10.5826/dpc.1401a45
Introduction: To date various oral manifestations in patients with coronavirus disease 2019 (COVID-19) have been reported.
Objectives: In the present study, we investigated the relationship between Polymerase Chain Reaction (PCR) positivity and oral signs in patients with suspected COVID-19.
Methods: A total of 383 patients who presented to the emergency department for the first time with any symptoms associated with COVID-19 were included in the study. Oral examinations were performed and the findings, PCR status, and thorax computerized tomography (CT) reports were recorded.
Results: Oral mucosa was involved in 246 (64.2%) patients. 175 (78,4%) of patients with COVID-19 confirmed the diagnosis with PCR test or CT results had oral manifestation. Dry mouth, microvesicles on the tonsils or pharynx, and petechiae in the oropharynx were significantly higher in patients with positive PCR tests (P = 0.001, P &lt; 0.001, P &lt; 0.001, respectively). The ratio of intact oral mucosa was statistically significantly higher in patients with negative PCR tests compared to those with positive PCR tests (P &lt; 0.001). Microvesicles on the tonsils or pharynx were most associated with PCR positivity in patients without lung involvement (P &lt; 0.001). Dry mouth, erythema of the tonsils and pharynx, petechiae in the oropharynx, and primary/secondary herpes infection are more related to PCR positivity in patients without lung involvement (P &lt; 0.05). Lung involvement in patients with PCR positivity is related to only cheilitis (P = 0.034).
Conclusions: Our study revealed that especially microvesicles, petechiae, erythema on the tonsils or pharynx, and some other oral lesions such as dry mouth, oral aphthae, and primary/secondary herpes infection are associated with PCR positivity.
text/xml
2160-9381
3486
en
Çağrı Turan
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
petechiae
Oral Mucosal Manifestations Associated With PCR Positivity in Patients With COVID-19
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2024-01-31
2023-04-29
2024-01-31
2024-02-21
e2024045
Dermatol Pract Concept
Introduction: To date various oral manifestations in patients with coronavirus disease 2019 (COVID-19) have been reported.
Objectives: In the present study, we investigated the relationship between Polymerase Chain Reaction (PCR) positivity and oral signs in patients with suspected COVID-19.
Methods: A total of 383 patients who presented to the emergency department for the first time with any symptoms associated with COVID-19 were included in the study. Oral examinations were performed and the findings, PCR status, and thorax computerized tomography (CT) reports were recorded.
Results: Oral mucosa was involved in 246 (64.2%) patients. 175 (78,4%) of patients with COVID-19 confirmed the diagnosis with PCR test or CT results had oral manifestation. Dry mouth, microvesicles on the tonsils or pharynx, and petechiae in the oropharynx were significantly higher in patients with positive PCR tests (P = 0.001, P &lt; 0.001, P &lt; 0.001, respectively). The ratio of intact oral mucosa was statistically significantly higher in patients with negative PCR tests compared to those with positive PCR tests (P &lt; 0.001). Microvesicles on the tonsils or pharynx were most associated with PCR positivity in patients without lung involvement (P &lt; 0.001). Dry mouth, erythema of the tonsils and pharynx, petechiae in the oropharynx, and primary/secondary herpes infection are more related to PCR positivity in patients without lung involvement (P &lt; 0.05). Lung involvement in patients with PCR positivity is related to only cheilitis (P = 0.034).
Conclusions: Our study revealed that especially microvesicles, petechiae, erythema on the tonsils or pharynx, and some other oral lesions such as dry mouth, oral aphthae, and primary/secondary herpes infection are associated with PCR positivity.
Çağrı Turan
2024/01/31
10.5826/dpc.1401a45
e2024045
Department of Dermatology and Venereology, the Republic of Turkey, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
2160-9381
petechiae
en
e2024045
Kämmerer T, Walch J, Flaig M, French LE. COVID-19-associated herpetic gingivostomatitis. Clin Exp Dermatol. 2021;46(1):174-176. DOI: 10.1111/ced.14402. PMID: 33405295. PMCID: PMC9213960.
Oral Mucosal Manifestations Associated With PCR Positivity in Patients With COVID-19
https://dpcj.org/index.php/dpc/article/download/3486/2416
  Oral Mucosal Manifestations Associated with PCR
        Positivity in Patients with COVID-19
                               Nurcan Metin1, Türkan Tuğba Yıldız1, Çağrı Turan2


1 Department of Dermatology and Venereology, the Republic of Turkey, Health Sciences University Erzurum Regional Training and Research
  Hospital, Erzurum, Turkey
2 Department of Dermatology and Venereology, the Republic of Turkey, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey



