CC BY 4.0 · Eur J Dent 2022; 16(03): 514-520
DOI: 10.1055/s-0041-1740223
Review Article

Is There a Link between COVID-19 and Periodontal Disease? A Narrative Review

1   Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece
2   Department of Periodontology, 424 General Military Training Hospital, Thessaloniki, Greece
,
Ismo T. Räisänen
3   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
,
Pirjo Pärnänen
3   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
,
Taina Tervahartiala
3   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
,
Timo Sorsa
3   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
4   Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Stockholm, Sweden
,
Dimitra Sakellari
1   Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece
› Author Affiliations

Abstract

The coronavirus disease 2019 (COVID-19) pandemic greatly affected human well-being, social behavior, global economy, and healthcare systems. Everyday clinical practice in dentistry has been adjusted to the increased hazards of aerosol production by routine dental procedures. The objective of this study was to assess the existing literature to determine possible mechanisms of a relationship between COVID-19 and periodontitis, as well as describe findings from relevant epidemiological studies.

Scarce data exist in the literature that directly addresses the relationship between the two diseases. However, several data describe the role of the oral cavity and periodontal tissues as portals of entry of severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2), and the contribution of cytokines known to be produced in periodontal disease to severe forms of COVID-19. It is also suggested from the current literature that periodontal disease, shown to be associated with systemic diseases such as diabetes mellitus, cardiovascular and respiratory diseases, shares common risk factors with—especially—severe forms of COVID-19.

Further clinical studies are required to establish the relationship between these diseases. Oral hygiene performance and intact periodontal tissues can assist in mitigating the pandemic, and it is suggested that dental practitioners can contribute to identifying at-risk patients.



Publication History

Article published online:
06 January 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 
  • References

