Periodontitis and COVID-19: Biological Mechanisms and Meta-analyses of Epidemiological Evidence

Abstract

Since the beginning of 2020, the entire global health care system has been severely challenged by the outbreak of coronavirus 2019 disease (COVID-19). Robust evidence has demonstrated a more severe course of COVID-19 in the presence of several comorbidities, such as cardiovascular diseases, diabetes mellitus, and obesity. Here, we critically appraise the recent research discoveries linking periodontitis to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to severe COVID-19, with a special focus on the associated biological mechanisms and the available epidemiological evidence. SARS-CoV-2 main receptors and coreceptors (ACE2, TMPRSS2, furin, CD147) are overexpressed in periodontal tissues of periodontitis patients, with inflammation, periodontal pathogens, and damage-induced pyroptosis triggering a positive feedback loop. However, meta-analyses of epidemiological studies only indicated a nonstatistically significant tendency for an increased risk of SARS-CoV-2 infection in subjects with periodontitis (odds ratio [OR] = 1.69; 95% CI, 0.91–3.13, P = 0.09). Furthermore, periodontitis may worsen clinical COVID-19 courses through multiple direct and indirect pathways, including damage to lower airways due to aspiration of periodontal pathogens, exacerbation of the cytokine storm via the low-grade chronic systemic inflammation, and SARS-CoV-2 dissemination through the ulcerated gingival epithelium with consequent induced pulmonary vessels vasculopathy. Indeed, meta-analyses of epidemiological studies indicated that periodontitis subjects are more likely to experience a more severe course of COVID-19. Specifically, periodontitis was associated with a 4-fold increased odds of hospitalization (OR = 4.72; 95% CI, 1.11–20.03, P = 0.04), 6-fold of requiring assisted ventilation (OR = 6.24; 95% CI, 2.78–14.02, P = 0.00), and more than 7-fold of death due to COVID-19 complications (OR = 7.51; 95% CI, 2.16–26.10, P = 0.00). The breakthrough analyzed here emphasizes the relevance of the mouth-systemic connection as a target to mitigate the current COVID-19 emergency and the future predicted coronavirus pandemics.

Association of periodontitis and COVID-19 – a narrative review

“…experience a more severe course of COVID-19. Specifically, periodontitis was associated with a 4-fold increase in the odds of hospitalization (OR = 4.72; 95% CI, 1.11-20.03; p = 0.04), 6-fold increase in requiring assisted ventilation (OR = 6.24; 95% CI, 2.78-14.02; p = 0.00), and a more than 7-fold increase in deaths due to COVID-19 complications (OR = 7.51; 95% CI, 2.16-26.10; p = 0.00) [14].…”

COVID and perio

“…2 The numbers of young carers are high, with a Barnado's report estimating there may be up to 700,000 young carers in the UK. 3 More locally, 907 young carers were identified through the 2020 Plymouth Young Carer School survey. 4 Of these, 522 (58%) were disadvantaged and 123 (14%) had an attendance of less than 90% at school due to caring responsibilities, which can vary considerably.…”

“…2 Meta-analyses of epidemiological studies have shown that patients with periodontitis are more likely to have a more severe course of COVID-19. 3 Current evidence suggests that this association can be explained by the direct role of periodontitis in exacerbating pulmonary infections and the indirect effect of periodontitis in triggering systemic inflammation and priming the immune system to increase the response to severe COVID-19 infection. 4 Mishra et al showed that the probability of developing severe COVID-19 was 2.81 times higher in patients with periodontitis.…”

Associations between Periodontitis, COVID-19, and Cardiometabolic Complications: Molecular Mechanisms and Clinical Evidence

“…Different reviews have indicated a series of possible shared risk factors such as aging, male sex, diabetes [ 3 , 4 , 50 ], hypertension and cardiovascular disease, coronary artery disease, atherosclerotic diseases, obesity [ 2 ], pregnancy, chronic obstructive pulmonary disease (COPD), smoking, asthma, HIV, cancer, oral dysbiosis, liver diseases, dementia, chronic kidney disease, Down syndrome, type A blood group, specific ethnic groups, physical disability/learning difficulty, and rheumatoid arthritis [ 77 , 88 , 89 ]. A very recent meta-analysis of epidemiological studies found that periodontal patients with COVID-19 have a four times higher risk of hospitalization, a six times higher risk of need for assisting ventilation, and seven times higher risk of death due to COVID-19 complications [ 90 ].…”