Association of Viral Infections With Oral Cavity Lesions: Role of SARS-CoV-2 Infection

Giusy Rita Maria La Rosa, Massimo Libra, Rocco De Pasquale, Sebastiano Ferlito, Eugenio Pedullà, Giusy Rita Maria La Rosa, Massimo Libra, Rocco De Pasquale, Sebastiano Ferlito, Eugenio Pedullà

Abstract

Different viral agents, such as herpesviruses, human papillomavirus, and Coxsackie virus, are responsible for primary oral lesions, while other viruses, such as human immunodeficiency virus, affect the oral cavity due to immune system weakness. Interestingly, it has been reported that coronavirus disease 2019 (COVID-19) patients can show cutaneous manifestations, including the oral cavity. However, the association between oral injuries and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. This narrative review aimed to summarize the available literature and provide an overview of oral lesions associated with COVID-19. An online literature search was conducted to select relevant studies published up to November 2020. The results of 17 studies showed variability in oral lesions associated with COVID-19, including ulcerations, aphthous-like lesions, and macules. The tongue, lips, and palate were the most frequent anatomical locations. According to current knowledge, the etiopathogenesis of multiple COVID-19-associated lesions seems to be multifactorial. The appearance of such lesions could be related to the direct or indirect action of SARS-CoV-2 over the oral mucosa cells, coinfections, immunity impairment, and adverse drug reactions. Nevertheless, COVID-19-associated oral lesions may be underreported, mainly due to lockdown periods and the lack of mandatory dispositive protection. Consequently, further research is necessary to determine the diagnostic and pathological significance of oral manifestations of COVID-19. All medical doctors, dentists, and dermatologists are encouraged to perform an accurate and thorough oral examination of all suspected and confirmed COVID-19 cases to recognize the disease's possible early manifestations.

Keywords: COVID-19; SARS-CoV-2; novel coronavirus; oral health; oral lesions; oral mucosa; viral infection.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 La Rosa, Libra, De Pasquale, Ferlito and Pedullà.

Figures

Figure 1
Figure 1
The principal host defense mechanisms in the oral cavity.
Figure 2
Figure 2
(A) Herpetic-like oral lesion. (B) Oral mucosal verruca lesion. (C) Opportunistic infection (candidiasis) in patient affected by HIV. (D) Unspecific ulcerous lesion in a SARS-CoV-2 infected patient. Image 2D is a case courtesy of Chaux-Bodard et al. (9).