Key words: COVID-19, PCR test, oral mucosa, manifestations, microvesicles, petechiae
Citation: Metin N, Yıldız TT, Turan C. Oral Mucosal Manifestations Associated with PCR Positivity in Patients with COVID-19.
Dermatol Pract Concept. 2024;14(1):e2024045. DOI: https://doi.org/10.5826/dpc.1401a45
Accepted: August 26, 2023; Published: January 2024
Copyright: ©2024 Metin et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Nurcan Metin, Department of Dermatology and Venereology, the Republic of Turkey, Health Sciences University
Erzurum Regional Training and Research Hospital, Erzurum, Turkey; ÜniversiteMahallesi, ÇatYolu Cd., Yakutiye/Erzurum, Post Code:
25240 telephone number: +905075806255 E-mail: drnurcanmetin@hotmail.com




  ABSTRACT             Introduction: To date various oral manifestations in patients with coronavirus disease 2019
                       (COVID-19) have been reported.
                       Objectives: In the present study, we investigated the relationship between Polymerase Chain Reaction
                       (PCR) positivity and oral signs in patients with suspected COVID-19.
                       Methods: A total of 383 patients who presented to the emergency department for the first time with any
                       symptoms associated with COVID-19 were included in the study. Oral examinations were performed
                       and the findings, PCR status, and thorax computerized tomography (CT) reports were recorded.
                       Results: Oral mucosa was involved in 246 (64.2%) patients. 175 (78,4%) of patients with COVID-19
                       confirmed the diagnosis with PCR test or CT results had oral manifestation. Dry mouth, microvesicles
                       on the tonsils or pharynx, and petechiae in the oropharynx were significantly higher in patients with
                       positive PCR tests (P = 0.001, P < 0.001, P < 0.001, respectively). The ratio of intact oral mucosa was
                       statistically significantly higher in patients with negative PCR tests compared to those with positive
                       PCR tests (P < 0.001). Microvesicles on the tonsils or pharynx were most associated with PCR positiv-
                       ity in patients without lung involvement (P < 0.001). Dry mouth, erythema of the tonsils and pharynx,
                       petechiae in the oropharynx, and primary/secondary herpes infection are more related to PCR positiv-
                       ity in patients without lung involvement (P < 0.05). Lung involvement in patients with PCR positivity
                       is related to only cheilitis (P = 0.034).
                       Conclusions: Our study revealed that especially microvesicles, petechiae, erythema on the tonsils or
                       pharynx, and some other oral lesions such as dry mouth, oral aphthae, and primary/secondary herpes
                       infection are associated with PCR positivity.


Original Article | Dermatol Pract Concept. 2024;14(1):e2024045                                                                       1
Introduction                                                        of 14 days were enrolled, as PCR test may become negative.
                                                                    The patients were questioned in terms of sore throat, loss of
Severe   acute    respiratory    syndrome      coronavirus     2    taste and smell, presence of back and chest pain, headache,
(SARS-CoV2) is a novel virus that generating coronavirus            and dry mouth sensation (xerostomia). The oral mucosa of
disease 2019 (COVID-19). The disease first started in China         patients was examined by a dermatologist and the findings
and spread rapidly all over the world in a short time. Trans-       (erythema, xerosis, vesicle, crypt, candida, tonsillar hyper-
mission mainly happens through large droplets that occur            trophy, leukoplakia, geographic tongue, scrotal tongue, her-
during coughing and sneezing by symptomatic patients. Also          pes simplex infections, aphthae/ulcer, other) were recorded.
contact with contaminated surfaces may be a risk for trans-         These disorders were diagnosed clinically. All necessary data
mission [1]. The respiratory tract is the primary site of in-       such as age, gender of the patients, complaints, oral mucosal
fection, with no symptoms or symptoms ranging from mild             findings, PCR status, and thorax computerized tomography
flu-like symptoms to fulminant pneumonia and potentially            (CT) reports were anonymized and obtained from the elec-
mortal respiratory distress [2]. The most common reported           tronic database and patient follow­-up forms. Behçet disease,
symptoms among patients with symptomatic COVID-19 are               recurrent aphthous stomatitis, inflammatory bowel diseases,
dry cough, myalgias, fever and headache. High fever (>38            and collagen tissue disease such as systemic lupus erythema-
°C) was found associated with COVID-19 PCR positivity [3].          tosus which may cause oral aphthae. In diabetes mellitus,
    Research shows that SARS-CoV-2 enters human cells by            anticholinergic drugs lead to dryness in the oral mucosa.
binding to the angiotensin-converting enzyme 2 (ACE2) re-           Various infection diseases such as hand, foot, and mouth
ceptor. The ACE2 receptor is detected in the cell membrane          disease, herpangina, and tularemia can cause oral mucosal
of many human organs and tissues, including the upper respi-        ulceration. Some drugs such as isotretinoin may be a reason
ratory tract, epithelial cells of the tongue and salivary glands,   for cheilitis. Oral lichen planus clinically presents as reticu-
and lungs. Thus, cells with ACE2 receptor distribution may          lar, erosive or ulcerative lesion with whitish streak or white,
become host cells for the virus and cause an inflammatory           lacy patches. The patients who have the above-mentioned
response [4]. The oral cavity is one of the main entryways          diseases and use drugs that may cause disorders of oral mu-
for SARS-CoV-2. Various oral mucosal symptoms and signs             cosa and also those with dermatological diseases such as
such as vesiculobullous lesions, taste disorder, nonspecific        oral lichen planus and bullous diseases with oral mucosal in-
oral ulcerations, cheilitis, desquamative gingivitis, petechiae,    volvement were excluded from the study. Moreover, patients
herpes virus infections, candidiasis and lingua villosa nigra       without CT were not included.
due to COVID-19 have been reported in the literature 5-8.              The study protocol was approved by the ethics commit-
However, it is still unknown whether these manifestations in        tee of the Erzurum Regional Training and Research Hospital
the oral cavity develop directly or indirectly [9].                 (reference no. 2021/12-187). An informed consent form was
                                                                    obtained from all participants. The study was performed as

