Alterations in Smell or Taste—Classic Coronavirus Disease 2019?

Abstract

To the Editor—There are increased reports of loss of smell (anosmia) and taste (ageusia) in patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19), in particular in the setting of mild disease. The data to date have been presented predominantly from postdiagnosis surveys or retrospective cohort series [1–5]. The pathogenesis is postulated to be due to invasion of the olfactory neuroepithelium and olfactory bulb, which has been seen previously in other coronaviruses, due to the high expression of angiotension-converting enzyme (the receptor that allows virus cellular entry) present in the respiratory system [1, 6]. From a retrospective adult cohort of confirmed SARS-CoV-2 in Germany (n = 72), Luers and colleagues noted that 74% of patients reported anosmia and 69% reported ageusia [7]. Prior to this, from a retrospective cohort study of COVID-19 patients interviewed 5–6 days postdiagnosis, Spinato et al also noted that 64.4% reported alterations in taste or smell [1]. However, both of these studies suffer from the absence of a control group and significant limitation of recall and selection bias. Further, both fail to answer the question of whether anosmia and ageusia are, in fact, more frequent in COVID-19 patients than in those with other upper respiratory tract infections. To address the identified deficiencies of current data presented, we used a prospectively collected dataset from patients assessed at our institution’s COVID-19 screening clinic (Melbourne, Australia) between 1 April 2020 and 22 April 2020 (data collection, see eMethods) to determine if anosmia and/or ageusia were more frequent in patients with confirmed SARS-CoV-2 infection. A total of 1788 patients underwent clinical evaluation; we identified 40 (2.2%) patients who reported both anosmia and ageusia, with 3.1% (56) for anosmia alone and 4.1% (74) for ageusia alone. Similar proportions were seen in the subgroup of 1236 patients who subsequently underwent SARS-CoV-2 testing (eTable 1). The distribution of symptom prevalence over time is shown in eFigure 1. In those who underwent SARS-CoV-2 testing, anosmia or ageusia was more frequently reported in females and in those who reported more symptoms (eTable1). Of those who reported anosmia or ageusia, 9.3% tested positive for COVID-19 (positive predictive value), while the negative predictive value was 98.5%. Anosmia and/or ageusia were more common in COVID-19–positive than in COVID-19–negative patients (39.3% vs 8.9%, P < .001) and were more common when examined in isolation: anosmia (25% vs 5%, P < .001) and ageusia (25% vs 6%, P = .002; Table 1). After adjusting for confounders, both anosmia and ageusia were independently associated with SARS-CoV-2 infection (eTable 2). Baseline Demographics of Patients Assessed for Coronavirus Disease 2019 at a Screening Clinic and Who Underwent Severe Acute Respiratory Syndrome Coronavirus 2 Testing Abbreviation: IQR, interquartile range. While supporting the observations made by Luers [7] and Spinato [1], our data also highlight a significantly lower prevalence of symptoms in a comparative outpatient COVID-19 population (39.3% Australia vs 64.4% United States vs 68% Germany) when prospective data are used. Also, we demonstrate similar olfactory symptoms in the control group (SARS-CoV-2–negative). It is important for clinicians to realize that anosmia and ageusia are likely to be commonly reported symptoms in other upper respiratory tract infections when appropriately questioned (8.9% of our COVID-19 test negative group) [3, 8]. From data available, anosmia and/or ageusia, while associated with COVID-19, should not yet be considered pathognomonic for the disease. Larger prospective population studies are required to validate these findings as we collectively search for key clinical predictors of COVID-19 that can aid clinical decision making. Financial support. J. A. T. is supported by a National Health and Medical Research Council Early Career Research Grant (GNT 1139902), Royal Australasian College of Physicians Research Establishment Fellowship, and a postdoctoral scholarship from the National Centre for Infections in Cancer. Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

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