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

## TL;DR

This study suggests that chronic inflammation and endothelial dysfunction after COVID-19 may increase the risk of developing atrial fibrillation over time.

## Contribution

The study identifies a potential inflammation–endothelial dysfunction axis linking post-COVID conditions to new-onset atrial fibrillation.

## Key findings

- Post-COVID patients had higher inflammatory markers and lower endothelial function compared to controls.
- At 12 months, AF prevalence was numerically higher in post-COVID patients, especially in those with higher baseline inflammation.
- AF clustered in individuals with higher baseline neutrophil-to-lymphocyte ratio and lower flow-mediated dilation.

## Abstract

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.