Oral and systemic health: is there a "new" link with COVID-19?

OBJECTIVES: The objective of the present narrative review was to evaluate the evidence of a possible association between periodontitis and COVID-19, and its biological plausibility, using as models the potential associations with cardiovascular diseases, diabetes, and some respiratory diseases. METHODS: A recent systematic review was used as main reference to explore the associations of periodontitis with different respiratory diseases, including COVID-19, following two focussed questions: a PECOS question, aimed to explore epidemiological evidence, and a PICOS question, designed to explore the evidence derived from intervention studies. In addition to that evidence, other relevant scientific documents, including consensus papers, were carefully selected and appraised. FINDINGS: Convincing evidence was found to support the association of periodontitis and cardiovascular diseases, diabetes, and some respiratory diseases. The biological plausibility behind those associations is based on four factors: (1) bacteraemia of oral bacteria and periodontal pathogens, (2) increased systemic inflammation, (3) common genetic factors, and (4) common environmental risk factors. Limited initial evidence is available to support an association between periodontitis and COVID-19 complications. Among the proposed factors to explain the suggested association, a combination of the previously mentioned factors, plus additional factors related with SARS-CoV-2 characteristics and pathogenicity, has been suggested. CONCLUSIONS: Initial evidence suggests that periodontitis may be associated with a more severe COVID-19 and with a higher risk of death due to COVID-19. CLINICAL RELEVANCE: Due to the possible association between periodontitis and an increased severity for COVID-19, additional efforts should be made to improve oral and periodontal health, including the promotion of oral healthy habits, such as oral hygiene.

Association between severity of COVID-19, Periodontal health and disease in Riyadh subpopulation.

Background: Periodontitis and coronavirus disease (COVID-19) both exhibit an exaggerated inflammatory response as common traits. Given that periodontal diseases have been linked to respiratory illnesses like pneumonia, it is quite possible that periodontitis and COVID-19 are related. Therefore, the purpose of the current study was to ascertain whether the severity of COVID-19 and periodontal disease are related. Methods: A retrospective study was done using the 3 years of patients' medical and dental records in the University Hospital. A telephone interview was employed to estimate the severity of symptoms got through COVID-19 infection. The data obtained were subjected to statistical analysis. The Chi-square test, with statistical significance set at 0.05, was used to determine the relationship between the severity of periodontal disease and the severity of COVID-19. Results: It was seen that there was a strong relationship between the severities of COVID-19 disease and periodontal disease. The mildest gingivitis cases (63%), Stage 1 periodontitis (62.9%), were associated with the COVID-19-negative group, whereas the most severe gingivitis cases (85.7%), Stage 4 periodontitis group (66.66%), were associated with COVID-19-positive group. In comparison to those without periodontitis, patients with periodontitis had a 1.54 times higher risk of COVID-19 complications (P = 0.048). Patients who had comorbidities were 2.49 times to have COVID-19 complications (P = 0.02). Conclusion: The observations presented above lead to the conclusion that COVID-19 and periodontal disease severities are related. Understanding the potential association between periodontitis and COVID-19 through systemic inflammation could be a means of achieving a high-quality medical care. To validate the findings, additional research with larger samples is required.

Periodontitis and COVID-19: Immunological Characteristics, Related Pathways, and Association.

Both periodontitis and Coronavirus disease 2019 (COVID-19) pose grave threats to public health and social order, endanger human life, and place a significant financial strain on the global healthcare system. Since the COVID-19 pandemic, mounting research has revealed a link between COVID-19 and periodontitis. It is critical to comprehend the immunological mechanisms of the two illnesses as well as their immunological interaction. Much evidence showed that there are many similar inflammatory pathways between periodontitis and COVID-19, such as NF-κB pathway, NLRP3/IL-1ß pathway, and IL-6 signaling pathway. Common risk factors such as gender, lifestyle, and comorbidities contribute to the severity of both diseases. Revealing the internal relationship between the two diseases is conducive to the treatment of the two diseases in an emergency period. It is also critical to maintain good oral hygiene and a positive attitude during treatment. This review covers four main areas: immunological mechanisms, common risk factors, evidence of the association between the two diseases, and possible interventions and potential targets. These will provide potential ideas for drug development and clinical treatment of the two diseases.

Association between periodontitis and COVID-19 infection: a two-sample Mendelian randomization study.

