Endothelial Collapse as a Convergent Immunovascular Phenotype in Sepsis and Severe Arboviral Disease: The SIMVAC Model.

Background/

Objectives

Severe bacterial sepsis and arboviral diseases may present with overlapping manifestations of vascular leakage, hemodynamic instability, thrombocytopenia, and organ dysfunction. We examined whether etiologically distinct severe infections may converge on selected components of immunovascular dysfunction and propose the Severe Infection-Mediated Vascular Activation and Collapse (SIMVAC) model as a hypothesis-generating framework.

Methods

This narrative mechanistic review integrates human clinical and physiological studies, translational biomarker evidence, experimental models, and pathogen-specific mechanistic studies, with particular attention to the relative strength of evidence across arboviruses.

Results

Dengue provides the strongest arboviral mechanistic support, linking plasma leakage with NS1-mediated endothelial barrier disruption, glycocalyx degradation, tissue-specific vascular effects, and inflammatory amplification. Evidence for yellow fever, West Nile virus, and Zika supports distinct organ-specific or systemic pathways but is less complete, whereas evidence for Mayaro, Oropouche, Venezuelan equine encephalitis, and Rocio viruses remains limited or hypothesis-generating. Candidate points of convergence include glycocalyx injury, Ang-2/Tie2 and S1P dysregulation, complement activation, NETosis, and vWF/ADAMTS13 imbalance.

Conclusions

SIMVAC should be regarded as a testable conceptual model rather than a validated syndrome or diagnostic tool. Prospective, pathogen-confirmed studies are required to determine whether reproducible immunovascular signatures exist across severe infections and whether they provide clinically meaningful information beyond conventional etiological and severity assessment.