SARS-CoV-2 spike protein-induced inflammation underlies proarrhythmia in COVID-19

Area of Science:

• Cardiology
• Virology
• Immunology

Background:

• Coronavirus disease 2019 (COVID-19) significantly increases arrhythmia risk, particularly atrial fibrillation (AF), in patients.
• Cardiac complications in COVID-19 range from 2% in non-ICU patients to 59% in non-survivors.
• While ACE2 expression in the heart suggests viral infection, prior studies found inflammatory markers and vascular damage, not direct SARS-CoV-2 infection, in fatal COVID-19 cardiac tissue.

Purpose of the Study:

• To investigate if the inflammatory response to the SARS-CoV-2 spike protein alone is sufficient to cause atrial arrhythmias.
• To explore the structural and functional cardiac changes induced by spike protein exposure.

Main Methods:

• Wild-type (WT) mice received a single intravenous injection of the SARS-CoV-2 spike protein.
• In vivo electrocardiograms (ECGs) were used to assess cardiac electrical activity and arrhythmia burden.
• Immunohistochemistry was performed to evaluate inflammatory markers, vascular damage, and the localization of key cardiac proteins (connexin-43 and Na_V1.5) at intercalated discs.

Main Results:

• Spike protein-injected mice exhibited a significant increase in atrial arrhythmia burden compared to controls.
• Elevated inflammatory markers and evidence of vascular damage were observed in the hearts of injected mice.
• Disruption of intercalated disc ultrastructure and mislocalization of connexin-43 and Na_V1.5 were noted in the atria.

Conclusions:

• The inflammatory insult caused by the SARS-CoV-2 spike protein, leading to vascular leakage, is sufficient to induce atrial arrhythmias.
• These findings suggest that inflammation, rather than direct viral infection, underlies cardiac dysfunction and arrhythmias in severe COVID-19.
• The observed disruption of intercalated discs and protein mislocalization contribute to the arrhythmogenic substrate following inflammatory insult.