Pesquisa Brasileira em Odontopediatria e Clínica Integrada 2021; 21:e0011

[Link]
ISSN 1519-0501 / eISSN 1983-4632

ORIGINAL ARTICLE

Analysis of Tongue Color-Associated Features among Patients

with PCR-Confirmed COVID-19 Infection in Ukraine

Liudmyla Horzov1 , Myroslav Goncharuk-Khomyn2 , Natalia Hema-Bahyna3 , Anastasia

Yurzhenko4 , Volodymyr Melnyk5

1Department of Therapeutic Dentistry, Uzhhorod National University, Uzhhorod, Ukraine.

2Department of Prosthetic Dentistry, Uzhhorod National University, Uzhhorod, Ukraine.
3Department of Clinical Disciplines, Uzhhorod National University, Uzhhorod, Ukraine.

4Department of Dentistry of Postgraduate Education, Uzhhorod National University, Uzhhorod, Ukraine.

5Department of Pediatric Dentistry, Uzhhorod National University, Uzhhorod, Ukraine.

Correspondence: Myroslav Goncharuk-Khomyn, Uzhhorod National University, Universitetska 16/a st., Uzhhorod,
88000, Ukraine. E-mail: [Link]-khomyn@[Link]

Academic Editor: Alessandro Leite Cavalcanti

Received: 19 January 2021 / Review: 24 February 2021 / Accepted: 05 March 2021

How to cite: Horzov L, Goncharuk-Khomyn M, Hema-Bahyna N, Yurzhenko A, Melnyk V. Analysis of tongue color-
associated features among patients with PCR-confirmed Covid-19 infection in Ukraine. Pesqui Bras Odontopediatria Clín
Integr. 2021; 21:e0011. [Link]

ABSTRACT
Objective: To evaluate and systematize tongue color-related manifestations among patients with PCR-
confirmed COVID-19 infection. Material and Methods: This retrospective study included analysis of
tongue images obtained from patients with PCR-confirmed COVID-19 infection. Evaluation of coronavirus
disease severity (mild, moderate, severe, critical) was provided, considering clinical symptomatology and
results of laboratorial and instrumental diagnostic methods. Each picture was analyzed considering the
parameters of color of the tongue and color of the tongue plaque by two dental specialists. Cochran-
Armitage test for trend was used to evaluate associations between the tongue color and tongue plaque color,
and coronavirus disease severity. Results: The most prevalent tongue colors were pale pink, red and dark
red (burgundy color). A total of 64.29% of patients with mild disease demonstrated pale pink color of the
tongue. Patients with moderate coronavirus disease were characterized with the adverse trend: 62.35% of
them presented with red-colored tongue, while in 37.64% of cases, the tongue was pale pink. Severe
COVID-19 patients, almost in 90% of the cases, had either red or burgundy color of the tongue.
Conclusion: SARS-COV-2 infection is not manifested by tongue-targeted or tongue-specific signs and
features; however, coronavirus disease itself provokes changes within the tongue color and tongue plaque
color similar to those registered during other internal pathologies.

Keywords: Coronavirus Infections; Severe Acute Respiratory Syndrome; Tongue.

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Association of Support to Oral Health Research - APESB
 Pesqui. Bras. Odontopediatria Clín. Integr. 2021; 21:e0011

