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Table of Contents   
ORIGINAL RESEARCH  
Year : 2022  |  Volume : 33  |  Issue : 3  |  Page : 307-312
Correlation of COVID-19 with severity of periodontitis-A clinical and biochemical study


1 Department of Dentistry, Government Institute of Medical Sciences, Gautham Buddha Nagar, Uttar Pradesh, India
2 Department of Periodontics, ITS Dental College, Greater Noida, Uttar Pradesh, India
3 Department of Periodontics, School of Dental Sciences, Sharda University, Greater Noida, Uttar Pradesh, India
4 Department of Periodontology, College of Dental Sciences, Davangere, Karnataka, India

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Date of Submission16-Dec-2021
Date of Decision19-Sep-2022
Date of Acceptance21-Sep-2022
Date of Web Publication17-Jan-2023
 

   Abstract 


Background: Various conceptual hypotheses have been put forth to link association of COVID-19 with various chronic diseases such as periodontitis. Empirical evidence is still lacking to correlate the severity of COVID-19 with periodontal diseases. Objectives: This study was undertaken with an objective to correlate COVID severity in systemically healthy patients suffering from periodontal diseases. Materials and Methods: 44 systemically healthy patients of both genders with minimum of 20 teeth in their oral cavity in age range of 20 to 50 years suffering from periodontitis were recruited and categorised into four stages as per American Academy of Periodontology (AAP) 2017 classification for periodontitis. Serum C-reactive protein (CRP) levels and periodontal disease parameters of all the patients were measured. Because of COVID-19 and the nationwide lockdown, the dental practice was highly affected. With the help of self-designed online questionnaire information regarding COVID-19 infection and associated symptoms were recorded. Cases were categorized into five groups based on the World Health Organization clinical progression scale of COVID severity. Results: All the patients suffering from COVID disease in moderate and severe forms had increased probing pocket depth, clinical attachment level, and raised serum C-reactive protein levels as compared to patients who were uninfected or suffering from mild COVID disease and the results were statistically significant. Conclusion: Prioritisation and Implementation of periodontal treatment as a preventive measure for COVID-19 should be done. A positive correlation is observed between the severity of periodontitis and COVID-19.

Keywords: COVID-19, C-reactive protein, periodontal medicine, Periodontal inflamed surface area (PISA), severe acute respiratory syndrome coronavirus 2

How to cite this article:
Kalsi R, Ahmad Z, Siddharth M, Vandana KL, Arora SA, Saurav K. Correlation of COVID-19 with severity of periodontitis-A clinical and biochemical study. Indian J Dent Res 2022;33:307-12

How to cite this URL:
Kalsi R, Ahmad Z, Siddharth M, Vandana KL, Arora SA, Saurav K. Correlation of COVID-19 with severity of periodontitis-A clinical and biochemical study. Indian J Dent Res [serial online] 2022 [cited 2023 Feb 5];33:307-12. Available from: https://www.ijdr.in/text.asp?2022/33/3/307/367872



   Introduction Top


Periodontal medicine is a field of concern in the branch of periodontology. It is a bidirectional interaction between periodontitis and systemic conditions. Patients with periodontitis suffer with a low-grade systemic inflammatory state when compared with healthy counterparts. The bi-directional link between periodontal diseases and systemic conditions, such as diabetes mellitus, cardiovascular diseases; pregnancy along with lung diseases is well documented.[1]

The prevalence of periodontal disease is high ranging from 28% to 100% in various states and sets of population.[2] Research suggests that inflammatory mediators like C-reactive protein increase in tandem with increased pocket depth in patients with periodontal disease.[3] Serum CRP along with computed tomography are suggested as important tools in early predilection of severity of COVID-19.[4] Looking at the high prevalence of the periodontal disease and its chronic inflammatory nature, its association with COVID-19 has been hypothetized by various researchers.

To date, no study has been done in the literature to correlate periodontal disease with COVID-19 severity in patients without any comorbid conditions. Thus, this study was undertaken with an objective to find out the association of COVID severity in systemically healthy patients suffering from periodontal diseases.


