Author(s):
Hasan Rezazadeh, Aria Salari, Hasti Hoseini
Email(s):
salari.aria@gmail.com
DOI:
10.52711/0974-360X.2025.00207 
Address:
Hasan Rezazadeh1, Aria Salari2*, Hasti Hoseini3
1Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.
2Faculty of Dentistry, Kerman University of Medical Sciences, Kerman, Iran.
3Student, Student research committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.
*Corresponding Author
Published In:
Volume - 18,
Issue - 3,
Year - 2025
ABSTRACT:
Numerous systemic illnesses and ailments have been related to periodontitis. Frequent studies have been conducted to investigate the relationship between COVID-19 and periodontitis due to their common comorbidity.An increasing amount of research indicates that periodontitis may raise the chance of contracting COVID-19 and its sequelae. The immunological states such as cytokines and chemokines coagulation conditions, underlying diseases besides genetic, sex, microbiological factors, dental care, and personal conservations might be at play in the correlation between the two illnesses. Male gender was shown to be related to both higher severity of COVID-19 and higher overall mortality, as well as with both severe (SP) and non-severe (NSP) types of periodontitis. Patients with diabetes type 2 and hypertension had an increased risk of COVID-19 problems and periodontal inflammation. The immune system's response to periodontitis may be enhanced by the production of receptors TMPRSS2, and ACE2 that SARS-CoV2 uses to infect cells. The potential presence of periodontitis could potentially contribute to SARS-CoV-2 infection via the CD147 pathway, given the elevated levels of CD147 expression in the oral epithelial cells within the subgingival region of periodontal pockets. Periodontal infections were found in the respiratory systems of individuals with severe COVID-19, and there is evidence that periodontitis may further raise the risk of COVID-19 problems by changing the coagulation pathways. IL-6, MMP8, and IL-1ß demonstrated a predictive value of 100%, suggesting their reliability in diagnosing periodontitis.Patients with periodontal disease who had COVID-19 had substantially higher blood levels of HbA1c, WBC, D-dimer, and CRP. Systemic inflammation from COVID-19 can exacerbate pre-existing periodontal conditions, potentially increasing the severity of both diseases and impacting patient outcomes.
Cite this article:
Hasan Rezazadeh, Aria Salari, Hasti Hoseini. Examine the Role of Systemic Inflammation from COVID-19 in Exacerbating Pre-existing Periodontal Conditions. Research Journal of Pharmacy and Technology. 2025;18(3):1439-5. doi: 10.52711/0974-360X.2025.00207
Cite(Electronic):
Hasan Rezazadeh, Aria Salari, Hasti Hoseini. Examine the Role of Systemic Inflammation from COVID-19 in Exacerbating Pre-existing Periodontal Conditions. Research Journal of Pharmacy and Technology. 2025;18(3):1439-5. doi: 10.52711/0974-360X.2025.00207 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-3-68
REFERENCES:
1. Gaurav Tiwari, Garima Singh, Ravi Shekhar, Ruchi Tiwari. Development and qualitative evaluation of periodontal gel containing an antibacterial agent for periodontal disease. Research Journal of Pharmacy and Technology. 2022; 15(11): 5225-1. doi: 10.52711/0974-360X.2022.00880