  • 1 COVID-19 situation in the WHO European Region. Available at: https://who.maps.arcgis.com/apps/dashboards/ead3c6475654481ca51c248d52ab9c61
  • 2 Lu R, Zhao X, Li J. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395 (10224): 565-574
  • 3 Zhang Y-Z, Holmes EC. A genomic perspective on the origin and emergence of SARS-CoV-2. Cell 2020; 181 (02) 223-227
  • 4 Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA 2020; 324 (08) 782-793
  • 5 Abdelrahman Z, Li M, Wang X. Comparative review of SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza a respiratory viruses. Front Immunol 2020; 11: 552909
  • 6 Hu T, Liu Y, Zhao M, Zhuang Q, Xu L, He Q. A comparison of COVID-19, SARS and MERS. PeerJ 2020; 8: e9725
  • 7 Johansson MA, Quandelacy TM, Kada S. et al. SARS-CoV-2 transmission from people without COVID-19 symptoms. JAMA Netw Open 2021; 4 (01) e2035057-e2035057
  • 8 Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci 2020; 12 (01) 9
  • 9 Guidance for dental settings. Accessed Nov 8, 2021 at. https://www.cdc.gov/coronavirus/2019-ncov/hcp/dental-settings.html
  • 10 EFP suggestions for the management of a dental clinic during the Covid-19 pandemic. Accessed Nov 8, 2021 at: https://www.efp.org/fileadmin/uploads/efp/Documents/covid19SafetyProtocol.pdf
  • 11 Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA 2020; 323 (18) 1824-1836
  • 12 COVID-19 vaccines. Accessed Nov 8, 2021 at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines
  • 13 Hoffmann M, Kleine-Weber H, Schroeder S. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181 (02) 271-280.e8
  • 14 Bourgonje AR, Abdulle AE, Timens W. et al. Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol 2020; 251 (03) 228-248
  • 15 Wrapp D, Wang N, Corbett KS. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020; 367 (6483): 1260-1263
  • 16 Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203 (02) 631-637
  • 17 Sakaguchi W, Kubota N, Shimizu T. et al. Existence of SARS-CoV-2 entry molecules in the oral cavity. Int J Mol Sci 2020; 21 (17) 6000
  • 18 Descamps G, Verset L, Trelcat A. et al. ACE2 protein landscape in the head and neck region: the conundrum of SARS-CoV-2 infection. Biology (Basel) 2020; 9 (08) 235
  • 19 Wu C, Zheng M. Single-cell RNA expression profiling shows that ACE2, the putative receptor of COVID-2019, has significant expression in nasal and mouth tissue, and is co-expressed with TMPRSS2 and not co-expressed with SLC6A19 in the tissues. Preprints 2020; DOI: 10.21203/rs.3.rs-16992/v1.
  • 20 Gabriele LG, Morandini AC, Dionísio TJ, Santos CF. Angiotensin II type 1 receptor knockdown impairs interleukin-1β-induced cytokines in human periodontal fibroblasts. J Periodontol 2017; 88 (01) e1-e11
  • 21 Santos CF, Morandini AC, Dionísio TJ. et al. Functional local renin-angiotensin system in human and rat periodontal tissue. PLoS One 2015; 10 (08) e0134601
  • 22 Santos CF, Akashi AE, Dionísio TJ. et al. Characterization of a local renin-angiotensin system in rat gingival tissue. J Periodontol 2009; 80 (01) 130-139
  • 23 Badran Z, Gaudin A, Struillou X, Amador G, Soueidan A. Periodontal pockets: a potential reservoir for SARS-CoV-2?. Med Hypotheses 2020; 143: 109907
  • 24 Kheur S, Kheur M, Gupta AA, Raj AT. Is the gingival sulcus a potential niche for SARS-corona virus-2?. Med Hypotheses 2020; 143: 109892
  • 25 Xu J, Li Y, Gan F, Du Y, Yao Y. Salivary glands: potential reservoirs for COVID-19 asymptomatic infection. J Dent Res 2020; 99 (08) 989-989
  • 26 Liu L, Wei Q, Alvarez X. et al. Epithelial cells lining salivary gland ducts are early target cells of severe acute respiratory syndrome coronavirus infection in the upper respiratory tracts of rhesus macaques. J Virol 2011; 85 (08) 4025-4030
  • 27 Wyllie AL, Fournier J, Casanovas-Massana A. et al. Saliva or nasopharyngeal swab specimens for detection of SARS-CoV-2. N Engl J Med 2020; 383 (13) 1283-1286
  • 28 Gupta S, Mohindra R, Chauhan P. et al. SARS-CoV-2 detection in gingival crevicular fluid. J Dent Res 2021; 100 (02) 187-193
  • 29 To KKW, Yip CCY, Lai CYW. et al. Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study. Clin Microbiol Infect 2019; 25 (03) 372-378