Introduction
State of health could be indirectly evaluated by the analysis of the tongue color and the color of plaque
accumulated on it before and during the clinical course of different internal diseases [1-5]. A clean tongue
without plaque is a sign of a healthy person, while some of the somatopathologies are characterized with
adjacent tongue manifestations, which either could be pathognomonic or included within the set of general
symptoms [6].
Tongue-related features could be used as valuable diagnostic signs for health evaluation purposes
under the machine learning processing approach, which includes the implementation of multi-modal
algorithms to relate tongue changes (as image biomarkers) with other symptoms and pathological conditions
(including coronavirus disease) [7-10]. Nevertheless, tongue features seem to be mostly related to the
syndrome rather than the disease itself [11]. Previously it was found that lung diseases, such as tuberculosis,
amyotrophic lateral sclerosis, a chronic obstructive pulmonary disease characterized with corresponding
tongue manifestations [12-15].
Globally at the date of 13th of January 2021, there have been more than 90 million confirmed cases of
COVID-19 reported to WHO, including 1,954,336 deaths [16]. In Ukraine, more than 1 million confirmed
cases of COVID-19 with 20,214 deaths have been reported to the above-mentioned date [16]. Considering the
COVID-19 pandemic situation, ongoing study of the manifestations related to this pathology within the oral
cavity, particularly on the tongue, remains as an important practical and scientific objective [17-20]. The most
common oral symptoms among persons who have suffered from a coronavirus infection include punctate
hemorrhages in the form of red bumps, candidiasis, ulcers and various other lesions of the tongue and mucous
membranes [17-19].
Chemosensory dysfunctions regarding smell and taste are considered one of the most prevalent
screening signs among patients with influenza-like symptomatology, who could potentially be diagnosed as
COVID-positive [21-23]. The nature of the COVID-related taste disorder remains under further investigation
since this sign could be conceivably associated with developing hyposalivation, changes in saliva composition
and neurological alterations [21,22].
Several studies have already investigated tongue-related features as the symptoms of COVID-19 and
found statistically significant differences between COVID-19 patients and healthy people [24,25]. But there
are only a small number of publications that address the topic of COVID-associated changes of the tongue
related to the coronavirus disease severity. Previously it was found that the level of greasy coating and
tenderness of the tongue are the most diagnostically sensitive signs for COVID-19 severity differentiation
[26]. Pang et al. [26] concluded that studies regarding the quantification of tongue manifestations during
coronavirus disease should be provided with the purpose to improve diagnostics, differentiation, and treatment
of COVID-19 during the present pandemic era.
This study aimed to evaluate and systematize tongue color-related manifestations among patients
with PCR-confirmed COVID-19 infection considering disease severity.

Material and Methods

Study Design and Data Collection
The design of the study was retrospective and included analysis of tongue images obtained from
patients with PCR-confirmed COVID-19 infection. Analyzed patients’ cohort was formed out of persons
hospitalized in the reorganized COVID-Department of Uzhhorod Regional Clinical Hospital with COVID-

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associated symptomatology and further identified having SARS-COV2 by PCR method using oropharyngeal
and nasal swabs samples.
Tongue pictures were obtained by the infectious disease specialist, who was directly providing
treatment for COVID-19 patients in the corresponding department using smartphone devices without
considering some specific technical characteristics of photodocumentation due to the relevant sanitary
restrictions limited possibilities to obtain high-quality photos. Each image was taken with no magnification
effect and no filters used. As a result, tongue photos were received with respect to all implemented restrictions
and sanitary requirements while not compromising any affiliated risk of infection for medical personal or
patients.
Obtained tongue pictures were coded and anonymized with the additional description provided just
for the severity of coronavirus disease associated with each photo at the day of its’ reception, age, and gender of
the patient. Evaluation of coronavirus disease severity (mild, moderate, severe, critical) was provided by
professional infectionists due to the World Health Organization recommendations [27], considering clinical
symptomatology of the patients and results of additional laboratorial and instrumental diagnostic methods.
Binary informational blocks in the amount of 167 pairs consisted of tongue photo in *.jpeg format and
text info with a description of verified COVID-19 severity, patient’s age and gender were sent to the
Department of Therapeutic Dentistry (Uzhhorod National University) via restricted access to Google Drive
folder. Each picture was analyzed considering the parameters of color of the tongue and color of the tongue
plaque by two dental specialists (experts) independently. Experts were assigned from the personal of the
Department of Therapeutic Dentistry and Department of Prosthetic Dentistry (Uzhhorod National
University) (chosen experts were previously calibrated by taking participation in various epidemiological and
clinical studies).
With the purpose to exclude the effect of the interpretation error, which could occur during expert
evaluation and comparison of study object (tongue image) with some addressable classification’ referent, dental
specialists who provided analysis of the tongue pictures were asked to describe them considering the color of
the tongue or the color of tongue plaque without referring to any classification or categorization system by one
or two color-associated adjective words.
Out of 167 tongue images, 32 were excluded from the study sample due to the presence of blurring
effect, critical contrasting, cropping of some tongue part on the picture and moving-associated artefacts.

Data Analysis
Statistical argumentation of obtained differences considering correspondences between the tongue
color and tongue plaque color to COVID-19 severity within groups of patients with mild, moderate and severe
stages of the coronavirus disease was based on inter-groups’ prevalence parameters comparison [28-30].
Cochran-Armitage test for trend was used to evaluate associations between the tongue color and tongue plaque
color and coronavirus disease severity [31,32]. Such an approach was modified from Pang et al. [26], at which
authors used the Chi-square test for trend analysis. Registered outcome values were validated as statistically
significant if p<0.05. Reproducibility of two dental specialists who provided analysis of tongue images
considering the evaluation of the tongue color and tongue plaque color was calculated by the Cohen’s kappa,
parameters of which reached 0.83 ± 0.06 and 0.80 ± 0.09 respectively, while inter-rater percentage agreement
was 86.7% and 83.4% respectively [32,33]. Final categorization of obtained tongue images, received
description and numerical values were provided due to the following targeted parameters: tongue color, tongue
plaque color, patient’s age group (due to the 10 years period distribution), patient’s gender (male/female).

