From Virus to Vessel: Viral Infections and Pulmonary Hypertension — A Systematic Review and Mechanistic Synthesis

Abstract

Pulmonary hypertension (PH) has been increasingly reported in association with several viral infections, including human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), herpesviruses, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and hepatitis C virus (HCV). However, the mechanisms linking viral infection to pulmonary vascular disease remain incompletely understood. This study was conducted as a systematic review with mechanistic synthesis in accordance with PRISMA 2020 guidelines. A structured search of PubMed, PubMed Central (PMC), the Cochrane Library, and MDPI was performed for studies published between January 2011 and February 2024. Evidence from observational human studies, animal models, case reports, and mechanistic and narrative reviews was synthesized qualitatively. Study quality was assessed using design-specific appraisal tools. Across diverse viral pathogens, pulmonary hypertension is frequently reported as a recurrent vascular phenotype characterized by immune dysregulation, endothelial injury, thrombo-inflammation, and pulmonary vascular remodeling. However, human evidence is predominantly observational and frequently based on echocardiographic assessment, limiting causal inference. Integrating clinical and experimental findings, this review proposes a stepwise pathophysiological framework linking viral infection to pulmonary hypertension. While the strongest clinical evidence exists for HIV-associated pulmonary hypertension, evidence for other viral infections remains more limited or indirect. These findings suggest a biologically plausible association between viral infection and pulmonary vascular disease while highlighting the need for prospective studies incorporating invasive hemodynamic assessment and longitudinal follow-up. Key methodological limitations include single-reviewer screening and the predominance of observational human studies relying on echocardiographic assessment and heterogeneous diagnostic approaches.