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Diagnostic Value of Patient-Reported and Clinically Tested Olfactory Dysfunction in a Population Screened for COVID-19

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Key Points

Question  What are the sensitivities and specificities of patient-reported olfactory dysfunction and gustatory dysfunction and of a newly developed simple and fast clinical test for assessing olfactory dysfunction (Clinical Olfactory Dysfunction Assessment) for diagnosing coronavirus disease 2019 (COVID-19) in outpatients with mild or no symptoms?

Findings  In this diagnostic study including 809 participants evaluated prior to reverse transcriptase–polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2, 35% of 58 participants with confirmed COVID-19 reported olfactory dysfunction, gustatory dysfunction, or both; this compared with only 4% of 751 without COVID-19. Olfactory anamnesis and clinical testing results were complementary, yielding similar, strong diagnostic values for COVID-19.

Meaning  Findings from this study indicate that, in a screening setting of outpatients with no or mild to moderate symptoms of COVID-19, olfactory dysfunction and gustatory dysfunction should be systematically assessed by anamnesis and by clinical testing because their results appear to have strong diagnostic value for COVID-19.

Abstract

Importance  Recent studies have suggested that olfactory dysfunction and gustatory dysfunction are associated with coronavirus disease 2019 (COVID-19). However, olfaction has been evaluated solely on reported symptoms, after COVID-19 diagnosis, and in both mild and severe COVID-19 cases, but rarely has it been assessed in prospectively unselected populations.

Objective  To evaluate the diagnostic value of a semiobjective olfactory test developed to assess patient-reported chemosensory dysfunction prior to testing for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients attending a COVID-19 screening facility.

Design, Setting, and Participants  This prospective diagnostic study with participants and observers blinded to COVID-19 status was conducted in a COVID-19 screening center of a tertiary university hospital in France from March 23 to April 22, 2020. Participants were 854 consecutively included health care workers or outpatients with symptoms or with close contact with an index case. Exclusion criteria were prior chemosensory dysfunction, testing inability, or contraindications (n = 45).

Main Outcomes and Measures  Participants were interviewed to ascertain their symptoms and then underwent Clinical Olfactory Dysfunction Assessment (CODA), an ad hoc test developed for a simple and fast evaluation of olfactory function. This assessment followed a standardized procedure in which participants identified and rated the intensity of 3 scents (lavender, lemongrass, and mint) to achieve a summed score ranging from 0 to 6. The COVID-19 status was assessed using reverse transcriptase–polymerase chain reaction to detect the presence of SARS-CoV-2 in samples collected via nasopharyngeal swab (reference standard) to calculate the diagnostic values of patient-reported chemosensory dysfunction and CODA.

Results  Of 809 participants, the female to male sex ratio was 2.8, and the mean (SD) age was 41.8 (13.0) years (range, 18-94 years). All participants, if symptomatic, had mild disease at the time of testing, and 58 (7.2%) tested positive for SARS-CoV-2. Chemosensory dysfunction was reported by 20 of 58 participants (34.5%) with confirmed COVID-19 vs 29 of 751 participants (3.9%) who tested negative for COVID-19 (absolute difference, 30.6% [95% CI, 18.3%-42.9%]). Olfactory dysfunction, either self-reported or clinically ascertained (CODA score ≤3), yielded similar sensitivity (0.31 [95% CI, 0.20-0.45] vs 0.34 [95% CI, 0.22-0.48]) and specificity (0.97 [95% CI, 0.96-0.98) vs 0.98 [95% CI, 0.96-0.99]) for COVID-19 diagnosis. Concordance was high between reported and clinically tested olfactory dysfunction, with a Gwet AC1 of 0.95 (95% CI, 0.93-0.97). Of 19 participants, 15 (78.9%) with both reported olfactory dysfunction and a CODA score of 3 or lower were confirmed to have COVID-19. The CODA score also revealed 5 of 19 participants (26.3%) with confirmed COVID-19 who had previously unperceived olfactory dysfunction.

Conclusions and Relevance  In this prospective diagnostic study of outpatients with asymptomatic or mild to moderate COVID-19, systematically assessed anamnesis and clinical testing with the newly developed CODA were complementary and specific for chemosensory dysfunction. Olfactory dysfunction was suggestive of COVID-19, particularly when clinical testing confirmed anamnesis. However, normal olfaction was most common among patients with COVID-19.

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Article Information

Accepted for Publication: November 9, 2020.

Published Online: January 7, 2021. doi:10.1001/jamaoto.2020.5074

Corresponding Author: Charles Villerabel, MD, Department of Otorhinolaryngology–Head and Neck Surgery and Maxillofacial Surgery–Hospital and University of Montpellier, Département ORL & CMF–CHU de Montpellier, Hôpital Gui de Chauliac, 80 Avenue Augustin Fliche, 34295 Montpellier, France (villerabel.charles@gmail.com).

Author Contributions: Drs Villerabel and Makinson contributed equally to this work and are considered co–first authors. Ms Jaussent and Dr Picot had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Villerabel, Makinson, Picot, Nègre-Pagès, Crampette, Reynes, Le Moing, Venail.

Acquisition, analysis, or interpretation of data: Villerabel, Makinson, Jaussent, Nègre-Pagès, Rouvière, Favier, Morquin, Reynes, Tuaillon, Venail.

Drafting of the manuscript: Villerabel, Makinson, Jaussent, Rouvière, Crampette, Venail.

Critical revision of the manuscript for important intellectual content: Makinson, Picot, Nègre-Pagès, Favier, Morquin, Reynes, Le Moing, Tuaillon.

Statistical analysis: Jaussent, Picot, Nègre-Pagès.

Administrative, technical, or material support: Makinson, Rouvière, Favier, Tuaillon, Venail.

Supervision: Makinson, Picot, Crampette, Reynes, Le Moing, Venail.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the French professional network of otorhinolaryngologists Doc@Doc, which has sensitized the French scientific community to chemosensory dysfunctions as important clinical features of coronavirus disease 2019 (COVID-19). Luc Bourdiol, MD, and Guillemette Combes, MD, both from the Clinique du Parc, assisted in data collection; Mathilde Raverdeau and Maelle Dereure, both from the University Hospital of Montpellier, assisted in data management; Emilie Barde, Thomas Landragin, and Sandrine Mas, also all from the University Hospital of Montpellier, provided administrative support. No one was compensated for the stated contribution.

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