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 periodontal diseases and cardiovascular diseases, diabetes and respiratory diseases: Consensus report of the Joint Workshop by the European Federation of Periodontology (EFP) and the European arm of the World Organization of Family Doctors (WONCA Europe).

AIM: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles. MATERIALS AND METHODS: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors. CONCLUSIONS: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated.

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.

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.

Association of periodontal therapy, with inflammatory biomarkers and complications in COVID-19 patients: a case control study.

BACKGROUND: In previous studies, COVID-19 complications were reported to be associated with periodontitis. Accordingly, this study was designed to test the hypothesis that a history of periodontal therapy could be associated with lower risk of COVID-19 complications. METHODS: A case-control study was performed using the medical health records of COVID-19 patients in the State of Qatar between March 2020 and February 2021 and dental records between January 2017 and December 2021. Cases were defined as COVID-19 patients who suffered complications (death, ICU admissions and/or mechanical ventilation); controls were COVID-19 patients who recovered without major complications. Associations between a history of periodontal therapy and COVID-19 complications were analysed using logistic regression models adjusted for demographic and medical factors. Blood parameters were compared using Kruskal-Wallis test. RESULTS: In total, 1,325 patients were included. Adjusted odds ratio (AOR) analysis revealed that non-treated periodontitis was associated with significant risk of need for mechanical ventilation (AOR = 3.91, 95% CI 1.21-12.57, p = 0.022) compared to periodontally healthy patients, while treated periodontitis was not (AOR = 1.28, 95% CI 0.25-6.58, p = 0.768). Blood analyses revealed that periodontitis patients with a history of periodontal therapy had significantly lower levels of D-dimer and Ferritin than non-treated periodontitis patients. CONCLUSION: Among COVID-19 patients with periodontal bone loss, only those that have not received periodontal therapy had higher risk of need for assisted ventilation. COVID-19 patients with a history of periodontal therapy were associated with significantly lower D-dimer levels than those without recent records of periodontal therapy. CLINICAL RELEVANCE: The fact that patients with treated periodontitis were less likely to suffer COVID-19 complications than non-treated ones further strengthen the hypothesis linking periodontitis to COVID-19 complications and suggests that managing periodontitis could help reduce the risk for COVID-19 complications, although future research is needed to verify this.

Does periodontitis influence the risk of COVID-19? A scoping review.

OBJECTIVE: Research has shown that the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly influences the oral microbiome to expedite systemic diseases by invading harmful oral pathogens near and distant organs. To identify, explore, and map the possible mechanisms underlying periodontitis in severe coronavirus disease 2019 (COVID-19) cases. MATERIAL AND METHODS: Relevant articles published from December 2019 to February 2022 were identified and screened using keywords and inclusion criteria from various databases. RESULTS: This review sheds light on multiple pathways of periodontitis, the spread of periodontal infection and microbial metabolites to the lungs, and the dysregulated immune system with elevated cytokines, reactive oxygen species generation, nuclear DNA damage, and senescence, which have the potential to promote stronger viral attachment to host cells and the onset of COVID-19 manifestation with increased severity and risk of mortality. In addition, the cytokine connection to SARS-CoV-2, T-cell responses against periodontitis, its connection with COVID-19, the role of host factors, and periodontal therapy have been discussed. CONCLUSIONS: The relationship between COVID-19 and periodontitis needs further investigation along with the development of alternative therapies to prevent periodontitis for better management and control of COVID-19.

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.

Periodontitis and coronavirus disease 2019.

The coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 is usually a mild condition; however, in some cases it can result in severe sickness and even death. Thus, understanding the reasons behind these grave outcomes is of great importance. Coronavirus disease 2019 and periodontitis share some intriguing characteristics. They can both lead to systemic inflammation and alterations of coagulation pathways, and both share confounding factors, such as diabetes, hypertension, and obesity. Accordingly, a possible association between these conditions has been hypothesized in the literature. The objective of this review was to evaluate the scientific evidence linking these diseases and the possible underlying mechanisms. Evidence has shown that coronavirus disease 2019 presents oral manifestations and can even affect periodontal tissues. Moreover, some studies have shown a possible association between coronavirus disease 2019 severity and the presence of periodontitis. Current evidence suggests that this association could be explained through the direct role of periodontal bacteria in aggravating lung infections, as well as through the indirect effect of periodontitis in inducing systemic inflammation and priming of the immune system to an exacerbated reaction to severe acute respiratory syndrome coronavirus 2 infection. Future research is needed to confirm these observations and explore the possible role that periodontal care might play in the coronavirus disease 2019 pandemic.

Periodontitis as an inflammatory trigger in hypertension: From basic immunology to clinical implications.

