Next Article in Journal
Urban Climate Policy and Action through a Health Lens—An Untapped Opportunity
Next Article in Special Issue
A Systematic Review on Nerve-Related Adverse Effects following Mandibular Nerve Block Anesthesia
Previous Article in Journal
Oral Mucosa Status and Saliva Parameters of Multimorbid Adult Patients Diagnosed with End-Stage Chronic Kidney Disease
Previous Article in Special Issue
Parents’ Willingness to Invest in Primary Oral Health Prevention for Their Preschool Children
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJERPH
Volume 18
Issue 23
10.3390/ijerph182312511
ijerph-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Systematic Review

Oral Manifestations of COVID-19 in Hospitalized Patients: A Systematic Review

by
Giulia Orilisi
1,†,
Marco Mascitti
1,†,
Lucrezia Togni
1,
Riccardo Monterubbianesi
1,
Vincenzo Tosco
1,
Flavia Vitiello
1,
Andrea Santarelli
1,2,
Angelo Putignano
1 and
Giovanna Orsini
1,*
1
Department of Clinical, Specialistic and Dental Sciences, Marche Polytechnic University, Via Tronto 10, 60126 Ancona, Italy
2
Dentistry Clinic, National Institute of Health and Science of Aging, IRCCS INRCA, Via Tronto 10, 60126 Ancona, Italy
*
Author to whom correspondence should be addressed.
†
Equal contribution.
Int. J. Environ. Res. Public Health 2021, 18(23), 12511; https://doi.org/10.3390/ijerph182312511
Submission received: 4 November 2021 / Revised: 24 November 2021 / Accepted: 25 November 2021 / Published: 27 November 2021
(This article belongs to the Special Issue Dental Public Health: Issues, Challenges and Opportunities)
Browse Figure
Versions Notes

Abstract

:
Background: COVID-19 disease first appeared in 2019 and quickly spread worldwide, causing a global pandemic. The oral cavity represents a target of SARS-CoV-2, and oral lesions are observed in both non-hospitalized and hospitalized patients. This systematic review aims to investigate the frequency of oral manifestations in COVID-19 hospitalized patients. Methods: An electronic search was conducted in PubMed, Scopus, and Web of Science databases, including articles published up to September 2021. The review protocol was based on PRISMA-P. The risk of bias of the studies was assessed using the Joana Briggs Institute. The certainty of evidence was assessed using the GRADE instrument. Results: Fifty-nine articles were included: 19 case reports, 17 case series, 2 case-control studies, 13 cross-sectional studies, 4 observational studies, and 4 retrospective studies. Oral ulcers, cheilitis, and tongue lesions were more common in patients before hospitalization, while perioral pressure ulcers, macroglossia, blisters, and oral candidiasis were more recurrent in patients during hospitalization. The first could be related directly to COVID-19, while the latter could be caused by medical devices, treatments, prone position, and immunological impairment. Conclusions: An accurate oral examination during the hospital admission of all confirmed COVID-19 cases is encouraged to recognize oral early manifestations and to apply appropriate treatments.

1. Introduction

The outbreak of novel coronavirus SARS-CoV-2 has created a global crisis and challenged healthcare systems across the world [1]. It was first identified in Wuhan, China, on 31 December 2019, in association with a severe human respiratory disease (COVID-19). On 30 January 2020, the World Health Organization (WHO) declared the COVID-19 infection as a Public Health Emergency of International Concern.
SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus with multiple spikes on the surface and a genome size of approximately 26–32 kilobases. Fever, dyspnea, body aches, and dry cough are the most common symptoms [2], but severe cases can develop pneumonia, severe acute respiratory syndrome, and kidney failure, representing a life-threatening condition [3,4]. Most patients display moderate symptoms (80%), while 20% of them may develop a severe disease and 5% may become critically ill, developing pneumonia or acute respiratory distress syndrome, which requires mechanical ventilation and intensive care unit hospitalization [5]. SARS-CoV-2 mainly spreads through respiratory droplets, aerosols, contact, and fomites [6,7,8,9].
A recent study has shown that coronavirus invades human cells via the receptor angiotensin-converting enzyme 2 (ACE2), using the spike-like protein [10]. The ACE2 receptors are located in many organs and tissues, such as skin, olfactory system, and oral cavity; therefore, these cells may host the virus, triggering the inflammatory response [11,12].
Oral manifestations have been reported in several literature studies [13,14,15,16]. The main symptoms, displayed during the pre-symptomatic stage, are ageusia (loss of taste), non-specific anosmia (loss of smell), and hyposalivation [17,18]. Moreover, the most frequently reported oral signs include ulcerative lesions, vesiculobullous/macular lesions, desquamative gingivitis, petechiae, and coinfections such as candidiasis [15,19]. Palate and tongue represent the most involved oral subsites, followed by gingiva and lips [15].
The morphological spectrum of mucocutaneous diseases is still uncertain, as is its relationship with the clinical pattern and course of affected patients. However, many hypotheses have been proposed regarding the etiology of these diseases: direct SARS-CoV-2 infection, a coinfection, a consequence of the impaired immune system, and an adverse reaction to medical treatments and devices [20,21,22]. According to Sarode et al., oral manifestations seen in COVID-19 could be related to SARS-CoV-2 induced anemia [23]. Indeed, ACE2, CD147, and CD26 receptors located on the erythrocytes are potential targets for SARS-CoV-2 attachment, which can lead to hemolysis [24]. On the other hand, some authors have suggested that mucosal ulcers could be considered, not as a primary manifestation of COVID-19, but as a secondary signs related to bacterial and viral coinfections [25]. According to Hocková et al., oral mucocutaneous complications could be caused by the prolonged prone position and mechanical ventilation devices of the intensive care unit (ICU) setting [21]. Most of these studies were case reports and case series; therefore, it is still unclear whether the reported cases were directly due to the COVID-19 infection or indirectly related to stress, anxiety, comorbidities, and medical treatments.
Since, in April 2020, Carreras-Presas et al. published the first work on oral manifestations associated with COVID-19, their prevalence is becoming an emerging concern for the management of these patients [26]. However, few studies have deeply examined this issue. Therefore, the objective of this systematic review was to provide a comprehensive up-to-date summary of the prevalence of oral manifestations in hospitalized patients with COVID-19, reviewing all relevant studies to answer the following question: What are the oral signs and symptoms in hospitalized patients with COVID-19? This systematic review could help the clinicians to focus on detailed intraoral examination of hospitalized patients before and during their admission.

2. Materials and Methods

2.1. Protocol

The systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), following their checklist [26,27]. The review protocol was based on PRISMA-P [27,28].

2.2. Search Strategy

An electronic search was conducted in PubMed, Scopus, and Web of Science for literature updated from 1 January 2020 until 30 September 2021. The following keywords were used in each database: “oral manifestation COVID-19”, “oral manifestation SARS-CoV-2”, “oral manifestation novel coronavirus disease”, “oral lesion COVID-19”, “oral lesion SARS-CoV-2”, and “oral lesion novel coronavirus disease”. Related articles in the reference lists, cited by relevant studies, were manually searched.

2.3. Article Selection and Eligibility Criteria

Studies were selected by title and abstract, and full-text screening. Articles were included if they reported oral manifestations in hospitalized patients with COVID-19 infection.
The full-text articles of all potential studies were evaluated according to the eligibility criteria. The inclusion criteria were: (1) hospitalized patient affected by COVID-19, confirmed through RT-PCR testing; (2) articles reporting oral manifestation associated with COVID-19; and (3) studies published in the English language. The exclusion criteria were: (1) not-confirmed COVID-19 cases; (2) duplicate studies and data; and (3) full-text not accessible. There were no disagreements during the article selection process.
The primary outcome was to highlight the oral signs and symptoms that can occur in hospitalized patients affected by COVID-19.
A flow diagram detailing the process is presented in Figure 1.

2.4. Quality Assessment

The risk of bias of each study was assessed by two blinded reviewers using the Joanna Briggs Institute (JBI) critical appraisal checklist for case reports [29,30]. The score system was agreed by all reviewers before the critical appraisal assessments, and studies were classified according to the following categories: (a) low risk of bias, if the studies reached more than 70% scores of “yes”; (b) moderate risk of bias, if “yes” scores ranged from 50% to 69%; and (c) high risk of bias, if “yes” scores were less than 49%. Data are reported in Supplementary Materials (Table S1).

2.5. Certainty of Evidence

The evidence levels of the selected studies were assessed using the GRADE instrument (http://gradepro.org (accessed on 28 October 2021)) [31]. The certainty of evidence was rated for oral lesions prevalence in hospitalized patient. This assessment was based on study design, risk of bias, inconsistency, indirectness, imprecision, and other considerations. Evidence quality was characterized as high, moderate, low, or very low [32]. Data are reported in Supplementary Materials (Table S2).

2.6. Statistical Analysis

Descriptive statistical analysis was conducted by grouping and comparing data using Microsoft Excel software (2019, Microsoft Corporation, Redmond, WA, USA)

3. Results

3.1. Study Selection and Characteristics

A total of 340 studies were identified from databases, and, after removing the duplicate, 193 studies remained for title and abstract screening. A full-text reading was conducted on 187 studies. A total of 128 studies were excluded according to the eligibility criteria. Therefore, 59 studies were selected: 19 case reports, 17 case series, 2 case-control studies, 13 cross-sectional studies, 4 observational studies, and 4 retrospective studies (Table S1). Due to the lack of available data, case reports and series were also included in this systematic review. Thus, the risk-of-bias of each study was evaluated using the JBI critical appraisal checklist [33]. A flowchart detailing the process is presented in Table S1.
A total of 35 articles were judged as low risk [21,26,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66], 12 as a moderate risk [67,68,69,70,71,72,73,74,75,76,77,78], and 12 as high risk [79,80,81,82,83,84,85,86,87,88,89,90] (Table S1).
The sample consisted of 1219 patients, of which there were 456 men (37.4%), 374 women (30.7%), and 389 patients with no specified sex (31.9%), with a mean age of 50.8 years. Results from each selected article were subdivided into “oral lesions appeared before hospital admission” and “oral lesions appeared during hospitalization”. The studies were set in two tables (Table 1 and Table 2), reporting the following data: first author’s name and year of publication, study design, sample size and gender, mean age, medical history, oral manifestations, time of onset, affected site, treatment of COVID-19, treatment of oral manifestation, disease duration, reported diagnosis, and the risk of bias.
Moreover, data were categorized and described according to the following eight groups: (1) tongue lesions; (2) ulcerative and erosive lesions; (3) aphthous-like lesions; (4) vesiculobullous lesions; (5) lip lesions; (6) functional disorders; (7) candidiasis; and (8) non-specific lesions (mucositis).

