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.

Periodontal disease and COVID-19: Prognosis and potential pathways of association in their pathogenesis.

Objective: The objective of this narrative review is to determine if periodontal disease is a factor in the development of a poor prognosis for COVID-19. Method: A bibliographic search was conducted in PubMed, Virtual Health Library, Google Scholar, and in the databases of Science Direct, Scopus, Lilacs, Bireme, Scielo, and Web of Science, using the following keywords: "COVID-19," "SARS-CoV-2," and "periodontal diseases." Results: Fifty-six records were retrieved from the database searches. After screening, 39 articles were selected for study: 13 reviews, 2 case-control studies, 1 systematic review, 8 letters to the editor, 2 cohort studies, 1 thesis, 7 hypotheses, 1 short communication, 3 commentaries, and 1 scoping review. Discussion: Both periodontal disease and COVID-19 produce an inflammatory response. This immune response generates an over-production of inflammatory cytokines that can harm overall health. Conclusion: The mouth serves as the entryway for many microorganisms that can harm health in general, among them SARS-CoV-2. It is important to maintain good oral health to lower the inflammatory load present in periodontal disease, lessening the possibility of complications from COVID-19.

Objectif: L'objectif de cette revue narrative est de déterminer si la maladie parodontale est un facteur dans le développement d'un mauvais pronostic de la COVID-19. Méthodologie: Une recherche bibliographique a été effectuée dans PubMed, la bibliothèque virtuelle de la santé, Google Scholar, et dans les bases de données de Science Direct, Scopus, Lilacs, Bireme, Scielo, et Web of Science, en utilisant les mots-clés suivants : « COVID-19 ¼, « SRAS-CoV-2 ¼ et « maladie parodontale ¼ (en anglais). Résultats : Cinquante-six dossiers ont été extraits à partir des recherches dans les bases de données. Après la sélection, 39 articles ont été choisis pour l'étude : 13 revues, 2 études cas-témoins, 1 revue systématique, 8 lettres à l'éditeur, 2 études de cohorte, 1 thèse, 7 hypothèses, 1 courte communication, 3 commentaires et 1 examen de la portée. Discussion: La maladie parodontale et la COVID-19 produisent toutes deux une réponse inflammatoire. Cette réponse immunitaire produit une surproduction de cytokines inflammatoires qui peuvent nuire à la santé globale. Conclusion: La bouche sert de voie d'entrée à de nombreux micro-organismes qui peuvent nuire à la santé en général, parmi lesquels le SRAS-CoV-2. Il est important de préserver une bonne santé buccodentaire pour diminuer la charge inflammatoire présente dans la maladie parodontale, réduisant ainsi la possibilité de complications de la 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.

Periodontal disease increases the host susceptibility to COVID-19 and its severity: a Mendelian randomization study.

BACKGROUND: Emerging evidence shows that periodontal disease (PD) may increase the risk of Coronavirus disease 2019 (COVID-19) complications. Here, we undertook a two-sample Mendelian randomization (MR) study, and investigated for the first time the possible causal impact of PD on host susceptibility to COVID-19 and its severity. METHODS: Summary statistics of COVID-19 susceptibility and severity were retrieved from the COVID-19 Host Genetics Initiative and used as outcomes. Single nucleotide polymorphisms associated with PD in Genome-wide association study were included as exposure. Inverse-variance weighted (IVW) method was employed as the main approach to analyze the causal relationships between PD and COVID-19. Three additional methods were adopted, allowing the existence of horizontal pleiotropy, including MR-Egger regression, weighted median and weighted mode methods. Comprehensive sensitivity analyses were also conducted for estimating the robustness of the identified associations. RESULTS: The MR estimates showed that PD was significantly associated with significantly higher susceptibility to COVID-19 using IVW (OR = 1.024, P = 0.017, 95% CI 1.004-1.045) and weighted median method (OR = 1.029, P = 0.024, 95% CI 1.003-1.055). Furthermore, it revealed that PD was significantly linked to COVID-19 severity based on the comparison of hospitalization versus population controls (IVW, OR = 1.025, P = 0.039, 95% CI 1.001-1.049; weighted median, OR = 1.030, P = 0.027, 95% CI 1.003-1.058). No such association was observed in the cohort of highly severe cases confirmed versus those not hospitalized due to COVID-19. CONCLUSIONS: We provide evidence on the possible causality of PD accounting for the susceptibility and severity of COVID-19, highlighting the importance of oral/periodontal healthcare for general wellbeing during the pandemic and beyond.

COVID-19 Pandemic and Periodontal Practice: The Immunological, Clinical, and Economic Points of View.