   Materials and Methods Top


Study design and participants

After obtaining ethical clearance from the Institutional ethical committee (Ref. No. IEC/PERIO/3/19), forty-four systemically healthy patients of both genders suffering from periodontitis in the age range of 20 to 50 years were enrolled from the observational study wherein quantitative estimation serum CRP was carried out and was correlated with various forms of periodontal diseases as per AAP 2017 classification from October 2019 to February 2020 from ITS dental college, Greater Noida just before the first wave of COVID-19 hit India. Subjects with a minimum of 20 teeth in their oral cavity with radiographic evidence of bone loss were recruited and categorized into four stages as per severity and complexity of management criteria given by case definition of AAP 2017 classification.[5]

Pregnant or lactating women, patients with habits such as alcohol consumption, tobacco consumption in any form, those who have received periodontal therapy in last 6 months or taken NSAIDS, on immunosuppressants, or have taken antibiotics in last 1 month were not recruited for the study. Primary patient data obtained after taking due consent inclusive of body mass index (BMI), probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), periodontal inflamed surface area (PISA), and biochemical parameters of serum CRP was available from the observational study. PISA that connotes to systemic inflammatory burden was calculated by entering PPD and BOP readings in the software by the website: www.parsprototo.info. PISA was calculated in one step by entering this information of six sites per tooth in this downloadable excel-sheet.[6],[7] Because of COVID-19 and nationwide lockdown, clincial dental practice was highly affected. Patients were not able to get their required periodontal therapy up to the required levels. After COVID entry this study was initiated which was an extension of an observational study for which secondary data related to COVID infection and its severity was collected with the help of self-designed online questionnaire. Survey consisted of any incidence of COVID-19 with a confirmatory report of RT-PCR during or after lockdown obtained over electronic media. Data collected was before the mass vaccination for COVID started and none of the participants of the study were vaccinated with any COVID vaccine. About 60 patients were asked to dichotomously respond to the questions with symptoms of fever, sore throat, loss of taste, loss of smell, GI upset, headache, weakness SPO2 <90%, normal pulse, normal BP, need of hospitalisation, need of ICU, need of ventilator/life support out of which 44 responded to the questionnaire. Based on the data acquired, cases were categorized into five groups as uninfected, mild, moderate, severe, and dead based on WHO clinical progression scale.[8]

Statistical analysis

Multiple observations were analyzed by statistical tests for interpretation of results. Results were considered significant with P value ≤0.05. Chi-square test, one way ANOVA, and post hoc Bonferroni tests were used for statistical testing.


   Results Top


Out of 23 males selected for study 12 (80%) developed severe COVID disease whereas among 21 females only 3 (20%) developed severe COVID disease and the results were significant (0.012 S). 16.7% males and 83.3% female subjects from the cohort selected remained uninfected [Figure 1].
Figure 1: Demographical distribution of mean age and gender according to COVID disease severity

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The mean age of patients suffering from severe COVID disease was (40.33 ± 7.45) and those who were not affected were (29.83 ± 7.06) and the difference was highly significant (<0.001, HS) [Figure 1].

The percentage of patients suffering from severe COVID disease was least (8.3%) in stage 1 of periodontitis and was highest (62.5%) in stage 4 of periodontitis. Whereas out of eight patients tested positive in stage 1 of periodontitis, 7 had only mild disease. Out of total of 8 patients with stage 4 category of periodontitis, two remain uninfected, five developed severe form of COVID, and only one patient had moderate COVID disease [Figure 2].
Figure 2: Distribution of study population according to COVID severity & Periodontal disease severity

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Periodontal disease parameters, such as PI, GBI, CAL, PISA, and biochemical parameters, such as serum CRP increased significantly when severity of periodontal disease progressed from stage 1 to stage 4 periodontitis [Table 1].
Table 1: Intra Group comparison of periodontal, biochemical and histological parameters to severity of periodontal disease

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The highest BMI level in the uninfected COVID group is (22.43 ± 2.94) followed by severe (22.35 ± 1.55) and then moderate (21.20 ± 1.60) and in mild COVID group (22.02 ± 2.15). There was no significant difference (P < 0.822) in groups for BMI levels [Table 2].
Table 2: Periodontal, biochemical and histological parameters according to COVID disease severity

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The highest BOP levels in severe COVID group is (43.28 ± 19.92) followed by moderate (38.00 ± 27.71) then uninfected (29.36 ± 21.97) and in mild COVID group (25.02 ± 17.48). There was no significant difference (P < 0.103) in groups for BOP levels [Table 2].

The highest PPD levels in the severe COVID group is (5.68 ± 1.92) followed by moderate (5.21 ± 2.53) and then mild (3.38 ± 2.05) and in the uninfected COVID group (4.33 ± 2.30). There was a significant difference (P < 0.042) in groups for PPD levels [Table 2].

The highest CAL levels in the moderate COVID group is (6.24 ± 1.69) followed by severe (6.12 ± 1.99) then mild (3.28 ± 1.94) and in the uninfected COVID group (5.04 ± 2.61). There was a significant difference (P < 0.007) in groups for CAL levels [Table 2].

The highest PISA levels in severe COVID group is (19.92 ± 12.90) followed by moderate (14.67 ± 15.06), then mild (10.04 ± 11.06) and in uninfected COVID group (12.43 ± 13.33). There was no significant difference (P < 0.199) in groups for PISA levels [Table 2].

The highest CRP levels in the severe COVID group is (4.28 ± 2.07) followed by moderate (4.11 ± 3.07) then mild (2.13 ± 1.7) and in the uninfected COVID group (3.21 ± 2.09). There was significant difference (P < 0.049) in groups at CRP levels [Table 2].

In 62.5% of patients with stage 1 periodontal disease hospitalization was not required. The hospitalization required in stage 4 cases was maximum (83.3%) followed by 71.4% in stage 2 and 54.5% of stage 3 cases. A total of 19/32 cases were hospitalized which was not significant (p < 0.315) [Table 3].
Table 3: Association of need of hospitalisation and life support system with different severity levels of periodontal diseases

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87.5% patients with stage 1 periodontal disease recovered without any requirement of life support although in more than 50% cases with stage 2 and 4 of periodontal disease, life support was necessitated. A total of 13/32 periodontitis patients needed life support which was not significant (P < 0.291) [Table 3].


   Discussion Top


Hypothetically, various authors have suggested association between dental diseases with COVID-19 and looking at chronic inflammatory nature of periodontal disease it is prudent to link it with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection as with other comorbid states.

In the current study, a significantly higher percentage (80%) of males developed severe COVID disease unlike the females (20%). However, higher percentages (83.3%) of the females were uninfected as compared to males. The gender association of COVID-19 is conflicting and a meta-analysis reported that males are vulnerable to severe forms of COVID-19.[9] The current study observed that males are more affected by COVID-19 than females despite the absence of smoking as it is believed that smoking predisposes to COVID-19.[10]

Looking at the demographic distribution of study participants the mean age of the patients increased significantly from uninfected to severe COVID disease and the results are statistically significant. (<0.001, HS). The results are in coherence with the a recent research which reports age as a key determiner for pathogenesis and severity of COVID-19. It has been reported that age-associated impaired immune retaliation is accountable for increased vulnerability and adverse outcomes of COVID-19.[11]

Our study revealed that active periodontal disease in stage III and stage IV makes an individual prone and puts them at risk of developing COVID disease in moderate and severe forms even in absence of any comorbid condition. Studies at molecular levels suggest that angiotensin-converting enzyme-2 (ACE2) receptor expressed on various cells of human species act as first binding molecule for SARS CoV-2.[12]

In current study, majority of patients suffering from severe COVID were falling in categories of advanced stages 3 and 4 of periodontitis but statistically the difference was not significant. This possibly because of smaller sample size in each stage of periodontal disease but were clinically meaningful as when the comparisons were made between COVID severity and periodontal disease parameters statistically significant results were appreciated. Literature supports the relevance of clinical significance for a study; it states that this should also be monitored based on extent of change in clinical practice and possibility of its implementation. This is important for our study in particular as the research data available is limited and lacks verification on the basis of long term studies.[13]

According to AAP 2017 classification, both stage III and IV category of periodontitis is associated with deep periodontal pockets, attachment loss, and inflammaion.[5] It has been postulated that inflammatory diseases, such as periodontitis increases release of certain protease like furin and cathepsin L. These enzymes help in cleaving of SARS CoV-2 glycoproteins into its subunits facilitating initial adhesion of SARS CoV-2 onto ACE receptors.[14],[15] Similar results are reflected in our study population. While correlating COVID disease severity with periodontal disease parameters, it was seen that the mean probing pocket depth and clinical attachment levels of patients suffering from moderate and severe COVID disease were significantly higher than the mean values of uninflected individuals.

There was significant increase in serum CRP levels of patients when disease progressed from stage to stage 4 of periodontal disease. (P < 0.001) Similar trend of serum CRP level escalation was observed when comparisons were made between uninfected cases with that of mild moderate and severe COVID cases. (P < 0.049) It has been quoted that normal range of CRP in plasma is less than 3-mg per liter and it is stated that if it raises upto 10-mg per liter it does not have any significance clinically but it does puts an individual at risk of developing various systemic diseases like undesired cardiac events. Literature is available stating that serum CRP values increase in a same trend as the teeth with deeper pockets increases in the oral cavity in patients having chronic periodontitis.[3] This same holds true with COVID-19 when it takes place in patients with periodontal diseases as it has been reported that inflammatory markers, especially acute phase proteins like C Reactive Protein, IL-6 and ESR rise proportionally with the severity of COVID-19.[15]

In a retrospective study authors have suggested that CRP in severe COVID-19 patients increased significantly at the initiation of disease well before any CT findings are evident.[4] Our study gives us an valuable insight that liberated serum CRP levels in patients suffering from periodontal diseases can add on upon the systemic burden of circulating cytokines and thus can effect and alter the course progression and outcome of COVID-19. It has been documented that systemic burden of circulating CRP can be controlled with timely periodontal intervention.[16]

In our study, association between bleeding on probing and PISA with that of COVID disease severity was not significant though mean bleeding on probing and PISA scores have shown a gradual increase from uninfected to severe COVID illness on world health oraganization progression scale. PISA is an histological aspect of pocket lining which is inflamed, ulcerated with numerous foci showing necrotic changes micro-topographically which is clinically displayed as bleeding on provocation while probing.[17] This PISA can be presumed as a sum of area which has engorged blood vessels with colossal infiltration of inflammatory cells in connective tissue which is the mainstay of cytokine liberation and microbial infiltration in systemic circulation of patients with periodontitis.[6],[7] Mean PISA scores were highest in patients with severe COVID disease and were least in cases with mild COVID disease though the results were not statistically significant. This possibly may be because of smaller sample size that must have failed to yield any statistically significant values. Similarly bleeding on probing is an indicator of periodontal disease activity and the sites with positive on bleeding on probing reflects the progressing periodontal disease and presence of periodontopathic red complex of microbes.[18] In our study mean bleeding on probing was highest in severe COVID cases followed by mild and moderate cases which is suggestive of inflammatory response due to underlying periodontal disease.

No correlation was appreciated of BMI and COVID disease severity in our study which possibly because BMI was well within the normal range for all patients, i.e., between 18.5 and 24.[19] It has been suggested that obese patients in general have higher BMI with increased bulk of adipose tissue which possibly leads to decreased immunity and increased expression of ACE receptors in lungs which act as primary site for viral binding and explains early progression to severity of COVID in obese patients.[1]

In 62.5% of patients with stage 1 of periodontal disease hospitalization was not required and 87.5% of them recovered without any requirement of life support. The hospitalization required in stage 4 cases was maximum (83.3%). No case of fatality was reported in our study. It has been reported that mortality risks for COVID patients are higher in the periodontitis cases with associated comorbidity like diabetes mellitus, hypertension.[20] None of our subjects recruited were medically compromised.

Our study is the first to correlate COVID-19 with various stages of periodontal disease as per case definition of most recent AAP 2017 classification. In this study we have tried to quantify and correlate periodontitis disease in terms of PISA as this is the total surface area which is responsible for liberation of cytokines and expression of ACE2 receptors. This study gives an insight that advanced stages of periodontititis can be a contributing factor for increasing incidence and severity of COVID related symptoms even in absence of any comorbid conditions. Studies with larger sample size should be undertaken to strengthen the evidence.


   Conclusion Top


Our study suggests prioritization of periodontal health for systemic well-being of an individual. A positive correlation is found between severity of periodontal disease and COVID-19. Further studies with larger sample size should be undertaken to substantiate this association.

Acknowledgement

A special thanks to Dr Ruchi Nagpal, Professor, Department of Public Health Dentistry, Sudha Rustagi College of Dental Sciences and Research, Faridabad, Haryana for her expertise and assistance in statistical analysis for this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Correspondence Address:
Dr. Rupali Kalsi
Associate Professor, Department of Dentistry, Government Institute of Medical Sciences, Gautam Buddha Nagar, Uttar Pradesh - 201310
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdr.ijdr_1168_21

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