  • 30 Zhu J, Guo J, Xu Y, Chen X. Viral dynamics of SARS-CoV-2 in saliva from infected patients. J Infect 2020; 81 (03) e48-e50
  • 31 Jamal AJ, Mohammad M, Coomes E. et al. Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). medRxiv 2020; DOI: 10.1101/2020.05.01.20081026.
  • 32 Pasomsub E, Watcharananan SP, Boonyawat K. et al. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study. Clin Microbiol Infect 2021; 27 (02) 285.e1-285.e4
  • 33 Butler-Laporte G, Lawandi A, Schiller I. et al. Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Intern Med.
  • 34 Coronavirus (COVID-19) Update: FDA Authorizes First Diagnostic Test Using At-Home Collection of Saliva Specimens. Accessed Nov 8, 2021 at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-diagnostic-test-using-home-collection-saliva
  • 35 Huang N, Pérez P, Kato T. et al; NIH COVID-19 Autopsy Consortium, HCA Oral and Craniofacial Biological Network. SARS-CoV-2 infection of the oral cavity and saliva. Nat Med 2021; 27 (05) 892-903
  • 36 Troeltzsch M, Berndt R, Troeltzsch M. Is the oral cavity a reservoir for prolonged SARS-CoV-2 shedding?. Med Hypotheses 2021; 146: 110419
  • 37 Fernandes Matuck B, Dolhnikoff M, Maia GVA. et al. Periodontal tissues are targets for Sars-Cov-2: a post-mortem study. J Oral Microbiol 2020; 13 (01) 1848135
  • 38 People with Certain Medical Conditions. Accessed Nov 8, 2021 at. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html
  • 39 Jordan RE, Adab P, Cheng K. COVID-19: risk factors for severe disease and death. BMJ 2020; DOI: 10.1136/bmj.m1198.
  • 40 Persson GR. Periodontal complications with age. Periodontol 2000 2018; 78 (01) 185-194
  • 41 Suvan J, Harrington Z, Petrie A. et al. Obesity as predictive factor of periodontal therapy clinical outcomes: a cohort study. J Clin Periodontol 2020; 47 (05) 594-601
  • 42 Sanz M, Marco Del Castillo A, Jepsen S. et al. Periodontitis and cardiovascular diseases: Consensus report. J Clin Periodontol 2020; 47 (03) 268-288
  • 43 Gomes-Filho IS, Cruz SSD, Trindade SC. et al. Periodontitis and respiratory diseases: A systematic review with meta-analysis. Oral Dis 2020; 26 (02) 439-446
  • 44 Huffnagle GB, Dickson RP, Lukacs NW. The respiratory tract microbiome and lung inflammation: a two-way street. Mucosal Immunol 2017; 10 (02) 299-306
  • 45 Sjögren P, Nilsson E, Forsell M, Johansson O, Hoogstraate J. A systematic review of the preventive effect of oral hygiene on pneumonia and respiratory tract infection in elderly people in hospitals and nursing homes: effect estimates and methodological quality of randomized controlled trials. J Am Geriatr Soc 2008; 56 (11) 2124-2130
  • 46 Qian Y, Yuan W, Mei N. et al. Periodontitis increases the risk of respiratory disease mortality in older patients. Exp Gerontol 2020; 133: 110878
  • 47 Sanz M, Ceriello A, Buysschaert M. et al. Scientific evidence on the links between periodontal diseases and diabetes: consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. J Clin Periodontol 2018; 45 (02) 138-149
  • 48 Carrasco-Sánchez FJ, López-Carmona MD, Martínez-Marcos FJ. et al; SEMI-COVID-19 Network. Admission hyperglycaemia as a predictor of mortality in patients hospitalized with COVID-19 regardless of diabetes status: data from the Spanish SEMI-COVID-19 Registry. Ann Med 2021; 53 (01) 103-116
  • 49 McGurnaghan SJ, Weir A, Bishop J. et al. Public Health Scotland COVID-19 Health Protection Study Group, Scottish Diabetes Research Network Epidemiology Group. Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland. Lancet Diabetes Endocrinol 2021; 9 (02) 82-93
  • 50 Schett G, Sticherling M, Neurath MF. COVID-19: risk for cytokine targeting in chronic inflammatory diseases?. Nat Rev Immunol 2020; 20 (05) 271-272
  • 51 Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect 2020; 53 (03) 368-370
  • 52 Sahni V, Gupta S. COVID-19 & Periodontitis: the cytokine connection. Med Hypotheses 2020; 144: 109908
  • 53 Fabri GMC. Potential Link between COVID-19 and Periodontitis: Cytokine Storm, Immunosuppression, and Dysbiosis. Oral Health Dent Manag 2020; 20: 1-5
  • 54 Mancini L, Quinzi V, Mummolo S, Marzo G, Marchetti E. Angiotensin-converting enzyme 2 as a possible correlation between COVID-19 and periodontal Disease. Appl Sci (Basel) 2020; 10: 6224
