Abstract
Objective:
To directly compare the prevalence of chemosensory dysfunction (smell and taste) in geographically distinct regions with the same questionnaires.
Methods:
A cross-sectional study was performed to evaluate the self-reported symptoms among adults (older than 18 years) who underwent COVID-19 testing at an ambulatory assessment center in Canada and at a hospital in Israel between March 16, 2020, and August 19, 2020. The primary outcome was the prevalence of self-reported chemosensory dysfunction (anosmia/hypomsia and dysgeusia/ageusia). Subgroup analysis was performed to evaluate the prevalence of chemosensory deficits among the outpatients.
Results:
We identified a total of 350 COVID-19–positive patients (138 Canadians and 212 Israelis). The overall prevalence of chemosensory dysfunction was 47.1%. There was a higher proportion of chemosensory deficits among Canadians compared to Israelis (66.7% vs 34.4%, P < .01). A subgroup analysis for outpatients (never hospitalized) still identified a higher prevalence of chemosensory dysfunction among Canadians compared to Israelis (68.2% vs 36.1%, P < 0.01). A majority of patients recovered their sense of smell after 4 weeks of symptom onset.
Conclusion:
Although the prevalence of chemosensory deficit in COVID-19 was found to be similar to previously published reports, the prevalence can vary significantly across different geographical regions. Therefore, it is important to obtain regionally specific data so that the symptom of anosmia/dysgeusia can be used as a guide for screening for the clinical diagnosis of COVID-19.
Introduction
Coronavirus Disease 2019 (COVID-19) is an international outbreak of respiratory illness with high transmission rates. Among all possible presentations of COVID-19, chemosensory dysfunction, including anosmia, hyposmia, ageusia, and dysgeusia, has been identified as key symptoms of COVID-19 due to its high prevalence.1-16 In fact, the strong association between chemosensory dysfunction and COVID-19 diagnosis led to advocating for the addition of these symptoms as part of the screening process.17,18
Since the first report of chemosensory dysfunction in COVID-19, there have been multiple studies in various regions demonstrating a range of prevalence.11,14,16,19 The findings have been compiled in several systematic reviews and meta-analyses, which corroborated the association of chemosensory dysfunction and COVID-19 diagnosis with geographic variances.1,2,10,12,14 Interestingly, one meta-analysis highlighted ethnic differences with higher prevalence of chemosensory dysfunction among Caucasians than Asians. 14 However, the included studies are survey based with variable question formats that can lead to retrospective bias. In our previous study, we demonstrated variable rates of anosmia, hyposmia, or dysgeusia depending on the question format, leading up to a 11% difference in the prevalence of chemosensory dysfunction (46.4%-57.1%). 7 The Global Consortium for Chemosensory Research group recently administered multilingual surveys internationally. 9 Despite the large number of participants, the study is limited by the self-reported COVID-19 status. Therefore, it is imperative to examine the prevalence of chemosensory dysfunction among test-proven COVID-19–positive patients in geographically distinct regions with the same questionnaire in different languages. This would allow for more accurate depiction of the characteristics of COVID-19–positive patients in different regions. The objective of this study was to evaluate and compare the rates of self-reported anosmia, hyposmia, and dysgeusia in patients who tested positive for COVID-19 in Canada and Israel.
Patients and Methods
Study Design and Patient Population
Approval of this study was granted by the Research Ethics Board at Unity Health Toronto, Toronto, Ontario, Canada, through Clinical Trials Ontario (CTO ID: 2142) and at Sheba Medical Centre, Israel (REB ID: 7282-20-SMC). We administered a cross-sectional survey of adults (older than 18 years) who tested positive following polymerase chain reaction-confirmed COVID-19 testing via nasopharyngeal swab at the COVID-19 Assessment Centre at St. Michael’s Hospital, Toronto, Canada, between March 16, 2020, and June 3, 2020, and at Sheba Medical Centre, Ramat-Gan, Israel, between June 10, 2020, and August 19, 2020. The questionnaire is available in the Supplementary Material. In Canada, patients were contacted by phone for an invitation to a secure online survey that was constructed using Snap Software, fully compliant with Personal Health Information Protection Act, after being notified of the results of their swab. In Israel, COVID-19–positive patients, who tested positive at the Assessment Centre, were contacted by text messages for an invitation to an online survey. Some patients and staff, who did not have access to the Internet, completed the survey by phone. During this period, we identified and collected information from 138 unique Canadian COVID-19–positive patients and 212 Israeli patients.
