key: cord-0922760-5ou52aaj
authors: Cirillo, Nicola
title: Taste alteration in COVID-19: significant geographical differences exist in the prevalence of the symptom
date: 2021-07-09
journal: J Infect Public Health
DOI: 10.1016/j.jiph.2021.07.002
sha: e1c301738021c6bf71be11cec10f8713f48dce5e
doc_id: 922760
cord_uid: 5ou52aaj

Early detection of COVID-19 is important for reduction in the spread of the disease and gustatory disturbances (GD) are known to have a strong predictive value. In the present study, we aimed to map the geographical differences in the prevalence of GD in individuals infected with SARS-CoV-2 in order to improve case identification and to facilitate prioritization. We undertook a rapid scoping review of articles published in the repository of the National Library of Medicine (MEDLINE/PubMed) and medRxiv from their inception until 3(rd) September, 2020. The minimum requirements for completing a restricted systematic review were fulfilled. Of the 431 articles retrieved, 61 studies (28,374 cases confirmed with COVID-19) from 20 countries were included in the analysis. GD were most prevalent in the Americas [66.78%, 95% CI 54.77–78.79%] compared to Europe [57.18%, 95% CI 52.35–62.01%], the Middle East [38.83%, 95% CI 27.47–50.19%] and East Asia [13.1%, 95% CI 0.14–26.06%]. No differences of GD prevalence were evident between February and August 2020. The data demonstrate that there is a marked geographical distribution of GD in COVID-19 patients which, possibly, might be explained by differences in diagnostic criteria for COVID-19 case definition.

The early identification and confirmation of suspected cases of Coronavirus Disease 2019 is fundamental to limiting the spread of the disease but is particularly challenging for asymptomatic or pauci-symptomatic patients. The sudden loss of taste (ageusia), with or without loss of smell (anosmia), have been cited as independent signs of the disease although, more frequently, these symptoms occur in association with the most common manifestations of the disease, namely, fever, cough and fatigue [1] . Unlike early studies [2, 3], recent systematic reviews have indicated that gustatory dysfunction (GD), including ageusia, hypogeusia and dysgeusia, is common in COVID-19 patients [4] . Furthermore, loss of taste and smell have been reported to be distinguishing symptoms of COVID-19 which have a high predictive value [5] .

The European Centre for Disease Prevention and Control (EDCD) was one of the first public health bodies to include sudden onset anosmia, ageusia or dysgeusia as clinical criteria to identify possible COVID-19 cases [6] . Unfortunately,, these symptoms have not been used unanimously for case identification and for testing prioritization. On 5 th August 2020, however, J o u r n a l P r e -p r o o f the Centers for Disease Control and Prevention in the USA updated their COVID-19 case definition to include GD as an important clinical criterion for diagnosis [7] . Soon afterwards (7 th August, 2020), the World Health Organization updated its COVID-19 case definition to include recent onset ageusia, in the absence of any other identifiable cause, as suggestive of

In the present study, we hypothesized that differences in the criteria used for COVID-19 identification by national and/or local public health bodies may reflect, at least in part, the changes of known prevalence rates of these symptoms over time and in a geographically specific manner. Specifically, we undertook a rapid systematic review of the prevalence of GD in COVID-19 cases and examined worldwide data from East Asia, the Middle East (including Turkey), Europe (including Britain) and the Americas.

We identified 431 studies; 91 relevant articles met the inclusion criteria. 61 of the 91 studies were included for data analysis (Figure 1 ). Why did you exclude 30 studies? The studies were from 20 different countries; 5 studies were derived from multi-national collaborations. The majority of cohorts were from Europe (n=40), followed by the Middle East (n=8), North and South America (n=6 and n=2, respectively), East Asia (n=6) and Africa (n=1). Two articles [9, 10] pooled multinational data within Europe and 3 studies [11-13] included cases from two main geographical areas. The study populations and prevalence range are depicted graphically in Figure 2 .

Worldwide, 14,486 of 28,374 confirmed COVID-19 cases (51.05%) reported subjective and/or objective GD (Table 1) . Strikingly, there were significant differences of prevalence between subgroups (ANOVA, p = 0.000106; Kruskal-Wallis, p = 0.00071). Further, when each geographical region was compared, there were significant differences between all of the subgroups except Europe vs America (Suppl Table 1 ). Studies from East Asia reported the J o u r n a l P r e -p r o o f lowest prevalence of GD (13.1%, 95% CI 0.14-26.06%), followed by the Middle East ( (Supplementary Figure 1) .