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Statistical data processing was held within Microsoft Excel software (Microsoft Office 2019, Microsoft
Corp., USA) with the additional use of add-ins, such as Analyse-it (Analyse-it Software Ltd., Leeds, UK) and
XLSTAT (Addinsoft Inc., New York, N.Y, USA).

Ethical Aspects
This study was previously affirmed by the Ethical Committee of Faculty of Dentistry at Uzhhorod
National University 2020 (Protocol No. 1/10092020). All the patients signed modified informed consent form
included in their general medical documentation, which contained the section about the possibility of using
their medical data with the research and investigation purposes for the improvement of medical care quality
during COVID-19 era while providing full guarantee and security of personal issues (including obligatory
anonymization) and in the correspondence of established ethical principles.

Results
Among 135 patients, who’s tongue images were analyzed, 64 were males (47.41%) and 71 were
females (52.59%). The average age was of the patients was 48.7 ± 13.2 years varying in the range from 18 to 82
years old. Distribution of patients regarding age criteria presented in Table 1.

Table 1. Distribution of patients with PCR-confirmed cases of COVID-

19 due to the age criteria.
Age Group (Years) N %
<20 8 5.88
21-30 15 11.03
31-40 17 12.50
41-50 28 20.50
51-60 23 16.91
61-70 17 12.50
71-80 14 10.29
> 80 13 9.56

“The distribution of patients regarding coronavirus disease severity was as follows: 14 (10.37%)
patients with mild coronavirus disease severity; 85 (62.96%) patients with moderate coronavirus disease
severity; 36 (26.67%) patients with severe coronavirus disease; and no patients with critical severity of
pathology were observed in this study.
The most prevalent tongue colors were pale pink, red and dark red (burgundy color). A percentual of
64.29% of patients (n=9) with mild disease demonstrated pale pink color of the tongue, while the rest, 35.71%
(n=5), had a red-colored tongue. Patients with moderate coronavirus disease were characterized with adverse
trend: 62.35% of them (n=53) presented with red-colored tongue, while in 37.64% cases (n=32), the tongue was
pale pink. Severe COVID-19 patients almost in 90% of the cases (n=32) had either red or burgundy color of the
tongue, while the rest of the patients (11.11%; n=4) in this group had pale pink tongue color (Figure 1).
A total of 91.11% of patients (n=123) were characterized by the presence of tongue plaque. Patients
with no tongue plaque were distributed among those having mild (n=9) and moderate (n=3) coronavirus
disease, while 100% of patients with severe pathology demonstrated the presence of tongue plaque.
The most common colors of the tongue plaque were white, gray, yellow. Among patients with mild
disease, no plaque was found in 64.28% of patients (n=9), while the other 35.71% of patients (n=5) had a white
plaque. Patients with moderate disease severity were mostly characterized with white (15.29%; n=13), yellow
(25.88%; n=22) and gray (55.29%; n=47) plaque. A total of 3.52% of patients (n=3) with moderate disease

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demonstrated no plaque present on the tongue. Patients presented with severe coronavirus disease had a white
plaque in 27 cases (75.0%) and yellow plaque in 9 cases (25.0%). Visually amount of white plaque in severe
patients’ cases was thicker than in mild or moderate diseases cases (Table 2 and Figure 2).

Severe 11.11% 41.66% 47.22%

Moderate 37.64% 62.35%

Mild 64.28% 35.72%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Pale pink Red Dark red (burgundy color)

Figure 1. Distribution of tongue colors among COVID-19 patients with different disease severity.

Table 2. Tongue features related to coronavirus disease severity.

Tongue Features Categories Coronavirus Disease Severity
Mild Moderate Severe
N (%) N (%) N (%)
Tongue Color Pale Pink 9 (64.28) 32 (37.64) 4 (11.11)
Red 5 (35.71) 52 (62.35) 15 (41.66)
Dark Red (Burgundy Color) - - 17 (47.22)
Tongue Plaque Color White 5 (35.71) 13 (15.29) 27 (75.0)
Grey - 47 (55.29) -
Yellow - 22 (25.88) 9 (25.0)
No Plaque Present 9 (64.28) 3 (3.52) -

Figure 2. (A) Patient with mild severity of coronavirus disease: red tongue with no plaque; (B) Patient
with mild severity of coronavirus disease: pale pink tongue with white plaque; (C) Patient with
moderate severity of coronavirus disease: red tongue with no plaque; (D) Patient with moderate
severity of coronavirus disease: pink tongue with grey plaque; (E) Patient with moderate severity of
coronavirus disease: red tongue with yellow plaque; (F) Patient with severe coronavirus disease: pink
tongue with white plaque; (G) Patient with severe coronavirus disease: pink tongue with white plaque;
(H) Patient with severe coronavirus disease: red tongue with white plaque.