Objectives                                                          per the latest version of the Helsinki Declaration and the
                                                                    Guidelines for Good Clinical Practice.
The gold standard for diagnosis of the disease is the find-
ing of viral genome by real-time polymerase chain reaction          Statistical Analysis
(RT-PCR) in respiratory tract secretions [10]. Although             All procedures were performed using Statistical Package for
many oral mucosal involvements associated with COVID-19             Social Sciences (SPSS Inc. v21.0) software. After checking the
have been reported in the literature, there is no data on oral      normality distribution of scale variables by Kolmogorov -
manifestations that may be associated with PCR positivity.          Smirnov test, the Pearson chi-square, and the Fisher exact
In this study, we aimed to investigate oral mucosal signs and       tests were used for the categorical variables where appro-
symptoms related to PCR positivity in patients with sus-            priate. Examination findings related to PCR results were
pected COVID-19.                                                    evaluated with univariate and multivariate logistic regres-
                                                                    sion analysis. Multivariate analysis was performed using the

Methods                                                             “Backward: Wald” method. A two­-sided P value less than
                                                                    0.05 was considered statistically significant.
All patients were recruited from the COVID-19 emergency
service in the Erzurum City Hospital, the only pandemic hos-
                                                                    Results
pital in the province, between 01 Januar-30 June 2020. Adult
patients who presented to the emergency department for the          A total of 383 patients with any symptoms associated with
first time with any symptoms in terms of COVID-19 were in-          COVID-19 were included in the study. Oral mucosal involve-
cluded in the study. Patients with complaints for a maximum         ment was present in 246 (64.2%) of all patients. The PCR



2                                                                       Original Article | Dermatol Pract Concept. 2024;14(1):e2024045
  Table 1. Distribution of oral mucosal examinations of patients evaluated for COVID-19 according
                                       to PCR and CT results.
                                                                    PCR negative, N (%)                 PCR positive, N (%)
                                                                    CT:               CT:               CT:               CT:
                                                                  normal/         COVID-19           normal/           COVID-19
                                                                 unknown         pneumonia          unknown          pneumonia
     Oral mucosa examination               Total N = 383          (N =160)         (N = 13)          (N = 168)          (N = 42)
 Normal oral mucosa findings                137 (35.8%)          89 (55.6%)       5 (38.5%)         35 (20.8%)         8 (19.0%)
 Erythema of tonsils and pharynx            187 (48.8%)          62 (38.8%)       6 (46.2%)         97 (57.7%)        22 (52.4%)
 Dry mouth sensation (Xerostomia)            41 (10.7%)          11 (6.9%)        3 (23.1%)         22 (13.1%)         5 (11.9%)
 Micro vesicles on tonsils or                77 (20.1%)           7 (4.4%)         1 (7.7%)         57 (33.9%)        12 (28.6%)
 pharynx
 Cryptic tonsillitis                          24 (6.3%)           3 (1.9%)         1 (7.7%)         15 (8.9%)          5 (12.2%)
 Oral candidiasis (Suspected)                74 (19.3%)          24 (15.0%)       5 (38.5%)         37 (22.0%)         8 (19.0%)
 Tonsillar hypertrophy                       57 (14.9%)          18 (11.3%)       4 (30.8%)         25 (14.9%)        10 (23.8%)
 Petechiae in the oropharynx                100 (26.1%)          19 (11.9%)       3 (23.1%)         60 (35.7%)        18 (42.9%)
 Geographic tongue                            7 (1.8%)            5 (3.1%)         1 (7.7%)          1 (0.6%)          0 (0.0%)
 Scrotal tongue                               33 (8.6%)          12 (7.5%)         1 (7.7%)         13 (7.8%)          7 (16.7%)
 Primary/secondary herpes infection           22 (5.8%)           3 (1.9%)         0 (0.0%)         15 (9.0%)          4 (9.5%)
 Oral aphthae                                66 (17.2%)          15 (9.4%)        4 (30.8%)         34 (20.2%)        13 (31.0%)
 Cheilitis or angular cheilitis               18 (4.7%)           2 (1.3%)         0 (0.0%)          8 (4.8%)          8 (19.0%)
 Other findings                               8 (2.1%)            5 (3.1%)         0 (0.0%)          2 (1.2%)          1 (2.4%)