The recent global health problem, COVID-19, has had far-reaching impacts on lifestyles. Although many effective WHO-approved vaccines have been produced that have reduced the spread and severity of the disease, it appears to persist in humans for a long time and possibly forever as everyday it turns out to have new mutations. COVID-19 involves the lungs and other organs primarily through cytokine storms, which have been implicated in many other inflammatory disorders, including periodontal diseases. COVID-19 is in a close association with dental and periodontal practice from two respects: first, repeated mandatory lockdowns have reduced patient referrals to dentists and limited the dental and periodontal procedures to emergency treatments, whereas it is important to recognize the oral manifestations of COVID-19 as well as the influence of oral and periodontal disease on the severity of COVID-19. Second, dentistry is one of the high-risk professions in terms of close contact with unmasked individuals, necessitating redefining the principles of infection control. The pressures of the economic recession on patients as well as dentists add to the difficulty of resuming elective dental services. Therefore, this study is divided into two parts corresponding to what mentioned above: the first part examines the clinical and immunological associations between COVID-19 and periodontal and oral diseases, and the second part delineates the measures needed to control the disease transmission in dental clinics as well as the economic impact of the pandemic era on dental services.

Periodontal Diseases: Major Exacerbators of Pulmonary Diseases?

Periodontal diseases are a range of polymicrobial infectious disorders, such as gingivitis and periodontitis, which affect tooth-supporting tissues and are linked to playing a role in the exacerbation of several pulmonary diseases. Pulmonary diseases, such as pneumonia, chronic obstructive pulmonary disease (COPD), asthma, tuberculosis, COVID-19, and bronchiectasis, significantly contribute to poor quality of life and mortality. The association between periodontal disease and pulmonary outcomes is an important topic and requires further attention. Numerous resident microorganisms coexist in the oral cavity and lungs. However, changes in the normal microflora due to oral disease, old age, lifestyle habits, or dental intervention may contribute to altered aspiration of oral periodontopathic bacteria into the lungs and changing inflammatory responses. Equally, periodontal diseases are associated with the longitudinal decline in spirometry lung volume. Several studies suggest a possible beneficial effect of periodontal therapy in improving lung function with a decreased frequency of exacerbations and reduced risk of adverse respiratory events and morbidity. Here, we review the current literature outlining the link between the oral cavity and pulmonary outcomes and focus on the microflora of the oral cavity, environmental and genetic factors, and preexisting conditions that can impact oral and pulmonary outcomes.

Additive Effect of Periodontal Disease and Obesity on COVID-19 Outcomes.

This study aims to examine the impact of periodontal disease in obesity on COVID-19 infection and associated outcomes. This retrospective longitudinal study included 58,897 UK Biobank participants tested for COVID-19 between March 2020 and February 2021. Self-reported oral health indicators (bleeding gums, painful gums, and loose teeth) were used as surrogates for periodontal disease. Body fat levels were quantified by body mass index (BMI) and categorized as normal weight (18.5 to 24.9 kg/m2), overweight (25 to 29.9 kg/m2), and obese (≥30 kg/m2). Multivariable logistic regression and Cox proportional hazard models were used to quantify risk of COVID-19 infection, hospital admission, and mortality, adjusted for participants' demographics and covariates. Of 58,897 participants, 14,466 (24.6%) tested positive for COVID-19 infection. COVID-19 infection was higher for participants who were overweight (odds ratio, 1.18; 95% CI, 1.12 to 1.24) and obese (odds ratio, 1.33; 95% CI, 1.26 to 1.41) as compared with those of normal weight, but infection was not affected by periodontal disease. The hospital admission rate was 57% higher (hazard ratio, 1.57; 95% CI, 1.25 to 1.97) in the obese group with periodontal disease than without periodontal disease, and admission rates increased with BMI category (normal weight, 4.4%; overweight, 6.8%; obese, 10.1%). Mortality rates also increased with BMI category (normal weight, 1.9%; overweight, 3.17%; obese, 4.5%). In addition, for participants with obesity, the mortality rate was much higher (hazard ratio, 3.11; 95% CI, 1.91 to 5.06) in participants with periodontal disease than those without. Obesity is associated with higher hospitalization and mortality rates, and periodontal disease may exacerbate this impact. The results could inform health providers, policy makers, and the general public of the importance to maintain good oral health through seamless provision of dental services and public oral health prevention initiatives.

Should We Be Concerned about the Association of Diabetes Mellitus and Periodontal Disease in the Risk of Infection by SARS-CoV-2? A Systematic Review and Hypothesis.

