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An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists


 
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Year : 2022  |  Volume : 26  |  Issue : 3  |  Page : 389-391
 

Exploring the correlation between COVID 19 and periodontal disease


1 Faculty of Dentistry, Jamia Millia Islamia, Jamia Nagar, New Delhi; Nair Hospital Dental College, Mumbai, Maharashtra, India
2 Department of Oral Pathology, Faculty of Dentistry, Jamia Millia Islamia, Jamia Nagar, New Delhi, India

Date of Submission20-May-2022
Date of Acceptance06-Jul-2022
Date of Web Publication17-Oct-2022

Correspondence Address:
Keya Sircar
Room No 302, Faculty of Dentistry, Jamia Millia Islamia, New Delhi - 110 025
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jomfp.jomfp_220_22

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   Abstract 


An association of periodontal disease with the severity of COVID 19 disease has been observed during COVID 19 pandemic. This article explores the various hypotheses that link the two conditions, to understand their interrelationship. Targeted research may help elucidate evidence for screening of high-risk groups and identification of therapeutic targets.


Keywords: COVID 19, high-risk groups, hypotheses, periodontal disease, therapeutic targets


How to cite this article:
Sayeed F, Sircar K. Exploring the correlation between COVID 19 and periodontal disease. J Oral Maxillofac Pathol 2022;26:389-91

How to cite this URL:
Sayeed F, Sircar K. Exploring the correlation between COVID 19 and periodontal disease. J Oral Maxillofac Pathol [serial online] 2022 [cited 2022 Dec 3];26:389-91. Available from: https://www.jomfp.in/text.asp?2022/26/3/389/358724





   Introduction Top


Over the last 2 years of the COVID 19 disease pandemic, an association was noted between periodontitis and COVID 19 disease.[1] Understanding the pathologic basis of the association between the two diseases may establish the role of treating periodontitis as part of the standard protocol of management of COVID 19. As both COVID 19 and periodontitis are characterized by chronic inflammation, the discovery of common immune mediators may lead to discovery of therapeutic targets.[2] This article is a brief compilation of the various hypotheses relating the two entities, to understand the importance of periodontal health in the management of COVID 19.


   Discussion Top


Studies have revealed that patients suffering from COVID 19 and periodontal disease are more likely to be hospitalized and require oxygen treatment as compared to those without coexisting periodontitis.[3] Various hypotheses have been proposed to explain the observed correlation between COVID 19 disease and periodontal disease.

1. Role of inflammatory Cytokines

A cytokine storm with elevation of various cytokines like IL-1 beta, IL-6, IL-7, TNF alpha, has been reported in COVID 19 and the cytokine level correlates well with disease severity[4]

In COVID 19 disease, interstitial pneumonia, attributed to overexpression of IL-6 is associated with higher fatality rates. A meta-analysis by Coomes et al.[5] suggested that IL-6 levels were 2.9-fold higher levels in patients with COVID-19, who were in critical state as compared to those suffering from mild or moderate illness. Periodontitis, a common oral disease independently elevates IL-6.[6] Thus, co-existing periodontitis in COVID 19 patients can contribute to elevated levels of IL-6, with worsening outcomes. Marouf et al.[3] report that 12% of COVID 19 patients with periodontitis experienced severe complications while only 2% of those without periodontitis suffered from severe COVID 19 disease.

Role of ACE-2 receptors

The binding of SARS CoV-2 to ACE 2 receptors, in the gingival crevice and periodontal pockets, leads to high viral load in the oral cavity ACE 2 expression is increased in diabetics, patients with COPD, asthma and liver disease, which explains the vulnerability of these patients to severe COVID 19.[7] These receptors are implicated in various oral manifestations reported in COVID-19 like dysgeusia, oral ulcers, vesicles, blisters, Kawasaki like disease, bleeding from lips, and strawberry tongue.[3] Takahashi Y et al.[8] have shown that aspiration of periodontopathic bacteria increases the expression of ACE 2 receptors in the lungs and bronchi, through bacterial endotoxins and other pathogenic products. Thus, persons with periodontal disease are likely to overexpress ACE 2 receptors in their respiratory mucosa, predisposing them to COVID 19.

2. Role of CD-147

The epithelial cells of gingiva and subgingival periodontal pockets express high levels of CD147. Wang et al.[9] demonstrated that SARS CoV-2 may gain entry into target cells by binding to the CD 147) on cell membranes in addition to the ACE-2 receptors. Thus, pre-existing periodontitis may facilitate the entry of SARS CoV2 through this route.

3. Role of Galectin mediated immune response

Galectins, a group of β-galactoside-binding lectins, produced by various immune and epithelial cells have pro or anti-inflammatory action, depending on their localization and the target cell.[10] Galectins induce ACE-2 receptors to generate the glycan lattice on the viral and endothelial cell surfaces, which leads to an enhanced inflammatory response and a conformational change in viral structure, facilitating entry of the virus into endothelial cells. Inflammatory diseases like periodontitis, which can lead to increased Gal-3 production may indirectly increase risk of COVID 19 through increased viral entry.[11]

A morphological similarity exists between Gal 3 and an important locus of the SARS- CoV-2 spike protein. Thus Gal 3 inhibitors may target this spike protein preventing viral entry into target cells.[12] Gal 3 inhibitors cause decreased production of inflammatory cytokines IL-1 and IL-6 and increased expression of the anti-inflammatory cytokines like IL-10.[13] Thus Gal-3 inhibitors can serve as a therapeutic target improving outcome of both COVID-19 and periodontitis.

4. Role of Neutrophil extracellular traps

Neutrophil extracellular traps (NETs) act as scaffolds that retain microorganisms, that get trapped in the DNA fibers, limiting their spread, and facilitating concentration of antimicrobial agents at that site.[14] NETosis is a multiple step process in which NADPH oxidase activates the neutrophils to release reactive oxygen species (ROS), which then acts on the nucleus and causes chromatin de-condensation and cytolysis to release NETs. NETs are associated with the pathophysiology of periodontitis as well as viral diseases like COVID-19. In periodontitis, high levels of Interferon Alpha, the main mediator for NETosis are observed, while, in viral diseases, host evasion mechanisms are responsible for triggering NETosis.[15] Further, NETosis induced by viruses results in an extreme systemic response, with increased production of cytokines, chemokines and immune complexes.[16] Thus, in COVID 19 patients with periodontitis, the combined resultant increase in NETs leads to severe disease.

5. Role of Oral Dysbiosis

Oral dysbiosis, resulting from loss of host-microbial homeostasis, is a known nosocomial complication in long term hospitalized patients and shows an association with periodontitis.[17] A metagenomic analysis of severe COVID 19 patients showed presence of periodontitis associated genera Fusobacterium, Veillonella and Prevotella[18] Thus hospitalized patients with COVID 19 can develop oral dysbiosis which can predispose to periodontitis, which in turn can negatively impact the severity of SARS CoV2 disease.

As periodontal disease is highly prevalent in the population, it may well be the 'elephant in the room' with respect to management of COVID 19. Understanding the underlying mechanism that connects the two conditions will open up novel research avenues for development of therapeutic targets for COVID 19 [Figure 1]. Recognizing the underlying pathophysiology will help to elucidate the importance of oral health status, particularly periodontal health in reducing disease severity in those infected with SARS CoV2.
Figure 1: Pictorial depiction of the factors linking periodontal disease with COVID 19 and their interdependence on one and another

Click here to view



   Conclusion Top


The pharmacotherapeutics for COVID 19 have changed several times since the first reported cases, based on the emerging evidence. A better understanding of the mechanism underlying the observed correlation between SARS CoV2 infection and periodontal health, may lead to inclusion of oral care as part of the standard protocol for management of COVID 19. Public health initiatives to screen for periodontal disease may effectively identify high risk groups for COVID 19. Effective treatment of periodontitis may help to mitigate the severity of COVID 19. Basic and clinical research must be directed towards understanding the importance of oral health status in improving the prognosis of SARS CoV2 infection.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Anand PS, Jadhav P, Kamath KP, Kumar SR, Vijayalaxmi S, Anil S. A case-control study on the association between periodontitis and coronavirus disease (COVID-19). J Periodontol 2022;93:584-90.  Back to cited text no. 1
    
2.
Bertolini M, Pita A, Koo S, Cardenas A, Meethil A. Periodontal disease in the COVID-19 era: Potential reservoir and increased risk for SARS-CoV-2. Pesqui Bras Odontopediatria Clín Integr 2020;20. doi: 10.1590/pboci. 2020.162.  Back to cited text no. 2
    
3.
Marouf N, Cai W, Said KN, Daas H, Diab H, Chinta VR, et al. Association between periodontitis and severity of Covid 19 infection: A case control study. J Clin Periodontol 2021;48:483-91.  Back to cited text no. 3
    
4.
Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev 2020;54:62-75.  Back to cited text no. 4
    
5.
Coomes EA, Haghbayan H. Interleukin-6 in COVID-19: A systematic review and meta-analysis. Rev Med Virol. 2020;30:1-9. doi: 10.1002/rmv. 2141.  Back to cited text no. 5
    
6.
Gani DK, Lakshmi D, Krishnan R, Emmadi P. Evaluation of C-reactive protein and interleukin-6 in the peripheral blood of patients with chronic periodontitis. J Indian Soc Periodontol 2009;13:69-74.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Scialo F, Daniele A, Amato F, Pastore L, Matera MG, Cazzola M, et al. ACE2: The major cell entry receptor for SARS-CoV-2. Lung 2020;198:867-77.  Back to cited text no. 7
    
8.
Takahashi Y, Watanabe N, Kamio N, Kobayashi R, Iinuma T, Imai K. Aspiration of periodontopathic bacteria due to poor oral hygiene potentially contributes to the aggravation of COVID-19. J Oral Sci 2020;63:1-3  Back to cited text no. 8
    
9.
Wang K, Chen W, Zhou Y-S, Lian J-Q, Zhang Z, Du P, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. Signal Transduct Target Ther 2020;5:283. doi: 10.1038/s41392-020-00426-x.  Back to cited text no. 9
    
10.
Liu FT. Galectins: A new family of regulators of inflammation. Clin Immunol 2000;97:79-88.  Back to cited text no. 10
    
11.
Velickovic M, Arsenijevic A, Acovic A, Arsenijevic D, Milovanovic J, Dimitrijevic J, et al. Galectin-3, possible role in pathogenesis of periodontal diseases and potential therapeutic target. Front Pharmacol 2021;12:638258. doi: 10.3389/fphar. 2021.638258.  Back to cited text no. 11
    
12.
Caniglia JL, Guda MR, Asuthkar S, Tsung AJ, Velpula KK. A potential role for Galectin-3 inhibitors in the treatment of COVID-19. Peer J 2020;8:9392. doi: 10.7717/peerj. 9392.  Back to cited text no. 12
    
13.
Chen SS, Sun LW, Brickner H, Sun PQ. Downregulating Galectin-3 inhibits proinflamatory cytokine production by human monocytederived dentritic cells via RNA interference. Cell Immunol 2015;294:44-53.  Back to cited text no. 13
    
14.
Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. 2004;03:1532-5.  Back to cited text no. 14
    
15.
Gupta S, Sahni V. The intriguing commonality of NETosis between COVID-19 and Periodontal disease. Med Hypotheses 2020;144:109968. doi: 10.1016/j.mehy. 2020.109968.  Back to cited text no. 15
    
16.
Nakazawa D, Ishizu A. Immunothrombosis in severe COVID-19. E-Biomedicine 2020;59:4-5.  Back to cited text no. 16
    
17.
Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: Dynamic communities and host interactions Nat Rev Microbiol 2018;16:745-59.  Back to cited text no. 17
    
18.
Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: Dynamic communities and host interactions. Nat Rev Microbiol 2018;16:745-59.  Back to cited text no. 18
    


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