Smell dysfunction: a biomarker for COVID-19

Abstract

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic since the 1918 influenza A virus subtype H1N1 influenza outbreak. The symptoms presently recognized by the World Health Organization are cough, fever, tiredness, and difficulty breathing. Patient-reported smell and taste loss has been associated with COVID-19 infection, yet no empirical olfactory testing on a cohort of COVID-19 patients has been performed.

Methods: The University of Pennsylvania Smell Identification Test (UPSIT), a well-validated 40-odorant test, was administered to 60 confirmed COVID-19 inpatients and 60 age- and sex-matched controls to assess the magnitude and frequency of their olfactory dysfunction. A mixed effects analysis of variance determined whether meaningful differences in test scores existed between the 2 groups and if the test scores were differentially influenced by sex.

Results: Fifty-nine (98%) of the 60 patients exhibited some smell dysfunction (mean [95% CI] UPSIT score: 20.98 [19.47, 22.48]; controls: 34.10 [33.31, 34.88]; p < 0.0001). Thirty-five of the 60 patients (58%) were either anosmic (15/60; 25%) or severely microsmic (20/60; 33%); 16 exhibited moderate microsmia (16/60; 27%), 8 mild microsmia (8/60; 13%), and 1 normosmia (1/60; 2%). Deficits were evident for all 40 UPSIT odorants. No meaningful relationships between the test scores and sex, disease severity, or comorbidities were found.

Conclusion: Quantitative smell testing demonstrates that decreased smell function, but not always anosmia, is a major marker for SARS-CoV-2 infection and suggests the possibility that smell testing may help, in some cases, to identify COVID-19 patients in need of early treatment or quarantine.

Keywords: COVID-19; UPSIT; biomarker; chronic rhinosinusitis; olfaction; olfactory disorders; olfactory test.

FIGURE 1

UPSIT scores of the COVID‐19 patients compared to those of healthy controls. The distribution of the participants’ scores in each group is depicted in violin plot. The white circles indicate the median of the score for each group. COVID‐19 = coronavirus disease 2019; UPSIT = University of Pennsylvania Smell Identification Test.

FIGURE 2

Performance on individual UPSIT odorants for the COVID‐19 patients and matched healthy controls. Note that dysfunction was evident for all 40 UPSIT odorants. Performance for each group is calculated as the percent of individuals having correctly identified the odorant. COVID‐19 = coronavirus disease 2019; UPSIT = University of Pennsylvania Smell Identification Test.