CT = Computed tomography; PCR = Polymerase Chain Reaction.




test was positive in 210 (54.8%) patients and 13 patients             of primary/secondary herpes infection, oral aphthae, and
whose PCR tests were negative had COVID-19 pneumonia                  erythema of tonsils and pharynx (P = 0.036, P = 0.040,
on thoracic CT. One hundred and seventy-seven patients                P = 0.022, respectively).
whose PCR tested positive and 8 patients whose PCR tested                 Assessment of examination findings and complaints ac-
negative but had pneumonia compatible with COVID-19                   cording to CT results of patients with a definitive diagnosis
had oral mucosal manifestations (175 (78.4%) out of 223               of COVID-19 are as Table 3. No difference was observed
COVID-19 patients). The distribution of oral mucosal ex-              between the PCR-positive patients with and without pneu-
aminations of patients according to PCR and CT results was            monia in terms of complaints and findings.
presented in Table 1.                                                     Parameters with P <0.1 in Table 2 were subjected to logis-
    Examination findings and complaints according to PCR              tic regression analysis. Tables 4 and 5 show the results of uni-
results of patients without pneumonia were evaluated in               variate and multivariate analyzes of parameters potentially
Table 2. The PCR test was positive in 71 of 139 patients              related to PCR positivity, respectively. It was found that mi-
without pneumonia. There was no difference between the                crovesicles on tonsils or pharynx were most associated with
two groups (PCR test positive and negative patients without           PCR positivity in patients without lung involvement accord-
pneumonia) in terms of age, gender, and duration of com-              ing to both univariate and multivariate analysis (OR = 14.11,
plaints. Dry mouth sensation (xerostomia) was significantly           95% CI: [4.04-.49.32], P < 0.001, OR = 15.64, 95% CI: [3.38-
higher in patients with positive PCR tests (P = 0.001). Nor-          .73.45], P < 0.001, respectively). Additionally, both analyses
mal oral mucosa findings were more common in patients                 revealed that dry mouth sensation (xerostomia), erythema
with negative PCR tests compared to those with positive               of the tonsils and pharynx, and petechiae in the oropharynx
PCR tests (P < 0.001). It was noteworthy that the frequency           were more related to PCR positivity in patients without lung
of microvesicles on the tonsils or pharynx and petechiae in           involvement (P < 0.05). Univariate analysis showed that oral
the oropharynx were significantly higher in those with posi-          aphthae were also associated with PCR positivity (OR = 2.55,
tive PCR tests (both with P < 0.001). In addition, there was a        95% CI: [1.03-6.34], P = 0.044). While it was not found that
significant difference between the patients with positive PCR         there was no relationship between primary/secondary herpes
tests and with negative PCR tests in terms of the presence            infection and PCR positivity according to univariate analysis,



