QT Prolongation in COVID and Long COVID

Dr Graham Exelby May 2025

Overview:

QT prolongation reflects delayed myocardial repolarization and increases the risk of ventricular arrhythmias such as torsades de pointes (TdP). In the context of COVID and Long COVID, QT interval abnormalities may arise from viral-induced myocardial inflammation, autonomic dysregulation, genetic predispositions, or pharmacological exposures. Standing and spinal ECG analyses have revealed characteristic patterns—including short PR intervals and QT prolongation—suggesting activation of the cardiac and coeliac plexuses

Genetic and Molecular Mechanisms:

• Congenital Long QT Syndromes (LQT1–LQT3) are commonly linked to mutations in KCNQ1 (LQT1), KCNH2/HERG (LQT2), and SCN5A (LQT3). These impact repolarizing potassium currents or depolarizing sodium currents.

• COVID-related inflammation may upregulate IL-6 and STAT3, suppressing HERG channel expression and prolonging repolarization.

• Other implicated polymorphisms include NOS1AP, CAV3, and KCNE1.

• Autonomic genetic variants (e.g., ADRB1, COMT) may influence heart rate variability (HRV) and QT dispersion.

Cardiac and Coeliac Plexus Influence:

• The cardiac plexus modulates SA and AV node conduction; its overstimulation can lead to vagal surges, short PR intervals, and prolongation of QTc via delayed repolarization.

• The coeliac plexus, via the greater splanchnic nerve, influences adrenal catecholamine output and systemic sympathetic tone. Coeliac plexus activation may lengthen QTc through β-adrenergic effects.

COVID-Specific Pathophysiology:

• Myocarditis, pericarditis, and endothelial injury can prolong QT via direct myocardial involvement.

• IL-6, TNF-α, and CCL2 are upregulated in COVID, affecting ion channel function via STAT3-mediated transcription.

• Hypoxia and metabolic derangements may impair repolarization reserves.

Medications Requiring Caution:

• QT-prolonging agents: Hydroxychloroquine, azithromycin, SSRIs (citalopram, escitalopram), certain antipsychotics, antiemetics (ondansetron), fluoroquinolones.

• Histamine blockers: Famotidine and cetirizine are generally safe but should be monitored when combined with other QT-prolonging drugs.

• LDN is typically safe but should be introduced cautiously in sensitive autonomic phenotypes.

• Electrolyte-depleting agents (e.g., diuretics) may unmask latent QT vulnerability.

Beta-Blocker Selection:

• Propranolol- Non-selective, crosses the BBB. May be beneficial by blunting sympathetic surges and suppressing IL-6/TNF-α. Preferred in centrally mediated QT prolongation and POTS with hyperadrenergic traits.

• Metoprolol: β1-selective; less CNS penetration. Suitable for rate control but may be less effective in plexus-driven neuroinflammatory settings.

• Atenolol: β1-selective with minimal CNS effects; typically avoided in neuroinflammatory phenotypes due to limited autonomic modulation.

• Ivabradine: Pure sinus node modulator without beta blockade. Does not prolong QTc and may be preferred when β-blockers are not tolerated.

Clinical Recommendations:

• Baseline and standing ECGs should be used to assess autonomic impact on PR and QT intervals.Consider 24-hr Holter with HRV metrics to assess autonomic tone and identify at-risk phenotypes.

• Acupuncture, especially Kiiko-Matsumoto in experienced hands can control QT prolongation

• Monitor electrolytes (Mg, K, Ca), and consider repletion with magnesium (and taurine subject to amino acid profiling) in those with QT variability.

• Evaluate for genetic predisposition in patients with persistent QT prolongation or family history of sudden cardiac death.

Summary:

QT prolongation in Long COVID involves an interplay of genetic susceptibility, autonomic plexus activation, inflammatory cytokines, and pharmacological factors. Standing ECGs may reveal autonomically mediated QT patterns not seen at rest.

Propranolol and  metoprolol, each serve different roles in management depending on the phenotype and comorbid dysautonomia.   A precision-based approach to ECG interpretation, pharmacotherapy, and autonomic phenotyping is essential to minimize arrhythmic risk and support long-term cardiovascular and neurological recovery.