Vascular Programs in Emerging and Re-Emerging RNA Virus Infections: Comparative Lessons from SARS-CoV-2, Flaviviruses, and Hantaviruses

Emerging and re-emerging RNA viruses frequently present with clinical phenotypes that extend beyond classical organ tropism and include vascular leakage, platelet dysregulation, coagulation imbalance, microvascular injury, and thromboinflammation. SARS-CoV-2, flaviviruses, and hantaviruses provide three complementary models of virus-induced vascular disease. This narrative review compares these viruses through a shared endothelial–coagulative framework and proposes four partially overlapping vascular programs: endothelial activation, endothelial barrier failure, coagulation activation, and platelet quantitative or qualitative dysfunction. These programs are intended as a conceptual synthesis of convergent clinical, pathological, and experimental evidence rather than as a quantitative classification system. The framework is used not only to organize known mechanisms, but also to generate testable predictions for cross-virus biomarker panels, organ-specific endothelial models, and phenotype-guided clinical studies. Severe COVID-19 illustrates inflammation-driven endothelial activation, platelet–leukocyte interactions, complement amplification, NETosis, and immunothrombosis. Within the flavivirus group, DENV is used as the principal model for systemic vascular leakage, thrombocytopenia, and hemorrhagic risk; selected non-dengue flaviviruses illustrate how shared endothelial, platelet, and coagulation modules are redirected toward placental dysfunction (ZIKV), neuroinvasion (WNV and JEV), or hepatic failure and coagulopathy (YFV). Hantavirus infections provide a distinctive model of capillary leak syndrome in which non-lytic endothelial infection, immune-mediated injury, and permeability signaling converge on renal and pulmonary microvascular beds. A comparative view suggests that thrombotic, hemorrhagic, and leaky phenotypes are not mutually exclusive categories, but different outcomes of overlapping vascular programs shaped by viral tropism, vascular-bed specialization, immune activation, and host susceptibility.