2. Sanjeela R. Guru, Suchetha Aghanashini, Nitin Saroch. Adipokines in Periodontal disease – Culprits or Accomplice?. Research Journal of Pharmacy and Technology. 2023; 16(4): 2061-7. doi: 10.52711/0974-360X.2023.00339
3. Pellokila, M. R., Nendissa, D. R., Kapa, M. M. J., Sui, J. M., Elbaa, E. F., Kana, Y. R., Elim, Y. V., Charlota Lerik, M. D. Environmental challenges due to COVID-19: Implications of altered distribution patterns and rice price dynamics in surplus and deficit areas of Indonesia. Caspian Journal of Environmental Sciences. 2023; 21(5): 1159-1170. doi: 10.22124/cjes.2023.7406
4. Sills E S, Wood S H. An Experimental Model for Peri-conceptual COVID-19 Pregnancy Loss and Proposed Interventions to Optimize Outcomes. Int J Mol Cell Med. 2020; 9 (3): 180-187. doi: 10.22088/IJMCM.BUMS.9.3.180
5. Widoyo, H., Mohammed, Z. Y., Ramírez-Coronel, A. A., Iswanto, A. H., Thattarauthodiyil, U., Alkhayyat, A. S., Karimi, M., Bahmani, M., Eftekhari, Z. Herbal therapy in Covid-19: A systematic review of medicinal plants effective against Covid-19. Caspian Journal of Environmental Sciences. 2023; 21(5): 1289-1298. doi: 10.22124/cjes.2023.7431
6. Najafipour R, Mohammadi D, Momeni M, Moghbelinejad S. ACE-2 Expression and Methylation Pattern in Bronchoalveolar Lavage Fluid and Bloods of Iranian ARDS Covid-19 Patients. Int J Mol Cell Med. 2022; 11 (1): 55-63, doi: 10.22088/IJMCM.BUMS.11.1.55
7. M. Martínez-García and E. Hernández-Lemus. Periodontal Inflammation and Systemic Diseases: An Overview. Front. Physiol.. 12, p. 709438, 2021, doi: 10.3389/fphys.2021.709438.
8. Himansu Bhusan Samal, Itishree Jogamaya Das, Ch. Niranjan Patra, P. N. Murthy. Design and Development of Dental Film Containing Aloe vera for the Treatment of Human Periodontal Diseases. Asian J. Pharm. Tech. 2015; 5(4): 273-280. doi: 10.5958/2231-5713.2015.00036.7
9. P. H. C. Leliefeld, C. M. Wessels, L. P. H. Leenen, L. Koenderman, and J. Pillay. The role of neutrophils in immune dysfunction during severe inflammation. Crit. Care. 2016; 20: 73 doi: 10.1186/s13054-016-1250-4.
10. G. Hajishengallis. New developments in neutrophil biology and periodontitis. Periodontol. 2000; 82(1): 78–92 doi: 10.1111/prd.12313.
11. I. Luchian, A. Goriuc, D. Sandu, and M. Covasa. The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes. Int. J. Mol. Sci. 2022; 23(3). doi: 10.3390/ijms23031806.
12. X. Zhu, H. Huang, and L. Zhao. PAMPs and DAMPs as the Bridge Between Periodontitis and Atherosclerosis: The Potential Therapeutic Targets. Front. cell Dev. Biol. 2022; 10: 856118 doi: 10.3389/fcell.2022.856118.
13. D. E. Ramadan, N. Hariyani, R. Indrawati, R. D. Ridwan, and I. Diyatri. Cytokines and Chemokines in Periodontitis. Eur. J. Dent. 2020; 14(3); 483–495 doi: 10.1055/s-0040-1712718.
14. G. P. Garlet. Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J. Dent. Res. 2010; 89(12): 1349–1363 doi: 10.1177/0022034510376402.
15. W. Pan, Q. Wang, and Q. Chen. The cytokine network involved in the host immune response to periodontitis. Int. J. Oral Sci. 2019; 11(3): 30 doi: 10.1038/s41368-019-0064-z.
16. K. Chen and J. K. Kolls. Interluekin-17A (IL17A). Gene. 2017; 614: 8–14 doi: 10.1016/j.gene.2017.01.016.
17. M.Y. Peng et al. Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. Int. J. Mol. Sci. 2021; 22(10). doi: 10.3390/ijms22105251.
18. B. Sposito et al. The interferon landscape along the respiratory tract impacts the severity of COVID-19. Cell. 2021; 184(19): 4953-4968.e16 doi: 10.1016/j.cell.2021.08.016.