References

    1. Lynch DP. Oral manifestations of viral diseases. In: Tyring S, editor. Mucosal Immunology and Virology. Cham: Springer; (2006). p. 99–156.
    1. Dolby AE. The host defence system of the mouth. In: Ivanyi L, editor. Immunological Aspects of Oral Diseases. London: MTP Press Limited; (1986). p. 1–11.
    1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. (2020) 323:1239–42. 10.1001/jama.2020.2648
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. . Clinical features of patients infected with 2019 novel coronavirus in wuhan, china. Lancet. (2020) 395:497–506. 10.1016/S0140-6736(20)30183-5
    1. Sachdeva M, Gianotti R, Shah M, Lucia B, Tosi D, Veraldi S, et al. . Cutaneous manifestations of COVID-19: report of three cases and a review of literature. J Dermatol Sci. (2020) 98:75–81. 10.1016/j.jdermsci.2020.04.011
    1. Gupta R, Ghosh A, Singh AK, Misra A. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes Metab Syndr. (2020) 14:211–2. 10.1016/j.dsx.2020.03.002
    1. Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty. (2020) 9:45. 10.1186/s40249-020-00662-x
    1. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. (2020) 34:e212–3. 10.1111/jdv.16387
    1. Chaux-Bodard AG, Deneuve S, Desoutter A. Oral manifestation of Covid-19 as an inaugural symptom? J Oral Med Oral Surg. (2020) 26:18 10.1051/mbcb/2020011
    1. Martín Carreras-Presas C, Amaro Sánchez J, López-Sánchez AF, Jané-Salas E, Somacarrera Pérez ML. Oral vesiculobullous lesions associated with SARS-CoV-2 infection. Oral Dis. (2020). 10.1111/odi.13382. [Epub ahead of print].
    1. Capocasale G, Nocini R, Faccioni P, Donadello D, Bertossi D, Albanese M, et al. . How to deal with coronavirus disease 2019: a comprehensive narrative review about oral involvement of the disease. Clin Exp Dent Res. (2020). 10.1002/cre2.332. [Epub ahead of print].
    1. Riad A, Klugar M, Krsek M. COVID-19-related oral manifestations: early disease features? Oral Dis. (2020). 10.1111/odi.13516. [Epub ahead of print].
    1. de Sousa FACG, Paradella TC. Considerations on oral manifestations of COVID-19. J Med Virol. (2020). 10.1002/jmv.26451
    1. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. . High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. (2020) 12:8. 10.1038/s41368-020-0074-x
    1. Amorim Dos Santos J, Normando AGC, Carvalho da Silva RL, Acevedo AC, De Luca Canto G, Sugaya N, et al. . Oral manifestations in patients with COVID-19: a living systematic review. J Dent Res. (2020). 10.1177/0022034520957289. [Epub ahead of print].
    1. Halboub E, Al-Maweri SA, Alanazi RH, Qaid NM, Abdulrab S. Orofacial manifestations of COVID-19: a brief review of the published literature. Braz Oral Res. (2020) 34:e124. 10.1590/1807-3107bor-2020.vol34.0124
    1. Ng TB, Cheung RCF, Wong JH, Wang Y, Ip DTM, Wan DCC, et al. . Antiviral activities of whey proteins. Appl Microbiol Biotechnol. (2015) 17:6997–7008. 10.1007/s00253-015-6818-4
    1. Wakabayashi H, Oda H, Yamauchi K, Abe F. Lactoferrin for prevention of common viral infections. J Infect Chemother. (2014) 20:666–71. 10.1016/j.jiac.2014.08.003
    1. Upadhyay J, Upadhyay RB, Agrawal P, Jaitley S, Shekhar R. Langerhans cells and their role in oral mucosal diseases. N Am J Med Sci. (2013) 5:505–14. 10.4103/1947-2714.118923
    1. Sistig S, Vucićević-Boras V, Lukac J, Kusić Z. Salivary IgA and IgG subclasses in oral mucosal diseases. Oral Dis. (2002) 8:282–6. 10.1034/j.1601-0825.2002.20844.x
    1. Kiselev NA, Sherman MB, Tsuprun VL. Negative staining of proteins. Electron Microsc Rev. (1990) 3:43–72. 10.1016/0892-0354(90)90013-I
