Purpose: COVID-19 infection has been associated with cardiovascular complications, including new-onset atrial fibrillation/flutter (NOAF). However, the potential protective effect of COVID-19 vaccination against long-term NOAF risk following COVID-19 infection remains unclear.
Methods: This retrospective cohort study used the TriNetX Research Network to identify adults diagnosed with COVID-19. Patients were divided into a vaccine group and control group (unvaccinated). After propensity score matching (238,750 patients per group), we assessed the primary outcome of 24-month NOAF incidence, with secondary outcomes at 1, 6 and 12 months. Subgroup analyses examined effects across patient characteristics and comorbidities. Sensitivity analysis was performed by excluding patients with severe COVID-19 illness.
Results: The 24-month NOAF incidence was significantly lower in the vaccine group compared to the control group (1.91% vs 2.18%; HR: 0.82, 95% CI: 0.78-0.85). This protective effect was also observed at 1 month (HR: 0.73, p < 0.001), 6 months (HR: 0.71, p < 0.001), and 12 months (HR: 0.77, p < 0.001). Sensitivity analysis confirmed these findings (HR: 0.79 at 24 months). Subgroup analyses demonstrated that COVID-19 vaccination provided significant protection against NOAF across all examined subgroups, with younger patients (18-60 years) showing greater risk reduction compared to older individuals.
Conclusion: COVID-19 vaccination was associated with a significantly reduced 24-month risk of NOAF after COVID-19 infection. These findings suggest vaccination may mitigate long-term cardiovascular sequelae of COVID-19. Future research should elucidate underlying protective mechanisms and optimize vaccination strategies for cardiovascular protection, particularly in high-risk populations.
Copyright: © 2026 Ko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.