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Statistically significant differences were observed regarding tongue color among groups of patients
with different coronavirus disease severity (p<0.05), while an analogical trend was also noted considering
tongue plaque color between mild and severe forms (p<0.05) and between moderate and mild forms (p<0.05).
Patients within age groups of 41-50 years, 51-60 years, 61-70 years, 71-80 years and more than 80 years
always demonstrated the presence of tongue plaque and more prevalent red and dark red color of the tongue,
supreme prevalence of which was statistically significant (p<0.05). A similar trend was also noted regarding
grey and yellow tongue plaque among the above-mentioned age groups (p<0.05). No gender-associated
differences were found regarding changes of tongue color and tongue plaque color within analyzed study
sample (p>0.05).

Discussion
All the signs, which potentially could be classified as COVID-distinctive, should be carefully verified
regarding their specificity and sensitivity as diagnostic markers, with further in-depth analysis of such at
different biological organizational levels.
Considering oral mucous changes during COVID-19, some clinical cases demonstrated the
development of oral ulceration and blisters formation, even though such also could be identified during other
virus diseases [17,19,21,22]. Moreover, it should be noted that the immunological status of patients with a
pronounced viral infection commonly is compromised, which also could play a role in the secondary
development of oral lesions associated with underlying pathology [22]. In the brief literature review, it was
found that the most frequently affected zones of the oral cavity during coronavirus disease include areas of
hard palate, dorsum of the tongue and labial mucosa [17], while specifically, ulcers were the most commonly
noted at the dorsum of the tongue.
Several researches demonstrated tropism relation of SARS-COV2 to the tongue and salivary glands
due to the expression of angiotensin-converting enzyme 2 by their epithelial cell [34,35]. In 8 described cases
of COVID-19 infection, Brandão et al. [34] collected next tongue-related manifestations: clinical case 1 –
painful ulcerations and necrotic ulceration of anterior dorsal tongue surface; clinical case 2 – shallow necrotic
lesions of anterior dorsal tongue part; clinical case 3 – painful ulcer lesion projected at the right margin of the
tongue; clinical case 4 – no specific tongue changes were described; clinical case 5 – multiple ulceration
elements located at the apex and lateral border of tongue; clinical case 6 – no specific tongue changes were
described; clinical case 7 – ulcer located at ventral part of tongue; clinical case 8 - aphthous-like ulceration with
necrotic crust localized above it projected at lateral tongue surface. Provided research highlights the potential
role of tongue and salivary glands as target organs regarding coronavirus invasion [34].
The biggest study related to the tongue’s manifestations among COVID-patients was provided by
Pang et al. [26] and included 1043 persons with different levels of coronavirus disease severity. Authors have
found that tongue color changes from pale to purple were related to disease progression, analogically to tongue
coating color from white to yellow and grayish-black [26]. Relations between such tongue features and
coronavirus disease severity were statistically significant (p < 0.001) [26]. An analogical trend was also noted
in our study since most patients with mild disease had pale pink tongue color, while patients with severe
COVID-19 infection demonstrated red and burgundy tongue color. But considering tongue plaque color, we
have found yellow and gray plaque mostly presented among patients with moderate disease, while yellow and
white were mostly registered among severe pathology cases. In Pang et al. [26] study, 54.90% of patients with
a moderate form of the disease were characterized with a white coating and 44.80% with yellow coating, while

