Comprehensive Chemosensory Psychophysical Evaluation of Self-reported Gustatory Dysfunction in Patients With Long-term COVID-19: A Cross-sectional Study

Olfactory and gustatory dysfunctions are among the most commonly self-reported symptoms of COVID-19, with a substantial fraction of patients still reporting them after the acute phase of the disease.^1,2 A substantial body of evidence has demonstrated the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on olfaction,³ although few observations exist regarding a direct involvement of the virus in the pathogenesis of gustatory impairment.⁴

While the correlation between self-reported olfactory function and psychophysical tests has been extensively analyzed, showing poor agreement between the 2 types of evaluation, no robust data exist concerning the gustatory function.⁵ To establish whether psychophysical tests confirm a self-reported alteration of taste, we assessed a series of patients self-reporting a persistent distorted perception of basic tastes after COVID-19 using a comprehensive gustatory and olfactory psychophysical evaluation.

Following institutional review board approval from the ethics committee of Friuli Venezia Giulia Region (CEUR-2020-Os-156), all patients referred to the ear, nose, and throat outpatient clinic of the Trieste University Hospital for taste and smell disorders were screened. Inclusion criteria were: (1) age 18 years or older; (2) reverse transcription polymerase chain reaction–confirmed SARS-CoV-2 infection; (3) self-reported altered sense of taste more than 3 months after the acute phase of SARS-CoV-2 infection (patients were asked: “Do you have a taste problem concerning the perception of sweet, sour, salty, or bitter?”); and (4) a psychophysical evaluation including orthonasal and retronasal olfactory testing and gustatory assessment. Exclusion criteria were: (1) history of previous sinonasal surgery; (2) neurological/psychiatric disorders; and (3) preexisting olfactory/gustatory dysfunction (patients were asked: “Did you have an impairment in the sense of smell or taste preceding COVID-19 diagnosis?”). Written informed consent was obtained from all participants. Orthonasal olfactory function was measured using the validated extended Sniffin’ Sticks test battery (Burghart Messtechnik, Wedel, Germany); gustatory evaluation was performed using the validated Taste Strips test (Taste Strips, Burghart Messtechnik, Wedel, Germany); and retronasal olfactory function was tested using 20 powdered tasteless aromas (Givaudan Schweiz AG, Dubendorf, Switzerland). Orthonasal function was expressed through a Threshold, Discrimination, and Identification (TDI) score, indicating normosmia (TDI ≥ 30.75), hyposmia (TDI 16.25-30.5) and anosmia (TDI ≤ 16.0). By Taste Strips test a Taste Strips Score (TSS) was calculated, used for the identification of hypogeusia (TSS < 9 points) and normogeusia (TSS ≥ 9 points). More details on psychophysical evaluation and statistical methods are in the eMethods in the Supplement.

From March 1 to July 31, 2021, a total of 172 patients were referred to the clinic for post–COVID-19 chemosensory disorders. Among these, 110 experienced a persistent COVID-related alteration in the perception of basic tastes. A total of 5 patients were excluded due to an incomplete psychophysical evaluation. Thus, 105 post–COVID-19 patients self-reporting an impaired sense of taste with no missing data were included in this cross-sectional study (median [range] age, 45 [20-76] years; 80 [76.2%] women). Most of the patients (n = 103, 98.1%) had mildly symptomatic COVID-19 with no evidence of pneumonia. The psychophysical evaluation was performed a median (range) of 226 (94-439) days after illness onset. Almost all patients (n = 99; 94.3%) self-reported an associated olfactory impairment. Based on the TSS, the prevalence of hypogeusia was 41.9% (Table) and dropped to 28.6% (eTable in the Supplement) when relating the scores to the age of the participants. Only 3 out of 105 patients (2.9%) had hypogeusia and were normosmic at psychophysical evaluation. The prevalence of normogeusic patients increased with increasing TDI (Table). Among 61 patients who, on psychophysical tests, were normogeusic, 51 (83.6%) had a TDI score less than 30.75, and 16 (26.2%) a retronasal score less than 12, while only 10 (16.4%) had both normal orthonasal and retronasal olfactory function.

It is widely believed that self-reported loss of taste can be an indirect consequence of retronasal olfactory dysfunction⁶; indeed, our study found that even when specifically asked about basic tastes, more than half of patients self-reporting an altered taste perception exhibited a normal gustatory function, while most of them had an olfactory impairment. However, 42% were found to have true hypogeusia. Following evaluation of the scores in relation to age, still 29% exhibited hypogeusia, which has largely been overlooked to date. While olfactory training may help the former group, additional strategies may be needed for those with gustatory impairment.

Limitations of the present study are related to the absence of a psychophysical evaluation performed during the acute phase of the disease, the fact that different patients were evaluated at different time points, and the lack of an age-matched control group. Also, questions on taste function are not validated tools and can be misleading. Furthermore, the use of a single sensory technique to characterize taste function may have produced false-negative results; and dysgeusia and phantogeusia, as well as parosmia and phantosmia, were not addressed in this study. Finally, the design was monocentric, the participants had mostly experienced a mildly symptomatic COVID-19 and were predominantly women, which limits the generalizability of the results. Despite these limitations, this psychophysical study uncovers overestimation of self-reported taste impairment and supports the use of validated psychophysical tests to estimate the burden of chemosensory dysfunction in people with long-term COVID-19.

Accepted for Publication: November 16, 2021.

Published Online: January 6, 2022. doi:10.1001/jamaoto.2021.3993

Corresponding Author: Paolo Boscolo-Rizzo, MD, Section of Otolaryngology, University of Trieste, Strada di Fiume, 447, 34149 Trieste, Italy (paolo.boscolorizzo@units.it).

Author Contributions: Dr Boscolo-Rizzo 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: Boscolo-Rizzo, Hopkins, Menini, Tirelli.

Acquisition, analysis, or interpretation of data: Boscolo-Rizzo, Hummel, Hopkins, D'Alessandro, Dibattista, Tirelli.

Drafting of the manuscript: Boscolo-Rizzo, Hopkins, Tirelli.

Critical revision of the manuscript for important intellectual content: All authors.

Obtained funding: Menini.

Administrative, technical, or material support: D’Alessandro.

Supervision: Boscolo-Rizzo, Hummel, Hopkins, Tirelli.

Other—analysis and interpretation of data: Dibattista.

Conflict of Interest Disclosures: Dr Hummel reported grants from Sony, Smell and Taste Lab, Takasago, aspuraclip, Baia Foods, Frequency Therapeutics, Bayer, Procter and Gamble, Burghart, Primavera, and Lundbeck outside the submitted work. No other disclosures were reported.

Additional Contributions: We thank Jerry Polesel, ScD (Centro di Riferimento Oncologico di Aviano [CRO] IRCCS, Aviano, Italy) for help with statistical analysis. He was not compensated for his work.