Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection

Since December 2019, a pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally.¹ A spectrum of disease severity has been reported, with main symptoms that include fever, fatigue, dry cough, myalgia, and dyspnea. Previous strains of coronavirus have been demonstrated to invade the central nervous system through the olfactory neuroepithelium and propagate from within the olfactory bulb.² Furthermore, nasal epithelial cells display the highest expression of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2, in the respiratory tree.³

Despite anecdotal reports of anosmia, only 1 study to our knowledge has evaluated the prevalence of smell and taste disturbance in hospitalized patients with COVID-19, reporting an overall prevalence of 34% but without data on timing of onset in relation to other symptoms.⁴

This study evaluated prevalence, intensity, and timing of an altered sense of smell or taste in patients with SARS-CoV-2 infections.

The study was approved by the ethics committee of Treviso and Belluno provinces, and informed consent was obtained verbally for telephone interviews. Adults (aged ≥18 years) consecutively assessed at Treviso Regional Hospital between March 19 and March 22, 2020, were included if they tested positive for SARS-CoV-2 RNA by polymerase chain reaction on nasopharyngeal and throat swabs that were performed according to the World Health Organization recommendation⁵ and if they were suitable for home management as mildly symptomatic.

Patients were contacted 5 to 6 days after the swab was performed, the demographic information was reported, and the Acute Respiratory Tract Infection Questionnaire (ARTIQ; with symptoms scored as none, 0; a little, 1; a lot, 2) was administered. During the telephone interview, they were asked whether they had experienced a sudden onset of an altered sense of smell or taste in the 2 weeks before the swab through completion of the Sino-nasal Outcome Test 22 (SNOT-22). The SNOT-22 grades symptom severity as none (0), very mild (1), mild or slight (2), moderate (3), severe (4), or as bad as it can be (5).⁶ Symptom prevalence was expressed as the percentage of total patients; 95% confidence intervals were calculated using the Clopper-Pearson method. Prevalence was compared using the Fisher exact test. A 2-sided P < .05 was considered statistically significant. Statistical analyses were performed using R version 3.6.

Of 374 eligible patients, contact information was available for 283; 202 (71.4%) completed the telephone survey.

Demographic data and clinical features are summarized in Table 1. The median age was 56 years (range, 20-89 years); 52.0% were women. Any altered sense of smell or taste was reported by 130 patients (64.4%; 95% CI, 57.3%-71.0%), with a median SNOT-22 score of 4 (interquartile range, 3-5); 23.8% reported a score of 5 (Table 2). Of 130 patients reporting an altered sense of smell or taste, 45 (34.6%) also reported blocked nose. Other frequent symptoms were fatigue (68.3%), dry or productive cough (60.4%), and fever (55.5%). Among all patients, the timing of an altered sense of smell or taste onset in relation to other symptoms occurred before other symptoms in 24 (11.9%); at same time as in 46 (22.8%); and after other symptoms in 54 (26.7%; Table 2). An altered sense of smell or taste was reported as the only symptom by 6 patients (3.0%). An altered sense of smell or taste was more frequent among 105 women (72.4%; 95% CI, 62.8%-80.7%) than among 97 men (55.7%; 95% CI, 45.2%-65.8%; P = .02).

Alterations in smell or taste were frequently reported by mildly symptomatic patients with SARS-CoV-2 infection and often were the first apparent symptom. The results must be interpreted with caution due to study limitations: data were self-reported and based on a cross-sectional survey, the sample was relatively small and geographically limited, more severe patients were not included, and data regarding the subsequent course of the disease was not available. Although the SNOT-22 questionnaire has been shown to correlate with objective testing of olfactory function, patients may have difficulty in quantifying olfactory function; objective tests should be included in future studies.

If these results are confirmed, consideration should be given to testing and self-isolation of patients with new onset of altered taste or smell during the COVID-19 pandemic.

Corresponding Author: Daniele Borsetto, MD, Guy’s Hospital, London SE1 9RT, United Kingdom (daniele.borsetto@gmail.com).

Accepted for Publication: April 14, 2020.

Published Online: April 22, 2020. doi:10.1001/jama.2020.6771

Author Contributions: Drs Spinato and Boscolo-Rizzo had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Spinato, Borsetto, Hopkins, Boscolo-Rizzo.

Acquisition, analysis, or interpretation of data: Fabbris, Polesel, Cazzador, Borsetto, Hopkins, Boscolo-Rizzo.

Drafting of the manuscript: Spinato, Fabbris, Borsetto, Boscolo-Rizzo.

Critical revision of the manuscript for important intellectual content: Spinato, Polesel, Cazzador, Borsetto, Hopkins, Boscolo-Rizzo.

Statistical analysis: Polesel.

Administrative, technical, or material support: Fabbris, Borsetto.

Supervision: Spinato, Cazzador, Borsetto, Hopkins, Boscolo-Rizzo.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Anna Menegaldo, MD, Daniele Frezza, MD, Francesca Mularoni, MD, Piergiorgio Gaudioso, MD, Silvia Marciani, MD, Samuele Frasconi, MD, Maria Ferraro, MD, Cecilia Berro, MD, and Chiara Varago, MD (University of Padova, Italy), for helping in the collection of patient data. We also thank Maria Cristina Da Mosto, MD, and Piero Nicolai, MD (University of Padova, Italy), Giancarlo Tirelli, MD (University of Trieste, Italy), Roberto Rigoli, MD (AULSS 2–Marca Trevigiana, Treviso, Italy), and Rupert Obholzer, MA(Oxon), MBBS(Lon) (Guy’s and St Thomas’ Hospitals, London, United Kingdom), for constructive criticism of the manuscript. None of these individuals received compensation for their contributions.