392 J Contemp Med Sci | Vol. 7, No. 6, November-December 2021: 392–393 Letter to the Editor Can Apical Periodontitis Exacerbate Covid-19 Damage? Umut Aksoy1*, Ahmet Özer Şehirli2, Serkan Sayiner3 1Near East University, Faculty of Dentistry, Department of Endodontics, Near East Avenue, Lefkosa, 99138, Mersin 10, Turkey. 2Near East University, Faculty of Dentistry, Department of Pharmacology, Near East Avenue, Lefkosa, 99138, Mersin 10, Turkey. 3Near East University, Faculty of Veterinary Medicine, Department of Biochemistry, Near East Avenue, Lefkosa, 99138, Mersin 10, Turkey. *Correspondence to: Umut Aksoy (E-mail: umut.aksoy@neu.edu.tr) ISSN 2413-0516 Dear Editor, The COVID-19 pandemic remains an important health problem, potentially worsened by emerging mutant strains. Although vaccination studies have been rapidly carried out, the definitive treatment protocol for the disease has not yet been established. Therefore, treatment suggestions and studies continue to have importance. Until the end of the 1980s, the systemic effects of dental infections were ignored except in immunodeficient patients. Later studies revealed a relationship between dental infections and myocardial and cerebral infarction, increasing research interest in this topic.1-2 The relationship between periodontitis – which has an important role in dental infections – and systemic diseases has been determined. Although the studies in this area have increased,3,4 the relationship between apical periodontitis and systemic disease has not yet been completely established. The periapical infections caused by intracanal microor- ganisms ensure the secretion of inflammatory cytokines and might accelerate systemic diseases by causing inflammation in distant organs. COVID-19 infection might be accompanied by the excessive production of proinflammatory cytokines, also called “cytokine storm”.5 The already increased circulatory proinflammatory cytokines in people with apical periodontitis might aggravate the COVID-19 disease by triggering the cytokine storm and might worsen prognosis. Apical periodontitis is a common infectious disease worldwide; it is also the most frequent inflammatory lesion in the jaw related to the teeth.6 Apical periodontitis is character- ized by an inflammatory response and bone destruction in the periapical tissues resulting from both bacterial infections in the dental pulp and immune response as part of the body’s defensive reaction. Epidemiological studies worldwide indi- cate that apical periodontitis is a widespread oral health problem that could threaten the general health of the population.7 Because high serum acute reactive phase proteins were found in those with apical periodontitis, this disease was thought to be systemic. Indeed, it was shown to be associated with high levels of tumour necrosis factor-alpha (TNF-α), interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6), and interferon-gamma (IFN-γ) in the serum. Aksoy et al.2 have shown that the activities of two serum matrix metallo- proteinases (MMP1 and MMP2) were increased in rats with apical periodontitis compared to healthy rats. Şehirli et al.8 showed that in those with apical periodontitis, serum levels of lactate dehydrogenase, alkaline phosphatase, and creatine kinase increased while superoxide dismutase activity decreased, resulting in structural damage to heart tissue. Apical periodontitis affects T helper cells, activating mac- rophages. The increase in cytokine expression is thought to increase sensitivity in people with systemic damage. After coronavirus disease 2019 (COVID-19) infection, people can undergo severe tissue damage resulting from the increased expression of cytokines such as TNF-α, IL-1, IL-6, and IFN-γ. It appears that COVID-19 activates various inflam- matory pathways together with oxidative stress, thus pro- ducing intense inflammation in tissues such as the lung, heart, brain, stomach, intestine, and kidney.9 Because of the reported increased expression of cytokines, particularly those that affect the immune system, people with lung disease, cardiovascular system disorders, neurological disorders, or gastrointestinal problems can be comparatively more affected by COVID-19, resulting in greater mortality rates than in the healthy popula- tion.10 To date, an evaluation and study of the relationship between apical periodontitis and COVID-19 have not been published. It is obvious that diseases increasing cytokine expression in the blood can negatively affect COVID-19 outcomes. There is a possibility of cytokine storm during COVID- 19, and the already existing elevated cytokine levels in apical periodontitis might increase the risk and lead to severe sys- temic effects on entire systems. In conclusion, the demon- strated increase in serum cytokine expression from apical periodontitis can pose a risk for those with COVID-19, and people with this disorder should be treated preferentially.  References 1. Zhang J, Huang X, Lu B, Zhang C, Cai Z. Can apical periodontitis affect serum levels of CRP, IL-2, and IL-6 as well as induce pathological changes in remote organs? Clin Oral Invest. 2016;20(7):1617–24. doi:10.1007/s00784- 015-1646-6. 2. Aksoy U, Savtekin G, Şehirli AÖ, Kermeoglu F, Kalender A, Ozkayalar H, et al. Effects of alpha-lipoic acid therapy on experimentally induced apical periodontitis: a biochemical, histopathological and micro-CT analysis. Int Endod J. 2019;52(9):1317–26. doi:10.1111/iej.13121 3. Sehirli AÖ, Chukwunyere U, Aksoy U, Sayiner S, Abacioglu N. The circadian clock gene Bmal1: Role in COVID-19 and periodontitis. Chronobiol Int. 2021;38(6):779–784. doi: 10.1080/07420528.2021.1895198. 4. Şehirli AÖ, Aksoy U, Koca-Ünsal RB, Sayıner S. Role of NLRP3 inflammasome in COVID-19 and periodontitis: Possible protective effect of melatonin. Med Hypotheses. 2021;30:110588. doi: 10.1016/j. mehy.2021.110588. 5. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, Kochanek M, Böll B, von Bergwelt-Baildon MS. Cytokine release syndrome. J Immunother Cancer. 2018;15;6(1):56. doi: 10.1186/ s40425-018-0343-9. 6. Becconsall-Ryan K, Tong D, Love RM. Radiolucent inflammatory jaw lesions: a twenty-year analysis. Int Endod J. 2010;43(10):859–65. doi: 10.1111/j.1365-2591.2010.01751.x. (Submitted: 02 December 2021 – Revised version received: 10 December 2021 – Accepted: 16 December 2021 – Published online: 26 December 2021) mailto:umut.aksoy@neu.edu.tr 393J Contemp Med Sci | Vol. 7, No. 6, November-December 2021: 392–393 U. Aksoy et al. Letter to the Editor Apical Periodontitis and Covid-19 7. Persoon IF, Özok AR. Definitions and Epidemiology of Endodontic Infections. Curr Oral Health Rep. 2017;4(4):278–85. doi:10.1007/s40496- 017-0161-z. 8. Şehirli AÖ, Aksoy U, Kermeoglu F, Kalender A, Savtekin G, Ozkayalar H, et al. Protective effect of alpha‐lipoic acid against apical periodontitis‐induced cardiac injury in rats. Eur J Oral Sci. 2019;127(4):333–9. doi:10.1111/ eos.12618 9. Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, Zhang P, Liu X, Gao G, Liu F, Jiang Y, Cheng X, Zhu C, Xia Y. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9(1):1123–30. doi: 10.1080/22221751.2020.1770129. 10. Sehirli AO, Sayiner S, Serakinci N. Role of melatonin in the treatment of COVID-19; as an adjuvant through cluster differentiation 147 (CD147). Mol Biol Rep. 2020;47(10),8229–33. doi: 10.1007/s11033-020-05830-8. This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly. https://doi.org/10.22317/jcms.v7i6.1113