Original Article | Dermatol Pract Concept. 2024;14(1):e2024045                                                                      3
    Table 2. Evaluation of examination findings according to PCR results and complaints of patients
                                          without pneumonia.
                                                                 No evidence of pneumonia on the CT
                                                                                             PCR positive
                       Parameters                            PCR negative (N = 68)              (N = 71)                  P
 Age (year); median (IQR)                                            40 (22.0)                   39 (23)               0.813
 Sex, N (%)                         Woman                           30 (44.1%)                40 (56.3%)               0.150
                                    Man                             38 (55.9%)                31 (43.7%)
 Complaint duration (day); median (IQR)                               4 (2.0)                    4 (2.0)               0.796
 Current complaints, N (%)
 Throat ache                                                        27 (39.7%)                27 (38.0%)               0.839
 Headache                                                           29 (42.6%)                28 (39.4%)               0.700
 Loss of taste and smell                                             2 (2.9%)                   6 (8.6%)               0.275
 Back or chest pain                                                 31 (45.6%)                43 (60.6%)               0.077
 Dry mouth sensation (Xerostomia)                                    2 (3.0%)                 15 (21.1%)               0.001
 Other symptoms (typical-atypical)                                  64 (94.1%)                69 (97.2%)               0.435
 Oral mucosa examination, N (%)
 Normal oral mucosa findings                                        37 (54.4%)                 9 (12.7%)               <0.001
 Erythema of tonsils and pharynx                                    28 (41.2%)                43 (60.6%)               0.022
 Micro vesicles on tonsils or pharynx                                3 (4.4%)                 28 (39.4%)               <0.001
 Cryptic tonsillitis                                                 1 (1.5%)                   6 (8.5%)               0.116
 Oral candidiasis (Suspected)                                       13 (19.1%)                20 (28.2%)               0.210
 Tonsillar hypertrophy                                              8 (11.8%)                 11 (15.5%)               0.522
 Petechiae in the oropharynx                                        10 (14.7%)                30 (42.3%)               <0.001
 Leukoplakia                                                         0 (0.0%)                   0 (0.0%)                N/A
 Geographic tongue                                                   1 (1.5%)                   1 (1.4%)               1.000
 Scrotal tongue                                                     7 (10.3%)                   5 (7.0%)               0.495
 Primary/secondary herpes infection                                  2 (3.0%)                  9 (12.7%)               0.036
 Oral aphthae                                                       8 (11.8%)                 18 (25.4%)               0.040
 Cheilitis or angular cheilitis                                      1 (1.5%)                   4 (5.6%)               0.366
 Other findings                                                      3 (4.5%)                   2 (2.8%)               0.674

CT = Computed tomography; IQR = Inter-quartile range; N/A = not applicable; PCR = Polymerase Chain Reaction.




they were related in multivariate analysis (OR = 11.15, 95%        lesions associated with COVID-19 infection have been re-
CI: [1.57-97.53], P = 0.029, Table 5). Moreover, PCR posi-         ported [5-9,12-15]. However, it remains unclear whether
tivity is nearly 8 times higher in patients with any oral mu-      oral manifestations develop directly from the SARS-CoV-2
cosa findings (OR = 8.22, 95% CI: [3.53­19.17], P < 0.001).        infection or due to systemic consequences of COVID-19,
Lung involvement in patients with PCR positivity is related to     given the possibility of co-infection and impaired immune
only cheilitis or angular cheilitis (OR = 3.94, 95% CI: [1.11-     response or drug side effects [9].
14.02], P = 0.034, Table 4).                                          The prevalence of oral cavity signs of COVID-19 is not
                                                                   known, but it was reported that oral manifestations were

Conclusions                                                        present in 25.65% of 666 patients in a large study [16]. Mild
                                                                   severity of the disease was assumed to be associated with no
Enanthema and various oral lesions are among the typical           or minor symptoms [16]. In the present study, there were
symptoms of many viral diseases [5]. In a large series of pa-      normal oral mucosa findings in 21.5 % of 223 patients with
tients with atypical exanthems, erythematous-vesicular and         confirmed COVID-19.
petechial patterns were found most commonly associated                According to our study results, the most common oral
with viral infections [11]. Up to date, numerous oral mucosal      manifestations associated with COVID-19 were erythema of