Outcome Measures and Data Collection
Baseline characteristics were collected and included age, gender, medical comorbidities, and smoking status. We listed chronic rhinosinusitis and history of recent severe upper respiratory tract infection (URTI) or flu as a separate comorbidity, as these may impact baseline sense of smell. COVID-19 diagnosis, symptoms, and hospitalizations were collected. Smell and taste-specific questions included the presence of smell or taste loss around the onset of COVID-like symptoms (5 days earlier or any time after) as well as the current ability to smell. The type of taste loss was collected (sweet, salty, sour, bitter, and savory).
Statistical Analysis
Demographic and clinical characteristics were summarized descriptively by reporting the median and interquartile range (IQR) for continuous variables and the frequency and proportion for categorical variables. Differences in characteristics between 2 comparison groups were compared using the Kruskal-Wallis test for continuous variables and Fisher exact test for categorical variables.
Results
Study Population and Baseline Characteristics
Baseline information is summarized in Table 1. In general, Canadian patients were younger than Israeli patients (38.0 [IQR 32.0-52.0] vs 51.0 [IQR 34.0-64.0], P < .01). Gender and previous history of chronic rhinosinusitis was well balanced. There was a significantly higher proportion of hospitalizations among Israeli patients. There was a longer time lapse between the symptom onset and the survey among the Israeli patients compared to the Canadian patients (95.9% for Israeli and 43.9% for Canadian for more than 4 weeks since the diagnosis).
Comparisons of Baseline Characteristics of Groups by Country of Origin.
Prevalence of Anosmia/Hyposmia and Dysgeusia
The overall symptoms are summarized in Table 1. Overall, there was a higher proportion of chemosensory dysfunction (anosmia, hyposmia, and/or dysgeusia) among Canadian patients than Israeli patients (66.7% vs 34.4%, P < .01) for both outpatients and inpatients. In specific, a significantly higher proportion of Canadian patients reported hyposmia and/or anosmia (55.8% vs 30.2%, P < .01) and dysgeusia (55.8% vs 19.8%, P < .01).
Prevalence of Anosmia/Hyposmia and Dysgeusia Among Outpatients
Due to a higher proportion of hospitalizations among the Israeli patients, a subgroup analysis was performed evaluating only those who were treated as outpatients (Table 2). Among the outpatients, there still is a higher proportion of chemosensory dysfunction among Canadian patients than Israeli patients (68.2% vs 36.1%, P < .01). There was a higher proportion of Canadian patients who reported olfactory dysfunction as well (57.4% vs. 32.0%, P < .01). There was no difference between outpatients and inpatients among Israeli participants in terms of olfactory or gustatory dysfunction.
Subgroup Analysis Between Canadian and Israeli Outpatients.
Abbreviations: IQR, interquartile range; URTI, upper respiratory tract infection.
Self-Reported Timing of Anosmia/Hyposmia and Recovery of Smell
Characterization of olfactory dysfunction is summarized in Table 3. There was a variable reported timing of olfactory dysfunction. Ten percent of patients reported olfactory dysfunction as the very first symptom of COVID-19, while others reported the development of anosmia or hyposmia after other symptoms. There was no difference between Canadians and Israelis. A majority of patients who reported complete recovery of smell (65.0% for Canadians and 94.0% for Israeli) completed the survey more than 4 weeks after the symptom onset. On the other hand, a large proportion of patients who have not recovered sense of smell were still within the 4-week window (80.0% for Canadians and 50.0% for Israelis).
Characterization of Olfactory Dysfunction Among Outpatients by Country of Origin.
Comparison of Patients With and Without Olfactory Dysfunction
There was no difference between patients with and without olfactory dysfunction in terms of age, smoking, and relevant comorbidities (chronic rhinosinusitis, recent URTI/flu, head trauma; Table 4). However, there was a significantly higher prevalence of rhinorrhea (28.6% vs 13.2%, P < .01) and nasal congestion (32.4% vs 12.4%, P < .01) among the ones with olfactory dysfunction.
Comparison of Clinically Relevant Variables Between the Outpatient Group With Olfactory Dysfunction and No Olfactory Dysfunction.
Abbreviations: IQR, interquartile range; URTI, upper respiratory tract infection.
Discussion
COVID-19 cases continue to rise in many nations and in fact is emerging as a second wave in several jurisdictions. With rising cases and limited testing capacity, especially in developing nations, it is important to characterize the prevalent symptoms to tailor screening strategies for COVID-19 testing. Although there have been numerous studies investigating chemosensory dysfunction in COVID-19, the studies use variable formats of questionnaires or self-reported COVID-19 diagnosis status that can lead to retrospective bias.1,2,9,10,12,14 In fact, our previous study demonstrated that there can be a variable rate of olfactory or gustatory dysfunction rate even within the same study, depending on the question format. To address this shortcoming, our current study sought to directly compare geographically distant areas in terms of chemosensory dysfunction using the identical questionnaires among COVID-19–positive patients.