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44.90% with severe pathology were characterized with white coating, 53.74% with yellow coating and 1.36%
with grayish-black coating. So main difference between our and Pang et al. study [26] was related due to the
distribution of tongue plaque colors. Such discrepancies in results could be augmented by the fact that in our
study, we have not used any classification system of tongue features for manifestations differentiation, but in
Pang et al. study [26], researchers used previously developed table included in Diagnostics of Chinese
Medicine and Color Atlas of Chinese Medical Tongue Diagnosis. Such an approach in Pang et al. study was
highly reasoned since images of the tongue further could be analyzed in a specifically designed Tongue
Features Objective Research System (TFORS) [26], while in our study, we wanted to exclude the effect of
interpretation error and identify the condition of each analyzed tongue on the image by fact without referring
it to any classification or categorization systems. Analogically to Pang et al. study [26], we have found that
patients of older age (above 40 years) are characterized with more prevalent red and dark red tongue color,
present tongue plaque and yellow coating of such. Also, the amount of identified tongue plaque among
COVID-positive patients was found to demonstrate greater visual accumulation in patients older than 40 years
and among those with severe pathology.
Dos Santos et al. [19] presented results of ongoing COVID patient’s monitoring supported by the
detailed analysis of tongue changes: 1) after four weeks of hospitalization patient developed white plaque on
tongue dorsum (treated with the antifungal drug but with no regression effect) with multiple pinpoint
yellowish ulcers (potentially herpetic lesion); 2) two weeks after that patient was observed with a developed
geographic tongue of severe manifestation form, but with no pain symptoms (areas of atrophy with adjacent
yellow-white lesions elevated above the surface level), white plaque covering was fully resolved; 3) geographic
tongue of moderate form was noted 10 days after discharge (44 days after hospitalization).
Such an approach of ongoing in-detail analysis of intraoral COVID-related signs used by Dos Santos
et al. [19] provides a variety of perspectives for further research since such methodology seems reasonable for
categorization and comparative analysis of tongue changes during coronavirus disease onset, progression and
resolution. In our study, we provided just analysis of correspondence between registered COVID-19 severity
and tongue color-associated manifestations, but our complex research is ongoing and at the nearest
publication, it will be possible to provide results for the above-mentioned comparative analysis of COVID-
associated oral features at different stages of pathology progression.
Within the case series study structured as a Web-based questionnaire among 140 COVID-patients,
just 9 persons demonstrated plaque-like changes of tongue and 4 reported swelling of the tongue [36]. Also,
the authors reported a statistical correlation between plaque-like changes of the tongue and altered tongue
sensation (p<0.001) [36]. Based on the described design of the study, all patients included in the Biadsee et al.
[36] research were characterized with mild symptoms of coronavirus diseases (categorized by WHO joint
report), while in our study patients demonstrated mild, moderate and severe clinical symptoms of COVID-19,
associated with corresponding facts of white or no plaque present on the tongue during mild severity of
pathology.
In three clinical cases described by Díaz Rodríguez et al. [37], two patients demonstrated following
tongue changes which potentially could be associated with COVID-19 infection, general state of
immunosuppression or influence of adjacent factors (such as stress or self-related habits): bilateral tongue
surface atrophy accompanied with lateral dorsum depapillation, and tongue surface atrophy associated with
fungal patch-like lesions (pseudomembranous candidiasis) and fissures localized at tongue dorsum. In addition,
several studies also demonstrated the following tongue manifestation during COVID-19: small painful

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ulcerations with non-regular borders on the reddish background of anterior tongue, asymptomatic ulcers at the
dorsum of the tongue, multiple macules of various size, aphthae on the ventral tongue side, tongue papilla
inflammation [17,38], asymptomatic purple bulla [39].
Riad et al. [40] presented an analysis of 26 COVID-positive patients with no adjacent
somathopathologies and mild or absent respiratory symptoms in which they noted the occurrence of ulcers on
the dorsum, side and ventral parts of the tongue with different onset time. Tongue ulcers appeared mostly 5
days after PCR-testing (among 53.8% patients), with 1-7 lesions per patient varying by 1-5 mm in size [40].
Researches also noted an interesting finding, that the localization of ulcers on the tongue was the only one in
the oral cavity with such lesions absent on other oral mucous regions [40]. Irregular tongue ulcer also was
mentioned as being an inaugural sign among COVID-19 patients [18].
Asymptomatic COVID-19 case presented by Corchuelo and Ulloa [41] was characterized with white
zones on the posterior tongue portion and bacterial plaque accumulation at the middle third of the tongue,
suggesting candidiasis diagnosis, which resolved two weeks after supportive treatment by antifungal drugs and
oral hygiene measures.
In da Silva Pedrosa et al. [22] review, the authors also mentioned that xerostomia associated with
reduced salivary flow among COVID-patients was noted to become more prominent with the age. In our
study, we could not relate potentially present age-associated lower salivary flow with greater deposition of
tongue plaque because of sanitary restrictions regarding the possibility of providing structured clinical
investigation among COVID-positive patients, but such dependencies could be logically prognosticated. Also,
older patients could be characterized by the possible presence of adjacent internal comorbidities, which could
impact the tongue condition independently of the presence or absence of coronavirus disease.
Nevertheless, the diagnostic role of tongue during COVID-19 infection remains under debate.
Resected specimen of ulcerated squamous cell lesion of the tongue of a patient with coronavirus disease
demonstrated the presence of SARS-CoV-2 strain’s RNA [42]. On the other hand, tongue swabs were
characterized with relatively lower sensitivity for detecting SARS-CoV-2 than swabs obtained from nose or
mid-turbinate [43].
For safety reasons, many physicians refrain from examining the oral cavity of patients with confirmed
COVID-19. Most patients do not remove the mask from the face at all while being in the hospital. Patients
themselves may simply ignore the changes of the tongue on the background of many other manifestations of
COVID-19 in the acute form. Photodocumentation of tongue condition represents argumented approach for its
further analysis regarding color of the tongue and color of the tongue plaque. Due to the quarantine
restrictions, photoregistration of the tongue could be provided either by the patient himself or by the staff
directly taking part in the treatment management of COVID-patients, with possible further transfer of such
images to the dental specialist considering all the ethical aspects and issues related to personal data safety.
Ethical aspects of personal medical data use (including personal data safety issues) are reasoning the
need for developing specific patient informed consent form under the condition of COVID-19 pandemic due to
which doctors could investigate anonymized and blinded patients’ information for the acceleration of
diagnostics and treatment, provision of rapid response in life-threatening cases and relevant upgrowth of the
evidence base.
Limitations of the present study related to the sanitary restrictions implemented to reduce COVID-19
spread within hospital conditions, which also influenced the possibility of more detailed analysis of other
tongue-related changes, including the thickness of present plaque, tenderness of the tongue, and its’ condition