4                                                                      Original Article | Dermatol Pract Concept. 2024;14(1):e2024045
Table 3. Evaluation of examination findings according to CT results and complaints of patients with
                               a definitive diagnosis of COVID-19.
                                                                          Patients with PCR positive
                                                                                                  CT: Pneumonia
                       Parameters                                CT: Normal (N = 71)                  (N = 42)                 P
 Age (year); median (IQR)                                              39 (23)                         49(21)                0.058
 Sex, N (%)                  Woman                                   40 (56.3%)                      21 (50.0%)              0.514
                             Man                                     31 (43.7%)                      21 (50.0%)
 Complaint duration (day); median (IQR)                                 4 (2)                           5 (4)                0.074
 Current complaints, N (%)
 Throat ache                                                         27 (38.0%)                      9 (21.4%)               0.067
 Headache                                                            28 (39.4%)                      16 (38.1%)              0.888
 Loss of taste and smell                                              6 (8.6%)                       6 (14.3%)               0.361
 Back or chest pain                                                  43 (60.6%)                      26 (61.9%)              0.988
 Other symptoms (typical-atypical)                                   69 (97.2%)                      40 (95.2%)              0.627
 Dry mouth sensation (Xerostomia)                                    15 (21.1%)                      5 (11.9%)               0.122
 Oral mucosa examination, N (%)
 Normal oral mucosa findings                                         9 (12.7%)                       8 (19.0%)               0.360
 Erythema of tonsils and pharynx                                     43 (60.6%)                      22 (52.4%)              0.395
 Micro vesicles on tonsils or pharynx                                28 (39.4%)                      12 (28.6%)              0.243
 Cryptic tonsillitis                                                  6 (8.5%)                       5 (12.2%)              0.527*
 Oral candidiasis (Suspected)                                        20 (28.2%)                      8 (19.0%)               0.278
 Tonsillar hypertrophy                                               11 (15.5%)                      10 (23.8%)              0.272
 Petechiae in the oropharynx                                         30 (42.3%)                      18 (42.9%)              0.950
 Leukoplakia                                                          0 (0.0%)                        0 (0.0%)                N/A
 Geographic tongue                                                    1 (1.4%)                        0 (0.0%)               1.000
 Scrotal tongue                                                       5 (7.0%)                       7 (16.7%)               0.125
 Primary/secondary herpes infection                                  9 (12.7%)                        4 (9.5%)               0.764
 Oral aphthae                                                        18 (25.4%)                      13 (31.0%)              0.519
 Cheilitis or angular cheilitis                                       4 (5.6%)                       8 (19.0%)               0.054
 Other findings                                                       2 (2.8%)                        1 (2.4%)               1.000

CT = Computed tomography; IQR = Inter-quartile range; N/A = not applicable; PCR = Polymerase Chain Reaction.




tonsils and pharynx (56.0%), petechiae in the oropharynx               gingival abnormalities, and finally blisters and pustules in
(36.3%), microvesicles on tonsils or pharynx (31.8%), oral             their study [12]. Martín Carreras-Presas et al reported dif-
aphthae (22.8%), oral candidiasis (suspected) (22.4%), and             ferent types of oral mucosal lesions (ulcer, vesicle, bulla, and
dry mouth sensation (xerostomia) (15.6%), primary/second-              desquamative gingivitis) in patients with COVID-19 [21].
ary herpes infection (8.5%). Oral lesions described in patients        Tuter et al showed that dry mouth is the most common and
with COVID-19 in the literature were highly heterogeneous.             oral ulcers and tongue lesions are the second common oral
In a few studies, oral vesiculobullous lesions and erosions            manifestation in COVID-19 patients [13]. Cuevas-Gonzalez
on the tongue and buccal mucosa, widespread erythema ap-               et al stated that the most common main oral manifestations
peared on the hard palate and oropharynx, and petechiae on             related to SARS-CoV-2 were dysgeusia, dry mouth, burning
the lower lip, palate, and oropharynx, herpes simplex lesion in        mouth, ulcerative lesions, and Candida Albicans infections in
the lip semi mucosa were reported [7,17-19]. Jimenez-Cauhe             their systematic review including a total of 18 studies [6]. A
et al presented 5 patients with COVID-19 who had pe-                   review article revealed that aphthous-like lesions, herpetiform
techiae on tonsils [20]. Egido-Moreno et al stated that the            lesions, candidiasis, and oral lesions of Kawasaki-like disease
most prevalent lesions were ulcers, aphthous-like lesions, or          are the most common oral manifestations of COVID-19 [22].
erosions, followed by macules and petechiae, plaques bullae,           Our findings were partially compatible with the literature.