3.2. Tongue Lesions

Tongue lesions appearing before hospital admission were reported in 14 studies [37,38,43,51,61,63,65,70,71,74,81,87,88,89], while 14 articles showed that tongue manifestations occurred during hospitalization [21,34,36,39,48,54,59,60,66,69,70,82,84]. The sample consisted of 172 males (age: 57.0 ± 15.1) and 155 females (age: 46.1 ± 22.1). Moreover, 135 patients with no specified sex and mean age were included.
Before hospitalization, white tongue, necrosis of the dorsal tongue, glossitis, geographic and fissured tongue, strawberry tongue, and depapillation of the tongue were the most common lesions diagnosed, directly related to SARS-CoV-2. One patient with a complex medical history showed a 1.5 × 1.5 cm ulcer in the right border of the tongue, while another patient reported a mucopurulent membrane in the anterior dorsal tongue [37]. Only three studies that reported tongue lesions referred to Kawasaki-like disease, potentially associated with COVID-19 [38,51,65].
During hospital admission, the main SARS-CoV-2 related lesions were tongue ulcers, especially in ICU patients [21]. Moreover, white plaque on tongue dorsum, geographic tongue, tongue redness, fissured tongue, and macroglossia were reported [35,54,66]. Macroglossia was reported in two patients who experienced prolonged pronation cycles for several days. Andrews et al. suggested 10 days of methylprednisolone in addition to a bite block to prevent this complication [35]; on the contrary, according to Mascitti et al., macroglossia could be referred to acute lymphatic and vascular obstruction due to COVID-19-related inflammatory response [54].

3.3. Ulcerative and Erosive Lesions

Ulcerative and erosive lesions were frequently present in COVID-19 patients, both before and during hospital admission. In particular, 14 studies reported that lesions appeared during hospitalization [21,34,36,37,42,45,47,48,52,57,64,69,70,82], while 6 articles referred to lesions that emerged before hospitalization [36,37,38,41,61,70]. The sample consisted of 111 males (age: 56.7 ± 15.3) and 90 females (age: 53.2 ± 22.4). Moreover, 123 patients with no specified sex and age were included.
Before and during hospitalization, ulcerative and erosive lesions were the most common orofacial manifestations of COVID-19. The ulcers emerged after a latency time of 4 to 7 days after the onset of COVID-19 symptoms, and most of them were diagnosed upon hospital admission. Only in one case did small oral ulcers appear 40 days after a COVID-19 positive test [42]. Some patients displayed painful herpetic and hemorrhagic ulcers with irregular margins, which were variable in size and number. Ulcers that appeared before hospital admission were located on the hard palate and lips, while the lesions that occurred during hospitalization mainly affected the tongue dorsum, lips, and buccal mucosa.
Some authors suggested different factors involved in the development of ulcerative and erosive lesions [12,41,60,61,91]. Ulcers could be related directly to SARS-CoV-2 infection or could be caused by drugs, vasculitis, or thrombotic vasculopathy secondary to COVID-19 [34,41]. Oral ulcerative lesions and erosive plaques appeared a few days after the onset of respiratory symptoms and worsened during hospitalization, due to persistent immunological impairment, and lesions did not heal after SARS-CoV-2 eradication [47]. In four ICU patients, the authors suggested that oral ulcers could be caused by medical devices during the prone positioning phases [21,57]. A wide range of therapies has been used for oral ulcers, including drugs (e.g., dexamethasone, tetracycline) and photobiomodulation therapies [37,57,64].

3.4. Aphthous-like Lesions

Aphthous-like lesions were reported in four studies, affecting six minors and three adults (>50 years). Moreover, aphthous-like lesions were showed in 78 cases with various oral signs and symptoms associated with COVID-19 [88]. Lesions were mainly related to COVID-19, probably due to the distribution of the ACE2 receptor on the oral mucosae [11,86], although one patient with minor aphthous ulcers was diagnosed with Sweet syndrome related to COVID-19 [62]. Stress and immunosuppression secondary to COVID-19 infection could be other possible reasons of these lesions [92].

3.5. Vesiculobullous Lesions

Vesiculobullous lesions, including herpetiform lesions, angina bullosa-like lesions, and oral blisters, were described in three studies [26,46,53,70]. Carreras-Presas et al. presented a 65-year-old female with lip blisters and desquamative gingivitis, occurring 22 days after viral infection. These lesions seem to be caused by COVID-19 through mechanisms shared with others virus, such as Herpes Simplex Virus-1 (HSV-1)-related gingivostomatitis [26].
Favia et al. detected oral blisters in 19 hospitalized patients (15.4%) that appeared during the first week after the onset of general symptoms and were mainly located on the tongue and palate [70]. According to the authors, lesions could be related to SARS-CoV-2, medical treatments, and/or poor oral hygiene.
Orolabial recurrent herpes simplex were observed in eight patients [46]. This manifestation was found in at HSV-1-positive patients, suggesting a possible superinfection of herpetic virus with COVID-19.

3.6. Lip Lesions

Thirteen studies showed patients with lip lesions that appeared before hospital admission [37,38,39,40,41,43,51,63,65,70,71,72,74], and 23 studies during the hospitalization [21,26,37,39,43,45,49,54,56,57,58,59,60,64,66,69,70,73,77,78,82,90]. The reports included 173 males (age: 41.2 ± 25.2), 114 females (age: 52.5 ± 24.3), and 118 patients with no specified sex and age.
Lip lesions included fissured lip, angular cheilitis, and perioral pressure ulcers. Fissured lips have been detected mainly in young patients, who were diagnosed with Kawasaki-like disease related to COVID-19 [39,40,51,54,65,71,72]. Mazzotta et al. described a 9-year-old male with Down syndrome and alopecia areata universalis, presenting glossitis and cheilitis, probably due to the excessive and persistent inflammation that occurred during the interstitial pneumonia with acute respiratory failure [74]. Angular cheilitis, due to stress and immunosuppression, was observed in a 53-year-old man a few days after hospital discharge; after the treatment, this lesion completely disappeared [43].
Prolonged prone position and endotracheal intubation were the most common risk factors for perioral and lip pressure ulcers, interfering with mechanical ventilation equipment in the critical care setting [21,49,56,58,59,66,73,77,78,90]. Most cases were treated with antimicrobial dressing, debridement of necrotic tissue, and paraffin gauze dressing. Finally, some articles reported lip lesions directly related to COVID-19, which appeared as a mucopurulent membrane with superficial necrosis or swollen lips and disappeared after 10–12 days of treatment [37,63,71].

3.7. Functional Disorders

Functional disorders included xerostomia, viscous saliva, ageusia and dysgeusia, halitosis, burning mouth, masticatory muscle weakness, salivary gland ectasia, temporo-mandibular article abnormalities, and facial tingling. These disorders were reported by several studies referred to hospitalized patients affected by COVD-19 [3,34,43,76,82,88]. The authors suggested these alterations could be directly related to SARS-CoV-2 and could be considered as an early manifestation of COVID-19 infection. Indeed, ACE2 receptors have been found in the taste buds and glandular epithelium, leading to salivary gland dysfunction and salivary flow impairment [93].
Masticatory muscle weakness, salivary gland ectasia, temporo-mandibular article abnormalities, and facial tingling were reported by Gherlone et al. [48]. The authors suggested that salivary gland ectasia reflected the hyperinflammatory response to SARS-CoV-2, as demonstrated by the significant relationship with C-reactive protein and lactate dehydrogenase levels at hospital admission, and antibiotics use during acute disease.

3.8. Candidiasis

Candidiasis appeared as white plaques on the dorsum of tongue, gingiva, and palate [43,44,66,70,75,80,81]. The authors suggested it could be related to the long-lasting antibiotic therapy, the deterioration of general status, and poor oral hygiene [80]. Salehi et al. isolated 65 species of Candida spp. (70.7% C. albicans) in a cohort of COVID-19 patients with oropharyngeal candidiasis [75]. Interestingly, Dima et al. reported oral candidiasis with diaper erythema in three newborns positive with COVID-19 [44]. The oral candidiasis in young patients was also reported by Bardellini et al. [81], describing two cases of oral pseudomembranous candidiasis diagnosed at the hospitalization.

3.9. Nonspecific Lesions (Mucositis)

Petechiae, macules, erythema, stomatitis, brown pigmentation, mucositis, enanthema, and desquamative gingivitis were reported in many hospitalized patients [26]. Vascular disorders could cause mucositis in the affected patients. Indeed, Cruz-Tapia et al. described a 51-year-old female with diffuse vascular-like purple macule on the left palate and a papule-plaque on the right palate [68]. Riad et al. described 13 patients affected by mucositis; enanthema of the buccal mucosa, palate, and gingiva; and depapillation of the tongue, at hospitalization. These lesions disappeared after 7–14 days of “Magic mouthwash” and paracetamol and could be related directly to COVID-19 infection [6,89]. Only one study described a patient affected by oral lichenoid reaction and a case with oral enanthema, directly due to COVID-19 [54]. Marouf et al. suggested that periodontitis was significantly associated with a higher risk of COVID-19 complications, such as ICU admission, assisted ventilation, and the increased markers levels of COVID-19 worse outcome [55].

