Intravenous injection of high-dose SARS-CoV-2 spike protein significantly increased the median duration of atrial arrhythmias compared to albumin control (3.7 vs 1.7 seconds, p=0.0153) in mice.
Does intravenous SARS-CoV-2 spike protein increase atrial arrhythmia burden and induce structural remodeling in wild-type mice?
SARS-CoV-2 spike protein alone is sufficient to induce vascular damage, inflammatory responses, and atrial arrhythmias in mice, suggesting a mechanism for COVID-19-related arrhythmias independent of direct viral infection.
Absolute Event Rate: 3.7% vs 1.7%
p-value: p=0.0153
Coronavirus disease 2019 (COVID-19) patients have a 1.7-fold higher arrhythmia risk with rates of cardiac complications ranging from 2% non-ICU patients to 59% in non-survivors. Atrial fibrillation (AF), the most common arrhythmia, is a frequent complication of acute and long COVID-19. The high expression of ACE2 in the heart suggested that infectious virus may underlie cardiac complications. However, we recently reported in human cardiac tissue from fatal COVID-19 cases perivascular spike protein, elevated pro-inflammatory cytokines, vascular damage, and cardiac remodeling without evidence for direct infection of cardiac cells by SARS-CoV2. Mislocalization of intercalated disc (ID) components, connexin-43 (Cx43) gap junctions and NaV1.5 sodium channels, was also evident in patients’ hearts, recapitulating structural remodeling we previously identified as providing a substrate for atrial arrhythmias following an acute inflammatory insult. Therefore, we hypothesized that the inflammatory response elicited by SARS-CoV2 spike protein is sufficient to provoke atrial arrhythmias. Structural and functional assessments of WT murine hearts were performed five days following a single bolus intravenous injection of the viral spike protein. In vivo ECGs demonstrated increased atrial arrhythmia burden in spike-injected mice vs. control. Immunohistochemistry studies revealed elevated expression of inflammatory markers and evidence of vascular damage in these mice. Additionally, we observed disruption of ID ultrastructure and mislocalization of Cx43 and NaV1.5 in the atria of spike protein-injected mice. Our results suggest that vascular-leak inducing inflammatory insult from viral spike protein, and not direct infection by SARS-CoV2 results in the pathophysiology of cardiac dysfunction in fatal COVID-19.
Mezache et al. (Tue,) conducted a other in COVID-19 associated arrhythmia (n=24). SARS-CoV-2 spike protein vs. Mouse albumin (100 µg) was evaluated on Median duration of atrial arrhythmias (seconds) (p=0.0153). Intravenous injection of high-dose SARS-CoV-2 spike protein significantly increased the median duration of atrial arrhythmias compared to albumin control (3.7 vs 1.7 seconds, p=0.0153) in mice.