    1. Caspar DL, Klug A. Physical principles in the construction of regular viruses. Cold Spring Harb Symp Quant Biol. (1962) 27:1–24. 10.1101/SQB.1962.027.001.005
    1. Ramesh N, Don KR. Oral manifestations of viral diseases. Drug Invent Today. (2019) 12:321–30.
    1. Grinde B, Olsen I. The role of viruses in oral disease. J Oral Microbiol. (2010) 2:2127. 10.3402/jom.v2i0.2127
    1. Pellett PE, Roizman B. The family herpesviridae: a brief introduction. In: Knipe DM, Howley PM, editors. Fields Virology. 5th ed Philadelphia, PA: Lippincott, Williams and Wilkins; (2007) p. 2479–99.
    1. Santosh A, Muddana K. Viral infections of oral cavity. J Family Med Prim Care. (2020) 9:36–42. 10.4103/jfmpc.jfmpc_807_19
    1. Scully C. Ulcerative stomatitis, gingivitis, and skin lesions. An unusual case of primary herpes simplex infection. Oral Surg Oral Med Oral Pathol. (1985) 59:261–3. 10.1016/0030-4220(85)90163-X
    1. Nahmias AJ, Roizman B. Infection with herpes simplex viruses 1 and 2. III. N Engl J Med. (1973) 289:781–9. 10.1056/NEJM197310112891505
    1. Weller T. Varicella and herpes zoster. N Engl J Med. (1983) 309:1362–8. 10.1056/NEJM198312013092205
    1. Sampathkumar P, Drage LA, Martin DP. Herpes zoster (shingles) and postherpetic neuralgia. Mayo Clin Proc. (2009) 84:274–80. 10.4065/84.3.274
    1. Lambore S, McSherry J, Kraus AS. Acute and chronic symptoms of mononucleosis. J Fam Pract. (1991) 33:33–7.
    1. Mach M, Stamminger T, Jahn G. Human cytomegalovirus: recent aspects from molecular biology. J Gen Virol. (1989) 70:3117–46. 10.1099/0022-1317-70-12-3117
    1. Bagg J. Human herpesvirus-6: the latest human herpes virus. J Oral Pathol Med. (1991) 20:465–8. 10.1111/j.1600-0714.1991.tb00404.x
    1. De Araujo T, Berman B, Weinstein A. Human herpesviruses 6 and 7. Dermatol Clin. (2002) 20:301–6. 10.1016/S0733-8635(01)00008-0
    1. Cannon M, Cesarman E. Kaposi's sarcoma-associated herpes virus and acquired immunodeficiency syndrome-related malignancy. Semin Oncol. (2000) 27:409–19.
    1. Handisurya A, Schellenbacher C, Kirnbauer R. Diseases caused by human papillomaviruses (HPV). J Dtsch Dermatol Ges. (2009) 7:453–66. 10.1111/j.1610-0387.2009.06988.x
    1. Garlick JA, Taichman LB. Human papillomavirus infection of the oral mucosa. Am J Dermatopathol. (1991) 13:386–95. 10.1097/00000372-199108000-00010
    1. Kellokoski J, Syrjanen S, Syrjanen K, Yliskoski M. Oral mucosal changes in women with genital HPV infection. J Oral Pathol Med. (1990) 19:142–8. 10.1111/j.1600-0714.1990.tb00813.x
    1. Ficarra G, Adler-Storthz K, Galeotti F, Shillitoe E. Focal epithelial hyperplasia (Heck's disease): the first reported case from Italy. Tumori. (1991) 77:83–5. 10.1177/030089169107700119
    1. Morrow DJ, Sandhu HS, Daley TD. Focal epithelial hyperplasia (Heck's disease) with generalized lesions of the gingiva. A case report. J Periodontol. (1993) 64:63–5. 10.1902/jop.1993.64.1.63
    1. Miller CS, Johnstone BM. Human papillomavirus as a risk factor for oral squamous cell carcinoma: a meta-analysis, 1982-1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. (2001) 91:622–35. 10.1067/moe.2001.115392
    1. Hennessey PT, Westra WH, Califano JA. Human papillomavirus and head and neck squamous cell carcinoma: recent evidence and clinical implications. J Dent Res. (2009) 88:300–6. 10.1177/0022034509333371
    1. German Advisory Committee Blood (Arbeitskreis Blut) Subgroup 'Assessment of Pathogens Transmissible by Blood' Human Immunodeficiency Virus (HIV). Transfus Med Hemother. (2016) 43:203–22. 10.1159/000445852
    1. Mbopi-Keou FX, Belec L, Teo CG, Scully C, Porter SR. Synergism between HIV and other viruses in the mouth. Lancet Infect Dis. (2002) 2:416–24. 10.1016/S1473-3099(02)00317-1
    1. Warrier SA, Sathasivasubramanian S. Human immunodeficiency virus induced oral candidiasis. J Pharm Bioallied Sci. (2015) 7:S81214. 10.4103/0975-7406.163577
    1. Shetti A, Gupta I, Charantimath SM. Oral candidiasis: aiding in the diagnosis of HIV-a case report. Case Rep Dent. (2011) 2011:929616. 10.1155/2011/929616
    1. Curtiss P, Strazzulla LC, Friedman-Kien AE. An update on Kaposi's Sarcoma: epidemiology, pathogenesis and treatment. Dermatol Ther. (2016) 6:465–70. 10.1007/s13555-016-0152-3
    1. Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D. Kaposi sarcoma. Nat Rev Dis Primers. (2019) 5:9 10.1038/s41572-019-0060-9
    1. Ansari R, Gheitani M, Heidari F, Heidari F. Oral cavity lesions as a manifestation of the novel virus (COVID-19). Oral Dis. (2020). 10.1111/odi.13465. [Epub ahead of print].
    1. Bezerra TMM, Feitosa SG, Carneiro DTO, Costa FWG, Pires FR, Pereira KMA. Oral lesions in COVID-19 infection: is long term follow-up important in the affected patients? Oral Dis. (2020). 10.1111/odi.13705. [Epub ahead of print].
    1. Brandão TB, Gueiros LA, Melo TS, Prado-Ribeiro AC, Nesrallah A, Prado G, et al. . Oral lesions in patients with SARS-CoV-2 infection: could the oral cavity be a target organ? Oral Surg Oral Med Oral Pathol Oral Radiol. (2020). 10.1016/j.oooo.2020.07.014. [Epub ahead of print].
    1. Cebeci Kahraman F, Çaşkurlu H. Mucosal involvement in a COVID-19-positive patient: a case report. Dermatol Ther. (2020) 33:e13797. 10.1111/dth.13797
    1. Ciccarese G, Drago F, Boatti M, Porro A, Muzic SI, Parodi A. Oral erosions and petechiae during SARS-CoV-2 infection. J Med Virol. (2020). 10.1002/jmv.26221. [Epub ahead of print].
    1. Cruz Tapia RO, Peraza Labrador AJ, Guimaraes DM, Matos Valdez LH. Oral mucosal lesions in patients with SARS-CoV-2 infection. Report of four cases. Are they a true sign of COVID-19 disease? Spec Care Dentist. (2020) 40:555–60. 10.1111/scd.12520
    1. Díaz Rodríguez M, Jimenez Romera A, Villarroel M. Oral manifestations associated with COVID-19. Oral Dis. (2020). 10.1111/odi.13555. [Epub ahead of print].
    1. Dominguez-Santas M, Diaz-Guimaraens B, Fernandez-Nieto D, Jimenez-Cauhe J, Ortega-Quijano D, Suarez-Valle A. Minor aphthae associated with SARS-CoV-2 infection. Int J Dermatol. (2020). 10.31128/AJGP-COVID-32. [Epub ahead of print].
    1. Kitakawa D, Oliveira FE, Neves de Castro P, Carvalho LFCS. Short report - Herpes simplex lesion in the lip semimucosa in a COVID-19 patient. Eur Rev Med Pharmacol Sci. (2020) 24:9151–3. 10.26355/eurrev_202009_22863
    1. Nuno-Gonzalez A, Martin-Carrillo P, Magaletsky K, Martin Rios MD, Herranz Mañas C, Artigas Almazan J, 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. (2020). 10.1111/bjd.19564. [Epub ahead of print].
    1. 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) 99:62–4. 10.1016/j.jdermsci.2020.05.002
    1. Soares CD, Carvalho RA, Carvalho KA, Carvalho MG, Almeida OP. Letter to editor: oral lesions in a patient with Covid-19. Med Oral Patol Oral Cir Bucal. (2020) 25:e563–4. 10.4317/medoral.24044
    1. Riad A, Kassem I, Hockova B, Badrah M, Klugar M. Tongue ulcers associated with SARS-CoV-2 infection: a case series. Oral Dis. (2020). 10.1111/odi.13635. [Epub ahead of print].
    1. Amorim Dos Santos J, Normando AGC, Carvalho da Silva RL, De Paula RM, Cembranel AC, Santos-Silva AR, et al. Oral mucosal lesions in a COVID-19 patient: New signs or secondary manifestations? Int J Infect Dis. (2020) 97:326–8. 10.1016/j.ijid.2020.06.012
    1. Corchuelo J, Ulloa FC. Oral manifestations in a patient with a history of asymptomatic COVID-19: case report. Int J Infect Dis. (2020) 100:154–7. 10.1016/j.ijid.2020.08.071
    1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in china. N Engl J Med. (2020) 382:1708–20. 10.1056/NEJMoa2002032
    1. Aziz M, Perisetti A, Lee-Smith WM, Gajendran M, Bansal P, Goyal H. Taste changes (dysgeusia) in Covid-19: a systematic review and metaanalysis. Gastroenterology. (2020) 159:1132–3. 10.1053/j.gastro.2020.05.003
    1. Gianotti R, Zerbi P, Dodiuk-Gad RP. Clinical and histopathological study of skin dermatoses in patients affected by COVID-19 infection in the Northern part of Italy. J Dermatol Sci. (2020) 98:141–3. 10.1016/j.jdermsci.2020.04.007
    1. Xue X, Mi Z, Wang Z, Pang Z, Liu H, Zhang F. High expression of ACE2 on the keratinocytes reveals skin as a potential target for SARS-CoV-2. J Invest Dermatol. (2020) 141:206–9.e1. 10.1016/j.jid.2020.05.087
    1. Lee JS, Kossard S, McGrath MA. Lymphocytic thrombophilic arteritis: a newly described medium-sized vessel arteritis of the skin. Arch Dermatol. (2008) 144:1175–82. 10.1001/archderm.144.9.1175
    1. Gianotti R. COVID 19 and the Skin-Heuristic Review. Milan: DermoSprint; (2020).
    1. Manalo IF, Smith MK, Cheeley J, Jacobs R. A dermatologic manifestation of COVID-19: transient livedo reticularis. J Am Acad Dermatol. (2020) 83:700 10.1016/j.jaad.2020.04.018
    1. Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, et al. . Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res. (2020) 220:1–13. 10.1016/j.trsl.2020.04.007
    1. Finsterer J, Stollberger C. Causes of hypogeusia/hyposmia in SARS- CoV2 infected patients. J Med Virol. (2020) 92:1793–4. 10.1002/jmv.25903
    1. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential effects of coronaviruses on the cardiovascular system: a review. JAMA Cardiol. (2020) 5:831–40. 10.1001/jamacardio.2020.1286
    1. Hedou M, Carsuzaa F, Chary E, Hainaut E, Cazenave-Roblot F, Masson Regnault M. Comment on 'Cutaneous manifestations in COVID-19: a first perspective' by Recalcati S. J Eur Acad Dermatol Venereol. (2020) 34:e299–300. 10.1111/jdv.16519
    1. Forbes H, Warne B, Doelken L, Brenner N, Waterboe T, Luben R, et al. . Risk factors for herpes simplex virus type-1 infection and reactivation: cross-sectional studies among EPIC- Norfolk participants. PLoS ONE. (2019) 14:e0215553. 10.1371/journal.pone.0215553
    1. Santacroce L, Charitos IA, Ballini A, Inchingolo F, Luperto P, De Nitto E, et al. . The human respiratory system and its microbiome at a glimpse. Biology. (2020) 9:318. 10.3390/biology9100318
    1. Pham VH, Gargiulo Isacco C, Nguyen KCD, Le SH, Tran DK, Nguyen QV, et al. . Rapid and sensitive diagnostic procedure for multiple detection of pandemic Coronaviridae family members SARS-CoV-2, SARS-CoV, MERS-CoV and HCoV: a translational research and cooperation between the Phan Chau Trinh University in Vietnam and University of Bari “Aldo Moro” in Italy. Eur Rev Med Pharmacol Sci. (2020) 24:7173–91. 10.26355/eurrev_202006_21713
    1. Charitos IA, Ballini A, Bottalico L, Cantore S, Passarelli PC, Inchingolo F, et al. . Special features of SARS-CoV-2 in daily practice. World J Clin Cases. (2020) 8:3920–33. 10.12998/wjcc.v8.i18.3920
    1. Bordea IR, Xhajanka E, Candrea S, Bran S, Oni?or F, Inchingolo AD, et al. . Coronavirus (SARS-CoV-2) pandemic: future challenges for dental practitioners. Microorganisms. (2020) 8:1704. 10.3390/microorganisms8111704
    1. Cantore S, Ballini A. Coronavirus disease 2019 (COVID-19) pandemic burst and its relevant consequences in dental practice. Open Dent J. (2020) 1:111–2. 10.2174/18742106020140111

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