4. Discussion

A broad spectrum of signs and symptoms were reported in association with COVID-19; however, only a few studies highlighted oral clinical manifestations observed in hospitalized patients. The pathogenesis remains unclear, but some hypotheses have been formulated. Xu et al. showed a higher expression of ACE2 in the oral mucosa, especially on the tongue and in the salivary glands [11]. Thus, the oral cavity might be an anatomical site susceptible to SARS-CoV-2 infection [94]. Consequently, the interaction between SARS-CoV-2 and ACE2 might dysregulate the oral keratinocytes’ function, leading to painful oral ulcers [37]. This mechanism could also be the basis of early manifestations of COVID-19, such as taste alteration and xerostomia [95]. The immune response to infection could activate Langerhans cells and lymphocytes, leading to vasculitis and thrombocytopenia, causing oral lesions related to vascular disorders (e.g., petechiae) [19,41,92,96].
It is still unclear whether oral lesions reflect a direct viral cytopathic effect or represent a consequence of stress, poor oral hygiene, systemic infections, medical treatments, or medical devices used during hospital admission [97]. However, to the best of our knowledge, no attempt has been made to review the available literature regarding oral lesions in hospitalized COVID-19 patients. Therefore, this systematic review is the first to characterizs the patterns of oral lesions that occurred in hospitalized patients affected by COVID-19. As intraoral examination has not yet been considered in the screening of the disease, literature still lacks evidence to better understand the onset of oral manifestations. In this review, the most common oral lesions seen in patients before hospital admission are painful ulcers, cheilitis, and tongue lesions. According to several authors, these lesions are related directly to COVID-19 [36,37,88,89]. Conversely, the most common oral lesions displayed by patients during hospitalization are perioral pressure ulcers, macroglossia, blisters, and oral candidiasis. These lesions may be due to the long-lasting prone position of ICU patients [21,90], increased pressure of the endotracheal tubes [59], prolonged inpatient care [52], persistent immunological impairment [43,47], and medical treatments [80].
The studies reporting that oral manifestations in COVID-19 are very low, leading to a considerable risk of bias. Most of the eligible studies showed a high risk of bias, due to insufficient simple size, poor methods, or inadequate designs. Case reports and case series have profoundly influenced the medical literature and continue to improve the current knowledge [98]. Although the evidence derived from case series and case reports is very low, a strong recommendation for oral lesions of hospitalized patients, affected by COVID-19, can be provide. Moreover, GRADE literature describes five paradigmatic situations in which a strong recommendation can be made based on low quality evidence, such as a condition of life threatening [99].
Considering the results of this systematic review, clinicians should consider the oral lesions affecting the hospitalized patients with COVID-19 to ensure an adequate prevention and therapeutic management. Thus, the importance of the oral examination should be emphasized in hospitalized patients with infectious diseases, to encourage the multidisciplinary management of COVID-19 patient.

5. Conclusions

The new SARS-CoV-2 has become a worldwide sanitary emergency. Understanding the manifestations and progression of COVID-19 is the first step in developing an adequate prevention and treatment management. Although the typical symptoms include fever, shortness of breath, and dry cough, oral lesions have also been reported. The association between oral diseases and SARS-CoV-2 infection is still unclear and is currently poorly investigated.
Based on this systematic review, it could be suggest that: (1) painful oral ulcers, cheilitis, and tongue lesions are more frequent in patients before hospital admission; (2) perioral pressure ulcers, macroglossia, blisters, and oral candidiasis are more evident in patients during hospitalization; (3) lesions that appeared before hospital admission are mainly related directly to COVID-19; (4) lesions that appeared during hospitalization are mainly associated with medical devices and treatments, prone position, and immunological impairment; (5) all clinicians, during the hospital admission, should be encouraged to perform an accurate oral examination of all confirmed COVID-19 cases to recognize the disease’s possible early manifestations; (6) further studies are necessary to establish the pathological significance of oral manifestations during COVID-19.

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/ijerph182312511/s1, Table S1: Risk of bias in the reported articles, Table S2: Certainty assessment and grading of the evidence.

Author Contributions

Conceptualization, G.O. (Giulia Orilisi), M.M., L.T. and G.O. (Giovanna Orsini); methodology, G.O. (Giulia Orilisi), L.T., A.S. and A.P.; investigation, G.O. (Giulia Orilisi), V.T. and F.V.; data curation, A.S., R.M. and F.V.; writing—original draft preparation, G.O. (Giulia Orilisi), M.M., L.T., R.M. and V.T.; writing—review and editing, A.S., A.P. and G.O. (Giovanna Orsini); supervision, G.O. (Giovanna Orsini). All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Acknowledgments

