COVID and AFib: Insights Into Infection-Related Arrhythmias

Atrial fibrillation (AFib) is the most common arrhythmia and has been linked to infections that cause systemic inflammation. COVID-19, caused by SARS-CoV-2, has been associated with new-onset AFib and worsening of preexisting cases, raising concerns about both short-term complications and long-term cardiovascular risks.

Understanding how COVID-19 contributes to AFib requires examining multiple mechanisms beyond general illness-related stress. Researchers are investigating inflammatory responses, immune system activity in heart tissue, autonomic nervous system disruptions, and laboratory markers of cardiac strain.

Cardiovascular Inflammation In SARS-CoV-2

The inflammatory response triggered by SARS-CoV-2 has significant effects on the cardiovascular system, with growing evidence linking this process to AFib. Endothelial dysfunction, a hallmark of COVID-19-related vascular injury, plays a central role in promoting heart inflammation. SARS-CoV-2 directly infects endothelial cells via the ACE2 receptor, increasing vascular permeability and creating a prothrombotic state. This damage fosters an environment where inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), rise to pathological levels, contributing to myocardial irritation and arrhythmias.

Beyond endothelial damage, direct myocardial inflammation has been observed in severe COVID-19 cases. Autopsy reports and cardiac MRI studies have identified myocarditis-like changes, including diffuse edema and fibrosis, which alter atrial electrical properties. Fibrotic remodeling disrupts normal conduction pathways, promoting reentrant circuits that sustain AFib. A study in JAMA Cardiology found that nearly 60% of recovered COVID-19 patients exhibited persistent myocardial inflammation on imaging, even in mild or asymptomatic cases. This lingering inflammation raises concerns about long-term arrhythmic risks, especially in individuals with hypertension or structural heart disease.

Systemic inflammation also contributes to oxidative stress, further increasing atrial vulnerability. Reactive oxygen species (ROS) generated during the inflammatory cascade impair ion channel function, leading to electrical instability. Elevated levels of C-reactive protein (CRP) and ferritin, markers of systemic inflammation, have been correlated with increased AFib incidence in hospitalized COVID-19 patients. A meta-analysis in The Lancet Respiratory Medicine found that patients with severe COVID-19 had significantly higher CRP levels than those with milder cases, suggesting a dose-dependent relationship between inflammation and arrhythmic burden.

Immune-Related Mechanisms In Atrial Tissue

The immune system’s role in atrial remodeling has gained attention in the context of COVID-19-associated AFib. SARS-CoV-2 infection triggers immune-driven changes that disrupt normal atrial electrophysiology, increasing susceptibility to arrhythmias. A key factor is the infiltration of immune cells into cardiac tissue, particularly macrophages and T lymphocytes, which contribute to structural alterations. Endomyocardial biopsies from COVID-19 patients have identified increased macrophage density in atrial tissue, suggesting ongoing immune activation even without overt myocarditis. This persistent response sustains a pro-arrhythmic environment by promoting fibrosis and altering ion channel expression.

Fibroblast activation is a major driver of atrial remodeling, with immune-mediated signaling playing a key role. Cytokines such as transforming growth factor-beta (TGF-β) stimulate fibroblast proliferation and extracellular matrix deposition, leading to fibrosis. This structural change disrupts electrical conduction, fostering reentrant circuits that sustain AFib. A study in Circulation: Arrhythmia and Electrophysiology found that COVID-19 patients with elevated TGF-β levels exhibited more pronounced atrial fibrosis on MRI, reinforcing the link between immune-induced fibrosis and arrhythmias.

Beyond structural remodeling, immune-related ion channel dysregulation further destabilizes atrial activity. Pro-inflammatory cytokines affect potassium and calcium channel function, which are essential for normal cardiac excitability. TNF-α and interleukin-1β (IL-1β) downregulate potassium channel expression, prolonging action potential duration and increasing the likelihood of early afterdepolarizations—an arrhythmic trigger. IL-6 also alters calcium handling, impairing the sarcoplasmic reticulum’s ability to regulate intracellular calcium levels. This disruption can lead to delayed afterdepolarizations, another known mechanism for AFib initiation.