19. J. Zhao et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proc. Natl. Acad. Sci. 2014; 111(13); 4970–4975.
20. D. Wu and X. O. Yang. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J. Microbiol. Immunol. Infect. 2020; 53(3); 368–370 doi: 10.1016/j.jmii.2020.03.005.
21. N. Kaneko, M. Kurata, T. Yamamoto, S. Morikawa, and J. Masumoto. The role of interleukin-1 in general pathology. Inflamm. Regen. 2019; 39: 12 doi: 10.1186/s41232-019-0101-5.
22. L. M. Bemquerer et al. Clinical, immunological, and microbiological analysis of the association between periodontitis and COVID-19: a case–control study. Odontology. 2024; 112(1): 208–220.
23. G. M. C. Fabri. Potential link between COVID-19 and periodontitis: cytokine storm, immunosuppression, and dysbiosis. Oral Health Dent. Manag. 2020; 20(1); 1–5.
24. S. A. Jones and B. J. Jenkins. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat. Rev. Immunol. 2018; 18(12); 773–789.
25. P. I. Eke, G. O. Thornton-Evans, L. Wei, W. S. Borgnakke, B. A. Dye, and R. J. Genco. Periodontitis in US Adults: National Health and Nutrition Examination Survey 2009-2014. J. Am. Dent. Assoc. 2018; 149(7): 576-588.e6 doi: 10.1016/j.adaj.2018.04.023.
26. A. Rhodes et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017; 43(3): 304–377.
27. I. Cuevas, A. Carbonero, D. Cano, I. L. Pacheco, J. C. Marín, and C. Borge. First outbreak of bovine haemorrhagic septicaemia caused by Pasteurella multocida type B in Spain - Short communication. Acta Vet. Hung. 2020; 68(1): 8–11 doi: 10.1556/004.2020.00014.
28. J. Patel and J. Woolley. Necrotizing periodontal disease: Oral manifestation of COVID-19. Oral Diseases. 2021; 27(Suppl 3): 768–769 doi: 10.1111/odi.13462.
29. N. Alnomay, L. Alolayan, R. Aljohani, R. Almashouf, and G. Alharbi. Association between periodontitis and COVID-19 severity in a tertiary hospital: A retrospective cohort study. Saudi Dent. J. 2022; 34(7); 623–628 doi: 10.1016/j.sdentj.2022.07.001.
30. S. Gupta and V. Sahni. The intriguing commonality of NETosis between COVID-19 & Periodontal disease. Medical Hypotheses. 2020; 144: 109968 doi: 10.1016/j.mehy.2020.109968.
31. Y. Takahashi, N. Watanabe, N. Kamio, R. Kobayashi, T. Iinuma, and K. Imai. Aspiration of periodontopathic bacteria due to poor oral hygiene potentially contributes to the aggravation of COVID-19. J. Oral Sci. 2020; 63(1): 1–3 doi: 10.2334/josnusd.20-0388.
32. C. Wang, D. Fei, X. Li, M. Zhao, and K. Yu. IL-6 may be a good biomarker for earlier detection of COVID-19 progression. Intensive Care Med. 2020; 46: 1475–1476.
33. F. Shi et al. Predictive salivary biomarkers for early diagnosis of periodontal diseases–current and future developments. Turkish J. Biochem. 2023; 48(4); 335–344.
34. D. A. Chambers, P. B. Imrey, R. L. Cohen, J. M. Crawford, M. E. A. F. Alves, and T. A. McSwiggin. A longitudinal study of aspartate aminotransferase in human gingival crevicular fluid. J. Periodontal Res. 1991; 26(2); 65–74.
35. O. Güven and J. G. A. M. De Visscher. Salivary IgA in periodontal disease. J. Periodontol. 1982; 53(5): 334–335,.
36. C. Cafiero, G. Spagnuolo, G. Marenzi, R. Martuscelli, M. Colamaio, and S. Leuci. Predictive periodontitis: the most promising salivary biomarkers for early diagnosis of periodontitis. J. Clin. Med. 2021; 10(7): 1488.