Original Article | Dermatol Pract Concept. 2024;14(1):e2024045                                                                       5
         Table 4. Evaluation of examination findings related to PCR result and lung involvement
                                with univariate logistic regression analysis
                                                                                   95% CI
 Univariate logistic regression analysis            βi        Odds ratio      Lower       Upper       Wald value            P         R2
 PCR positivity in patients without lung involvement (N = 71/139)
 Back or chest pain                                0.61          1.83          0.93        3.60           3.11           0.078       0.02
 Dry mouth sensation (xerostomia)                  2.16          8.71          1.91       39.72           7.81           0.005       0.08
 Any oral mucosa findings                          2.11          8.22          3.53       19.17           23.80         <0.001       0.19
 Erythema of tonsils and pharynx                   0.79          2.19          1.11        4.32           5.16           0.023       0.04
 Micro vesicles on tonsils or pharynx              2.65         14.11          4.04       49.32           17.18         <0.001       0.18
 Petechiae in the oropharynx                       1.45          4.24          1.87        9.63           11.94          0.001       0.09
 Primary/secondary herpes infection                1.55          4.72          0.98       22.70           3.75           0.053       0.03
 Oral aphthae                                      0.94          2.55          1.03        6.34           4.05           0.044       0.03
 Lung involvement in patients with PCR positivity (N = 42/113)
 Age (year)                                        0.30          1.03          0.99        1.06           3.48           0.062       0.03
 Complaint duration (day)                          0.16          1.17          0.99        1.38           3.42           0.064       0.03
 Cheilitis or angular cheilitis                    1.37          3.94          1.11       14.02           4.49           0.034       0.04

PCR= Polymerase Chain Reaction.


      Table 5. Evaluation of examination findings related to PCR result with multivariate logistic
                                         regression analysis.
                                                                                      95% CI
 Multivariate logistic regression analysis               βi    Odds ratio       Lower         Upper      Wald value         P         R2
 PCR positivity in patients without lung involvement; Step 4 (N = 71/139)
 Dry mouth sensation (xerostomia)                    2.14          8.48           1.67        43.11          6.65         0.010     0.32
 Micro vesicles on tonsils or pharynx                2.75         15.64           3.38        72.45          12.36       <0.001
 Petechiae in the oropharynx                         1.05          2.86           1.10         7.44          4.63         0.032
 Primary/secondary herpes infection                  2.41         11.15           1.27        97.53          4.75         0.029

Multivariate analysis was performed using the “Backward: Wald” method. It was carried out with examination findings such as “Back or
chest pain, dry mouth sensation, erythema of tonsils and pharynx, microvesicles on tonsils or pharynx, petechiae in the oropharynx, primary/
secondary herpes infection, oral aphthae” with a significance level of p<0.01.
PCR = Polymerase Chain Reaction.


    To date, reports generally provide information about                directly from the disease. The expression of ACE2 and trans-
the signs and symptoms of the oral mucosa in patients with              membrane serine protease (TMRPSS2) are confirmed in oral
COVID-19; however, the relationship between PCR positiv-                mucosal epithelia and salivary glands, approving evidence
ity and pneumonia and the oral signs and symptoms has not               of SARS-CoV-2 direct infection [23]. In addition, since the
yet been studied. In the present study, it was found that mi-           oral mucosa was the first to be infected with SARS-CoV-2, it
crovesicles on the tonsils or pharynx were most associated              was suggested that oral lesions could be the first symptom of
with PCR positivity in patients without lung involvement                COVID-19 [24]. A study has revealed that viruses affect epi-
(P < 0.001).                                                            thelial cells and damage tissue integrity by causing inflamma-
    Petechiae in the oropharynx, dry mouth sensation (xero-             tory reactions [25]. It was suggested that SARS-CoV-2 infects
stomia), erythema of tonsils and pharynx, oral aphthae, and             salivary glands, resulting in hyposalivation, taste disorders,
primary/secondary herpes infection were also related to PCR             xerostomia, and halitosis [23]. According to our study re-
positivity (P < 0.05). Cheilitis or angular cheilitis were the          sults, we can make the following comment: For COVID-19,
only oral signs associated with lung involvement in patients            a PCR swab is obtained from the tonsillar-pharynx and
with PCR positivity (P = 0.034). The patients with negative             nasopharynx [8]. Thus, tonsillar-pharynx lesions such as
PCR tests had more common normal oral mucosa (P < 0.001).               microvesicles on the tonsils or pharynx, petechiae in the
Various hypotheses have been recommended for the etiology               oropharynx, erythema of tonsils and pharynx, oral aphthae
of oral lesions. According to some authors, the lesions arise           (only on the tonsillar-pharynx) which were related to PCR