Background and Objective: Epidemiological studies report associations between coronavirus disease 2019 (COVID-19) and periodontitis; however, causality has not been proven. The aim of this study is to assess the associations between COVID-19 susceptibility and periodontitis with two-sample Mendelian randomization (MR) analyses. Methods: A two-sample summary MR analysis was performed using data for outcome and exposure from the OpenGWAS database on people of European descent. Periodontal complex traits (PCTs) were chosen as a proxy for the periodontitis phenotype. The causal association between PCT3 (Aggregatibacter actinomycetemcomitans), PCT5 (Porphyromonas gingivalis), and gingival crevicular fluid (GCF) interleukin-1ß (IL-1ß) and COVID-19 were considered. Genome-wide association study (GWAS) data with the two largest sample sizes were selected as COVID-19 outcomes (datasets ebi-a-GCST010776 and ebi-a-GCST010777). Single-nucleotide polymorphisms (SNPs) associated with PCT3, PCT5, and GCF IL-1ß at statistical significance at genome-wide level (P < 5 × 10-8) were identified as genetic instruments. We used two-sample summary MR methods and tested the existence of a pleiotropic effect with MR-Egger. Results: Inverse-variance weighted (IVW) estimates showed that there was a positive association between COVID-19 risk and periodontitis (ebi-a-GCST010776: odds ratio [OR] = 1.02 (95% confidence interval (CI), 1.00-1.05), P = 0.0171; ebi-a-GCST010777: OR = 1.03 (95% CI, 1.00-1.05), P = 0.0397). The weighted median also showed directionally similar estimates. Exploration of the causal associations between other PCTs and COVID-19 identified a slight effect of local inflammatory response (GCF IL-1ß) on COVID-19 risk across the two datasets (ebi-a-GCST010776: IVW OR = 1.02 (95% CI, [1.01-1.03]), P < 0.001; ebi-a-GCST010777: IVW OR = 1.03 (95% CI, [1.02-1.04]), P < 0.001). The intercepts of MR-Egger yielded no proof for significant directional pleiotropy for either dataset (ebi-a-GCST010776: P = 0.7660; ebi-a-GCST010777: P = 0.6017). Conclusions: The findings suggests that periodontitis and the higher GCF IL-1ß levels is causally related to increase susceptibility of COVID-19. However, given the limitations of our study, the well-designed randomized controlled trials are needed to confirm its findings, which may represent a new non-pharmaceutical intervention for preventing COVID-19.

The association between respiratory diseases and periodontitis: A systematic review and meta-analysis.

AIM: To evaluate (1) whether periodontitis has an influence on the prevalence/incidence of respiratory diseases (chronic obstructive pulmonary disease [COPD], asthma, community-acquired pneumonia [CAP], obstructive sleep apnoea [OSA] and COVID-19), and (2) what is the impact of periodontal therapy on the onset or progression of respiratory diseases. MATERIALS AND METHODS: An electronic search was performed on Pubmed, Cochrane Library and Scopus databases up to October 2021, to identify studies answering the PECOS and PICOS questions. RESULTS: Seventy-five articles were selected. Meta-analyses identified statistically significant associations of periodontitis with COPD (nstudies  = 12, odds ratio [OR] = 1.28, 95% confidence interval [CI] [1.16; 1.42], p < .001), and OSA (ns  = 6, OR = 1.65, 95% CI [1.21; 2.25], p = .001), but not for asthma (ns  = 9, OR = 1.53, 95% CI [0.82; 2.86], p = .181). For acute conditions, two studies were found for CAP, while for COVID-19, significant associations were found for the need of assisted ventilation (ns  = 2, OR = 6.24, 95% CI [2.78; 13.99], p < .001) and COVID-related mortality (ns  = 3, OR = 2.26, 95% CI [1.36, 3.77], p = .002). Only four intervention studies were found, showing positive effects of periodontal treatment on COPD, asthma and CAP. CONCLUSIONS: A positive association between periodontitis and COPD, OSA and COVID-19 complications has been found, while there is a lack of intervention studies.

A pilot clinical and radiographic study on the association between periodontitis and serious COVID-19 infection.

BACKGROUND: During the pandemic of COVID-19, the scientific community tried to identify the risk factors that aggravate the viral infection. Oral health and specifically periodontitis have been shown to have a significant impact on overall health. Current, yet limited, evidence suggests a link between periodontal status and severity of COVID-19 infection. OBJECTIVES: The present pilot study aimed to assess whether younger patients (≤60 years) that have been hospitalized in the intensive care unit (ICU) for severe COVID-19 infection were susceptible to severe periodontitis. MATERIAL AND METHODS: All dentate patients ≤60 years of age diagnosed with COVID-19 and surviving hospitalization in the ICU were considered for inclusion. Susceptibility to periodontitis was determined by assessing radiographic bone loss (RBL) in recent dental radiographs (posterior bitewings, periapical, and panoramic X-rays). RBL in % was obtained from the most affected tooth and patients were classified into: Stage I, RBL ≤ 15%; Stage II, RBL = 15%-33% and Stage III/IV, RBL ≥ 33%. The grade was defined using the RBL to age ratio on the most severely affected tooth. Patients were attributed to: Grade A, ratio <0.25; Grade B, ratio 0.25-1 and Grade C, ratio >1. Patients classified into Stage III/IV and Grade C were considered highly susceptible to periodontitis. RESULTS: Of 87 eligible patients, 30 patients were finally assessed radiographically and/or clinically; from the remaining 57 patients, 16 refused participation for various reasons and 41 could not be reached. Based on the radiographic assessment, all patients were periodontally compromised. Half of them were classified with Stage III/IV and Grade B or C; 26.7% were classified with Stage III/IV and Grade C. CONCLUSIONS: The present pilot study showed that about half of the patients suffering from severe forms of COVID-19 infection in need of ICU admission suffered also from severe periodontitis, and about one-fourth of them were highly susceptible to it.

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

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.

