvania Smell Identification Test.

FIGURE 3

Comparison of UPSIT scores of patients tested 6 to 8 weeks after onset of initial COVID‐19 symptoms (6‐8 W COVID‐19) vs those of healthy age‐ and sex‐matched controls. White circles: medians; vertical dark lines: interquartile ranges. COVID‐19 = coronavirus disease‐2019.

FIGURE 4

Proportion of patients with differing degrees of function relative to time since onset of COVID‐19 symptoms. All initial and follow‐up scores are combined for the purpose of visualization. COVID‐19 = coronavirus disease‐2019.