The objective of this article was to conduct a systematic review of the literature to contrast the existing evidence regarding the relationship between periodontal disease (PD) and diabetes mellitus (DM) with the possibly increased risk of SARS-CoV-2 infection, as well as to establish a hypothesis that explains the ways in which this interaction could take place. A literature search up from 1 January 2020 to 21 March 2021 was conducted in three electronic databases, namely, PubMed, Web of Science, and Scopus, in order to identify studies on periodontal disease alone or in conjunction with diabetes mellitus, reporting any relation with SARS-CoV-2 infection as a primary outcome. Only articles published in the English language were included. Due to the lack of studies, we decided to collect all the theoretical and clinical evidence suggesting a possible biological pathway evidencing the relationship among PD, DM, and SARS-CoV-2 infection. From a total of 29 articles, 12 were included for final review studies (five reviews, two hypotheses, one Special Issue, one perspective, one commentary, one case-control study, and one case report). In addition, this systematic review article hypothesizes the correlation between PD and type 2 diabetes mellitus (T2DM) by expression of angiotensin-converting enzyme 2 (ACE2) in periodontal tissue and the risk of SARS-CoV-2 infection. T2DM is a metabolic disorder characterized by high blood glucose levels resulting from altered insulin secretion or action. Likewise, periodontitis and T2DM are inflammatory disorders with a bidirectional association, and both diseases have a similar immunomodulatory cascade and cytokine profile. ACE2 is a crucial component of the renin-angiotensin system (RAS) and the key factor of entry in the cells by the new SARS-CoV-2. ACE2 is widely distributed in the lung and kidneys, and interestingly has a great distribution in the oral cavity, principally in the tongue and periodontal tissue. ACE2 in periodontal tissue plays a crucial role between health and disease. Moreover, the ACE2/Ang-(1-7)/MasR axis is downregulated in the dysbiotic and inflammatory periodontal environment. Nevertheless, the balance of ACE2 activity is modified in the context of concurrent diabetes, increasing the expression of ACE2 by the uncontrolled glycemia chronic in T2DM. Therefore, the uncontrolled hyperglycemia possibly increases the risk of developing periodontitis and triggering overexpression of ACE2 in periodontal tissue of T2DM patients, with these events potentially being essential to SARS-CoV-2 infection and the development of mild-to-severe form of COVID-19. In this sense, we would like to point out that the need for randomized controlled trials is imperative to support this association.

Covid-19 and oral diseases: Crosstalk, synergy or association?

The coronavirus disease 2019 (Covid-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that clinically affects multiple organs of the human body. Cells in the oral cavity express viral entry receptor angiotensin-converting enzyme 2 that allows viral replication and may cause tissue inflammation and destruction. Recent studies have reported that Covid-19 patients present oral manifestations with multiple clinical aspects. In this review, we aim to summarise main signs and symptoms of Covid-19 in the oral cavity, its possible association with oral diseases, and the plausible underlying mechanisms of hyperinflammation reflecting crosstalk between Covid-19 and oral diseases. Ulcers, blisters, necrotising gingivitis, opportunistic coinfections, salivary gland alterations, white and erythematous plaques and gustatory dysfunction were the most reported clinical oral manifestations in patients with Covid-19. In general, the lesions appear concomitant with the loss of smell and taste. Multiple reports show evidences of necrotic/ulcerative gingiva, oral blisters and hypergrowth of opportunistic oral pathogens. SARS-CoV-2 exhibits tropism for endothelial cells and Covid-19-mediated endotheliitis can not only promote inflammation in oral tissues but can also facilitate virus spread. In addition, elevated levels of proinflammatory mediators in patients with Covid-19 and oral infectious disease can impair tissue homeostasis and cause delayed disease resolution. This suggests potential crosstalk of immune-mediated pathways underlying pathogenesis. Interestingly, few reports suggest recurrent herpetic lesions and higher bacterial growth in Covid-19 subjects, indicating SARS-CoV-2 and oral virus/bacteria interaction. Larger cohort studies comparing SARS-CoV-2 negative and positive subjects will reveal oral manifestation of the virus on oral health and its role in exacerbating oral infection.

Is periodontal disease a risk factor for developing severe Covid-19 infection? The potential role of Galectin-3.

IMPACT STATEMENT: There could be a close relationship between periodontal diseases (PDs) severity and Covid-19 infections. This relationship could be caused by Galectin-3-mediated increased immune response and increased viral attachment. Keeping PDs under control and maintaining rigorous oral hygiene during this troubled Covid-19 pandemic period is very important.Patients with older age and pre-existing conditions like cardiovascular disease, hypertension, diabetes, and obesity are in the higher risk group for developing severe Covid-19 infections. The inflammatory pathways that are involved in these conditions are the same pathways that we see in periodontal diseases (PDs). This raises a significant question: Is PD a pre-existing condition that can increase the risk of developing severe Covid-19 infection? Several studies have shown that Galectins play a key role in the homeostasis of immune cells, and recently, a relationship was found between Covid-19 and Galectin-3 (Gal-3).It has been determined that an important area in the spike protein of Coronavirus-19 is almost exactly the same as the morphology of Gal-3, and these spike proteins are critical for the entry of the virus into host cells. We suspect that there is enough evidence to support a close relationship between PDs severity and Covid-19 infections. There is accumulating evidence to suggest a relationship between the severity of PD and the risk of infection with Covid-19, which requires further investigation. This relationship could be caused by Gal-3-mediated increased immune response and increased viral attachment. In this context, we want to emphasize the importance of keeping PD under control by maintaining rigorous oral hygiene during this troubled Covid-19 pandemic period. We would also like to point out the possibility that having PD may be a pre-disposition toward developing a severe Covid-19 infection.