Interconnection of periodontal disease and comorbidities: Evidence, mechanisms, and implications.

Periodontitis, a microbiome-driven inflammatory disease of the tooth-attachment apparatus, is epidemiologically linked with other disorders, including cardio-metabolic, cognitive neurodegenerative and autoimmune diseases, respiratory infections, and certain cancers. These associations may, in part, be causal, as suggested by interventional studies showing that local treatment of periodontitis reduces systemic inflammation and surrogate markers of comorbid diseases. The potential cause-and-effect connection between periodontitis and comorbidities is corroborated by studies in preclinical models of disease, which additionally provided mechanistic insights into these associations. This overview discusses recent advances in our understanding of the periodontitis-systemic disease connection, which may potentially lead to innovative therapeutic options to reduce the risk of periodontitis-linked comorbidities.

The clinical association between Periodontitis and COVID-19.

OBJECTIVES: The study aimed to clinically assess the association between periodontitis and COVID-19-related outcomes. MATERIAL AND METHODS: Data pertaining to patient demographics, medical history, blood parameters, periodontal clinical examination and aMMP-8 point-of-care diagnostics (both site-level and patient-level) was recorded for eighty-two COVID-19-positive patients. COVID-19-related outcomes such as COVID-19 pneumonia, death/survival, types of hospital admission and need of assisted ventilation were also assessed. RESULTS: Males were predominantly afflicted with COVID-19, with advanced age exhibiting a greater association with the presence of periodontitis. Higher severity of periodontitis led to 7.45 odds of requiring assisted ventilation, 36.52 odds of hospital admission, 14.58 odds of being deceased and 4.42 odds of COVID-19-related pneumonia. The aMMP-8 mouthrinse kit was slightly more sensitive but less specific than aMMP-8 site-specific tests. CONCLUSIONS: Based on the findings of the present study, periodontitis seems to be related to poorer COVID-19-related outcomes. However, within the constraints of this work, a direct causality may not be established. Periodontitis, by means of skewing the systemic condition for a number of comorbidities, may eventually influence COVID-19 outcomes in an indirect manner. CLINICAL RELEVANCE: The study is the first to clinically, and by means of a validated point-of-care diagnostic methodology, assess the association between periodontal health and COVID-19-related outcomes. Assessment of the periodontal status of individuals can aid in the identification of risk groups during the pandemic along with reinforcing the need to maintain oral hygiene and seeking periodontal care.

Interruption of regular dental visits during the COVID-19 pandemic due to concerns regarding dental visits was associated with periodontitis in Japanese office workers.

OBJECTIVE: To investigate the interrelationships among concerns regarding dental visits, the status of regular dental visits, and periodontal health during the coronavirus disease 2019 (COVID-19) pandemic. BACKGROUND: Continuous oral health care and regular dental visits are important for maintaining periodontal health. Due to the possibility of contracting COVID-19, individuals have been reluctant to visit medical institutions. It is unclear how the periodontal health of the Japanese population has been affected by the interruption of regular dental visits during the COVID-19 pandemic and how concerns regarding dental visits have affected attendance at regular dental visits. METHODS: This study included 199 Japanese office workers in one municipal office at Fukuoka Prefecture, Japan (average age = 42.6 years; age range = 19-77 years; 123 men and 76 women). Periodontitis was defined based on a full-mouth periodontal examination. The status of regular dental visits during the COVID-19 pandemic and concerns regarding dental visits were obtained via questionnaire. We tested the hypothesis that concerns regarding dental visits would indirectly affect periodontal health through the interruption of regular dental visits during the COVID-19 pandemic. We used mediation analysis, in which concerns regarding dental visits (present or absent) were set as the exposure, periodontitis (present or absent) was set as the outcome, and the status of regular dental visits (continued during the COVID-19 pandemic or not) was set as the mediator. RESULTS: Of the 199 study participants, 108 had a habit of attending regular dental visits. Of these, 31 (28.7%) discontinued regular dental visits during the COVID-19 pandemic. Compared to the individuals who continued regular dental visits, those who discontinued regular dental visits had a higher prevalence of periodontitis (49.4% vs 77.4%, p < 0.05) and concerns regarding dental visits (22.1% vs 64.5%, p < 0.05). Discontinuing regular dental visits significantly mediated the association between concerns regarding dental visits and periodontitis (natural indirect effect: odds ratio = 1.68, 95% confidence interval = 1.02-2.79, proportion mediated = 64.3%). CONCLUSION: The study results showed that individuals who discontinued regular dental visits during the COVID-19 pandemic due to concerns regarding dental visits had relatively poor periodontal health.

Dyslipidemia and severe periodontitis among patients with type 2 diabetes.

Not available.

Association between periodontitis and severity of COVID-19 infection: A case-control study.

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.

Does COVID-19 Affect Periodontal and Peri-Implant Diseases?

COVID-19 has imposed tremendous burden on the healthcare systems and healthcare professionals worldwide. As periodontitis and peri-implantitis are chronic diseases, regular recall visits play a critical role in management of these conditions; however, the current situation may stop patients from attending their regular maintenance. Therefore, it may be necessary to reconsider and revise the treatment protocols.