ECCE-COST ACTION CA 16234 is kindly acknowledged.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Wu, F.; Zhao, S.; Yu, B.; Chen, Y.-M.; Wang, W.; Song, Z.-G.; Hu, Y.; Tao, Z.-W.; Tian, J.-H.; Pei, Y.-Y.; et al. A New Coronavirus Associated with Human Respiratory Disease in China. Nature 2020, 579, 265–269. [Google Scholar] [CrossRef] [Green Version]
  2. Jiang, F.; Deng, L.; Zhang, L.; Cai, Y.; Cheung, C.W.; Xia, Z. Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19). J. Gen. Intern. Med. 2020, 35, 1545–1549. [Google Scholar] [CrossRef] [Green Version]
  3. Chen, N.; Zhou, M.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; Wei, Y.; et al. Epidemiological and Clinical Characteristics of 99 Cases of 2019 Novel Coronavirus Pneumonia in Wuhan, China: A Descriptive Study. Lancet 2020, 395, 507–513. [Google Scholar] [CrossRef] [Green Version]
  4. CDC Weekly, C. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19)—China, 2020. China CDC Wkly. 2020, 2, 113–122. [Google Scholar] [CrossRef]
  5. Yue, H.; Bai, X.; Wang, J.; Yu, Q.; Liu, W.; Pu, J.; Wang, X.; Hu, J.; Xu, D.; Li, X.; et al. Clinical Characteristics of Coronavirus Disease 2019 in Gansu Province, China. Ann. Palliat. Med. 2020, 9, 1404–1412. [Google Scholar] [CrossRef] [PubMed]
  6. Ionescu, A.C.; Brambilla, E.; Manzoli, L.; Orsini, G.; Gentili, V.; Rizzo, R. Efficacy of Personal Protective Equipment against Coronavirus Transmission via Dental Handpieces. J. Am. Dent. Assoc. 2021, 152, 631–640. [Google Scholar] [CrossRef]
  7. Ionescu, A.C.; Brambilla, E.; Manzoli, L.; Orsini, G.; Gentili, V.; Rizzo, R. Aerosols Modification with H2O2 Reduces Airborne Contamination by Dental Handpieces. J. Oral Microbiol. 2021, 13, 1881361. [Google Scholar] [CrossRef]
  8. Farid, H.; Khan, M.; Jamal, S.; Ghafoor, R. Oral Manifestations of Covid-19-A Literature Review. Rev. Med. Virol. 2021, e2248. [Google Scholar] [CrossRef]
  9. Ionescu, A.C.; Brambilla, E.; Manzoli, L.; Orsini, G.; Gentili, V.; Rizzo, R. Efficacy of Personal Protective Equipment and H2O2—Based Spray against Coronavirus in Dental Setting. Oral Dis. 2020. [Google Scholar] [CrossRef]
  10. Zou, X.; Chen, K.; Zou, J.; Han, P.; Hao, J.; Han, Z. Single-Cell RNA-Seq Data Analysis on the Receptor ACE2 Expression Reveals the Potential Risk of Different Human Organs Vulnerable to 2019-NCoV Infection. Front. Med. 2020, 14, 185–192. [Google Scholar] [CrossRef] [Green Version]
  11. Xu, H.; Zhong, L.; Deng, J.; Peng, J.; Dan, H.; Zeng, X.; Li, T.; Chen, Q. High Expression of ACE2 Receptor of 2019-NCoV on the Epithelial Cells of Oral Mucosa. Int. J. Oral Sci. 2020, 12, 8. [Google Scholar] [CrossRef] [PubMed]
  12. Chaux-Bodard, A.-G.; Deneuve, S.; Desoutter, A. Oral Manifestation of Covid-19 as an Inaugural Symptom? J. Oral Med. Oral Surg. 2020, 26, 18. [Google Scholar] [CrossRef]
  13. Tong, J.Y.; Wong, A.; Zhu, D.; Fastenberg, J.H.; Tham, T. The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-Analysis. Otolaryngol. Head Neck Surg. 2020, 163, 3–11. [Google Scholar] [CrossRef] [PubMed]
  14. Tsuchiya, H. Oral Symptoms Associated with COVID-19 and Their Pathogenic Mechanisms: A Literature Review. Dent. J. 2021, 9, 32. [Google Scholar] [CrossRef] [PubMed]
  15. dos Santos, J.A.; Normando, A.G.C.; da Silva, R.L.C.; Acevedo, A.C.; Canto, G.D.L.; Sugaya, N.; Santos-Silva, A.R.; Guerra, E.N.S. Oral Manifestations in Patients with COVID-19: A Living Systematic Review. J. Dent. Res. 2020, 100, 141–154. [Google Scholar] [CrossRef]
  16. Mascitti, M.; Campisi, G. Dental Public Health Landscape: Challenges, Technological Innovation and Opportunities in the 21st Century and COVID-19 Pandemic. Int. J. Environ. Res. Public Health 2020, 17, 3636. [Google Scholar] [CrossRef]
  17. Vaira, L.A.; Deiana, G.; Fois, A.G.; Pirina, P.; Madeddu, G.; De Vito, A.; Babudieri, S.; Petrocelli, M.; Serra, A.; Bussu, F.; et al. Objective Evaluation of Anosmia and Ageusia in COVID-19 Patients: Single-Center Experience on 72 Cases. Head Neck 2020, 42, 1252–1258. [Google Scholar] [CrossRef]
  18. Lee, Y.; Min, P.; Lee, S.; Kim, S.W. Prevalence and Duration of Acute Loss of Smell or Taste in COVID-19 Patients. J. Korean Med. Sci. 2020, 35, e174. [Google Scholar] [CrossRef]
  19. Halboub, E.; Al-Maweri, S.A.; Alanazi, R.H.; Qaid, N.M.; Abdulrab, S. Orofacial Manifestations of COVID-19: A Brief Review of the Published Literature. Braz. Oral Res. 2020, 34, e124. [Google Scholar] [CrossRef]
  20. Dziedzic, A.; Wojtyczka, R. The Impact of Coronavirus Infectious Disease 19 (COVID-19) on Oral Health. Oral Dis. 2020. [Google Scholar] [CrossRef]
  21. Hocková, B.; Riad, A.; Valky, J.; Šulajová, Z.; Stebel, A.; Slávik, R.; Bečková, Z.; Pokorná, A.; Klugarová, J.; Klugar, M. Oral Complications of ICU Patients with COVID-19: Case-Series and Review of Two Hundred Ten Cases. J Clin. Med. 2021, 10, 581. [Google Scholar] [CrossRef]
  22. Rochefort, J.; Chaux, A.G. Oral Mucosal Lesions and Covid-19: Symptoms and/or Complication? J. Oral Med. Oral Surg. 2021, 27, 23. [Google Scholar] [CrossRef]
  23. Sarode, G.S.; Sarode, S.C.; Gadbail, A.R.; Gondivkar, S.; Sharma, N.K.; Patil, S. Are Oral Manifestations Related to SARS-CoV-2 Mediated Hemolysis and Anemia? Med. Hypotheses 2020, 146, 110413. [Google Scholar] [CrossRef]
  24. Cavezzi, A.; Troiani, E.; Corrao, S. COVID-19: Hemoglobin, Iron, and Hypoxia beyond Inflammation. A Narrative Review. Clin. Pr. 2020, 10, 24–30. [Google Scholar] [CrossRef]
  25. Galván Casas, C.; Català, A.; Carretero Hernández, G.; Rodríguez-Jiménez, P.; Fernández-Nieto, D.; Rodríguez-Villa Lario, A.; Navarro Fernández, I.; Ruiz-Villaverde, R.; Falkenhain-López, D.; Llamas Velasco, M.; et al. Classification of the Cutaneous Manifestations of COVID-19: A Rapid Prospective Nationwide Consensus Study in Spain with 375 Cases. Br. J. Dermatol. 2020, 183, 71–77. [Google Scholar] [CrossRef] [PubMed]
  26. Martín Carreras-Presas, C.; Amaro Sánchez, J.; López-Sánchez, A.F.; Jané-Salas, E.; Somacarrera Pérez, M.L. Oral Vesiculobullous Lesions Associated with SARS-CoV-2 Infection. Oral Dis. 2020, 27, 710–712. [Google Scholar] [CrossRef]
  27. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G.; PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009, 6, e1000097. [Google Scholar] [CrossRef] [Green Version]
  28. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
  29. JBI. Global/Critical-Appraisal-Tools. Available online: https://jbi.global/critical-appraisal-tools (accessed on 13 October 2021).
  30. Moola, S.; Munn, Z.; Sears, K.; Sfetcu, R.; Currie, M.; Lisy, K.; Tufanaru, C.; Qureshi, R.; Mattis, P.; Mu, P. Conducting Systematic Reviews of Association (Etiology): The Joanna Briggs Institute’s Approach. Int. J. Evid.-Based Health 2015, 13, 163–169. [Google Scholar] [CrossRef]
  31. Guyatt, G.H.; Oxman, A.D.; Vist, G.E.; Kunz, R.; Falck-Ytter, Y.; Alonso-Coello, P.; Schünemann, H.J.; GRADE Working Group. GRADE: An Emerging Consensus on Rating Quality of Evidence and Strength of Recommendations. BMJ 2008, 336, 924–926. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  32. Atkins, D.C.; Eccles, M.P.; Flottorp, S.; Guyatt, G.H.; Henry, D.; Hill, S.; Liberati, A.; O’Connell, D.; Oxman, A.D.; Phillips, B.; et al. Systems for Grading the Quality of Evidence and the Strength of Recommendations I: Critical Appraisal of Existing Approaches The GRADE Working Group. BMC Health Serv. Res. 2004, 4, 38. [Google Scholar] [CrossRef]
  33. Munn, Z.; Moola, S.; Lisy, K.; Riitano, D.; Tufanaru, C. Methodological Guidance for Systematic Reviews of Observational Epidemiological Studies Reporting Prevalence and Cumulative Incidence Data. Int. J. Evid.-Based Health 2015, 13, 147–153. [Google Scholar] [CrossRef] [PubMed]
  34. dos Santos, J.A.; Normando, A.G.C.; da Silva, R.L.C.; De Paula, R.M.; Cembranel, A.C.; Santos-Silva, A.R.; Guerra, E.N.S. Oral Mucosal Lesions in a COVID-19 Patient: New Signs or Secondary Manifestations? Int. J. Infect. Dis. 2020, 97, 326–328. [Google Scholar] [CrossRef]
  35. Andrews, E.; Lezotte, J.; Ackerman, A.M. Lingual Compression for Acute Macroglossia in a COVID-19 Positive Patient. BMJ Case. Rep. 2020, 13, e237108. [Google Scholar] [CrossRef] [PubMed]
  36. Ansari, R.; Gheitani, M.; Heidari, F.; Heidari, F. Oral Cavity Lesions as a Manifestation of the Novel Virus (COVID-19). Oral Dis. 2021, 27 (Suppl. 3), 771–772. [Google Scholar] [CrossRef]