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during palpation. Nevertheless, we have found that even visually identified changes of the tongue color and
tongue plaque color could support coronavirus disease severity differentiation when combined with other
clinical symptoms. Another limitation of present research related to the study's design, since we have evaluated
tongue-associated features only once for each patient at the specific severity of coronavirus disease relevant for
some certain moment. But in future studies, we will provide results of ongoing monitoring of tongue
manifestations during long period screening, which will help us to verify how the color of the tongue and color
of the tongue plaque are changing during pathology onset, progression and further resolution. Also, we have
obtained information about coronavirus disease severity of each patient included in the study sample from the
infectious disease specialists via digital information transferring to reduce the risk of infection for dentists, but
in the future, it would be beneficial to analyze medical documentation of such patients with possibility to find
some potential relationships not only among tongue manifestations and severity of pathology, but also among
tongue signs and some other COVID-related clinical and laboratorial parameters changes.

Conclusion
Considering limitations of provided study and restrictions related to the lack of dental screening
methodology developed specifically for COVID-positive patients, it could be concluded that SARS-COV-2
infection is not manifested by tongue-targeted or tongue-specific signs and features; however, coronavirus
disease itself provoke changes within the tongue color and tongue plaque color similar to those registered
during other internal pathologies. Taste disturbances remain the most diagnostically-prominent tongue-
related symptom during COVID-infection, nevertheless conclusion about the absence of other high-avid
tongue signs during coronavirus disease should be made with caution, since the corresponding database
continues to grow and some pathology-specific manifestations could be recognized at system-, organ- or tissue-
levels among greater study cohort or during further epidemiological studies. Due to the received data, we may
hypothesize that tongue color and color parameters of tongue plaque related to the COVID-infection severity
with positive type of interrelation: red tongue color and prominent white-yellow tongue plaque were identified
the most frequently among severe disease cases. However, further clinical investigations should be provided to
distinguish tongue-related manifestations on such, caused specifically by COVID-infection, and such,
associated with the effect of provided treatment.

Authors’ Contributions
LH [Link] Conceptualization, Methodology, Writing - Review and Editing, Supervision and Project
Administration.
MG [Link] Conceptualization, Validation, Formal Analysis, Investigation, Data Curation, Writing - Original
Draft, Visualization and Supervision.
NH [Link] Resources, Writing - Review and Editing and Supervision.
AY [Link] Writing - Review and Editing and Supervision.
VM [Link] Writing - Review and Editing, Visualization and Supervision.
All authors declare that they contributed to critical review of intellectual content and approval of the final version to be published.

Financial Support
None.

Conflict of Interest
The authors declare no conflicts of interest.

Data Availability
The data used to support the findings of this study can be made available upon request to the corresponding author.