  • 55 Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000 2014; 64 (01) 57-80
  • 56 Sorsa T, Tjäderhane L, Salo T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 2004; 10 (06) 311-318
  • 57 Sorsa T, Tjäderhane L, Konttinen YT. et al. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med 2006; 38 (05) 306-321
  • 58 Lee W, Aitken S, Sodek J, McCulloch CA. Evidence of a direct relationship between neutrophil collagenase activity and periodontal tissue destruction in vivo: role of active enzyme in human periodontitis. J Periodontal Res 1995; 30 (01) 23-33
  • 59 Sorsa T, Ingman T, Suomalainen K. et al. Cellular source and tetracycline-inhibition of gingival crevicular fluid collagenase of patients with labile diabetes mellitus. J Clin Periodontol 1992; 19 (02) 146-149
  • 60 Ryan ME, Ramamurthy NS, Sorsa T, Golub LM. MMP-mediated events in diabetes. Ann N Y Acad Sci 1999; 878: 311-334
  • 61 Safkan-Seppälä B, Sorsa T, Tervahartiala T, Beklen A, Konttinen YT. Collagenases in gingival crevicular fluid in type 1 diabetes mellitus. J Periodontol 2006; 77 (02) 189-194
  • 62 Rathnayake N, Åkerman S, Klinge B. et al. Salivary biomarkers of oral health: a cross-sectional study. J Clin Periodontol 2013; 40 (02) 140-147
  • 63 Grigoriadis A, Sorsa T, Räisänen I, Pärnänen P, Tervahartiala T, Sakellari D. Prediabetes/diabetes can be screened at the dental office by a low-cost and fast chair-side/point-of-care aMMP-8 immunotest. Diagnostics (Basel) 2019; 9 (04) 151
  • 64 Grigoriadis A, Räisänen IT, Pärnänen P, Tervahartiala T, Sorsa T, Sakellari D. Prediabetes/diabetes screening strategy at the periodontal clinic. Clin Exp Dent Res 2021; 7 (01) 85-92
  • 65 Chaparro A, Realini O, Hernández M. et al. Early pregnancy levels of gingival crevicular fluid matrix metalloproteinases-8 and− 9 are associated with the severity of periodontitis and the development of gestational diabetes mellitus. J Periodontol 2021; 92 (02) 205-215
  • 66 Keskin M, Lähteenmäki H, Rathnayake N. et al. Active matrix metalloproteinase-8 and interleukin-6 detect periodontal degeneration caused by radiotherapy of head and neck cancer: a pilot study. Expert Rev Proteomic 2021; 17 (10) 777-784
  • 67 Räisänen IT, Umeizudike KA, Pärnänen P. et al. Periodontal disease and targeted prevention using aMMP-8 point-of-care oral fluid analytics in the COVID-19 era. Med Hypotheses 2020; 144: 110276
  • 68 Bertolini M, Pita A, Koo S, Cardenas A, Methil A. Periodontal disease in the COVID-19 era: potential reservoir and increased risk for SARS-CoV-2. Pesqui Bras Odontopediatria Clin Integr 2020; 20 (supp1): e0134 https://doi.org/10.1590/pboci.2020.162
  • 69 Sharma A, Chauhan S, Sharma R, Jindal V, Rajput P, Jindal V. How chronic periodontitis associated with systemic diseases increases the case fatality rate among COVID-19 Patients. J Adv Med Dent Scie Res 2020; 8: 71-77
  • 70 Pitones-Rubio V, Chávez-Cortez EG, Hurtado-Camarena A, González-Rascón A, Serafín-Higuera N. Is periodontal disease a risk factor for severe COVID-19 illness?. Med Hypotheses 2020; 144: 109969
  • 71 Siddharthan S, Naing NN, Wan-Arfah N. Periodontal disease and COVID 19. J Pharm Res Int 2020; 32 (32) 88-91 DOI: 10.9734/JPRI/2020/v32i3230937.
  • 72 Kadkhodazadeh M, Amid R, Moscowchi A. Does COVID-19 affect periodontal and peri-implant diseases?. J Long Term Eff Med Implants 2020; 30 (01) 1-2
  • 73 Madapusi Balaji T, Varadarajan S, Rao USV. et al. Oral cancer and periodontal disease increase the risk of COVID 19? A mechanism mediated through furin and cathepsin overexpression. Med Hypotheses 2020; 144: 109936
  • 74 Larvin H, Wilmott S, Wu J, Kang J. The impact of periodontal disease on hospital admission and mortality during COVID-19 pandemic. Front Med (Lausanne) 2020; 7: 604980
  • 75 Marouf N, Cai W, Said KN. et al. Association between periodontitis and severity of COVID-19 infection: a case-control study. J Clin Periodontol 2021; 48 (04) 483-491
  • 76 Sampson V, Kamona N, Sampson A. Could there be a link between oral hygiene and the severity of SARS-CoV-2 infections?. Br Dent J 2020; 228 (12) 971-975
  • 77 Herrera D, Serrano J, Roldán S, Sanz M. Is the oral cavity relevant in SARS-CoV-2 pandemic?. Clin Oral Investig 2020; 24 (08) 2925-2930