Olfactory dysfunction (OD) is one of the earliest and strongest predictors of COVID-19 infection, and thus is promising as a disease screening tool.1,2 Compared with objective testing, subjective olfactory assessments significantly underreport OD.3,4 Thus, an inexpensive, quick, and sensitive method of assessing olfaction may be beneficial for the early diagnosis and spread prevention of COVID-19. In this study, we evaluate the feasibility of a novel, objective olfactory test as part of an initial screening for COVID-19 in adults with unknown disease status.
This prospective, cross-sectional study enrolled healthy adults (aged ≥ 18 years) from a single college campus COVID-19 screening site. The study was approved by the Southern Methodist University institutional review board and all participants provided written informed consent. Participants were screened for OD using a novel scent card (SAFER Diagnostics) followed immediately by polymerase chain reaction (PCR) testing for SARS-CoV-2 from nasopharyngeal swabs. The SAFER card contained a single scent in a scratch-and-sniff label that the participant identified from 8 answer options: lemon, grape, floral, blueberry, banana, mint, unsure, or no scent. Answers were processed electronically via a QR code. An incorrect choice was classified as OD. Participant demographics, medical history, COVID-19 symptoms, and subjective smell function on a binary and 10-point visual analog scale (VAS, with 0 indicating no sense of smell and 10 indicating normal sense of smell) were also collected.
Multivariable logistic regression was conducted to assess the association between SAFER and COVID-19 PCR results while controlling for variables selected a priori as common symptoms of COVID-19: fever, fatigue, and cough.5 Data analysis was conducted using SPSS version 27.0 (IBM Corp).
A total of 163 participants were prospectively screened for OD using the scent card followed by SARS-CoV-2 PCR testing with characteristics summarized in Table 1. Of those who tested PCR-positive for COVID-19, 75% (12 out of 16) failed olfactory screening compared with 4.8% (7 out of 147) among those testing PCR-negative for COVID-19. The sensitivity, specificity, positive predictive value, and negative predictive value of the scent card in detecting those with COVID-19 were 75.0%, 95.2%, 63.2%, and 97.2%, respectively (Table 2). Including the symptom fatigue along with OD achieved a 93.8% sensitivity and 89.8% specificity in disease screening. The addition of fever and cough did not further increase sensitivity (Table 2).
While only 37.5% (6 out of 16) of COVID-19 test-positive participants reported subjective anosmia, 75% failed screening with the scent card. A failed scent card screen was the greatest predictor of COVID-19 positivity (odds ratio [OR], 80.24; 95% CI, 14.77-435.90) when compared with other symptoms including cough, fever, fatigue, and a history of COVID-19 exposure.
In this study, we demonstrate that a rapid psychophysical olfaction test is feasible as a screening tool for COVID-19. Current literature suggests that individuals may fail to recognize OD that is detectable on objective testing.3,4 Furthermore, screening questionnaires may miss more than 50% of COVID-19 cases,6 owing to screening question variation, subjective interpretation of symptom severity, and intentional patient evasion. Meanwhile, antigen-based point-of-care screening remains time intensive, expensive, and unrealistic in certain environments.
In this pilot study, a novel olfactory test alone had a sensitivity of 75% and specificity of 95.2% in detecting COVID-19 using PCR testing as the gold standard. A screening test ideally prioritizes high sensitivity with potential lower specificity. Olfactory screening using a single scent may demonstrate lower test sensitivity in exchange for expediency. The optimal number of screening odorants required to achieve high sensitivity while maintaining practicality may be a topic for future studies. Furthermore, not all patients with COVID-19 experience OD. The combined screening of OD with other common COVID-19 symptoms, in this case fatigue, can help increase sensitivity. Alone, OD screening remained the greatest predictor of COVID-19 positivity compared with other symptoms.
This pilot study is limited by its small sample size, small percentage of COVID-19 PCR test-positive participants, and single-institution recruitment. Future studies with a larger sample size and a heterogeneous population may better account for other OD risk factors and optimize sensitivity using a combination of OD testing with other symptoms for screening COVID-19.
Accepted for Publication: May 26, 2021.
Published Online: July 15, 2021. doi:10.1001/jamaoto.2021.1456
Corresponding Author: Carol H. Yan, MD, Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of California, San Diego, 9350 Campus Point Dr, Mail Code 0970, La Jolla, CA 92037 (firstname.lastname@example.org).
Author Contributions: Dr Yan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Said, P. Davis, S. A. Davis, S. Davis, Yan.
Acquisition, analysis, or interpretation of data: Said, S. A. Davis, Smart, S. Davis, Yan.
Drafting of the manuscript: Said, S. A. Davis, Yan.
Critical revision of the manuscript for important intellectual content: Said, P. Davis, Smart, S. Davis, Yan.
Statistical analysis: Said, Yan.
Administrative, technical, or material support: Said, P. Davis, S. A. Davis, S. Davis, Yan.
Conflict of Interest Disclosures: Dr Davis is the founder of SAFER Diagnostics. No other disclosures were reported.
Funding/Support: This work was supported by SAFER Diagnostics.
Role of the Funder/Sponsor: SAFER Diagnostics had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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