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References
[1] Seerangaiyan K, Jüch F, Winkel EG. Tongue coating: its characteristics and role in intra-oral halitosis and general
health - a review. J Breath Res 2018; 12(3):034001. [Link]
[2] Wang X, Zhang B, Yang Z, Wang H, Zhang D. Statistical analysis of tongue images for feature extraction and
diagnostics. IEEE Trans Image Process 2013; 22(12):5336-47. [Link]
[3] Jung CJ, Jeon YJ, Kim JY, Kim KH. Review on the current trends in tongue diagnosis systems. Integr Med Res 2012;
1(1):13-20. [Link]
[4] Anastasi JK, Chang M, Quinn J, Capili B. Tongue inspection in TCM: observations in a study sample of patients
living with HIV. Med Acupunct 2014; 26(1):15-22. [Link]
[5] Zhang B, Kumar BV, Zhang D. Detecting diabetes mellitus and nonproliferative diabetic retinopathy using tongue
color, texture, and geometry features. IEEE Trans Biomed Eng 2013; 61(2):491-501.
[Link]
[6] Gaddey HL. Oral manifestations of systemic disease. Gen Dent 2017; 65(6):23-9.
[7] Zhang B, Wang X, You J, Zhang D. Tongue color analysis for medical application. Evid-Based Complement Alternat
Med 2013; 2013:1-11. [Link]
[8] Kawanabe T, Kamarudin ND, Ooi CY, Kobayashi F, Mi X, Sekine M, et al. Quantification of tongue colour using
machine learning in Kampo medicine. Eur J Integr Med 2016; 8(6):932-41.
[Link]
[9] Velasco J, Rojas J, Ramos JP, Muaña HM, Salazar KL. Health evaluation device using tongue analysis based on
sequential image analysis. IJATCSE 2019; 8(3):451-7. [Link]
[10] Wang ZC, Zhang SP, Yuen PC, Chan KW, Chan YY, Cheung CH, et al. Intra-rater and inter-rater reliability of
tongue coating diagnosis in traditional chinese medicine using smartphones: Quasi-delphi study. JMU 2020;
8(7):e16018. [Link]
[11] Tania MH, Lwin K, Hossain MA. Advances in automated tongue diagnosis techniques. Integr Med Res 2019; 8(1):42-
56. [Link]
[12] Kim SY, Byun JS, Choi JK, Jung JK. A case report of a tongue ulcer presented as the first sign of occult tuberculosis.
BMC Oral Health 2019; 19(1):1-5. [Link]
[13] Jain P, Jain I. Oral manifestations of tuberculosis: step towards early diagnosis. J Clin Diag Res 2014; 8(12):ZE18.
[Link]
[14] Souza PV, Pinto WB, Oliveira AS. Bright tongue sign: a diagnostic marker for amyotrophic lateral sclerosis. Arq
Neuro-Psiquiatr 2014; 72(7):572. [Link]
[15] Ayinampudi BK, Gannepalli A, Pacha VB, Kumar JV, Khaled S, Naveed MA. Association between oral manifestations
and inhaler use in asthmatic and chronic obstructive pulmonary disease patients. J Dr NTR Univ Health Sci 2016;
5(1):17. [Link]
[16] World Health Organization. Coronavirus Disease (COVID-19) Dashboard. 2021. Available from:
[Link] [Accessed on January 13, 2020].
[17] Halboub E, Al-Maweri SA, Alanazi RH, Qaid NM, Abdulrab S. Orofacial manifestations of COVID-19: a brief review
of the published literature. Braz Oral Res 2020; 34:e124. [Link]
[18] Chaux-Bodard AG, Deneuve S, Desoutter A. Oral manifestation of Covid-19 as an inaugural symptom?. J Oral Med
Oral Surg 2020; 26(2):18. [Link]
[19] dos Santos JA, Normando AG, da Silva RL, De Paula RM, Cembranel AC, Santos-Silva AR, et al. Oral mucosal
lesions in a COVID-19 patient: new signs or secondary manifestations?. Int J Infect Dis 2020; 97:326-8.
[Link]
[20] Horzov L, Goncharuk-Khomyn M, Kostenko Y, Melnyk V. Dental Patient Management in the Context of the
COVID-19 Pandemic: Current Literature Mini-Review. Open Public Health J 2020; 13(1):459-63.
[Link]
[21] da Silva Pedrosa M, Sipert CR, Nogueira FN. Altered taste in patients with COVID-19: the potential role of salivary
glands. Oral Dis 2020; Suppl 3:798-800. [Link]
[22] da Silva Pedrosa M, Sipert CR, Nogueira FN. Salivary glands, saliva and oral findings in COVID-19 infection. Pesqui
Bras Odontopediatria Clín Integr 2020; 20:e0104. [Link]
[23] Yan CH, Faraji F, Prajapati DP, Boone CE, De Conde AS. Association of chemosensory dysfunction and Covid-19 in
patients presenting with influenza-like symptoms. Int Forum Allergy Rhinol 2020; 10(7):806-13.
[Link]
[24] Wang B, Pang K, Chen S, Gong J, Deng J, Liu J. A preliminary study of tongue image in 78 patients with COVID-19.
Jiangsu Tradit Chin Med 2020; 53:84-6. [Link]
[25] Zhou G, Huang D, Cai Y, Huang K, Xie D. Relationship between tongue characteristics and clinical typing in
COVID-19 patients. J Tradit Chin Med 2020:1-4.
[26] Pang W, Zhang D, Zhang J, Li N, Zheng W, Wang H, et al. Tongue features of patients with coronavirus disease
2019: a retrospective cross-sectional study. Integr Med Res 2020; 9(3):100493.
[Link]