Hypertension and periodontitis are both highly prevalent co-morbidities worldwide, and their occurrence increases with age. Multiple observational epidemiological studies have shown that periodontitis is associated with an increased cardiovascular disease (CVD) occurrence. Large systematic reviews and metanalyses further show that periodontitis increases the risk of hypertension and is associated with increased systolic and diastolic blood pressure. Genetic and clinical evidence, utilizing mendelian randomization and randomized clinical trials, support the causal role of periodontitis in hypertension. The mechanisms of this link remain unclear. Critical components of immune and inflammatory pathogenesis of periodontitis considerably overlap with immune mechanisms of hypertension. Clinical studies support that both C-reactive protein (CRP) levels and white blood cell counts (WBC) mediate the relationship between periodontal disease and high blood pressure. In particular, activation of Th1, Th17, T regulatory cells, and proinflammatory monocytes has been shown to be essential in both conditions. Immunosenescent dysregulated CD28null T cells have been implicated, along with key effector cytokines such as interleukin 6 (IL-6), TNF-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin 17 (IL-17). A better understanding of the relationships between hypertension and periodontitis is essential not only for possible utilization of this knowledge for a non-pharmacological approach to improving blood pressure control. It may also provide valuable pathogenetic clues linking inflammation and hypertension, which has become particularly relevant in the light of links between hypertension and autoimmune disorders or, more recently, COVID-19.

A case-control study on the association between periodontitis and coronavirus disease (COVID-19).

BACKGROUND: Coronavirus disease (COVID-19) and periodontitis share common characteristics, such as an exaggerated inflammatory response. As periodontal diseases were shown to be associated with respiratory diseases, such as pneumonia, it is quite possible that a relationship may exist between periodontitis and COVID-19. Hence, the aim of the present study was to determine whether periodontitis and poor oral hygiene are associated with COVID-19. METHODS: A case-control study was conducted. Patients who had positive real-time reverse transcription polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were included in the case group (n = 79), and patients with negative results were included in the control group (n = 71). The periodontal examination involved recording the plaque scores, calculus scores, tooth mobility, gingival bleeding, probing depth, recession, and clinical attachment level (CAL). RESULTS: Logistic regression analysis showed significant associations of mean plaque scores ≥ 1 (odds ratio (OR), 7.01; 95% confidence interval (CI), 1.83 to 26.94), gingivitis (OR, 17.65; 95% CI, 5.95 to 52.37), mean CAL ≥ 2 mm (OR, 8.46; 95% CI, 3.47 to 20.63), and severe periodontitis (OR, 11.75; 95% CI, 3.89 to 35.49) with COVID-19; these findings were more prevalent in the case group. CONCLUSION: Based on the above mentioned observations, it can be concluded that there is an association between periodontitis severity and COVID-19. Gingival bleeding and dental plaque accumulation are also more frequent among COVID-19 patients. Hence, it is essential to maintain periodontal health and good oral hygiene as an important measure for COVID-19 prevention and management.

Active matrix metalloproteinase-8 (aMMP-8) point-of-care test (POCT) in the COVID-19 pandemic.

INTRODUCTION: Active matrix metalloproteinase (aMMP)-8 utilized in point-of-care testing (POCT) is regarded as a potential biomarker for periodontal and peri-implant diseases. Various host and microbial factors eventually influence the expression, degranulation, levels and activation of aMMP-8. The type of oral fluids (saliva, mouthrinse, gingival crevicular, and peri-implant sulcular fluids [GCF/PISF], respectively) affect the analysis. AREAS COVERED: With this background, we aimed to review here the recent studies on practical, inexpensive, noninvasive and quantitative mouthrinse and GCF/PISF chair-side POCT lateral flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyzer) and how they help to detect, predict, monitor the course, treatment and prevention of periodontitis and peri-implantitis. The correlations of aMMP-8 POCT to other independent and catalytic activity assays of MMP-8 are also addressed. EXPERT OPINION: The mouthrinse aMMP-8 POCT can also detect prediabetes/diabetes and tissue destructive oral side-effects due to the head and neck cancers' radiotherapy. Chlorhexidine and doxycycline can inhibit collagenolytic human neutrophil and GCF aMMP-8. Furthermore, by a set of case-series we demonstrate the potential of mouthrinse aMMP-8 POCT to real-time/online detect periodontitis as a potential risk disease for coronavirus disease 2019 (COVID-19). The clinical interdisciplinary utilization of aMMP-8 POCT requires additional oral, medical, and interdisciplinary studies.

Is periodontitis associated with the severity of COVID-19?