The results of our study show that olfactory and gustatory dysfunction are prevalent symptoms among COVID-19 patients. When comparing 2 geographically distinct centers, we found that Canadians had a higher prevalence of chemosensory dysfunction than Israeli (66.7% vs 34.4%). Interestingly, this difference in the prevalence of chemosensory dysfunction persisted in a subgroup analysis of outpatients only. Most patients, however, after 4 weeks from the symptom onset, recovered their sense of smell, demonstrating the transient nature of olfactory dysfunction in COVID-19.
Our overall rate of chemosensory dysfunction of 47% is within the rate of 40% to 50% in recently published meta-analyses on this topic.1,2,10,12,14 The higher rate of chemosensory dysfunction among the Canadian population in our series is consistent with another Canadian report of 65%. 3 Meanwhile, the lower rate of chemosensory dysfunction among the Israeli population in our series is again consistent with other Israeli reports of 27% to 36%.19,20 In fact, the regional differences have been demonstrated in a recent meta-analysis, which suggested potential ethnic differences in the development of chemosensory deficits. 14 The potential reasons for this phenomenon may be 2-fold. First, there may be geographic variation with respect to the virus and its mutation. While the G614 strain was more dominant in Western countries, the D614 strain was more dominant in Asia.21,22 In general, there have been lower rates of olfactory dysfunction reported in Asia compared to the Western countries. There have also been genomic studies that demonstrated the presence of mutant strains with potentially varying pathogenicity along with ethnic differences for receptors.23-25 Second, there may be cultural differences in the perception of olfactory or gustatory dysfunction.26-28 While we did not explicitly collect data on the ethnicity, Toronto, Canada, is a multiethnic city, while Ramat-Gan, Israel, has a more homogenous population. 29 Therefore, it is possible that the cultural perception may be the dominant power in self-reported chemosensory impairment. Regardless, it is important to collect and examine regional data to depict a representative landscape for each regional population.
Previous studies have also demonstrated a lower rate of chemosensory deficits among hospitalized patients than nonhospitalized patients.12,14,30 Our study did not clearly demonstrate this, as there was no difference among the Israeli patients. This may be due to the policy at Sheba Medical Centre that patients over certain age with comorbidities were admitted for observation with COVID-19 diagnosis. In other words, hospitalization may not be an indicator of disease severity in our particular population, and this may explain the similar rates of chemosensory deficits among those who were hospitalized and who were not.
Limitations of our study include recall bias with a significant time lapse between the symptom onset and survey administration. Specifically, there is a higher chance of recall bias among the Israeli population with a longer lapse of time period. This could have resulted in a lower rate of self-reported chemosensory dysfunction. The public awareness of COVID-19–related chemosensory dysfunction may have resulted in elevated rates of self-reported chemosensory deficits. We also acknowledge nonresponse bias. Finally, with ethical concerns related to transmission in the context of the current pandemic, we are unable to objectively measure the sense of smell or taste for COVID-19 patients during the point of assessment.
Conclusion
Our results demonstrate that there is a different prevalence of self-reported chemosensory dysfunction in COVID-19 patients between Canada and Israel. Given this geographic variation, there is a need to systematically collect symptoms from different regions of the world to fully utilize the loss of smell and taste as key symptoms for the clinical diagnosis of COVID-19.
Supplemental Material
Supplemental Material, sj-pdf-1-ear-10.1177_01455613211000170 - Comparative Study of Chemosensory Dysfunction in COVID-19 in 2 Geographically Distinct Regions
Supplemental Material, sj-pdf-1-ear-10.1177_01455613211000170 for Comparative Study of Chemosensory Dysfunction in COVID-19 in 2 Geographically Distinct Regions by Daniel J. Lee, Daniella Daliyot, Ri Wang, Joel Lockwood, Paul Das, Eyal Zimlichman and John M. Lee in Ear, Nose & Throat Journal
Footnotes
Authors’ Note
D. Lee, J. Lockwood, P. Das, R. Wang, D. Daliyot, E. Zimlichman, J. Lee contributed to study concept and design. D. Lee, J. Lockwood, P. Das, D. Daliyot, E. Zimlichman, J. Lee contributed to acquisition of data. D. Lee, R. Wang, J. Lee contributed to analysis and interpretation of data. D. Lee contributed to initial draft of the manuscript. D. Lee, J. Lockwood, P. Das, D. Daliyot, E. Zimlichman, R. Wang, J. Lee contributed to critical revision of the manuscript for important intellectual content. D. Lee, J. Lee contributed to administrative, technical, or material support. J. Lee contributed to study supervision. All authors have given their agreement for this study.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JML is on the advisory board for Sanofi Genzyme.
Funding
The author(s) disclosed receipt of the financial support for the research, authorship, and/or publication of this article: The Dunin Foundation.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
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