Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by the George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Research Grant number 164/20/10.01.2023. Background Epicardial fat (EF) and pericoronary adipose tissue (PCAT) have been extensively studied in the last decade as markers and promotors of local coronary inflammation. Quantification of EF and PCAT via CCTA, can predict the risk of acute events across various cardiovascular disorders, and has been linked to markers of local or systemic inflammation. Mapping the fat attenuation index (FAI) on routine CCTA can detect coronary artery inflammation at different levels of the coronary tree. Objectives This study aimed to evaluate the regional differences between left and right coronary inflammation in patients who had CCTA examinations for chest pain in the early stages after COVID-19 infection COVID-19 infection, using the AI-powered CaRi-Heart® medical software. Methods In this study, we included 172 patients (mean age: 62.43 ± 11.62 years) with chest pain and low to intermediate clinical likelihood of CAD, who underwent 128-slice CCTA to assess coronary anatomy, atherosclerosis, and FAI – Score determination. The study population was divided into two groups: Group 1 (n = 80) – with COVID-19 infection 2–3 months prior to their CCTA examination, Group 2 (n = 92) – adjusted for age and gender, without COVID-19 infection. For each patient, we recorded and analyzed demographic and clinical characteristics, cardiovascular risk factors, and the onset of signs and symptoms before the CCTA examination. Results The FAI - Score was considerably higher in the non COVID-19 group: LAD (11.87 ± 8.23 vs. 9.12 ± 6.20, p = 0.05), LCX (13.02 ± 6.76 vs. 10.77 ± 6.13, p = 0.05), RCA (15.88 ± 10.36 vs. 14.74 ± 12.24, p = ns), the average FAI - Score (13.23 ± 8.92 vs. 10.34 ± 7.22, p = 0.001). Comparing the FAI - Score between the left and right coronary artery, we found that for the entire study population, the FAI score was significantly higher at the RCA level (15.23 ± 11.97 vs. 11.21 ± 6.98, p = 0.02), and this difference was also maintained in the COVID-19 positive group (14.54 ± 12.17 vs. 9.77 ± 5.94, p = 0.0002), but not in the non-COVID-19 group (14.20 ± 10.78 vs. 12.88 ± 7.41, p = ns). In both groups, the CaRi Heart® Risk (p < 0.0001) and Duke Score (p < 0.0001) were significantly higher for the COVID-negative patients. Conclusions COVID-19 infection is associated with a higher risk of coronary plaque destabilization, as shown by increased inflammation in the PCAT. For the entire study population, the FAI - Score was significantly higher at the RCA level, the difference being driven by the increased RCA inflammation in the post-COVID group. This indicates a potential role of local hemorheological factors in the complex process of inflammation-mediated plaque vulnerabilization.