6                                                                            Original Article | Dermatol Pract Concept. 2024;14(1):e2024045
positivity according to our study could suggest the direct ef-          5. Petrescu N, Lucaciu O, Roman A. Oral mucosa lesions in
fect of SARS-CoV-2. However, dry mouth probably occurs                     COVID-19. Oral Dis. 2022;28 Suppl 1(Suppl 1):935-936. DOI:
                                                                           10.1111/odi.13499. PMID: 32558983. PMCID: PMC7323044.
secondary to involvement of the salivary glands and herpes
                                                                        6. Erbaş GS, Botsali A, Erden N, Arı C, et al. COVID-19-related
infections may be an opportunistic coinfection. Nevertheless,
                                                                           oral mucosa lesions among confirmed SARS-CoV-2 patients:
as these lesions were associated with PCR positivity, the pres-            a systematic review. Int J Dermatol. 2022;61(1):20-32. DOI:
ence of these findings may indicate the presence of the virus              10.1111/ijd.15889. PMID: 34549816. PMCID: PMC8652904.
in the tonsillar-pharynx. Some studies have suggested that              7. Cuevas-Gonzalez MV, Espinosa-Cristóbal LF, Donohue-Cornejo
some manifestations such as herpes infections and angular                  A, et al. COVID-19 and its manifestations in the oral cavity: A
                                                                           systematic review. Medicine (Baltimore). 2021;100(51):e28327.
cheilitis are opportunistic coinfection [26,27]. In the present
                                                                           DOI: 10.1097/MD.0000000000028327. PMID: 34941133.
study, angular cheilitis was more frequent in patients with
                                                                           ­PMCID: PMC8701462.
pneumonia, suggesting opportunistic coinfection.                        8. Piccolo V, Bassi A, Grimalt R, et al. Lingua villosa nigra in a child
    This study has some limitations. Firstly, we only included              after COVID: Review and differential diagnosis with oral pig-
symptomatic patients with mild-to-moderate disease in the                   mentations of childhood. J Eur Acad Dermatol Venereol. 2023
study. Thus, our data cannot support oral lesions in asymp-                 Mar 27. DOI: 10.1111/jdv.19070. PMID: 36974423.
                                                                        9. Amorim Dos Santos J, Normando AGC, et al. Oral Manifestations
tomatic patients or with severe COVID-19. Secondly, as all
                                                                            in Patients with COVID-19: A Living Systematic Review. J Dent
patients were adults, the study does not provide information
                                                                            Res. 2021;100(2):141-154. DOI: 10.1177/0022034520957289.
on the relationship between oral findings and PCR positivity                PMID: 32914677.
in children.                                                           10. Goudouris ES. Laboratory diagnosis of COVID-19. J Pediatr
    Oral aphthae and herpes lesions on the entire oral mu-                  (Rio J). 2021;97(1):7-12. DOI: 10.1016/j.jped.2020.08.001.
cosa were evaluated. Thus, direct virus infection on the ton-               PMID: 32882235. PMCID: PMC7456621.
                                                                       11. Drago F, Paolino S, Rebora A, et al. The challenge of diag-
sillar pharynx could not be differentiated. Another limitation
                                                                           nosing atypical exanthems: a clinico-laboratory study. J Am
was that oral examination of patients and clinical imaging of
                                                                           Acad Dermatol. 2012;67(6):1282-1288. DOI: 10.1016/j
lesions were difficult due to the high risk of contamination               .jaad.2012.04.014. PMID: 22627037.
at the beginning of the pandemic. Nonetheless, we made an              12. Egido-Moreno S, Valls-Roca-Umbert J, Jané-Salas E, López-López J,
effort to evaluate patients correctly and our study provides               Estrugo-Devesa A. COVID-19 and oral lesions, short communi-
valuable observations of a large number of cases.                          cation and review. J Clin Exp Dent. 2021;13(3):e287-e294. DOI:
                                                                           10.4317/jced.57981. PMID: 33680331. PMCID: PMC7920556.
    Our study showed that especially microvesicles, pete-
                                                                       13. Tuter G, Yerebakan M, Celik B, Kara G. Oral manifestations
chiae, erythema on the tonsils or pharynx, and some other
                                                                           in SARS-CoV-2 infection. Med Oral Patol Oral Cir Bucal.
oral lesions such as dry mouth, oral aphthae, and primary/                 2022;27(4):e330-e339. DOI: 10.4317/medoral.25259. PMID:
secondary herpes infection are associated with PCR positiv-                35717616. PMCID: PMC9271340.
ity and can guide us in terms of definite disease. However, the        14. Doceda MV, Gavriiloglou M, Petit C, Huck O. Oral Health
pathophysiological mechanism and relationship of these oral                Implications of SARS-CoV-2/COVID-19: A Systematic Review.
                                                                           Oral Health Prev Dent. 2022;20(1):207-218. DOI: 10.3290/j
manifestations in COVID-19 should be further investigated.
                                                                           .ohpd.b2960801. PMID: 35481345.
                                                                       15. Reis VP, Bezerra AR, Maia ABP, Marques LC, Conde DC.
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8                                                                           Original Article | Dermatol Pract Concept. 2024;14(1):e2024045
