Autophagy, telomerase, and endothelial dysfunction in COVID-19-induced cardiac injury: an evidence-graded genetic and epigenetic synthesis.

<h4>Background</h4>Cardiac injury is a frequent and severe complication of COVID-19, yet the molecular mechanisms driving myocardial involvement remain incompletely understood. Dysregulated autophagy(definition), telomerase/telomere(definition) biology, and endothelial dysfunction have emerged as biologically plausible and potentially interconnected contributors to COVID-19-associated cardiac injury.<h4>Methods</h4>We conducted a narrative, evidence-graded review of literature retrieved from PubMed and EMBASE, with Google Scholar used selectively as a supplementary source to capture emerging or cross-disciplinary studies. Eligible studies included human investigations and relevant animal models reporting genetic, epigenetic, or molecular alterations in autophagy, telomerase, or endothelial pathways with cardiovascular relevance. Non-English publications, studies lacking primary data, and reports unrelated to cardiovascular or systemic disease mechanisms were excluded. Evidence was stratified as Level I (direct evidence in COVID-19-associated cardiac injury), Level II (COVID-19 systemic or vascular evidence with plausible cardiac relevance), and Level III (non-COVID cardiovascular or systemic disease; hypothesis-generating).<h4>Findings</h4>Across viral, cardiovascular, and systemic contexts, key candidate genes, including <i>ATG5, ATG7, Beclin-1, TERT, ICAM1</i>, and <i>eNOS</i> <b>-</b>emerged as potential mediators of COVID-19-related cardiac injury. While endothelial activation is supported by relatively consistent clinical and molecular evidence, direct cardiac-tissue data linking autophagy and telomerase pathways to COVID-19-associated myocardial injury remain limited. These gaps highlight substantial uncertainty regarding causal mechanisms and inter-individual susceptibility.<h4>Conclusion</h4>Autophagy dysregulation, telomere attrition, and endothelial dysfunction represent convergent and biologically plausible mechanisms contributing to COVID-19-associated cardiac injury; however, current evidence remains largely indirect and derived from systemic or vascular compartments rather than cardiac tissue. Cardiac-specific, longitudinal genetic and epigenetic studies are required before these pathways can be considered for biomarker development or therapeutic targeting.