Association between periodontitis and severity of COVID-19 infection: A case-control study

Nadya Marouf, Wenji Cai, Khalid N Said, Hanin Daas, Hanan Diab, Venkateswara Rao Chinta, Ali Ait Hssain, Belinda Nicolau, Mariano Sanz, Faleh Tamimi, Nadya Marouf, Wenji Cai, Khalid N Said, Hanin Daas, Hanan Diab, Venkateswara Rao Chinta, Ali Ait Hssain, Belinda Nicolau, Mariano Sanz, Faleh Tamimi

Abstract

Aim: COVID-19 is associated with an exacerbated inflammatory response that can result in fatal outcomes. Systemic inflammation is also a main characteristic of periodontitis. Therefore, we investigated the association of periodontitis with COVID-19 complications.

Materials and methods: A case-control study was performed using the national electronic health records of the State of Qatar between February and July 2020. Cases were defined as patients who suffered COVID-19 complications (death, ICU admissions or assisted ventilation), and controls were COVID-19 patients discharged without major complications. Periodontal conditions were assessed using dental radiographs from the same database. Associations between periodontitis and COVID 19 complications were analysed using logistic regression models adjusted for demographic, medical and behaviour factors.

Results: In total, 568 patients were included. After adjusting for potential confounders, periodontitis was associated with COVID-19 complication including death (OR = 8.81, 95% CI 1.00-77.7), ICU admission (OR = 3.54, 95% CI 1.39-9.05) and need for assisted ventilation (OR = 4.57, 95% CI 1.19-17.4). Similarly, blood levels of white blood cells, D-dimer and C Reactive Protein were significantly higher in COVID-19 patients with periodontitis.

Conclusion: Periodontitis was associated with higher risk of ICU admission, need for assisted ventilation and death of COVID-19 patients, and with increased blood levels of biomarkers linked to worse disease outcomes.

Keywords: Covid-19; ICU admissions; death; periodontitis; ventilation.

Conflict of interest statement

The authors declare no conflict of interest relevant to this study.

© 2021 The Authors. Journal of Clinical Periodontology published by John Wiley & Ltd.