37. T. S. Miranda, N. de Freitas Figueiredo, L. C. Figueiredo, H. D. P. da Silva, F. R. G. Rocha, and P. M. Duarte. Cytokine profiles of healthy and diseased sites in individuals with periodontitis. Arch. Oral Biol. 2020; 120: 104957.
38. U. K. Gursoy and E. Könönen. Use of saliva in diagnosis of periodontitis: cumulative use of bacterial and host-derived biomarkers. Frontiers in Cellular and Infection Microbiology. 2016; 6: 196.
39. M. Al‐Sabbagh et al. Bone remodeling‐associated salivary biomarker MIP‐1α distinguishes periodontal disease from health. J. Periodontal Res. 2012; 47(3): 389–395.
40. M. Shojaee, M. F. Golpasha, G. Maliji, A. Bijani, S. M. A. Mir, and S. N. M. Kani. C-reactive protein levels in patients with periodontal disease and normal subjects. Int. J. Mol. Cell. Med. 2013; 2(3); 151.
41. J. Lam, S. Takeshita, J. E. Barker, O. Kanagawa, F. P. Ross, and S. L. Teitelbaum. TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J. Clin. Invest. 2000; 106(12); 1481–1488 doi: 10.1172/JCI11176.
42. W. Udomsinprasert, J. Jittikoon, S. Sangroongruangsri, and U. Chaikledkaew. Circulating Levels of Interleukin-6 and Interleukin-10, But Not Tumor Necrosis Factor-Alpha, as Potential Biomarkers of Severity and Mortality for COVID-19: Systematic Review with Meta-analysis. J. Clin. Immunol. 2021; 41(1): 11–22 doi: 10.1007/s10875-020-00899-z.
43. H. Hu, H. Pan, R. Li, K. He, H. Zhang, and L. Liu. Increased Circulating Cytokines Have a Role in COVID-19 Severity and Death With a More Pronounced Effect in Males: A Systematic Review and Meta-Analysis. Front. Pharmacol. 2022; 13: 802228 doi: 10.3389/fphar.2022.802228.
44. A. J. Abdullah et al. Assessing serum C-reactive protein as a predictor of COVID-19 outcomes: a retrospective cross-sectional study. Ann. Med. Surg. 2023; 85(7): 3359–3363 doi: 10.1097/MS9.0000000000000761.
45. S. Gupta et al. Validation of a noninvasive aMMP-8 point-of-care diagnostic methodology in COVID-19 patients with periodontal disease. Clin. Exp. Dent. Res. 2022; 8(4); 988–1001 doi: 10.1002/cre2.589.
46. U. K. Gursoy et al. Salivary interleukin-1beta concentration and the presence of multiple pathogens in periodontitis. J. Clin. Periodontol. 2009; 36(11); 922–927 doi: 10.1111/j.1600-051X.2009.01480.x.
47. J. L. Ebersole, R. Nagarajan, D. Akers, and C. S. Miller. Targeted salivary biomarkers for discrimination of periodontal health and disease(s). Front. Cell. Infect. Microbiol. 2015; 5: 62 doi: 10.3389/fcimb.2015.00062.
48. M. Levit and L. Levit. Infection Risk of COVID-19 in Dentistry Remains Unknown: A Preliminary Systematic Review. Infect. Dis. Clin. Pract. (Baltim. Md). 2021; 29(2); e70–e77 doi: 10.1097/IPC.0000000000000939.
49. G. M. Agostini-Walesch et al. Aerosols in Ultrasonic Instrumentation: Comparison of particle spread utilizing saliva ejectors versus high-volume evacuation. Am. Dent. Hyg. Assoc. 2021; 95(3): 18–24.
50. H. Larvin, S. Wilmott, J. Wu, and J. Kang. The Impact of Periodontal Disease on Hospital Admission and Mortality During COVID-19 Pandemic. Front. Med. 2020; 7: 604980 doi: 10.3389/fmed.2020.604980.