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Histological and molecular response of oral cavity tissues to Covid-19

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Abstract

The world is still dealing with Covid-19 waves, and maintaining good oral health has systemic effects on overall health. This review’s objective is to identify the main oral manifestations of this illness, its effects on oral tissues at their histological bases, their molecular cell mechanisms, and the relationship issues between Covid-19 outcomes and oral health conditions. The main sources of the review are research articles published from 2000 to 2023. The main used terms in search were Covid-19 oral manifestations, Corona virus and Taste, or Olfaction, Covid and periodontitis, or Oral cavity. the angiotensin-converting enzyme II receptor (ACE2), which serves as a cellular entry point for viral entry into the cell to cause Covid-19 infection, is the target of corona virus attacks on human cells. The destruction of keratinocytes and oral fibroblasts, which is an indication of the virus’s direct impact on oral tissues, results in inflammatory reactions in the salivary glands, tongue, and gingiva, which may explain both the loss of taste and the mouth ulceration. Additionally, there is a significant correlation between Covid-19 outcome and periodontitis. This results from the connection between hyperinflammation and poor oral hygiene.

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Data Availability

all data and material are available upon request.

Abbreviations

ACE2 :

Angiotensin-converting enzyme II receptor

scRNA-Seq :

Single-cell RNA-seq

RAAS :

Renin-angiotensin-aldosterone system

TMPRSS2 :

Transmembrane protease serine 2

TNF :

Tissue necrosis factor

TACE :

Transforming enzyme-α

IL-6 :

Interleukin-6

CRP :

C- Reactive Protein

TRC :

Taste receptor cell

TB :

Taste bud

GPCR :

G protein-coupled receptor

TLR :

Toll like receptor

MyD88 :

Myeloid differentiation main response 88

NF-B :

Nuclear factor kappa B

AT1R :

Angiotensin II receptor type 1

TMPRSS2 :

Transmembrane serine protease 2

MAVS :

Mitochondrial antiviral-signaling protein

TH17 :

T helper 17

References

  1. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS (2020) Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020; 46:586–590. https://doi.org/10.1007/s00134-020-05985-9

  2. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X (2020) High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020; 12:8. https://doi.org/10.1038/s41368-020-0074-x

  3. Manzalawi R, Alhmamey K, Abdelrasoul M (2021) Gingival bleeding associated with COVID-19 infection. Clin Case Rep. 2021; 9:294–297. https://doi.org/10.1002/ccr3.3519

  4. Gherlone EF, Polizzi E, Tetè G, De Lorenzo R, Magnaghi C, RovereQuerini P et al (2021) Frequent and persistent salivary gland ectasia and oral disease after COVID-19. J Dent Res. 2021.https://doi.org/10.1177/0022034521997112

  5. Cox MJ, Loman N, Bogaert D, O’Grady J (2020) Co-infections: potentially lethal and unexplored in COVID-19. Lancet Microbe. 2020;1: e11. https://doi.org/10.1016/S2666-5247(20)30009-4

  6. Datta PK, Liu F, Fischer T, Rappaport J, Qin X (2020) SARS-CoV-2 pandemic and research gaps: understanding SARS-CoV-2 interaction with the ACE2 receptor and implications for therapy. Theranostics 10:7448–7464. https://doi.org/10.7150/thno.48076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Neuman BW, Buchmeier MJ (2016) Supramolecular architecture of the coronavirus particle. Adv Virus Res. (2016) 96:1–27. https://doi.org/10.1016/bs.aivir.2016.08.005

  8. Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W (2020) Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses. (2020) 12:372. https://doi.org/10.3390/v12040372

  9. Haga S, Yamamoto N, Nakai-Murakami C, Osawa Y, Tokunaga K, Sata T et al (2008) Modulation of TNF-alpha-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral entry. Proc Natl Acad Sci USA. (2008) 105:7809–14. https://doi.org/10.1073/pnas.0711241105

  10. Barlow LA (2015) Progress and renewal in gustation: new insights into taste bud development. Development 142:3620–3629. https://doi.org/10.1242/dev.120394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Idriss HT, Naismith JH (2000) TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech 50:184–195. https://doi.org/10.1002/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO;2-H

    Article  CAS  PubMed  Google Scholar 

  12. Cruz Tapia RO, Peraza Labrador AJ, Guimaraes DM, Matos Valdez LH (2020) 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 Dentistry 40:555–560. https://doi.org/10.1111/scd.12520

    Article  Google Scholar 

  13. Gianotti R, Zerbi P, Dodiuk-Gad RP (2020) Clinical and histopathological study of skin dermatoses in patients affected by COVID-19 infection in the Northern part of Italy. J Dermatol Sci 98:141–143. https://doi.org/10.1016/j.jdermsci.2020.04.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Santosh ABR, Muddana K (2020) Viral infections of oral cavity. J Family Med Prim Care 9:36–42. https://doi.org/10.4103/jfmpc.jfmpc_807_19

