Cardiac Tissue Damage in a Female Animal Post-COVID Model: Relevance of Chemokine-Mediated Inflammation

Post-COVID cardiac complications have emerged as a significant and persistent clinical concern, yet their underlying mechanisms remain poorly understood. Animal models can act as proxies to investigate the pathophysiology of the human, post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this experimental study was to evaluate the expression of inflammatory biomarkers in cardiac tissue 28 days after SARS-CoV-2 infection in a female hACE2 mouse model, with a focus on chemokine-mediated immune activation. Twelve female C57BL/6 hACE2 mice were infected with the Omicron variant (BA.1.17 lineage) of SARS-CoV-2, and eleven non-infected mice served as controls. Cardiac tissue was analyzed via Western blot for markers of innate immune activation (TLR4, MyD88, NF-κB) and pro-inflammatory cytokines (IL-6, IL-18, IL-1β, TNF-α, CD11d). Cardiac tissue injury markers (iNOS, PAI-1 and Connexin43) were also analyzed. Compared to non-infected mice, cardiac tissue from infected mice showed significantly higher expression of IL-6 (p = 0.028), indicating an inflammatory state, and CD11d (p = 0.016), suggesting an inflammatory stage accompanied by sustained activation of chemokine-mediated inflammatory signaling. No significant differences in TLR4 (p = 0.340), MyD88 (p = 0.410), NF-κB p65 (p = 0.780), IL-18 (p = 0.548), IL-1β (p = 0.455), and TNF-α (p = 0.125) expressions were observed Similarly, no changes in cardiac damage markers (iNOS: p = 0.4684; PAI-1: p = 0.5345; Connexin 43: p = 0.2879) were found. The results of this experimental study would support the hypothesis of persistent low-grade inflammation as a contributor to post-COVID cardiac sequelae in females that is not accompanied by severe tissue damage, as also observed in clinical studies. This study also reinforces the need for studies evaluating the functional and structural evolution of the myocardium after an acute SARS-CoV-2 infection.