J Korean Med Sci.  2021 Jan;36(4):e40. 10.3346/jkms.2021.36.e40.

Regional and Chronological Variation of Chemosensory Dysfunction in COVID-19: a Meta-Analysis

• Kim JW
• Han SC
• Jo HD
• Cho SW
• Kim JY

• KMID: 2511637
• DOI: http://doi.org/10.3346/jkms.2021.36.e40

Abstract

Background
Olfactory and gustatory dysfunction are frequently reported in patients with coronavirus disease 2019 (COVID-19). However, the reported prevalence of olfactory and/or gustatory dysfunction varies widely, and the reason for the inter-study differences is unclear. Hence, in this meta-analysis, we performed subgroup analyses to investigate the factors that contribute to the inter-study variability in the prevalence of olfactory and gustatory dysfunction.
Methods
Out of 943 citations, we included 55 eligible studies with 13,527 patients with COVID-19 for a meta-analysis. Calculating the data extracted from each study, the weighted summary prevalence of olfactory and gustatory dysfunction was estimated using a FreemanTukey transformation with models based on random-effects assumptions. A meta-analysis of variance compared the prevalence of olfactory and gustatory dysfunction according to regional, chronological, demographic, and methodologic factors, respectively.
Results
The overall pooled prevalence rates of olfactory and gustatory dysfunction were 51.4% and 47.5%, respectively, in the random-effect model. In subgroup analyses, the prevalence rates of olfactory and gustatory dysfunction were significantly different among four geographical regions (both P < 0.001, respectively). Although the prevalence rates of olfactory and gustatory dysfunction did not significantly differ according to the time of enrollment, the subgroup analyses including only studies from the same geographical region (Europe) revealed a significant difference in olfactory dysfunction according to the time of enrollment.
Conclusion
The regional and chronological differences in the prevalence rates of olfactory and gustatory dysfunctions partly explain the wide inter-study variability.

Keyword

Coronavirus; Smell; Taste; Meta-Analysis; Geographic Location

Figure

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  Fig. 1 Study selection diagram.

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  Fig. 2 Subgroup analysis on region. (A) Forest plot meta-analysis of the prevalence of olfactory dysfunction of four regions (East Asia, Europe, North America, and Middle East) showed 25.3%, 57.5%, 41.8%, and 59.8% pooled subgroup prevalence rates in the random-effect model, respectively (P < 0.001 for subgroup difference). (B) Forest plot meta-analysis of the prevalence of gustatory dysfunction of four regions (East Asia, Europe, North America, and Middle East) showed 19.4%, 53.1%, 46.2%, and 47.9% pooled subgroup prevalence rates in the random-effect model, respectively (P < 0.001 for subgroup difference). The diamonds represent pooled prevalence rates with 95% CI, and the estimates of individual studies are represented as squares, with 95% CIs represented as horizontal lines.CI = confidence interval.

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  Fig. 3 World map of the prevalence rates of olfactory and gustatory dysfunction in coronavirus disease 2019 patients. The colored regions indicate the geographically classified regions in this study (aqua blue: East Asia, yellow: Europe, red: North America, navy: Middle East). The prevalence rates of olfactory and gustatory dysfunction, number of included studies and patients, and number of studies according to the evaluation method are presented for each region.

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  Fig. 4 Subgroup analysis on the time of enrollment. The time of enrollment was clarified in 29 out of 55 studies. After calculating the median date (mid-date) between beginning and end date of the time of enrollment, the individual studies were categorized into three groups: 1st period (mid-date February 2, 2020 to March 17, 2020), 2nd period (mid-date March 20, 2020 to March 29, 2020), and 3rd period (mid-date March 30, 2020 to April 9, 2020). (A) Forest plot meta-analysis of the prevalence of olfactory dysfunction of the three periods showed 39.5%, 57.7%, and 49.0% pooled subgroup prevalence rates in the random-effect model, respectively (P = 0.391 for subgroup difference). (B) Forest plot meta-analysis of the prevalence of gustatory dysfunction of the three periods showed 40.9%, 51.2%, and 40.5% pooled subgroup prevalence rates in the random-effect model, respectively (P = 0.778 for subgroup difference). (C) Forest plot meta-analysis of the prevalence of olfactory dysfunction only including studies conducted in Europe for the three periods showed 45.2%, 65.4%, and 59.0% pooled subgroup prevalence rates in the random-effect model, respectively (P = 0.013 for subgroup difference). (D) Forest plot meta-analysis of the prevalence of gustatory dysfunction of the three periods showed 49.8%, 60.2%, and 49.3% pooled subgroup prevalence rates in the random-effect model, respectively (P = 0.538 for subgroup difference). The diamonds represent pooled prevalence rates with 95% CI, and the estimates of individual studies are represented as squares, with 95% CIs represented as horizontal lines.CI = confidence interval.

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  Fig. 5 The pooled prevalence of olfactory and gustatory dysfunction was presented chronologically. The overall and European pooled prevalence rates of olfactory and gustatory dysfunction are shown, discriminated by color. The prevalence rates of both olfactory and gustatory tended to increase from the 1st to 2nd period but decreased from the 2nd to 3rd period.

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  Fig. 6 Subgroup analysis on the evaluation method. The evaluation method was classified into history taking, self-reported survey, validated survey, and validated instrument. (A) Forest plot meta-analysis of the prevalence rates of olfactory dysfunction of the four evaluation methods showed 23.4%, 52.1%, 72.9%, and 69.2% pooled subgroup prevalence rates in random-effect model, respectively (P < 0.001 for subgroup difference). (B) Forest plot meta-analysis of the prevalence rates of gustatory dysfunction of the four evaluation methods showed 23.5%, 53.2%, 68.5%, and 48.4% pooled subgroup prevalence rates in random-effect model, respectively (P < 0.001 for subgroup difference). The diamonds represent pooled prevalence rates with 95% CI, and the estimates of individual studies are represented as squares, with 95% CIs represented as horizontal lines.CI = confidence interval.

• 

  Fig. 7 Subgroup analysis on the characteristics of population. The characteristics of population was classified into general population, hospitalized population, non-hospitalized population, and population of healthcare workers. (A) Forest plot meta-analysis of the prevalence of olfactory dysfunction of the four demographics showed 58.7%, 36.7%, 52.3%, and 48.9% pooled subgroup prevalence rates in the random-effect model, respectively (P < 0.001 for subgroup difference). (B) Forest plot meta-analysis of the prevalences of gustatory dysfunction of the four demographics showed 56.2%, 28.3%, 51.1%, and 51.5% pooled subgroup prevalence rates in random-effect model, respectively (P < 0.001 for subgroup difference). The diamonds represent pooled prevalence rates with 95% CI, and the estimates of individual studies are represented as squares, with 95% CIs represented as horizontal lines.CI = confidence interval.

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