    Article  PubMed  PubMed Central  Google Scholar 

  15. Iranmanesh B, Khalili M, Amiri R, Zartab H, Aflatoonian M (2020) Oral manifestations of COVID-19 disease: a review article. Dermatol Ther 34:e14578. https://doi.org/10.1111/dth.14578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Brandão TB, Gueiros LA, Melo TS, Prado-Ribeiro ACA, Nesrallah CFA, Prado GVB et al (2020) 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. 131:e45–51. https://doi.org/10.1016/j.oooo.2020.07.014

  17. Carreras-Presas CM, Sanchez JA, Lopez-Sanchez AF, Jane-Salas E, Perez MLS (2020) Oral vesiculobullous lesions associated with SARS-CoV-2 infection. Oral Dis 3:13382. https://doi.org/10.1111/odi.13382

    Article  Google Scholar 

  18. Amorim Dos Santos J, Normando AGC, Carvalho da Silva RL, De Paula RM, Cembranel AC, Santos-Silva AR et al (2020) Oral mucosal lesions in a COVID-19 patient: new signs or secondary manifestations? Int J Infect Dis 97:326–328. https://doi.org/10.1016/j.ijid.2020.06.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Heitzman J (2020) Impact of COVID-19 pandemic on mental health. Psychiatr Pol 54:187–198. https://doi.org/10.12740/PP/120373

    Article  PubMed  Google Scholar 

  20. Carrouel F, Gonçalves LS, Conte MP, Campus G, Fisher J, Fraticelli L et al (2021) Antiviral activity of reagents in mouth rinses against SARS-CoV-2. J Dent Res 100:124–132. https://doi.org/10.1177/0022034520967933

    Article  CAS  PubMed  Google Scholar 

  21. Yoon JG, Yoon J, Song JY, Yoon SY, Lim CS, Seong H et al (2020) Clinical significance of a high SARS-CoV-2 viral load in the Saliva. J Korean Med Sci 35:e195. https://doi.org/10.3346/jkms.2020.35.e195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Xu J, Li Y, Gan F, Du Y, Yao Y (2020) Salivary glands: potential reservoirs for COVID-19 asymptomatic infection. J Dent Res. 2020; 99(8): 989. https://doi.org/10.1177/0022034520918518

  23. Lanese N (2020) COVID-19 infects the mouth. Could that explain patients’ taste loss? Live Science. November 2, 2020. https://www.livescience.com/oral-infection-coronavirus-spread.html

  24. Tanaka T, Narazaki M, Kishimoto T (2016) Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8(8):959–970. https://doi.org/10.2217/imt-2016-0020

  25. Marouf N, Cai W, Said KN, Daas H, Diab H, Chinta VR, Hssain AA, Nicolau B, Sanz M, Tamimi F (2021) Association between periodontitis and severity of COVID-19 infection: A case-control study. J Clin Periodontol. 2021;48(4):483–491. https://doi.org/10.1111/jcpe.13435

  26. D’Aiuto F, Orlandi M, Gunsolley JC (2013) Evidence that periodontal treatment improves biomarkers and CVD outcomes. J Clin Periodontol 40(Suppl 14):S85–105. https://doi.org/10.1111/jcpe.12061

    Article  PubMed  Google Scholar 

  27. Sampson V, Kamona N, Sampson A (2020) Could there be a link between oral hygiene and the severity of SARS-CoV-2 infections? Br Dent J. 2020; 228(12):971–975. https://doi.org/10.1038/s41415-020-1747-8

  28. Chen T (2020) A dentist sees more cracked teeth. What is going on? The New York Times. September 8, 2020. Updated September 11, 2020. https://www.nytimes.com/2020/09/08/well/live/dentists-tooth-teeth-cracks-fractures-coronavirus-stress-grinding.html

  29. Agyeman AA, Chin KL, Landersdorfer CB, Liew D, Ofori-Asenso R (2020) Smell and taste dysfunction in patients with COVID-19: a systematic review and meta-analysis. Mayo Clin Proc. 2020;95(8):1621–1631. https://doi.org/10.1016/j.mayocp.2020.05.030

  30. Brann DH, Tsukahara T, Weinreb C et al (2020) Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19–associated anosmia. Sci Adv. 2020;6(31): eabc5801. https://doi.org/10.1126/sciadv.abc5801

  31. Mullol J, Alobid I, Mariño-Sánchez F, Izquierdo-Domínguez A, Marin C, Klimek L et al (2020) The loss of smell and taste in the COVID-19 outbreak: a tale of many countries. Curr Allergy Asthma Rep 20:61. https://doi.org/10.1007/s11882-020-00961-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lechner M, Chandrasekharan D, Jumani K, Liu J, Gane S, Lund VJ et al (2020) Anosmia as a presenting symptom of SARS-CoV-2 infection in healthcare workers - a systematic review of the literature, case series, and recommendations for clinical assessment and management. Rhinology 58:394–399. https://doi.org/10.4193/Rhin20.189

    Article  CAS  PubMed  Google Scholar 

  33. Song J, Deng Y-K, Wang H, Wang Z-C, Liao B, Ma J et al (2020) Self-reported taste and smell disorders in patients with COVID-19: distinct features in China. https://doi.org/10.1101/2020.06.12.20128298. medRxiv [Preprint]