Data sources The national electronic health records of the Hamad Medical Corporation (HMC) in the State of Qatar.Data extraction and synthesis This case-control study included 568 patients from the HMC electronic database for data eliciting from 27 February 2020 to 31 July 2020. Patients with coronavirus disease 2019 (COVID-19) complications were considered as cases. Controls were defined as COVID-19 patients without major complications (discharged). Multivariate logistic regression was performed to assess the association between the exposures (periodontitis, demographics and medical conditions) and outcomes (COVID-19 complications). The association was adjusted for possible confounding factors. Additionally, sensitivity analyses were performed to account for stronger risk factors of the determined complications. The results were reported using the odds ratio (OR) and 95% confidence intervals (CIs). Laboratory data (blood parameters concerning the course of COVID-19) were also compared between the case and control groups.Results The patients were divided into 40 cases and 528 controls. Among the patients with periodontitis, 12.8% (33/258) went through COVID-19 complications, whereas 2.2% (7/310) of those without periodontitis experienced complications. The adjusted OR of patients with periodontitis was 3.67 (95% CI 1.46-9.27) for all COVID-19 complications, 8.81 (95% CI 1.00-77.7) for death, 3.54 (95% CI 1.39-9.05) for intensive care unit admission and 4.57 (95% CI 1.19-17.4) for the need of assisted ventilation. After conducting subgroup analyses for age, diabetes and smoking, periodontitis was still significantly associated with all the outcomes. Laboratory biomarkers (haemoglobin A1c, white blood cells and C-reactive protein) had higher levels in COVID-19 patients with periodontitis than those without periodontal disease.Conclusions This study concluded that periodontitis was significantly associated with higher risks of COVID-19 complications and higher blood marker levels. These results, however, are not of high quality and further research in this regard is required.

Nexus between COVID-19 and periodontal disease.

Over the past several decades, studies have demonstrated the existence of bi-directional relationships between periodontal disease and systemic conditions. Periodontitis is a polymicrobial and multifactorial disease involving both host and environmental factors. Tissue destruction is primarily associated with hyperresponsiveness of the host resulting in release of inflammatory mediators. Pro-inflammatory cytokines play a major role in bacterial stimulation and tissue destruction. In addition, these cytokines are thought to underlie the associations between periodontitis and systemic conditions. Current research suggests that increased release of cytokines from host cells, referred to as the cytokine storm, is associated with disease progression in patients with coronavirus disease 2019 (COVID-19). An intersection between periodontitis and pulmonary disease is biologically plausible. Hence, we reviewed the evidence linking COVID-19, cytokines, and periodontal disease. Plaque control is essential to prevent exchange of bacteria between the mouth and the lungs, reducing the risk of lung disease. Understanding these associations may help identify individuals at high risk and deliver appropriate care at early stages.

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.

Periodontal disease and targeted prevention using aMMP-8 point-of-care oral fluid analytics in the COVID-19 era.

Periodontal disease is a chronic multifactorial infectious and inflammatory disease associated with several chronic systemic diseases, such as diabetes, cardiovascular diseases (CVD), chronic obstructive pulmonary disease, hypertension, Alzheimer's disease and so on. These same systemic diseases have been associated with severe COVID-19 infections. Several recent studies have suggested hypotheses for the potential association between periodontal disease and severe COVID-19. Periodontal disease is also one of the most prevalent diseases globally. All this supports the importance of good oral health, also in the COVID-19 era. Thus, new strategies and approaches to identify patients at risk of periodontal disease could be beneficial to enhance secondary prevention, especially if targeted to COVID-19 risk groups. Diagnostic biomarkers for periodontal disease have been researched extensively. Potential biomarkers in oral fluid with currently available rapid non-invasive point-of-care technology, such as aMMP-8, could help to extend screening and identification of patients at risk for periodontal disease also to situations and places where professional dental expertise and equipment are limited or unavailable. i.e., nursing and care homes, and rural and distant places. The oral fluid point-of-care technologies could also be useful in the hands of medical professionals (diabetes, CVD, etc.) to identify patients at risk for undiagnosed periodontal disease and to refer them to a dentist for examination and evaluation. Finally, if there is a causality between periodontal disease and severe COVID-19 infections, these point-of-care oral fluid biomarker technologies could possibly also help in the assessment of the risk of deterioration and complications.

COVID-19 & Periodontitis: The cytokine connection.

COVID-19 is now recognized as a pandemic throughout the world, leading to a scramble in order to gather knowledge as well as evidence regarding the 'novel' corona virus which causes this disease. Chemokines are a family of cytokines which are chemotactic in nature and cause the recruitment of cells of inflammation. Periodontitis has long been attributed to having its pathophysiology rooted in a cytokine response. The recent COVID-19 pandemic has been reported to have adverse outcomes related to the establishment of a cytokine storm, many of the components of which are common with the cytokine expression profile of periodontitis. This communication explores the connection between COVID-19 and periodontal disease through their cytokine connection to form a translational basis for recommending maintenance of oral hygiene in the COVID era and to red flag patients with periodontitis as having an increased risk of exhibiting COVID related adverse outcomes.