  37. Brandão, T.B.; Gueiros, L.A.; Melo, T.S.; Prado-Ribeiro, A.C.; Nesrallah, A.C.F.A.; Prado, G.V.B.; Santos-Silva, A.R.; Migliorati, C.A. 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. 2021, 131, e45–e51. [Google Scholar] [CrossRef]
  38. Chérif, M.Y.; de Filette, J.M.K.; André, S.; Kamgang, P.; Richert, B.; Clevenbergh, P. Coronavirus Disease 2019-Related Kawasaki-like Disease in an Adult: A Case Report. JAAD Case Rep. 2020, 6, 780–782. [Google Scholar] [CrossRef]
  39. Chiotos, K.; Bassiri, H.; Behrens, E.M.; Blatz, A.M.; Chang, J.; Diorio, C.; Fitzgerald, J.C.; Topjian, A.; John, A.R.O. Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series. J. Pediatr. Infect. Dis. Soc. 2020, 9, 393–398. [Google Scholar] [CrossRef] [PubMed]
  40. Chiu, J.S.; Lahoud-Rahme, M.; Schaffer, D.; Cohen, A.; Samuels-Kalow, M. Kawasaki Disease Features and Myocarditis in a Patient with COVID-19. Pediatr. Cardiol. 2020, 41, 1526–1528. [Google Scholar] [CrossRef]
  41. Ciccarese, G.; Drago, F.; Boatti, M.; Porro, A.; Muzic, S.I.; Parodi, A. Oral Erosions and Petechiae during SARS-CoV-2 Infection. J. Med. Virol. 2020, 93, 129–132. [Google Scholar] [CrossRef]
  42. De Medeiros, V.L.S.; Monteiro-Neto, A.U.; França, D.D.T.; Branco, R.C.; de Miranda Coelho, É.O.; Takano, D.M. Pemphigus Vulgaris After COVID-19: A Case of Induced Autoimmunity. SN Compr. Clin. Med. 2021, 3, 1768–1772. [Google Scholar] [CrossRef] [PubMed]
  43. Rodríguez, M.D.; Romera, A.J.; Villarroel, M. Oral Manifestations Associated with COVID-19. Oral Dis. 2020. [Google Scholar] [CrossRef]
  44. Dima, M.; Enatescu, I.; Craina, M.; Petre, I.; Iacob, E.R.; Iacob, D. First Neonates with Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Romania. Medicine 2020, 99, e21284. [Google Scholar] [CrossRef] [PubMed]
  45. Fathi, Y.; Hoseini, E.G.; Mottaghi, R. Erythema Multiform-like Lesions in a Patient Infected with SARS-CoV-2: A Case Report. Future Virol. 2021, 16, 157–160. [Google Scholar] [CrossRef]
  46. Fernandez-Nieto, D.; Ortega-Quijano, D.; Suarez-Valle, A.; Burgos-Blasco, P.; Jimenez-Cauhe, J.; Fernandez-Guarino, M. Comment on: “To Consider Varicella-like Exanthem Associated with COVID-19, Virus Varicella Zoster and Virus Herpes Simplex Must Be Ruled out. Characterization of Herpetic Lesions in Hospitalized COVID-19 Patients”. J. Am. Acad. Dermatol. 2020, 83, e257–e259. [Google Scholar] [CrossRef]
  47. Gabusi, A.; Gissi, D.B.; Rossi, R.; Foschini, M.P.; Montebugnoli, L. Persistent Lesions in Oral Cavity after SARS-CoV-2 Infection. Oral Dis. 2021, 00, 1–2. [Google Scholar] [CrossRef]
  48. Gherlone, E.F.; Polizzi, E.; Tetè, G.; De Lorenzo, R.; Magnaghi, C.; Querini, P.R.; Ciceri, F. Frequent and Persistent Salivary Gland Ectasia and Oral Disease After COVID-19. J. Dent. Res. 2021, 100, 464–471. [Google Scholar] [CrossRef]
  49. Ibarra, G.; Rivera, A.; Fernandez-Ibarburu, B.; Lorca-García, C.; Garcia-Ruano, A. Prone Position Pressure Sores in the COVID-19 Pandemic: The Madrid Experience. J. Plast. Reconstr. Aesthet. Surg. 2020, 74, 2141–2148. [Google Scholar] [CrossRef]
  50. Jimenez-Cauhe, J.; Ortega-Quijano, D.; Carretero-Barrio, I.; Suarez-Valle, A.; Saceda-Corralo, D.; Del Real, C.M.-G.; Fernandez-Nieto, D. Erythema Multiforme-like Eruption in Patients with COVID-19 Infection: Clinical and Histological Findings. Clin. Exp. Dermatol. 2020, 45, 892–895. [Google Scholar] [CrossRef] [PubMed]
  51. Jones, V.G.; Mills, M.; Suarez, D.; Hogan, C.A.; Yeh, D.; Segal, J.B.; Nguyen, E.L.; Barsh, G.R.; Maskatia, S.; Mathew, R. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp. Pediatr. 2020, 10, 537–540. [Google Scholar] [CrossRef]
  52. Kämmerer, T.; Walch, J.; Flaig, M.; French, L.E. COVID-19-Associated Herpetic Gingivostomatitis. Clin. Exp. Dermatol. 2021, 46, 174–176. [Google Scholar] [CrossRef]
  53. Llamas-Velasco, M.; Rodríguez-Jiménez, P.; Chicharro, P.; De Argila, D.; Muñoz-Hernández, P.; Daudén, E. Reply to “Varicella-like Exanthem as a Specific COVID-19-Associated Skin Manifestation: Multicenter Case Series of 22 Patients”: To Consider Varicella-like Exanthem Associated with COVID-19, Virus Varicella Zoster and Virus Herpes Simplex Must Be Ruled Out. J. Am. Acad. Dermatol. 2020, 83, e253–e254. [Google Scholar] [CrossRef]
  54. Mascitti, H.; Bonsang, B.; Dinh, A.; Assan, F.; Perronne, V.; Leblanc, T.; Duran, C.; Bouchand, F.; Matt, M.; Le Gal, A.; et al. Clinical Cutaneous Features of Patients Infected With SARS-CoV-2 Hospitalized for Pneumonia: A Cross-Sectional Study. Open Forum Infect. Dis. 2020, 7, ofaa394. [Google Scholar] [CrossRef] [PubMed]
  55. Marouf, N.; Cai, W.; Said, K.N.; Daas, H.; Diab, H.; Chinta, V.R.; Hssain, A.A.; Nicolau, B.; Sanz, M.; Tamimi, F. Association between Periodontitis and Severity of COVID-19 Infection: A Case-Control Study. J. Clin. Periodontol. 2021, 48, 483–491. [Google Scholar] [CrossRef]
  56. Perrillat, A.; Foletti, J.-M.; Lacagne, A.-S.; Guyot, L.; Graillon, N. Facial Pressure Ulcers in COVID-19 Patients Undergoing Prone Positioning: How to Prevent an Underestimated Epidemic? J. Stomatol. Oral Maxillofac. Surg. 2020, 121, 442–444. [Google Scholar] [CrossRef]
  57. Ramires, M.C.C.H.; Mattia, M.B.; Tateno, R.Y.; Palma, L.F.; Campos, L. A Combination of Phototherapy Modalities for Extensive Lip Lesions in a Patient with SARS-CoV-2 Infection. Photodiagnosis Photodyn. Ther. 2021, 33, 102196. [Google Scholar] [CrossRef]
  58. Ramondetta, A.; Ribero, S.; Costi, S.; Dapavo, P. Pression-Induced Facial Ulcers by Prone Position for COVID-19 Mechanical Ventilation. Dermatol. Ther. 2020, 33, e13748. [Google Scholar] [CrossRef]
  59. Rekhtman, S.; Tannenbaum, R.; Strunk, A.; Birabaharan, M.; Wright, S.; Grbic, N.; Joseph, A.; Lin, S.K.; Zhang, A.C.; Lee, E.C.; et al. Eruptions and Related Clinical Course among 296 Hospitalized Adults with Confirmed COVID-19. J. Am. Acad. Dermatol. 2021, 84, 946–952. [Google Scholar] [CrossRef] [PubMed]
  60. Singh, C.; Tay, J.; Shoqirat, N. Skin and Mucosal Damage in Patients Diagnosed With COVID-19: A Case Report. J. Wound Ostomy Cont. Nurs. 2020, 47, 435–438. [Google Scholar] [CrossRef]
  61. Soares, C.D.; de Carvalho, R.A.; de Carvalho, K.A.; de Carvalho, M.G.F.; de Almeida, O.P. Letter to Editor: Oral Lesions in a Patient with Covid-19. Med. Oral Patol. Oral Cir. Bucal 2020, 25, e563–e564. [Google Scholar] [CrossRef] [PubMed]
  62. Taşkın, B.; Vural, S.; Altuğ, E.; Demirkesen, C.; Kocatürk, E.; Çelebi, İ.; Ferhanoğlu, B.; Alper, S. Coronavirus 19 Presenting with Atypical Sweet’s Syndrome. J. Eur. Acad. Dermatol. Venereol. 2020, 34, e534–e535. [Google Scholar] [CrossRef]
  63. Taşlıdere, B.; Mehmetaj, L.; Özcan, A.B.; Gülen, B.; Taşlıdere, N. Melkersson-Rosenthal Syndrome Induced by COVID-19. Am. J. Emerg. Med. 2021, 41, 262-e5–262-e7. [Google Scholar] [CrossRef]
  64. Teixeira, I.S.; Leal, F.S.; Tateno, R.Y.; Palma, L.F.; Campos, L. Photobiomodulation Therapy and Antimicrobial Photodynamic Therapy for Orofacial Lesions in Patients with COVID-19: A Case Series. Photodiagnosis Photodyn. Ther. 2021, 34, 102281. [Google Scholar] [CrossRef] [PubMed]
  65. Verdoni, L.; Mazza, A.; Gervasoni, A.; Martelli, L.; Ruggeri, M.; Ciuffreda, M.; Bonanomi, E.; D’Antiga, L. An Outbreak of Severe Kawasaki-like Disease at the Italian Epicentre of the SARS-CoV-2 Epidemic: An Observational Cohort Study. Lancet 2020, 395, 1771–1778. [Google Scholar] [CrossRef]
  66. Zingarelli, E.M.; Ghiglione, M.; Pesce, M.; Orejuela, I.; Scarrone, S.; Panizza, R. Facial Pressure Ulcers in a COVID-19 50-Year-Old Female Intubated Patient. Indian J. Plast. Surg. 2020, 53, 144–146. [Google Scholar] [CrossRef] [Green Version]
  67. Chen, L.; Zhao, J.; Peng, J.; Li, X.; Deng, X.; Geng, Z.; Shen, Z.; Guo, F.; Zhang, Q.; Jin, Y.; et al. Detection of SARS-CoV-2 in Saliva and Characterization of Oral Symptoms in COVID-19 Patients. Cell Prolif. 2020, 53, e12923. [Google Scholar] [CrossRef]
  68. Tapia, R.O.C.; Labrador, A.J.P.; Guimaraes, D.M.; Valdez, L.H.M. 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, 555–560. [Google Scholar] [CrossRef]
  69. Emelyanova, N.; Isayeva, G.; Komir, I.; Shalimova, A.; Buriakovska, O.; Vovchenko, M. Changes in the Oral Cavity of a Patient after Suffering from Coronavirus Infection COVID-19: A Clinical Case. Acta Med. Mediterr. 2021, 37, 827–831. [Google Scholar]