References

    1. Acharya, A. B. , Thakur, S. , Muddapur, M. V. , & Kulkarni, R. D. (2017). Cytokine ratios in chronic periodontitis and type 2 diabetes mellitus. Diabetes & Metabolic Syndrome, 11(4), 277–278. 10.1016/j.dsx.2016.12.007.
    1. Badran, Z. , Gaudin, A. , Struillou, X. , Amador, G. , & Soueidan, A. (2020). Periodontal pockets: A potential reservoir for SARS‐CoV‐2? Medical Hypotheses, 143, 109907. 10.1016/j.mehy.2020.109907.
    1. Bao, L. , Zhang, C. , Dong, J. , Zhao, L. , Li, Y. , & Sun, J. (2020). Oral microbiome and SARS‐CoV‐2: Beware of lung co‐infection. Frontiers in Microbiology, 11, 1840. 10.3389/fmicb.2020.01840.
    1. Botros, N. , Iyer, P. , & Ojcius, D. M. (2020). Is there an association between oral health and severity of COVID‐19 complications? Biomedical Journal, 43(4), 325–327. 10.1016/j.bj.2020.05.016.
    1. Chambrone, L. , Foz, A. M. , Guglielmetti, M. R. , Pannuti, C. M. , Artese, H. P. , Feres, M. , & Romito, G. A. (2013). Periodontitis and chronic kidney disease: A systematic review of the association of diseases and the effect of periodontal treatment on estimated glomerular filtration rate. Journal of Clinical Periodontology, 40(5), 443–456. 10.1111/jcpe.12067.
    1. Chapple, I. L. C. , Genco, R. , & Working Group 2 of the Joint EFP/AAP workshop (2013). Diabetes and periodontal diseases: Consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. Journal of Clinical Periodontology, 40(s14), S106–S112. 10.1111/jcpe.12077.
    1. Chen, N. , Zhou, M. , Dong, X. , Qu, J. , Gong, F. , Han, Y. , Qiu, Y. , Wang, J. , Liu, Y. , Wei, Y. , Xia, J. , Yu, T. , Zhang, X. , & Zhang, L. I. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. The Lancet, 395(10223), 507–513. 10.1016/s0140-6736(20)30211-7.
    1. Curtis, M. A. , Diaz, P. I. , & VanDyke, T. E. (2020). The role of the microbiota in periodontal disease. Periodontology 2000, 83(1), 14–25. 10.1111/prd.12296.
    1. D'Aiuto, F. , Orlandi, M. , & Gunsolley, J. C. (2013). Evidence that periodontal treatment improves biomarkers and CVD outcomes. Journal of Clinical Periodontology, 40(Suppl 14), S85–105. 10.1111/jcpe.12061.
    1. Eke, P. I. , Dye, B. A. , Wei, L. , Slade, G. D. , Thornton‐Evans, G. O. , Borgnakke, W. S. , Taylor, G. W. , Page, R. C. , Beck, J. D. , & Genco, R. J. (2015). Update on prevalence of periodontitis in adults in the United States: NHANES 2009 to 2012. Journal of Periodontology, 86(5), 611–622. 10.1902/jop.2015.140520.
    1. Genco, R. J. , & Sanz, M. (2020). Clinical and public health implications of periodontal and systemic diseases: An overview. Periodontology 2000, 83(1), 7–13. 10.1111/prd.12344.
    1. Gomes‐Filho, I. S. , Cruz, S. S. D. , Trindade, S. C. , Passos‐Soares, J. D. S. , Carvalho‐Filho, P. C. , Figueiredo, A. C. M. G. , Lyrio, A. O. , Hintz, A. M. , Pereira, M. G. , & Scannapieco, F. (2020). Periodontitis and respiratory diseases: A systematic review with meta‐analysis. Oral Diseases, 26(2), 439–446. 10.1111/odi.13228.
    1. Gupta, S. , & Sahni, V. (2020). The intriguing commonality of NETosis between COVID‐19 & Periodontal disease. Medical Hypotheses, 144, 109968. 10.1016/j.mehy.2020.109968.
    1. Hellen‐Halme, K. , Lith, A. , & Shi, X. Q. (2020). Reliability of marginal bone level measurements on digital panoramic and digital intraoral radiographs. Oral Radiology, 36(2), 135–140. 10.1007/s11282-019-00387-0.
    1. Herrera, D. , Serrano, J. , Roldan, S. , & Sanz, M. (2020). Is the oral cavity relevant in SARS‐CoV‐2 pandemic? Clinical Oral Investigations, 24(8), 2925–2930. 10.1007/s00784-020-03413-2.
