Potential links between COVID-19 and periodontitis: a bioinformatic analysis based on GEO datasets.

BACKGROUND: 2019 Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has already had a serious influence on human existence, causing a huge public health concern for countries all around the world. Because SARS-CoV-2 infection can be spread by contact with the oral cavity, the link between oral illness and COVID-19 is gaining traction. Through bioinformatics approaches, we explored the possible molecular mechanisms linking the COVID-19 and periodontitis to provide the basis and direction for future research. METHODS: Transcriptomic data from blood samples of patients with COVID-19 and periodontitis was downloaded from the Gene Expression Omnibus database. The shared differentially expressed genes were identified. The analysis of Gene Ontology, Kyoto Encyclopedia of Genesand Genomes pathway, and protein-protein interaction network was conducted for the shared differentially expressed genes. Top 5 hub genes were selected through Maximal Clique Centrality algorithm. Then mRNA-miRNA network of the hub genes was established based on miRDB database, miRTarbase database and Targetscan database. The Least absolute shrinkage and selection operator regression analysis was used to discover possible biomarkers, which were then investigated in relation to immune-related genes. RESULTS: Fifty-six shared genes were identified through differential expression analysis in COVID-19 and periodontitis. The function of these genes was enriched in regulation of hormone secretion, regulation of secretion by cell. Myozenin 2 was identified through Least absolute shrinkage and selection operator regression Analysis, which was down-regulated in both COVID-19 and periodontitis. There was a positive correlation between Myozenin 2 and the biomarker of activated B cell, memory B cell, effector memory CD4 T cell, Type 17 helper cell, T follicular helper cell and Type 2 helper cell. CONCLUSION: By bioinformatics analysis, Myozenin 2 is predicted to correlate to the pathogenesis and immune infiltrating of COVID-19 and periodontitis. However, more clinical and experimental researches are needed to validate the function of Myozenin 2.

microRNA-146a and -155, upregulated by periodontitis and type 2 diabetes in oral fluids, are predicted to regulate SARS-CoV-2 oral receptor genes.

BACKGROUND: Type 2 diabetes and periodontitis predispose to a higher risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recent studies show upregulation of innate immuno-regulatory microRNA-146a and -155 in oral fluids of patients with type 2 diabetes as well as of patients with periodontitis. The aim was to investigate whether upregulation of these microRNAs may relate to patient susceptibility to the infection via modulation of SARS-CoV-2 cellular entry factors expression. METHODS: Due to limited experimental feasibility and health risks in Coronavirus Disease 2019, bioinformatic analyses combining with system biology were used as initial investigation of interaction between microRNA-146 and -155 and genes encoding SARS-CoV-2 entry factors. RESULTS: SARS-CoV-2 cellular entry factors are expressed in salivary glands and masticatory mucosa (tongue) at different expression levels, comparable with those measured in lungs and tonsil. MicroRNA-146 and -155 are widely involved in the regulation of SARS-CoV-2 oral cellular entry factors and may enhance expression of ACE2 and modulate genes involved in host immunity. CONCLUSIONS: Diabetes- and periodontitis-induced increase in microRNA-146a and -155 in oral cavity is predicted to upregulate angiotensin-converting enzyme 2 expression, essential SARS-CoV-2 entry receptors, and modulate host antiviral response. As it could suggest increased infectivity of diabetes and periodontitis patients, additional protective measures for periodontists are recommended.

Human oral mucosa cell atlas reveals a stromal-neutrophil axis regulating tissue immunity.

The oral mucosa remains an understudied barrier tissue. This is a site of rich exposure to antigens and commensals, and a tissue susceptible to one of the most prevalent human inflammatory diseases, periodontitis. To aid in understanding tissue-specific pathophysiology, we compile a single-cell transcriptome atlas of human oral mucosa in healthy individuals and patients with periodontitis. We uncover the complex cellular landscape of oral mucosal tissues and identify epithelial and stromal cell populations with inflammatory signatures that promote antimicrobial defenses and neutrophil recruitment. Our findings link exaggerated stromal cell responsiveness with enhanced neutrophil and leukocyte infiltration in periodontitis. Our work provides a resource characterizing the role of tissue stroma in regulating mucosal tissue homeostasis and disease pathogenesis.

The circadian clock gene Bmal1: Role in COVID-19 and periodontitis.

The physiological processes of most living organisms follow a rhythmic pattern, which is controlled by the interaction between environmental cues and the internal circadian timing system. Different regulatory circadian genes are expressed in most cells and tissues, and disruptions in the sleep-wake cycle affect these genes, which may result in metabolic disorders and cause alterations of the immune system. The manifestations of these disrupted genes are evident in inflammatory conditions such as periodontitis and some viral diseases, including COVID-19. The brain and muscle ARNT-like protein-1 (Bmal1), an important circadian regulatory gene, decreases when the sleep-wake cycle is disrupted. Circadian genes have been linked to different events, including cytokine storm in inflammatory conditions and virus invasion. The evaluation of the effects of these regulatory circadian genes, especially Bmal1, in periodontitis and viral infection suggests that both diseases may have a common pathogenesis via the NF-κB pathway. This brief review highlights the role and importance of the circadian clock gene Bmal1 in the disease process of periodontitis and suggests its role and importance in viral infections, including COVID-19.

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.