Viral infections and atherosclerosis : a systematic literature review

Abstract Introduction Atherosclerosis is a chronic inflammatory disease of the arterial wall and remains the leading global cause of cardiovascular morbidity and mortality. While traditional risk factors as hypertension, diabetes mellitus, and dyslipidemia account for much of its burden, increasing evidence suggests that viral infections may represent important yet under recognised contributors to atherogenesis. Purpose This systematic review aimed to do a synthesis of clinical, experimental, and pathological data investigating the relationship between viral infections and atherosclerosis, clarifying the biological mechanisms involved, and identifying potential preventive or therapeutic strategies targeting infection-driven vascular injury. Methods A systematic review was conducted in accordance with PRISMA recommendations. Studies published between 1978 and 2025 in English or French were screened. Clinical, pathological, and experimental investigations were included to evaluate epidemiological associations, mechanistic pathways, and therapeutic implications. Data extraction focused on viral detection within plaques, systemic inflammatory signatures, cardiovascular outcomes among infected populations, and interventional strategies. Results Included studies consistently showed that viral pathogens can promote atherogenesis through both direct and indirect mechanisms. Direct mechanisms involved productive or abortive infection of endothelial and vascular smooth muscle cells, leading to cellular dysfunction, apoptosis, and impaired repair. Indirect mechanisms included persistent immune activation, systemic inflammation, endothelial activation, and enhanced prothrombotic activity. Histopathological analyses identified viral DNA, RNA, and proteins within human atherosclerotic plaques. Clinical cohorts demonstrated increased rates of cardiovascular events among patients with chronic viral infections such as CMV, HIV, hepatitis viruses, and more recently SARS-CoV-2. COVID-19–related vascular inflammation and thrombo-inflammatory complications provided additional evidence that viral pathogens can accelerate or destabilise atherosclerotic disease. Fig A Conclusion Viral infections appear to represent an underestimated risk factor for atherosclerosis. Preventive strategies—including vaccination, antiviral therapy, and targeted immunomodulation—may help reduce infection-driven cardiovascular risk. Future research should prioritise multicentre prospective studies, standardised viral detection techniques, and randomised clinical trials assessing antiviral and vaccine-based interventions, including emerging experimental vaccines targeting atherosclerosis itself. Fig BEndothelial dyfunction in covid 19For image description, please refer to the figure legend and surrounding text. Atheroslcerosis vaccineFor image description, please refer to the figure legend and surrounding text.