Chronic Low-Grade Inflammation: A Possible Link Between COVID-19 and New-Onset Atrial Fibrillation

Background: Persistent inflammation and endothelial dysfunction have been proposed as key mechanisms of post-COVID cardiovascular sequelae and may contribute to atrial fibrillation (AF). We examined whether inflammatory/prothrombotic biomarkers and endothelial function differ between post-COVID patients and controls, and whether baseline inflammation/endothelial dysfunction relates to AF burden at 12 months. Methods: In this single-center, retrospective observational study, 198 outpatients were enrolled: 99 post-COVID patients evaluated 3-6 months after documented SARS-CoV-2 infection (Group 1) and 99 age- and sex-matched controls without prior COVID-19 (Group 2). At baseline (t0), clinical characteristics, inflammatory/prothrombotic biomarkers, brachial artery flow-mediated dilation (FMD), and 24 h Holter ECG were assessed in both groups. Univariable linear regression tested associations between baseline variables and FMD in Group 1. At 12 months (t1), 24 h Holter ECG was repeated in both groups. Quartile analyses were performed according to baseline neutrophil-to-lymphocyte ratio (NLR) to explore AF distribution across inflammatory strata. Results: At baseline, post-COVID patients had higher inflammatory and prothrombotic markers than controls (ESR, CRP, fibrinogen, and D-dimer; all p < 0.0001) and markedly lower FMD (7.72 vs. 13.72; p < 0.0001). In Group 1, FMD was inversely associated with multiple inflammatory/prothrombotic markers (all p < 0.0001), with the strongest association for ESR (R² = 0.6297). Holter-detected AF prevalence at baseline did not differ significantly between groups (25/99 [25.3%] vs. 18/99 [18.2%]). At 12 months, AF prevalence was numerically higher in the post-COVID group (32/99 [32.3%] vs. 21/99 [21.2%]); on two-sided testing, this difference was borderline (p = 0.047) and should be interpreted cautiously. Across increasing baseline NLR quartiles, AF prevalence increased stepwise in both groups (post-COVID: 2/25, 5/25, 10/24, 15/25; controls: 1/25, 3/25, 7/24, 10/25), consistent with the enrichment of AF in higher-inflammatory strata. Conclusions: Post-COVID patients exhibited a persistent inflammatory-prothrombotic profile and pronounced endothelial dysfunction at baseline. At 12 months, AF burden was numerically higher post-COVID, and AF clustered in strata characterized by higher baseline NLR and lower FMD, consistent with an inflammation-endothelial dysfunction axis associated with subsequent AF burden. Prospective studies with standardized rhythm monitoring and comprehensive multivariable adjustment are warranted.