    1. Huang, C. , Wang, Y. , Li, X. , Ren, L. , Zhao, J. , Hu, Y. I. , Zhang, L. I. , Fan, G. , Xu, J. , Gu, X. , Cheng, Z. , Yu, T. , Xia, J. , Wei, Y. , Wu, W. , Xie, X. , Yin, W. , Li, H. , Liu, M. , … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497–506. 10.1016/s0140-6736(20)30183-5.
    1. Jepsen, S. , Caton, J. G. , Albandar, J. M. , Bissada, N. F. , Bouchard, P. , Cortellini, P. , Demirel, K. , de Sanctis, M. , Ercoli, C. , Fan, J. , Geurs, N. C. , Hughes, F. J. , Jin, L. , Kantarci, A. , Lalla, E. , Madianos, P. N. , Matthews, D. , McGuire, M. K. , Mills, M. P. , … Yamazaki, K. (2018). Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri‐Implant Diseases and Conditions. Journal of Periodontology, 89(Suppl 1), S237–S248. 10.1002/JPER.17-0733.
    1. Kassebaum, N. J. , Bernabe, E. , Dahiya, M. , Bhandari, B. , Murray, C. J. , & Marcenes, W. (2014). Global burden of severe periodontitis in 1990–2010: A systematic review and meta‐regression. Journal of Dental Research, 93(11), 1045–1053. 10.1177/0022034514552491.
    1. Kheur, S. , Kheur, M. , Gupta, A. A. , & Raj, A. T. (2020). Is the gingival sulcus a potential niche for SARS‐Corona virus‐2? Medical Hypotheses, 143, 109892. 10.1016/j.mehy.2020.109892.
    1. LaMonte, M. J. , Genco, R. J. , Hovey, K. M. , Wallace, R. B. , Freudenheim, J. L. , Michaud, D. S. , Mai, X. , Tinker, L. F. , Salazar, C. R. , Andrews, C. A. , Li, W. , Eaton, C. B. , Martin, L. W. , & Wactawski‐Wende, J. (2017). History of periodontitis diagnosis and edentulism as predictors of cardiovascular disease, stroke, and mortality in postmenopausal women. Journal of the American Heart Association, 6(4), e004518 10.1161/JAHA.116.004518.
    1. Madapusi Balaji, T. , Varadarajan, S. , Rao, U. S. V. , Raj, A. T. , Patil, S. , Arakeri, G. , & Brennan, P. A. (2020). Oral cancer and periodontal disease increase the risk of COVID 19? A mechanism mediated through furin and cathepsin overexpression. Medical Hypotheses, 144, 109936. 10.1016/j.mehy.2020.109936.
    1. Mehta, P. , McAuley, D. F. , Brown, M. , Sanchez, E. , Tattersall, R. S. , & Manson, J. J. (2020). COVID‐19: Consider cytokine storm syndromes and immunosuppression. The Lancet, 395(10229), 1033–1034. 10.1016/s0140-6736(20)30628-0.
    1. Monsarrat, P. , Blaizot, A. , Kemoun, P. , Ravaud, P. , Nabet, C. , Sixou, M. , & Vergnes, J. N. (2016). Clinical research activity in periodontal medicine: A systematic mapping of trial registers. Journal of Clinical Periodontology, 43(5), 390–400. 10.1111/jcpe.12534.
    1. Montero, E. , López, M. , Vidal, H. , Martínez, M. , Virto, L. , Marrero, J. , Herrera, D. , Zapatero, A. , & Sanz, M. (2020). Impact of periodontal therapy on systemic markers of inflammation in patients with metabolic syndrome: A randomized clinical trial. Diabetes, Obesity & Metabolism, 10.1111/dom.14131.
    1. Muñoz Aguilera, E. , Suvan, J. , Buti, J. , Czesnikiewicz‐Guzik, M. , Barbosa Ribeiro, A. , Orlandi, M. , Guzik, T. J. , Hingorani, A. D. , Nart, J. , & D’Aiuto, F. (2020). Periodontitis is associated with hypertension: A systematic review and meta‐analysis. Cardiovascular Research, 116(1), 28–39. 10.1093/cvr/cvz201.
    1. NCPERE, T. (2020). The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID‐19) in China. Chinese Journal of Epidemiology, 41(2), 145–151. 10.3760/cma.j.issn.0254-6450.2020.02.003.
    1. Nwizu, N. , Wactawski‐Wende, J. , & Genco, R. J. (2020). Periodontal disease and cancer: Epidemiologic studies and possible mechanisms. Periodontology 2000, 83(1), 213–233. 10.1111/prd.12329.