10
 Pesqui. Bras. Odontopediatria Clín. Integr. 2021; 21:e0011

[27] World Health Organization. Clinical management of COVID-19 (interim guidance). 2021. Available from:
[Link] [Accessed on January 13, 2020].
[28] Tatem KS. Comparing prevalence estimates from population-based surveys to inform surveillance using electronic
health records. Prev Chronic Dis 2017; 14:E44. [Link]
[29] van Baal PH, Engelfriet PM, Hoogenveen RT, Poos MJ, van den Dungen C, Boshuizen HC. Estimating and
comparing incidence and prevalence of chronic diseases by combining GP registry data: the role of uncertainty. BMC
Public Health 2011; 11(1):163. [Link]
[30] Tekindal MA, Gullu O, Yazici AC, Yavuz Y. The Cochran-Armitage test to estimate the sample size for trend of
proportions for biological data. Turk J Field Crops 2016; 21(2):286-97. [Link]
[31] Buonaccorsi JP, Laake P, Veierød MB. On the power of the Cochran–Armitage test for trend in the presence of
misclassification. Stat Methods Med Res 2014; 23(3):218-43. [Link]
[32] McHugh ML. Interrater reliability: the Kappa statistic. Biochem Med 2012; 22(3):276-82.
[33] Hsu LM, Field R. Interrater agreement measures: Comments on Kappan, Cohen's Kappa, Scott's π, and Aickin's α.
Understanding Statistics 2003; 2(3):205-19. [Link]
[34] Brandão TB, Gueiros LA, Melo TS, Prado-Ribeiro AC, Nesrallah AC, Prado GV, et al. Oral lesions in patients with
SARS-CoV-2 infection: could the oral cavity be a target organ?. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2020; S2212-4403(20)31119-6. [Link]
[35] Nemeth-Kohanszky ME, Matus-Abásolo CP, Carrasco-Soto RR. Manifestaciones orales de la infección por COVID-
19. Int J Odontostomat 2020; 14(4):555-60. [Link]
[36] Biadsee A, Biadsee A, Kassem F, Dagan O, Masarwa S, Ormianer Z. Olfactory and oral manifestations of COVID-19:
sex-related symptoms — a potential pathway to early diagnosis. Otolaryngol Head Neck Surg 2020; 163(4):722-8.
[Link]
[37] Rodríguez MD, Romera AJ, Villarroel M. Oral manifestations associated with COVID-19. Oral Dis 2020; 1-3.
[Link]
[38] Liang K, Huang X, Chen H, Qiu L, Zhuang Y, Zou C, et al. Tongue diagnosis and treatment in traditional Chinese
medicine for severe COVID-19: a case report. Ann Palliat Med 2020; 9(4):2400-7.
[Link]
[39] Cruz Tapia RO, Peraza Labrador AJ, Guimaraes DM, Matos Valdez LH. Oral mucosal lesions in patients with SARS-
CoV-2 infection. Report of four cases. Are they a true sign of COVID-19 disease?. Spec Care Dent 2020; 40(6):555-60.
[Link]
[40] Riad A, Klugar M, Krsek M. COVID-19-related oral manifestations: early disease features?. Oral Dis 2020.
[Link]
[41] Corchuelo J, Ulloa FC. Oral manifestations in a patient with a history of asymptomatic COVID-19: Case report. Int J
Infect Dis 2020; 100:154-7. [Link]
[42] Guerini-Rocco E, Taormina SV, Vacirca D, Ranghiero A, Rappa A, Fumagalli C, et al. SARS-CoV-2 detection in
formalin-fixed paraffin-embedded tissue specimens from surgical resection of tongue squamous cell carcinoma. J Clin
Pathol 2020; 73(11):754-7. [Link]
[43] Tu YP, Jennings R, Hart B, Cangelosi GA, Wood RC, Wehber K, et al. Swabs collected by patients or health care
workers for SARS-CoV-2 testing. N Engl J Med 2020; 383(5):494-6. [Link]

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