  70. Favia, G.; Tempesta, A.; Barile, G.; Brienza, N.; Capodiferro, S.; Vestito, M.C.; Crudele, L.; Procacci, V.; Ingravallo, G.; Maiorano, E.; et al. Covid-19 Symptomatic Patients with Oral Lesions: Clinical and Histopathological Study on 123 Cases of the University Hospital Policlinic of Bari with a Purpose of a New Classification. J. Clin. Med. 2021, 10, 757. [Google Scholar] [CrossRef] [PubMed]
  71. Halepas, S.; Lee, K.C.; Myers, A.; Yoon, R.K.; Chung, W.; Peters, S.M. Oral Manifestations of COVID-2019-Related Multisystem Inflammatory Syndrome in Children: A Review of 47 Pediatric Patients. J. Am. Dent. Assoc. 2021, 152, 202–208. [Google Scholar] [CrossRef]
  72. Labé, P.; Ly, A.; Sin, C.; Nasser, M.; Chapelon-Fromont, E.; Ben Saïd, P.; Mahé, E. Erythema Multiforme and Kawasaki Disease Associated with COVID-19 Infection in Children. J. Eur. Acad. Dermatol. Venereol. 2020, 34, e539–e541. [Google Scholar] [CrossRef]
  73. Martel, T.; Orgill, D.P. Medical Device-Related Pressure Injuries During the COVID-19 Pandemic. J. Wound Ostomy Cont. Nurs. 2020, 47, 430–434. [Google Scholar] [CrossRef] [PubMed]
  74. Mazzotta, F.; Troccoli, T.; Caselli, D.; Bonifazi, E. Acral Rash in a Child with COVID-19. Eur. J. Pediatric Dermatol. 2020, 30, 79–82. [Google Scholar] [CrossRef]
  75. Salehi, M.; Ahmadikia, K.; Mahmoudi, S.; Kalantari, S.; Jamalimoghadamsiahkali, S.; Izadi, A.; Kord, M.; Dehghan Manshadi, S.A.; Seifi, A.; Ghiasvand, F.; et al. Oropharyngeal Candidiasis in Hospitalised COVID-19 Patients from Iran: Species Identification and Antifungal Susceptibility Pattern. Mycoses 2020, 63, 771–778. [Google Scholar] [CrossRef] [PubMed]
  76. Sinjari, B.; D’Ardes, D.; Santilli, M.; Rexhepi, I.; D’Addazio, G.; Di Carlo, P.; Chiacchiaretta, P.; Caputi, S.; Cipollone, F. SARS-CoV-2 and Oral Manifestation: An Observational, Human Study. J. Clin. Med. 2020, 9, 3218. [Google Scholar] [CrossRef]
  77. Siotos, C.; Bonett, A.M.; Hansdorfer, M.A.; Siotou, K.; Kambeyanda, R.H.; Dorafshar, A.H. Medical Device Related Pressure Ulcer of the Lip in a Patient with COVID-19: Case Report and Review of the Literature. J. Stomatol. Oral Maxillofac. Surg. 2020. [Google Scholar] [CrossRef] [PubMed]
  78. Sleiwah, A.; Nair, G.; Mughal, M.; Lancaster, K.; Ahmad, I. Perioral Pressure Ulcers in Patients with COVID-19 Requiring Invasive Mechanical Ventilation. Eur. J. Plast. Surg. 2020, 43, 727–732. [Google Scholar] [CrossRef]
  79. Askin, O.; Altunkalem, R.N.; Altinisik, D.D.; Uzuncakmak, T.K.; Tursen, U.; Kutlubay, Z. Cutaneous Manifestations in Hospitalized Patients Diagnosed as COVID-19. Dermatol. Ther. 2020, 33, e13896. [Google Scholar] [CrossRef]
  80. Baraboutis, I.G.; Gargalianos, P.; Aggelonidou, E.; Adraktas, A. Initial Real-Life Experience from a Designated COVID-19 Centre in Athens, Greece: A Proposed Therapeutic Algorithm. SN Compr. Clin. Med. 2020, 2, 689–693. [Google Scholar] [CrossRef]
  81. Bardellini, E.; Bondioni, M.-P.; Amadori, F.; Veneri, F.; Lougaris, V.; Meini, A.; Plebani, A.; Majorana, A. Non-Specific Oral and Cutaneous Manifestations of Coronavirus Disease 2019 in Children. Med. Oral Patol. Oral Cir. Bucal. 2021, 26, e549–e553. [Google Scholar] [CrossRef]
  82. El Kady, D.M.; Gomaa, E.A.; Abdella, W.S.; Hussien, R.A.; ElAziz, R.H.A.; Khater, A.G.A. Oral Manifestations of COVID-19 Patients: An Online Survey of the Egyptian Population. Clin. Exp. Dent. Res. 2021, 7, 852–860. [Google Scholar] [CrossRef] [PubMed]
  83. Hedou, M.; Carsuzaa, F.; Chary, E.; Hainaut, E.; Cazenave-Roblot, F.; Regnault, M.M. Comment on “Cutaneous Manifestations in COVID-19: A First Perspective” by Recalcati S. J. Eur. Acad. Dermatol. Venereol. 2020, 34, e299–e300. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. 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 Clínica Integr. 2021, 21, 0011. [Google Scholar] [CrossRef]
  85. Jimenez-Cauhe, J.; Ortega-Quijano, D.; de Perosanz-Lobo, D.; Burgos-Blasco, P.; Vañó-Galván, S.; Fernandez-Guarino, M.; Fernandez-Nieto, D. Enanthem in Patients With COVID-19 and Skin Rash. JAMA Dermatol. 2020, 156, 1134–1136. [Google Scholar] [CrossRef]
  86. Katz, J.; Yue, S. Increased odds ratio for COVID-19 in patients with recurrent aphthous stomatitis. J. Oral Pathol. Med. 2020, 50, 114–117. [Google Scholar] [CrossRef]
  87. McGoldrick, D.M.; Sarai, R.; Green, J. Tongue and Floor of Mouth Swelling: A Potential Rare Manifestation of COVID-19. Br. J. Oral Maxillofac. Surg. 2021, 59, 500–501. [Google Scholar] [CrossRef]
  88. Nuno-Gonzalez, A.; Martin-Carrillo, P.; Magaletsky, K.; Rios, M.D.M.; Mañas, C.H.; Almazan, J.A.; Casasola, G.G.; Castro, E.P.; Arenas, A.G.; Ibarguren, A.M.; et al. Prevalence of Mucocutaneous Manifestations in 666 Patients with COVID-19 in a Field Hospital in Spain: Oral and Palmoplantar Findings. Br. J. Dermatol. 2021, 184, 184–185. [Google Scholar] [CrossRef]
  89. Riad, A.; Kassem, I.; Badrah, M.; Klugar, A.M. The Manifestation of Oral Mucositis in COVID-19 Patients: A Case-Series. Dermatol. Ther. 2020, 33, e14479. [Google Scholar] [CrossRef] [PubMed]
  90. Shearer, S.C.; Parsa, K.M.; Newark, A.; Peesay, T.; Walsh, A.R.; Fernandez, S.; Gao, W.Z.; Pierce, M.L. Facial Pressure Injuries from Prone Positioning in the COVID-19 Era. Laryngoscope 2021, 131, E2139–E2142. [Google Scholar] [CrossRef] [PubMed]
  91. Sakaida, T.; Tanimoto, I.; Matsubara, A.; Nakamura, M.; Morita, A. Unique Skin Manifestations of COVID-19: Is Drug Eruption Specific to COVID-19? J. Dermatol. Sci. 2020, 99, 62–64. [Google Scholar] [CrossRef]
  92. Iranmanesh, B.; Khalili, M.; Amiri, R.; Zartab, H.; Aflatoonian, M. Oral Manifestations of COVID-19 Disease: A Review Article. Dermatol. Ther. 2021, 34, e14578. [Google Scholar] [CrossRef]
  93. Srinivasan, S.; Gopal, K.S.; Kumar, P.M.; Poongodi, V.; Anitha, R. COVID 19-An Update on Oral Changes. J. Pharm. Res. Int. 2021, 32, 74–79. [Google Scholar] [CrossRef]
  94. La Rosa, G.R.M.; Libra, M.; De Pasquale, R.; Ferlito, S.; Pedullà, E. Association of Viral Infections With Oral Cavity Lesions: Role of SARS-CoV-2 Infection. Front. Med. 2020, 7, 571214. [Google Scholar] [CrossRef]
  95. Capocasale, G.; Nocini, R.; Faccioni, P.; Donadello, D.; Bertossi, D.; Albanese, M.; Zotti, F. How to Deal with Coronavirus Disease 2019: A Comprehensive Narrative Review about Oral Involvement of the Disease. Clin. Exp. Dent. Res. 2021, 7, 101–108. [Google Scholar] [CrossRef]
  96. Martelli Júnior, H.; Machado, R.A.; Martelli, D.R.B.; Barbosa, M.C.; Bonan, P.R.F.; Coletta, R.D. Potential Link between SARS-CoV-2 and Kawasaki Disease: Importance of Dentists for the Diagnosis. Braz. Oral Res. 2021, 35, e047. [Google Scholar] [CrossRef] [PubMed]
  97. Ye, G.; Pan, Z.; Pan, Y.; Deng, Q.; Chen, L.; Li, J.; Li, Y.; Wang, X. Clinical Characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 Reactivation. J. Infect. 2020, 80, e14–e17. [Google Scholar] [CrossRef] [PubMed]
  98. Murad, M.H.; Sultan, S.; Haffar, S.; Bazerbachi, F. Methodological Quality and Synthesis of Case Series and Case Reports. BMJ Evid.-Based Med. 2018, 23, 60–63. [Google Scholar] [CrossRef] [Green Version]
  99. Brito, J.P.; Domecq, J.P.; Murad, M.H.; Guyatt, G.H.; Montori, V.M. The Endocrine Society Guidelines: When the Confidence Cart Goes before the Evidence Horse. J. Clin. Endocrinol. Metab. 2013, 98, 3246–3252. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Ijerph 18 12511 g001 550
Figure 1. Flow diagram of literature search and selection criteria adapted from PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).
Figure 1. Flow diagram of literature search and selection criteria adapted from PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).
Ijerph 18 12511 g001
Table
Table 1. Descriptive characteristics of included studies regarding oral lesions that appeared before hospitalization in patients affected by COVID-19. F: female; M: male; CS: cases series; RS: retrospective study; CSS: cross-sectional study; CR: case report; OS: observational study; NA: not available; COPD: chronic obstructive pulmonary disease; AZT: azithromycin; CRST: corticosteroids; IVIG: Intravenous immunoglobulin; PDT: Photodynamic therapy; PBMT: Photobiomodulation therapy; HCH: hydroxychloroquine; ASA: acetylsalicylic acid.