    1. Papapanou, P. N. , Sanz, M. , Buduneli, N. , Dietrich, T. , Feres, M. , Fine, D. H. , Flemmig, T. F. , Garcia, R. , Giannobile, W. V. , Graziani, F. , Greenwell, H. , Herrera, D. , Kao, R. T. , Kebschull, M. , Kinane, D. F. , Kirkwood, K. L. , Kocher, T. , Kornman, K. S. , Kumar, P. S. , … Tonetti, M. S. (2018). Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri‐Implant Diseases and Conditions. Journal of Periodontology, 89(Suppl 1), S173–S182. 10.1002/JPER.17-0721.
    1. Patel, J. , & Woolley, J. (2020). Necrotizing periodontal disease: Oral manifestation of COVID‐19. Oral Diseases, 10.1111/odi.13462.
    1. Petersen, P. E. , & Ogawa, H. (2012). The global burden of periodontal disease: Towards integration with chronic disease prevention and control. Periodontology 2000, 60(1), 15–39. 10.1111/j.1600-0757.2011.00425.x
    1. Pihlstrom, B. L. , Michalowicz, B. S. , & Johnson, N. W. (2005). Periodontal diseases. The Lancet, 366(9499), 1809–1820. 10.1016/s0140-6736(05)67728-8.
    1. Romandini, M. , Baima, G. , Antonoglou, G. , Bueno, J. , Figuero, E. , & Sanz, M. (2020). Periodontitis, edentulism, and risk of mortality: A systematic review with meta‐analyses. Journal of Dental Research, 31, 22034520952401. 10.1177/0022034520952401.
    1. Ruan, Q. , Yang, K. , Wang, W. , Jiang, L. , & Song, J. (2020). Clinical predictors of mortality due to COVID‐19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Medicine, 46(5), 846–848. 10.1007/s00134-020-05991-x
    1. Sahni, V. , & Gupta, S. (2020). COVID‐19 & Periodontitis: The cytokine connection. Medical Hypotheses, 144, 109908. 10.1016/j.mehy.2020.109908.
    1. Sanz, M. , Ceriello, A. , Buysschaert, M. , Chapple, I. , Demmer, R. T. , Graziani, F. , Herrera, D. , Jepsen, S. , Lione, L. , Madianos, P. , Mathur, M. , Montanya, E. , Shapira, L. , Tonetti, M. , & Vegh, D. (2018). 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. Journal of Clinical Periodontology, 45(2), 138–149. 10.1111/jcpe.12808.
    1. Sanz, M. , Marco del Castillo, A. , Jepsen, S. , Gonzalez‐Juanatey, J. R. , D’Aiuto, F. , Bouchard, P. , Chapple, I. , Dietrich, T. , Gotsman, I. , Graziani, F. , Herrera, D. , Loos, B. , Madianos, P. , Michel, J.‐B. , Perel, P. , Pieske, B. , Shapira, L. , Shechter, M. , Tonetti, M. , … Wimmer, G. (2020). Periodontitis and cardiovascular diseases: Consensus report. Journal of Clinical Periodontology, 47(3), 268–288. 10.1111/jcpe.13189.
    1. Schenkein, H. A. , Papapanou, P. N. , Genco, R. , & Sanz, M. (2020). Mechanisms underlying the association between periodontitis and atherosclerotic disease. Periodontology 2000, 83(1), 90–106. 10.1111/prd.12304.
    1. Sharma, P. , Dietrich, T. , Ferro, C. J. , Cockwell, P. , & Chapple, I. L. (2016). Association between periodontitis and mortality in stages 3–5 chronic kidney disease: NHANES III and linked mortality study. Journal of Clinical Periodontology, 43(2), 104–113. 10.1111/jcpe.12502.
    1. Slots, J. (2017). Periodontitis: Facts, fallacies and the future. Periodontology 2000, 75(1), 7–23. 10.1111/prd.12221.
    1. Suvan, J. E. , Petrie, A. , Nibali, L. , Darbar, U. , Rakmanee, T. , Donos, N. , & D'Aiuto, F. (2015). Association between overweight/obesity and increased risk of periodontitis. Journal of Clinical Periodontology, 42(8), 733–739. 10.1111/jcpe.12421.
    1. Takahashi, Y. , Watanabe, N. , Kamio, N. , Kobayashi, R. , Iinuma, T. , & Imai, K. (2020). Aspiration of periodontopathic bacteria due to poor oral hygiene potentially contributes to the aggravation of COVID‐19. Journal of Oral Science, 10.2334/josnusd.20-0388.