Autonomic Dysregulation And Arrhythmias

Disruptions in autonomic nervous system function have been increasingly recognized as contributors to arrhythmias in COVID-19 patients, particularly in AFib development and exacerbation. The autonomic nervous system regulates heart rate and rhythm through sympathetic and parasympathetic inputs, which can become imbalanced due to viral infections, leading to abnormal cardiac excitability. SARS-CoV-2 has been linked to heightened sympathetic activity, characterized by increased catecholamine release, elevated heart rate variability, and a predisposition to atrial arrhythmias. COVID-19 patients often exhibit signs of sympathetic overdrive, including tachycardia and excessive norepinephrine levels, which shorten atrial refractory periods and promote reentrant circuits that sustain AFib.

The parasympathetic branch, which counterbalances sympathetic stimulation, is also affected, though in a less predictable manner. Some patients experience vagal withdrawal, leading to unchecked sympathetic dominance, while others develop paradoxical vagal hyperactivity, triggering bradycardia and conduction abnormalities. This variability complicates arrhythmia management, as interventions targeting one branch may inadvertently worsen dysfunction in the other. Heart rate variability analysis in COVID-19 patients has shown reduced parasympathetic tone, a marker of poor cardiovascular prognosis and a potential contributor to AFib persistence post-infection.

Neuroinflammatory processes further compound autonomic instability, with SARS-CoV-2 affecting brainstem structures involved in cardiovascular regulation. Reports of post-COVID dysautonomia, characterized by persistent tachycardia and orthostatic intolerance, suggest lasting autonomic impairment that may extend beyond the acute illness phase. This dysfunction can create a pro-arrhythmic state even in individuals without prior cardiac conditions. Beta-adrenergic blockers and vagus nerve stimulation are being explored to mitigate these autonomic shifts, though their efficacy in post-COVID AFib remains under investigation.

Laboratory Findings Related To Cardiovascular Stress

Biochemical markers of cardiovascular stress provide insights into COVID-19’s impact on AFib. Elevated cardiac troponins, typically markers of myocardial injury, have been detected in many hospitalized COVID-19 patients, even without acute coronary syndromes. This suggests myocardial strain contributing to arrhythmogenesis. A retrospective analysis in The New England Journal of Medicine found that patients with elevated troponin levels had a higher incidence of new-onset AFib, reinforcing the link between myocardial stress and atrial electrical abnormalities.

B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP), biomarkers of cardiac wall stress, have also been significantly elevated in COVID-19 patients developing AFib. These peptides, typically associated with heart failure, are released in response to increased atrial pressure and stretch, conditions that can promote arrhythmias. A multicenter study in JACC: Heart Failure found that BNP levels were markedly higher in COVID-19 patients with AFib, suggesting heightened atrial strain as a contributing factor.

Underlying Cardiac Conditions And Potential Interactions

Preexisting cardiovascular disease has been consistently associated with worse COVID-19 outcomes, and its interaction with AFib presents additional concerns. Patients with hypertension, coronary artery disease, and heart failure already have structural and electrical abnormalities that increase their susceptibility to arrhythmias. COVID-19 introduces additional stressors, including hypoxia, systemic inflammation, and hemodynamic instability, exacerbating these conditions. Individuals with left atrial enlargement or previous AFib episodes may experience higher recurrence rates due to infection-related myocardial strain and autonomic dysregulation.

Patients with heart failure, particularly those with reduced ejection fraction, face an increased risk of AFib exacerbation due to heightened cardiac workload and fluid shifts. The interplay between heart failure and AFib is well-documented, with each condition worsening the other through mechanisms like atrial stretch and neurohormonal activation. Additionally, COVID-19-induced endothelial dysfunction can accelerate atherosclerosis in those with coronary artery disease, potentially triggering ischemia-related atrial arrhythmias.

Antithrombotic management is particularly challenging in patients with both AFib and COVID-19, as the virus’s prothrombotic effects heighten stroke risk. This necessitates careful anticoagulation strategies tailored to individual bleeding risks.