Table 1. Descriptive characteristics of included studies regarding oral lesions that appeared before hospitalization in patients affected by COVID-19. F: female; M: male; CS: cases series; RS: retrospective study; CSS: cross-sectional study; CR: case report; OS: observational study; NA: not available; COPD: chronic obstructive pulmonary disease; AZT: azithromycin; CRST: corticosteroids; IVIG: Intravenous immunoglobulin; PDT: Photodynamic therapy; PBMT: Photobiomodulation therapy; HCH: hydroxychloroquine; ASA: acetylsalicylic acid.
StudyDesignSample
(n, Sex)		Mean Age
(Year)		Medical HistoryOral Manifestations Time of OnsetAffected SiteTreatment COVID-19Treatment Oral Manifestations Duration (Days)Reported DiagnosisRisk of Bias
Ansari et al., 2021 [36]CS1, F56DiabetesPainful ulcers 5 days after COVID-19 symptomsHard palateRemdesivir, AZTDiphenhydramine, CRST, tetracycline, and lidocaine7Oral lesions due to COVID-19 Low
Bardellini et al., 2021 [81]RS19, M
8, F		4.2
1.7		NAHyperemic pharynx (n. 10),
Pseudomembranous candidiasis (n. 2),
Coated tongue (n. 2),
Geographic tongue (n. 1) 		Hospital admissionTongue, pharynx, Oral mucosaNANANAOral lesions due to COVID-19 High
Brandão et al., 2021 [37]CS1, M
2, F		81
77		Hypertension, COPD, Diabetes, Obesity, PancreatitisMucopurulent membrane, Ulcers, Petechia, Necrosis Hospital admissionUpper and lower lips, Anterior dorsal tongueAZT, Piperacillin/Tazobactam, Ceftriaxone Acyclovir, PBMT 5–11Oral lesions due to COVID-19 Low
Chen et al., 2020 [67]CSS15, M
16, F		60.6NADry mouthNAOral mucosaNANANAPoor oral hygiene or microbiota imbalance due to drugs Moderate
Chérif et al., 2020 [38]CR1, F35NAUlcers, EnanthemHospital admissionTongue, LipNAHCH, AZT, Cefuroxime10Kawasaki-like due to COVID-19Low
Chiotos et al., 2020 [39]CS1, M
1, F		12
5		NAFissured lipHospital admissionLipIVIG, CRST, MilrinoneNANAKawasaki-like due to COVID-19Low
Chiu et al., 2020 [40]CR1, M10NACracked lip, ErythemaHospital admissionLip, OropharynxDopamineNANAKawasaki-like due to COVID-19Low
Ciccarese et al, 2021 [41]CR1, F19NAErosions, Ulcers, Petechiae2 days before hospital admissionPalate, Lips Cefixime, IVIG, CRSTNA10Petechiae due to thrombocytopeniaLow
Cruz-Tapia et al., 2020 [68]CS1, F51NAVascular-like purple maculeHospital admissionPalateCRST, Azithromycin, IndomethacinNA6Vascular disorder due to COVID-19Moderate
Díaz Rodríguez et al., 2020 [43]CS1, F78NADry mouth, Pseudomembranous candidiasis Hospital admissionTongue, Hard and soft palate, LipNACRST, Neomycin, Mouthwash, Nystatin solution, triamcinolone acetonideAfter treatmentStress and immunosoppressionLow
Dima et al., 2020 [44]CS2, M
1, F		14.3 daysNAOral candidiasisHospital admission (2 weeks after birth)NAVitamin DNystatin NANALow
Favia et al., 2021 [70]CSS70, M
53, F		72NAGeographic tongue, Fissured tongue, Ulcers, Blisters, Hyperplasia of papillae, Angina bullosa, Candidiasis, Ulceronecrotic gingivitis, PetechiaeOnset of COVID-19 symptoms; within or after 1 week of COVID-19 symptomsTongue, Palate, Lip, CheekNAHyaluronic acid gel, chlorhexidine, Miconazole, Nitrate Tranexamic acidNAOral lesions due to COVID-19 and poor oral hygieneModerate
Halepas et al., 2021 [71]CSS2321NASwollen lips, Strawberry tongueHospital admissionLip, TongueNANANAOral lesions due to COVID-19 Moderate
Jones et al., 2020 [51]CR1, F0.5NACracked lip, Tongue prominent papilla NALip, TongueIVIG, ASA NANAKawasaki-like due to COVID-19Low
Katz et al., 2021 [86]CR6, FNANAOral aphthae NANANANANAOral lesions due to COVID-19 High
Labè et al., 2020 [72]CS1, M6NAErosive cheilitis, Diffuse gingival erosionsHospital admissionLip, GingivaNANA14Kawasaki like disease due to COVID-19Moderate
Mazzotta et al., 2020 [74]CR1, M9Down syndrome, Alopecia areata universalisGlossitis, Cheilitis 3 weeks after COVID-19 symptomsLip, TongueCRSTNANAOral lesions due to COVID-19Moderate
McGoldrick et al., 2021 [87]CS1, M53NASwelling1 day before hospital admissionTongue, Floor of mouthCRSTNANAOral lesions due to COVID-19High
Nuno-Gonzalez et al. 2021 [88]CSS78NANALingual papillitis, Glossitis, Aphthous-like lesions, Patchy depapillation, Mucositis, Burning sensation, DysgeusiaNATongue, Oral mucosa NANANAOral lesions due to COVID-19High
Riad A et al., 2020 [89]CS5, M
8, F		51.08Hypertension, Diabetes, Asthma Mucositis, Enanthema, Tongue depapillation0–2 days after COVID-19 symptomsPalate, Tongue, Buccal mucosa, GingivaParacetamol (n. 9),
CRST (n. 2),
Chloroquine (n. 2)		Mouthwash and paracetamol7–14 Oral lesions due to COVID-19High
Salehi et al., 2020 [75]CSS23, M
30, F		27–90Cardiovascular diseases (n. 28),
Diabetes (n. 20),
Chronic kidney diseases (n. 11),
Hematological malignancies (n. 5)		Oropharyngeal candidiasis1–30 days after COVID−19 symptomsOral mucosaBroad-spectrum antibiotics (n. 49),
CRST (n. 25)		Fluconazole (n. 21),
Fluconazole and Nystatin (n. 13), Nystatin (n. 13)		NAOral lesions due to COVID-19Moderate
Soares et al., 2020 [61]CR1, M42Diabetes, HypertensionUlcers, Reddish macules NALip, Buccal mucosa, Hard palate, TongueCRST; DipyroneNA21Oral lesions due to COVID-19Low
Taşkın et al., 2020 [62]CR1, F61NAMinor aphthous ulcer Hospital admissionHard palate, Buccal mucosaAZT, HCH, Oseltamivir Tocilizomab, FavipiravirNANAOral lesions due to COVID-19Low
Taşlıdere et al., 2021 [63]CR1, F51Melkersson– Rosenthal syndromeSwollen lip, Fissured tongue Hospital admissionLip, Tongue AZT, HCH, CRSTNANAOral lesions due to COVID-19Low
Verdoni et al., 2020 [65]OS2, M4.5Kawasaki-like disease Erosive cheilitis, Diffuse gingival erosions, Glossitis1 week before/during hospital admissionLip, TongueIVIG, ASA, CRSTNANAKawasaki like disease due to COVID-19Low
Table
Table 2. Descriptive characteristics of included studies regarding oral lesions that appeared during hospitalization in patients affected by COVID-19. F: female; M: male; CS: cases series; RS: retrospective study; CSS: cross-sectional study; CR: case report; OS: observational study; NA: not available; AZT: azithromycin; CRST: corticosteroids; IVIG: Intravenous immunoglobulin; PDT: Photodynamic therapy; PBMT: Photobiomodulation therapy; HCH: hydroxychloroquine; ASA: acetylsalicylic acid; ICU: intensive care unit.
Table 2. Descriptive characteristics of included studies regarding oral lesions that appeared during hospitalization in patients affected by COVID-19. F: female; M: male; CS: cases series; RS: retrospective study; CSS: cross-sectional study; CR: case report; OS: observational study; NA: not available; AZT: azithromycin; CRST: corticosteroids; IVIG: Intravenous immunoglobulin; PDT: Photodynamic therapy; PBMT: Photobiomodulation therapy; HCH: hydroxychloroquine; ASA: acetylsalicylic acid; ICU: intensive care unit.
StudyDesignSample (n, Sex)Mean Age (Year)Medical HistoryICUOral ManifestationsTime of OnsetAffected SiteTreatment COVID-19Treatment Oral ManifestationsDuration (Days)Reported DiagnosisRisk of Bias
Amorim Dos Santos et al., 2020 [34]CR1, M67Coronary disease, Hypertension, Autosomal dominant polycystic kidney disease, Kidney transplantICU + Orotracheal intubation White plaque, Multiple pinpoint yellowish ulcers, Geographic and fissured tongue, Viscous saliva24 days after COVID-19 symptomsTongueInitially: AZT, HCH, Ceftriaxone
Later: Meropenem, Sulfamethoxazole, Trimethoprim, Immunosuppressants, Anticoagulants		Fluconazole, Nystatin, Chlorhexidine digluconate, mouth rinses, Hydrogen peroxide15 (tongue lesions)
17 (geographic tongue)		Oral lesions due to COVID-19Low
Andrews et al., 2020. [35]CR1, F40Diabetes, Pancreatic insufficiency, Asthma, Hypertension, Ulcerative colitisICU + TracheostomyAcute macroglossia11 days after prone positionTongueInitially: HCH, CRST, Tocilizumab. Later: Prone positionCRST, Bite block 11Oral lesions due to prone positionLow
Ansari et al., 2021 [36]CS1, M75HypertensionHospital admissionPainful ulcers 1 week after hospitalizationAnterior tongue AZTCRST, Diphenhydramine, Tetracycline, Lidocaine7Oral lesions due to COVID-19Low
Askin et al., 2020 [79]OS123, M
87, F		57.44(M)
58.80(F) 		NAHospital admission (n. 163),
ICU (n. 47)		Necrosis (n. 4),
Enanthem,
Aphthous stomatitis (n. 2)		NAMaxillary region, Oral mucosaNANANAOral lesions due to COVID-19 and medical treatmentsHigh
Baraboutis et al., 2020 [80]CSS49NANAHospital admissionOral candidiasis 5 days after antimicrobial therapyNAHCH (n. 46),
AZT (n. 48)		CRSTNAOral lesions due to medical treatmentsHigh
Brandão et al., 2021 [37]CS1, M72Diabetes, Hypertension 30 days of hospitalization + ICUHemorrhagic ulcerations A few days after hospital admissionUpper and lower lipPiperacillin/Tazobactam, AZT, CeftriaxoneAcyclovir, PBMT 7Oral lesions due to COVID-19Low