    1. Teeuw, W. J. , Gerdes, V. E. A. , & Loos, B. G. (2010). Effect of periodontal treatment on glycemic control of diabetic patients: A systematic review and meta‐analysis. Diabetes Care, 33(2), 421–427. 10.2337/dc09-1378.
    1. Teeuw, W. J. , Slot, D. E. , Susanto, H. , Gerdes, V. E. A. , Abbas, F. , D'Aiuto, F. , Kastelein, J. J. P. , & Loos, B. G. (2014). Treatment of periodontitis improves the atherosclerotic profile: A systematic review and meta‐analysis. Journal of Clinical Periodontology, 41(1), 70–79. 10.1111/jcpe.12171.
    1. Thounaojam, N. (2019). Effects of chronic periodontitis in serum ferritin levels before and 1 month after nonsurgical periodontal therapy: An intervention study. International Journal of Preventive and Clinical Dental Research, 6(2), 10.4103/inpc.Inpc_29_19.
    1. Tonetti, M. S. , D'Aiuto, F. , Nibali, L. , Donald, A. , Storry, C. , Parkar, M. , Suvan, J. , Hingorani, A. D. , Vallance, P. , & Deanfield, J. (2007). Treatment of periodontitis and endothelial function. New England Journal of Medicine, 356(9), 911–920. 10.1056/NEJMoa063186.
    1. Tonetti, M. S. , Greenwell, H. , & Kornman, K. S. (2018). Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. Journal of Periodontology, 89(Suppl 1), S159–S172. 10.1002/JPER.18-0006.
    1. Tonetti, M. S. , & Van Dyke, T. E. (2013). Periodontitis and atherosclerotic cardiovascular disease: Consensus report of the Joint EFP/AAPWorkshop on Periodontitis and Systemic Diseases. Journal of Periodontology, 84(4‐s), S24–S29. 10.1902/jop.2013.1340019.
    1. WHO . (2020a). Clinical management of severe acute respiratory infection (SARI) when COVID‐19 disease is suspected: Interim guidance. Mar 13, 2020. Retrieved from .
    1. WHO (2020b). COVID‐19 weekly epidemiological update 20201222. .
    1. Wu, C. , Chen, X. , Cai, Y. , Xia, J. , Zhou, X. , Xu, S. , Huang, H. , Zhang, L. I. , Zhou, X. , Du, C. , Zhang, Y. , Song, J. , Wang, S. , Chao, Y. , Yang, Z. , Xu, J. , Zhou, X. , Chen, D. , Xiong, W. , … Song, Y. (2020). Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Internal Medicine, 180(7), 934–10.1001/jamainternmed.2020.0994
    1. Xu, H. , Zhong, L. , Deng, J. , Peng, J. , Dan, H. , Zeng, X. , Li, T. , & Chen, Q. (2020). High expression of ACE2 receptor of 2019‐nCoV on the epithelial cells of oral mucosa. International Journal of Oral Science, 12(1), 8. 10.1038/s41368-020-0074-x.
    1. Yang, X. , Yu, Y. , Xu, J. , Shu, H. , Xia, J. , Liu, H. , Wu, Y. , Zhang, L. U. , Yu, Z. , Fang, M. , Yu, T. , Wang, Y. , Pan, S. , Zou, X. , Yuan, S. , & Shang, Y. (2020). Clinical course and outcomes of critically ill patients with SARS‐CoV‐2 pneumonia in Wuhan, China: A single‐centered, retrospective, observational study. The Lancet Respiratory Medicine, 8(5), 475–481. 10.1016/S2213-2600(20)30079-5.
    1. Yang Y., Shen C., Li J., Yuan J., Wei J., Huang F., Wang F., Li G., Li Y., Xing L., Peng L., Yang M., Cao M., Zheng H., Wu W., Zou R., Li D., Xu Z., Wang H., Zhang M., Zhang Z., Gao G. F., Jiang C., Liu L., Liu Y. (2020). Plasma IP‐10 and MCP‐3 levels are highly associated with disease severity and predict the progression of COVID‐19. Journal of Allergy and Clinical Immunology, 146(1), 119–127.e4. 10.1016/j.jaci.2020.04.027
    1. Zhou, F. , Yu, T. , Du, R. , Fan, G. , Liu, Y. , Liu, Z. , Xiang, J. , Wang, Y. , Song, B. , Gu, X. , Guan, L. , Wei, Y. , Li, H. , Wu, X. , Xu, J. , Tu, S. , Zhang, Y. I. , Chen, H. , & Cao, B. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID‐19 in Wuhan, China: A retrospective cohort study. The Lancet, 395(10229), 1054–1062. 10.1016/s0140-6736(20)30566-3.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren