IADR Abstract Archives
Higher Periodontal Inflammation, ACE2, and IL-6 Expression in COVID-19 Subjects
Objectives: Our goal is to investigate the impact of periodontal disease on SARS-CoV-2 infection and chronicity. We examine the underlying molecular mechanism by measuring ACE2 and IL-6 expression in ex-vivo human gingiva, saliva, and cultured human oral keratinocytes (HOKs) infected with periodontitis-associated pathogens, P. gingivalis (Pg) and A.actinomycetemcomitans (Aa).
Methods: We performed comprehensive oral health examinations by assessing DMFS, bleeding on probing, and periodontal pocket depth (> 3mm) in COVID-19 positive and negative subjects (n=269 per group). Using RT-qPCR, we measured ACE2 and IL-6 expression in the following tissues/cells: (1) gingival biopsies collected from periodontally healthy and diseased subjects before pandemic (August 2017; n=6/group), (2) total RNA isolated from human saliva (adults with or without a history of SARS-CoV-2 infection), and (3) HOKs challenged with Aa and Pg (100 MOI), collected at different time points (12 hours and 36 hours post-challenge) for total RNA isolation. Statistical evaluations used multivariate analyses and ANOVA (p<0.0001, OR (CI=95%), and RR). For RT-qPCR data, we used Student’s t-test (p<0.05).
Results: We observed statistically significant (p<0.0001) association between COVID-19 positive and periodontal disease (PPD>3mm). In a pre-pandemic cohort, inflamed gingival tissue displayed a 30-fold increase in IL-6 and a 2.5-fold increase in ACE2 expression compared to healthy gingiva. Similarly, total RNA isolated from the saliva of adults with a history of SARS-CoV-2 infection (~3 months before saliva collection) showed an increase in ACE2 and IL-6 expression compared to healthy or COVID-19 negative adults. Finally, HOKs infected with Aa (but not Pg) showed a 6-fold and 2.5-fold increase in ACE-2 expression, respectively, at 12h and 36h post-infection.
Conclusions: SARS-CoV-2 infection correlates with poor periodontal health outcomes. Increased ACE2 and IL-6 expression in inflamed periodontal tissues, COVID-19(+) saliva, and Aa-infected HOK show that inflammation facilitates SARS-CoV-2 infection and exacerbates periodontal disease severity.
Methods: We performed comprehensive oral health examinations by assessing DMFS, bleeding on probing, and periodontal pocket depth (> 3mm) in COVID-19 positive and negative subjects (n=269 per group). Using RT-qPCR, we measured ACE2 and IL-6 expression in the following tissues/cells: (1) gingival biopsies collected from periodontally healthy and diseased subjects before pandemic (August 2017; n=6/group), (2) total RNA isolated from human saliva (adults with or without a history of SARS-CoV-2 infection), and (3) HOKs challenged with Aa and Pg (100 MOI), collected at different time points (12 hours and 36 hours post-challenge) for total RNA isolation. Statistical evaluations used multivariate analyses and ANOVA (p<0.0001, OR (CI=95%), and RR). For RT-qPCR data, we used Student’s t-test (p<0.05).
Results: We observed statistically significant (p<0.0001) association between COVID-19 positive and periodontal disease (PPD>3mm). In a pre-pandemic cohort, inflamed gingival tissue displayed a 30-fold increase in IL-6 and a 2.5-fold increase in ACE2 expression compared to healthy gingiva. Similarly, total RNA isolated from the saliva of adults with a history of SARS-CoV-2 infection (~3 months before saliva collection) showed an increase in ACE2 and IL-6 expression compared to healthy or COVID-19 negative adults. Finally, HOKs infected with Aa (but not Pg) showed a 6-fold and 2.5-fold increase in ACE-2 expression, respectively, at 12h and 36h post-infection.
Conclusions: SARS-CoV-2 infection correlates with poor periodontal health outcomes. Increased ACE2 and IL-6 expression in inflamed periodontal tissues, COVID-19(+) saliva, and Aa-infected HOK show that inflammation facilitates SARS-CoV-2 infection and exacerbates periodontal disease severity.