Chiotos et al., 2020 [39]CS1, F9NAICUFissured lip, Strawberry tongue5 days after hospital admissionLip, TongueIVIG, CS, ASA, MilrinoneNANAKawasaki-like due to COVID-19Low
De Medeiros et al., 2021 [42]CR1, M43Hodgkin’s lymphomaHospital admission Ulcers40 days after COVID-19 diagnosisNACRST; Methotrexate NANAOral lesions due to COVID-19Low
Díaz Rodríguez et al., 2020 [43]CS1, M53NAHospital admission Burning mouth sensation, Commissural fissuresA few days after hospital dischargedLip, MouthNANystatin, CRST Neomycin, MouthwashAfter treatmentOral lesions due to immunosuppressionLow
El Kady et al., 2021 [82]CSS31, M
27, F		18–46NAHospital admission Oral ulcers; tongue redness, gingival bleeding and burning sensation NALip, Tongue, GingivaNANANANAHigh
Emelyanova et al., 2021 [69]CR1, M38NAHospital admission Redness and scale-crusts lips, Keratosis, Desquamations 5 days after COVID-19 symptomsLip, TongueNACRST, Levaxela, Clexane, Vitamin C-D, Zinc, Famotidine NANAModerate
Fathi et al., 2021 [45]CR1, F22NAICUUlcersThree days after ICULip, MouthMetronidazole, Ceftriaxone, Meropenem, Ribavirin, HCHOral valaciclovir NAOral lesions due to COVID-19Low
Favia et al., 2021 [70]CSS70, M
53, F		72NAHospital admission + ICUGeographic and fissured tongue, Ulcers, Blisters, Hyperplasia of papillae, Angina bulllosa, Candidiasis, ulcero-necrotic Gingivitis, PetechiaeOnset of COVID-19 symptoms; within 1 week after COVID-19 symptoms; after 1 week of COVID-19 symptomsTongue, Palate, Lip, CheekNAHyaluronic acid gel, Chlorhexidine, Miconazole, Nitrate Tranexamic acidNAOral lesions due to COVID-19 and poor oral hygieneModerate
Fernandez-Nieto et al., 2020 [46]CSS5, M
3, F		61.8
72.7		Hypertension, Chronic kidney disease, Hyperuricemia, Dyslipidemia, Colorectal cancer Hospital admission; ICUHerpes simplexNALipHCH, AZT, ceftriaxone, acyclovir NANAHerpetic infections and superinfections in patients with COVID-19Low
Gabusi et al., 2021 [47]CR178NAHospital admissionUlcers, Erosive plaquesA few days after COVID-19 symptomsNAHCH, CRST, Ciprofloxacin, TocilizumabCRST, Chlorhexidine gel, and topical lidocaineNAPersistent immunological impairmentLow
Gherlone et al., 2021 [48]CSS12262.5NAHospital admission + ICUSalivary gland ectasia (n. 46),
TMJ alterations (n. 9), Masticatory muscle weakness, Oral ulcers, Dry mouth, Facial tingling, White tongue.		NASalivary gland, TMJ, Oral mucosae, Facial tissues, TongueNANANAOral lesions due to COVID-19Low
Hedou et al., 2020 [83]CSS447NAICUErythematous rashNANANANANANAHigh
Hocková et al., 2021 [21]CS3, M64.3Hypertension, chronic hepatopathy, Hypercholesterolemia, Gastroesophageal reflux disease, Obesity,ICUHaemorrhagic ulcers, Acute bilateral parotitisAfter ICU admissionTongue, Lip, ParotidCeftriaxone, Clarithromycin, Remdesivir, Paracetamol, CRST, Vitamin C and B1, Nadroparin, Inosine pranobex, Atorvastatin, Lagosa, Vitamin D, Zinc, FamotidineDressing, position Adjustment, antifungals, antivirals, Surgical interventions7–14Oral lesions due to medical devicesLow
Horzov et al., 2021 [84]RS64, M
71, F		48.7NAHospital admission Tongue plaqueNATongueNANANAOral lesions due to COVID-19High
Ibarra et al., 2021 [49]CCS41, M
16, F		61NAICUPerioral pressure ulcersDuring ICUPerioral tissuesProne positionDressingNAProne positionLow
Jiménez-Cahué et al., 2020 [50]CS3, F63NAHospital admission Macules, Petechiae 24 days after COVID-19 symptoms Palatelopinavir, HCH, AZT, CRST, Ceftriaxone AZT, Ceftriaxone, CRST, HCHNAOral lesions due to COVID-19Low
Jiménez-Cauhè et al., 2020 [85]CSS640–69NAICUEnanthema2–24 days from COVID-19 symptomsPalateNANANANAHigh
Kämmerer et al., 2020 [52]CR1, M46Hypercholesterinemia, Coronary heart diseaseHospital admission + ICUHerpetic ulcers3 days after intubationOral cavity, Gingiva AciclovirNANAHerpetic infections and superinfections in patients with COVID-19Low
Llamas-Velasco et al., 2020 [53]CS1, F59NAICUVesicles25 days after COVID-19 symptomsPerioral tissuesHCH, Lopinavir/Ritonavir, CeftriaxoneNANAOral lesions due to COVID-19Low
Martel and Orgill, 2020 [73]CS18NANAICUPerioral pressure ulcersDuring ICUPerioral tissuesNADressingNAProne position and medical devicesModerate
Carreras-Presas et al., 2021 [26]CS1, F65Obesity, HypertensionHospital admission Blisters, Desquamative gingivitis 22 days after COVID-19 symptoms; 4 days after hospital dischargedGingiva, LipLopinavir, Ritonavir, HCHHyaluronic acid and chlorhexidine mouthwash, CRST3Oral lesions due to COVID-19Low
Mascitti et al., 2021 [54]CSS39NANAHospital admission Oral lichenoid reaction, Enanthema, Macroglossia, CheilitisNAOral mucosae, Tongue, LipAntibiotics, AZT, HCH NANAOral lesions due to COVID-19Low
Marouf et al., 2021 [55]CCS20, M
20, F		53.6NAHospital admission + ICUPeriodontitisNAPeriodontiumNANANANALow
Perrillat et al., 2020 [56]CS2, M38.5ObesityICUPerioral pressure ulcersAfter ICU admissionPerioral tissuesProne positionDressingNAProne positionLow
Ramires et al., 2021 [57]CR1, F50Obesity, Hypertension, DiabetesICUUlcers4 days after extubationLipNAPBMT, PDT4Prone positionLow
Ramondetta et al., 2020 [58]CR1, M48NAICUPerioral pressure ulcers15 days after ICU admissionPerioral tissuesInitially: HCH, antivirals
Later: prone position		DressingNAProne positionLow
Rekhtman et al., 2021 [59]CSS3NANAICUPerioral pressure ulcersNALip, TongueMechanical ventilationNANAOral lesions due to medical devicesLow
Shearer et al., 2021 [90]RS6861.3NAHospital admission + ICUPerioral pressure ulcersNAPerioral tissuesMechanical ventilation,
Prone positioning, Endotracheal intubation		DressingNAProne positionHigh
Singh et al., 2020 [60]CS1, M
1, F		44
71		Diabetes, Hypertension Hospital admission + ICUExtensive mucosal damage, Discolorations of lip and tongue 4/5 days after prone positioningLip, TongueAZT, CRST, Mechanical ventilationProne position, dressingNAProne positionLow
Sinjari et al., 2020 [76]OS2069.2Hypertension, Heart, Respiratory and Thyroid disease, Cancer, DiabetesHospital admission Dysgeusia (n. 5), Burning sensation (n. 3), Dysphagia (n. 4)NAMouthNANANAOral lesions due to COVID-19Moderate
Siotos et al., 2020 [77]CR1, F82Hypertension, HyperlipidemiaICUPerioral pressure ulcers10 days after prone positioningPerioral tissuesMechanical ventilation,
Prone position		DressingNAProne positionModerate
Sleiwah et al., 2020 [78]RS14, M
2, F		58.6NAICUPerioral pressure ulcersNAPerioral tissuesMechanical ventilation,
Prone position		NANAProne positionModerate
Teixeira et al., 2021 [64]CS1, M
3, F		57
72.7		Hypertension, Hypothyroidism, Rectal tumorHospital admission, ICUNA10 days after hospital readmission; after ICU admissionLipAZT, Piperacillin and Tazobactam, Ceftraxone/Cefuroxime, IvermectinPBMT, PDT1–4Oral lesions due to COVID-19Low
Zingarelli et al., 2020 [66]CR1, F50NAICUPerioral pressure ulcers, Candidiasis, Stomatitis, Macroglossia15 days after ICU admissionPerioral tissues, TongueMechanical ventilationDressing7Prone positionLow
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Orilisi, G.; Mascitti, M.; Togni, L.; Monterubbianesi, R.; Tosco, V.; Vitiello, F.; Santarelli, A.; Putignano, A.; Orsini, G. Oral Manifestations of COVID-19 in Hospitalized Patients: A Systematic Review. Int. J. Environ. Res. Public Health 2021, 18, 12511. https://doi.org/10.3390/ijerph182312511

AMA Style

Orilisi G, Mascitti M, Togni L, Monterubbianesi R, Tosco V, Vitiello F, Santarelli A, Putignano A, Orsini G. Oral Manifestations of COVID-19 in Hospitalized Patients: A Systematic Review. International Journal of Environmental Research and Public Health. 2021; 18(23):12511. https://doi.org/10.3390/ijerph182312511

Chicago/Turabian Style

Orilisi, Giulia, Marco Mascitti, Lucrezia Togni, Riccardo Monterubbianesi, Vincenzo Tosco, Flavia Vitiello, Andrea Santarelli, Angelo Putignano, and Giovanna Orsini. 2021. "Oral Manifestations of COVID-19 in Hospitalized Patients: A Systematic Review" International Journal of Environmental Research and Public Health 18, no. 23: 12511. https://doi.org/10.3390/ijerph182312511

APA Style

Orilisi, G., Mascitti, M., Togni, L., Monterubbianesi, R., Tosco, V., Vitiello, F., Santarelli, A., Putignano, A., & Orsini, G. (2021). Oral Manifestations of COVID-19 in Hospitalized Patients: A Systematic Review. International Journal of Environmental Research and Public Health, 18(23), 12511. https://doi.org/10.3390/ijerph182312511

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop