Periodontitis Is Associated With a Higher Risk of Severe COVID-19 Complications

 

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  • In this case–control study designed to establish the extent to which periodontitis is associated with COVID-19 complications, after adjusting for potential confounders and comorbidities, multivariate analysis showed an adjusted odds ratio of 3.67 for all COVID-19 complications, 8.81 for death, 3.54 for ICU admission, and a 4.57 for need of assisted ventilation. Concentrations of D-dimer (P < .001), white blood cell count (WBC; P < .001), and C-reactive protein (CRP; P < .001) were significantly higher in COVID-19–deceased patients compared with surviving patients, while concentrations of lymphocytes (P < .005) were significantly lower in deceased patients. Patients admitted to the ICU and patients requiring assisted ventilation also had significantly higher D-dimer, WBC, and CRP serum levels than patients not admitted to the ICU or requiring assisted ventilation.

  • Even though periodontitis and COVID-19 have both been associated with common comorbidities, there has heretofore been no evidence of a possible direct association between these two diseases. In this study, the risk of COVID-19 complications was significantly higher among patients with moderate to severe periodontitis compared with those with mild or no periodontitis. The authors conclude that these compelling results confirm the association between periodontitis and worse progression of COVID-19.
–  Laurie C. Carter, DDS, PhD

Written by
 
 
Satheesh Elangovan BDS, DSc, DMSc

As of May 3, 2021, the coronavirus disease-19 (COVID-19) pandemic (caused by SARS-CoV-2) has affected more than 150 million people and led to more than 3.2 million deaths worldwide. Patients with comorbidities such as diabetes or hypertension, when infected with the virus, are highly prone to develop serious complications and can eventually die. These serious complications are often a consequence of a surge in inflammatory mediators called “cytokine storm.”

Periodontitis is one of the most common chronic inflammatory conditions in the world and a substantial body of earlier work had brought to light the associations between periodontitis and several systemic inflammatory conditions such as diabetes and cardiovascular disease. In this case–control study performed using electronic dental/medical records of 568 patients, the authors looked into the association of periodontitis (as defined by radiographic bone loss [RBL] at two or more non-adjacent teeth after excluding conditions such as fractured/cracked roots, periodontal–endodontic lesions, caries, etc) with COVID-19 complications.

After adjustment for potential confounders such as sex, age, smoking behavior, and comorbidities, the analyses showed that, compared with patients with no RBL or with incipient bone loss, patients with moderate to severe RBL had statistically significant greater odds for: 1) all COVID-19 complications (that includes death); 2) admission to the intensive care unit; and 3) need for assisted ventilation. The authors additionally reported that patients with periodontitis presented with higher levels of the following serum biomarkers that are associated with COVID-19 complications: serum C-reactive protein (CRP), white blood cell count, and D-dimer.

In spite of the limitations of this study, such as the use of only one parameter (RBL) to diagnose periodontitis, as authors pointed out, the establishment and maintenance of optimal periodontal health becomes vital, especially in patients with comorbidities that already put them at higher risk for COVID-19 complications.

The following are some of the hypotheses highlighted by authors in their discussion that may explain the association between periodontitis and COVID-19 complications:

  • Aspiration of periodontopathogenic bacteria could increase the expression of angiotensin-converting enzyme-2 (ACE-2) receptors and cytokines in the lower respiratory tract.1
  • Cleavage of S-glycoprotein of SARS-CoV-2 by periodontopathogenic bacteria could increase its virulence.1,2
  • Oral cavity and periodontal pockets could act as reservoirs for viruses, including SARS-CoV-2.3-5
  • Periodontal disease can induce a strong T-helper–17 cell (Th17) response, which could exacerbate the cytokine storm, leading to COVID-19 complications.6

References

  1. Takahashi Y, Watanabe N, Kamio N, et al. 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. https://www.jstage.jst.go.jp/article/josnusd/63/1/63_20-0388/_article
  2. 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. https://www.sciencedirect.com/science/article/abs/pii/S0306987720311476
  3. Bao L, Zhang C, Dong J, et al. Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection. Front Microbiol. 2020;11:1840. https://www.frontiersin.org/articles/10.3389/fmicb.2020.01840/full
  4. Badran Z, Gaudin A, Struillou X, et al. Periodontal pockets: a potential reservoir for SARS-CoV-2? Med Hypotheses. 2020;143:109907. https://linkinghub.elsevier.com/retrieve/pii/S0306-9877(20)31369-4
  5. Herrera D, Serrano J, Roldán S, Sanz M. Is the oral cavity relevant in SARS-CoV-2 pandemic? Clin Oral Investig. 2020;24(8):2925-2930. https://link.springer.com/article/10.1007%2Fs00784-020-03413-2
  6. Sahni V, Gupta S. COVID-19 & periodontitis: the cytokine connection. Med Hypotheses. 2020;144:109908. https://www.sciencedirect.com/science/article/abs/pii/S0306987720313578

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.

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