  34. Horio N, Yoshida R, Yasumatsu K, Yanagawa Y, Ishimaru Y, Matsunami H et al (2011) Sour taste responses in mice lacking PKD channels. PLoS ONE 6:e20007. https://doi.org/10.1371/journal.pone.0020007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D et al (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112:293–301. https://doi.org/10.1016/S0092-8674(03)00071-0

    Article  CAS  PubMed  Google Scholar 

  36. Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H et al (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5:1169–1176. https://doi.org/10.1038/nn952

    Article  CAS  PubMed  Google Scholar 

  37. Okada S (2015) The taste system of small fish species. BiosciBiotechnolBiochem 79:1039–1043. https://doi.org/10.1080/09168451.2015.1023251

    Article  CAS  Google Scholar 

  38. de Araujo ie, Simon SA (2009) The gustatory cortex and multisensory integration. Int J Obes (Lond) Suppl 233. https://doi.org/10.1038/ijo.2009.70

  39. Cooper KW, Brann DH, Farruggia MC, Bhutani S, Pellegrino R, Tsukahara T et al (2020) COVID-19 and the chemical senses: supporting players take center stage. Neuron 107:219–233. https://doi.org/10.1016/j.neuron.2020.06.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jaggupilli A, Singh N, Upadhyaya J, Sikarwar AS, Arakawa M, Dakshinamurti S et al (2017) Analysis of the expression of human bitter taste receptors in extraoral tissues. Mol Cell Biochem 426:137–147. https://doi.org/10.1007/s11010-016-2902-z

    Article  CAS  PubMed  Google Scholar 

  41. da Silva Pedrosa M, Sipert CR, Nogueira FN (2020) Altered taste in patients with COVID-19: the potential role of salivary glands. Oral Dis. https://doi.org/10.1111/odi.13496

    Article  PubMed  PubMed Central  Google Scholar 

  42. BaghizadehFini M (2020) Oral saliva and COVID-19. Oral Oncol 108:104821. https://doi.org/10.1016/j.oraloncology.2020.104821

    Article  CAS  Google Scholar 

  43. Moein ST, Hashemian SM, Mansourafshar B, Khorram-Tousi A, Tabarsi P, Doty RL (2020) Smell dysfunction: a biomarker for COVID-19. Int Forum Allergy Rhinol 10:944–950. https://doi.org/10.1002/alr.22587

    Article  PubMed  PubMed Central  Google Scholar 

  44. Mullol J, Mariño-Sánchez F, Valls M, Alobid I, Marin C (2020) The sense of smell in chronic rhinosinusitis. J Allergy Clin Immunol 145:773–776. https://doi.org/10.1016/j.jaci.2020.01.024

    Article  PubMed  Google Scholar 

  45. Abdelalim AA, Mohamady AA, Elsayed RA, Elawady MA, Ghallab AF (2021) Corticosteroid nasal spray for recovery of smell sensation in COVID-19 patients: a randomized controlled trial. Am J Otolaryngol 42:102884. https://doi.org/10.1016/j.amjoto.2020.102884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Izquierdo-Domínguez A, Rojas-Lechuga MJ, Chiesa-Estomba C, Calvo-Henríquez C, Ninchritz-Becerra E, Soriano-Reixach M et al (2020) Smell and taste dysfunction in COVID-19 is associated with younger age in ambulatory settings: a multicenter cross-sectional study. J InvestigAllergol Clin Immunol 30:346–357. https://doi.org/10.18176/jiaci.0595

    Article  CAS  Google Scholar 

  47. Bousquet J, Akdis C, Jutel M, Bachert C, Klimek L, Agache I et al (2020) Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: an ARIA-EAACI statement. Allergy 75:2440–2444. https://doi.org/10.1111/all14302

    Article  CAS  PubMed  Google Scholar 

  48. Qi M, Sun W, Wang K, Li W, Lin J, Gong J, Wang L (2023) Periodontitis and COVID-19: Immunological Characteristics, Related Pathways, and Association. Int. J. Mol. Sci. 2023, 24, 3012. https://doi.org/10.3390/ijms24033012

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Authors and Affiliations

  1. Department of Oral Biology, Faculty of Oral and Dental Medicine, Future University in Egypt, Cairo, Egypt

    Nehad M. Abd-elmonsif

  2. Research labs supervisor, Faculty of pharmacy, Future University in Egypt, Cairo, Egypt

    Sherif Gamal

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Contributions

Nehad M. Abd-elmonsif contributed to interpretation of data and writing the review. Sherif Gamal contributed to interpretation of data, revision of the review and design the illustration figures. Both authors revise and approve the final version to be submitted.

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Correspondence to Nehad M. Abd-elmonsif.

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Abd-elmonsif, N.M., Gamal, S. Histological and molecular response of oral cavity tissues to Covid-19. Mol Biol Rep 50, 7893–7899 (2023). https://doi.org/10.1007/s11033-023-08607-x

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