Periodontal Disease Markers among Patients with Long COVID: A Case-control Study

Background: Long-COVID affects approximately 32-87% of COVID-19 patients and causes persistent symptoms that last more than 4 weeks after initial infection. Long COVID is associated with a notable cytokine triad, namely IL-1β, IL-6, and TNF-α. Periodontal disease also involves proinflammatory cytokines production, including IL-1β, IL-6, and TNF-α. Consequently, long-COVID, which has an impact on proinflammatory cytokine release, could have an impact on periodontal status. Objective: This study aims to see whether long COVID affects periodontal status severity based on proinflammatory cytokines levels involved in both diseases, namely IL-1β, IL-6, and TNF-α. Methods: Patients were divided into periodontitis or gingivitis patients and then were further divided into two groups, previous COVID-19 patients and non- COVID-19 patients (controls). Gingival sulcus fluids were obtained from each patient using paper points inserted in the patients’ sulcus, and ELISA tests were carried out to measure IL-1β, IL-6, and TNF-α levels. Results: Levene Test indicated that there were no substantial differences between IL-1β, IL-6, and TNF-α levels (0.057, 0.135, and 0.341, respectively) in COVID-19 patients with gingivitis in comparison to the control group with gingivitis, with average IL-1β, IL-6 and TNF-α levels seen higher in the control group compared to COVID-19 patients. There were also no substantial differences between IL-1β, IL-6, and TNF-α levels (1.00, 0.567, and 0.666, respectively) between COVID-19 patients with periodontitis and the control group with periodontitis. Although higher levels of IL-6 and TNF-α were found higher in COVID-19 patients in comparison to the control group. Conclusion: Levels of IL-6 and TNF-α in periodontitis patients with long COVID were higher than controls. But despite that, higher IL-1β, IL-6, and TNF-α levels were not found in long COVID subjects with gingivitis, as well as IL-β levels in the periodontitis group. Further studies with more subjects are needed to determine the connection between these two diseases further. Clinical Trial Registration No: The clinical trial registration of this research is 014/S3/KEPK/FKG/10/2021.