Aim: To investigate serum biomarkers of inflammation 2 years following non‐surgical root canal re‐treatment (Re‐RCT) and peri‐apical surgery (PS). The results were correlated with signs and symptoms, treatment outcome, metabolic syndrome factors, infection with severe acute respiratory syndrome coronavirus 2 SARS‐CoV‐2 (COVID‐19) infection and COVID‐19 vaccination.Methodology: Subjects from our previous study were recalled for 2 years post‐treatment follow‐up. Changes to the patient's history (medical, dental, social) were noted. Periapical health of the treated teeth was examined both clinically and radiographically. Blood pressure, fasting HbA1C and low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglycerides and total cholesterol (TC) levels were measured. Serum inflammatory marker levels were assayed using a Bio‐Rad Bio‐Plex 200 analyser and values at different time points within the same group were compared using a Wilcoxon signed‐rank test and differences between groups with a Mann–Whitney test. Linear associations were tested using Pearson's correlations.Results: The recall percentage at 2 years was 56.9% (n = 37), with a 100% radiographic success rate using periapical radiographs. In total, 21 cases (56.8%) were completely healed, and 16 cases (43.2%) were healing. Higher matrix metalloprotease 2 (MMP2) levels were present in the healing group compared to the healed group. Serum levels of high‐sensitivity C‐reactive protein (hs‐CRP), asymmetric dimethylarginine (ADMA) and MMP‐2 were significantly reduced (p ≤ .001) whereas other biomarkers showed significant increases at 2 year compared to pre‐operative levels, while FGF‐23 and ICAM‐1 were not significantly increased. HbA1C (p = .015), TC (p = .003), LDL (p = .003) and HDL (p = .003) reduced significantly at 2 years post‐treatment compared to their preoperative levels. COVID infection showed a significant association with MMP‐9 (p = .048).Conclusions: hs‐CRP, ADMA and MMP‐2 can be regarded as prognostic biomarkers of successful Re‐RCT and PS as they reduced at 2 year recall in cases which showed evidence of clinical and radiographic success. The successful treatment of chronic apical periodontitis is correlated with improvements in metabolic syndrome indicators, better glycemic control, and reduction at 2 year of some systemic inflammatory markers which are related to risks of cardiovascular disease events.

This study aimed to assess the effect of apical periodontitis and its treatment on the profile of salivary inflammatory markers and to investigate its correlation with serum inflammatory markers. Saliva samples were collected from 115 recruited participants. Patients were reviewed after 1 and 2 years following treatment. Saliva samples were analysed using Multiplex microbead immunoassay for identifying the inflammatory biomarkers’ profile. Biomarker levels were compared against healthy controls at baseline. Longitudinal comparison of those markers was further analysed for the review appointments and correlated with the size of the periapical radiolucency, treatment outcome and serum inflammatory biomarker levels. The salivary cytokines, matrix metalloproteinases (MMPs) and vascular adhesion molecules were higher at the review appointments. Pre-operative salivary levels of high-sensitivity C-reactive protein (hs-CRP) were significantly higher in the treatment group than in the control group (p < 0.001). At 1 year, hs-CRP was decreased than baseline. While, in 2 years, fibroblast growth factor (FGF)-23 was significantly lower compared to baseline levels (p = 0.005). Furthermore, the post-operative size of radiolucency was significantly correlated with the levels of several markers. When correlating the salivary levels of biomarkers with the serum levels, a significant correlation was seen in FGF-23 (p = 0.04) at baseline; in intercellular adhesion molecule (ICAM)-1 (p = 0.02) at 1 year post-treatment; and in TNF-α, ICAM-1 and E-Selectin at 2 years post-treatment (p = 0.046; p = 0.033; p = 0.019, respectively). Therefore, his study suggests that higher salivary cytokines, MMPs and vascular adhesion molecules at the post-treatment reviews are related to periapical bone healing and remodelling, whereas salivary FGF-23 and hs-CRP could be prognostic biomarkers. Correlation of some salivary with serum biomarkers suggests that saliva sampling could be a feasible non-invasive option for the measurement of inflammatory marker levels; however, further longitudinal studies are required.