Vascular Programs in Emerging and Re-Emerging RNA Virus Infections: Comparative Lessons from SARS-CoV-2, Flaviviruses, and Hantaviruses.
- 1Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy.
- 2Department of Life Sciences, University of Ferrara, 44121 Ferrara, Italy.
Abstract
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.
Related
- Mapping neuro-vascular unit communications reveals distinct angiogenic programs across developing mouse brain regions
- Editor's Choice – European Society for Vascular Surgery (ESVS) 2026 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections
- Pyelonephritis is associated with persistent alterations in immune-stromal and vascular programs in the human placenta
- Spatial Transcriptomic Profiling of the Human Placenta in Congenital Cytomegalovirus Infection: A Broad Antiviral Response with Concurrent Suppression of Trophoblast and Vascular Programs.
- Addressing Efficacy Uncertainties in Expedited Programs for Gene Therapy Products: A Comparative Assessment of Post-Approval Requirements by the FDA and EMA.
BibTeX
@article{beltrami2026vascular,
title = {{Vascular Programs in Emerging and Re-Emerging RNA Virus Infections: Comparative Lessons from SARS-CoV-2, Flaviviruses, and Hantaviruses.}},
author = {Silvia Beltrami and Giovanni Strazzabosco and Giovanna Schiuma and Sabrina Rizzo and Marcello Baroni and Daria Bortolotti},
journal = {Viruses},
year = {2026},
month = oct,
doi = {10.3390/v18101160},
url = {https://europepmc.org/article/MED/42944079},
note = {CC BY},
}
RIS
TY - JOUR
TI - Vascular Programs in Emerging and Re-Emerging RNA Virus Infections: Comparative Lessons from SARS-CoV-2, Flaviviruses, and Hantaviruses.
AU - Silvia Beltrami
AU - Giovanni Strazzabosco
AU - Giovanna Schiuma
AU - Sabrina Rizzo
AU - Marcello Baroni
AU - Daria Bortolotti
PY - 2026
DA - 2026/10/19
JO - Viruses
DO - 10.3390/v18101160
UR - https://europepmc.org/article/MED/42944079
AB - 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.
SN - 1999-4915
ER -