An awareness of the association between taste alterations and COVID-19 infection is important for diagnosing the disease, particularly in dental and oral health settings [14] . In the present study, we followed a streamlined approach to synthesizing evidence (the rapid review) which patients, researchers found the symptom to be of "limited and inconclusive" value [3]. The first study reporting a 5.1 and 5.6% prevalence of hyposmia and hypogeusia, respectively, was a pre-print (non-peer-reviewed) case series of a Chinese population [15] . In sharp contrast, the most recent meta-analysis analyzing smell and taste alterations not only reported that almost half of COVID-19 patients had these symptoms but also, that 15% of patients had olfactory and gustatory abnormalities as their initial presenting symptoms [16] .

Recent systematic reviews have assessed chemosensory alterations in COVID-19 patients [4, [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] . Only one review, however, has focused specifically on taste changes [31] . In their pooled analysis, Aziz et al. [31] found that almost half of patients (49.8%) with COVID-19 had altered taste sensation. Similarly, when the data was pooled in the reviews assessing A major limitation of the present study is that it includes research with diverse study designs and patients with different disease severity, e.g. severe, mild, or asymptomatic COVID-19

cases. Further, the majority of the studies that were analysed were cross-sectional, retrospective and observational, hence recollection bias may have been present. Most studies were similar to those previously graded as "moderate risk of bias" [29] . Importantly, the presence of taste alterations may not have been reported in the presence of other more severe symptoms such as dyspnea, fever and productive cough which could explain the lack of association between GD and COVID-19 in the first studies published in February and March 2020.. For these reasons, the true prevalence of ageusia, hypogeusia and dysgeusia might be significantly higher than reported [31] . The data that were examined in the present study involved the subjective (self-reported) and objective (testing with the four basic tastes of sweet, sour, salty and bitter modalities sprayed onto the tongue in a supra-threshold doses) interpretation of GD. Previous findings, however, have shown that there are no significant differences between the subjective and objective interpretation of gustatory function [18] and, therefore, we suggest that self-reported taste alterations can be considered a reliable parameter for GD in COVID-19 patients.

In conclusion, we show that GD in COVID-19 exhibits distinct geographical patterns of prevalence. Given the potential usefulness of taste assessment in the diagnosis of mildly and pauci-symptomatic patients, we believe that it is imperative to recognize ageusia/hypogeusia/dysgeusia as a potential clinical manifestation of COVID-19, particularly in Europe and America. Dentists, therefore, may be the first healthcare providers to diagnose taste disturbances and are likely to play an important role in case identification and early diagnosis of COVID-19 cases in the future.

This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and used a rapid review approach due to time constraints [89] . The study complied with the minimum requirements for completing a restricted systematic review [90] . Accordingly, the search was performed by one investigator (N.C.) and verification of a random sample of full texts for accuracy of title/abstract screening J o u r n a l P r e -p r o o f and data extraction was undertaken by the same reviewer. Key terms used for the search were (SARS-CoV-2 or COVID or COVID-19) in association with taste or ageusia or hypogeusia or dysgeusia or gustatory. The search was conducted in PubMed/MEDLINE as well as medRxiv using the advanced search (title and abstract) tool.

The exclusion criteria were as follows: articles not in English, duplicate publications, irrelevant articles, studies where the infection status was not clearly confirmed, studies that did not evaluate gustatory outcomes individually, simple case reports, and review or systematic review articles. Studies using telephone surveys or Apps were only included where the respondents had a confirmed COVID-19 diagnosis. For studies reporting cases from two or more geographical areas (e.g. East Asia and Europe), the data for subgroup analysis were extracted only when information from individual countries was available. Where the date of patient recruitment was not provided, the date of the article submission was used as a surrogate source of information. The primary outcome was to assess the prevalence of gustatory alterations (ageusia, hypogeusia, dysgeusia) in confirmed COVID-19 cases worldwide and in distinct geographical areas; the secondary outcome was to establish a spatio-temporal pattern of GD in published cases. No constraints were placed on the size of the cohorts to ensure a comprehensive search and to identify the maximum number of potential articles.

Subgroup analyses were based on the country of origin of the studies by pooling the actual data reported in each individual study. Differences in prevalence (% and category) among subgroups

were assessed with chi-square statistics and one-way ANOVA, as appropriate. Tukey's posthoc test or Student's t tests were used for comparison between group pairs. By making a further assumption that the dependent variable may not be normally distributed, the Kruskal-Wallis J o u r n a l P r e -p r o o f test was also used to compare overall differences in prevalence. Where appropriate, Pearson's coefficient was used to assess the correlation between time and prevalence. A level of p <0.05 was chosen to determine statistical significance.

Ethics approval and consent to participate: Not applicable Consent for publication: N.C. approved the final version of the manuscript.

Availability of data and material: The datasets used and/or analyzed during the current study can be made available by the corresponding author on a reasonable request. 

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