Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells.

Summary

Under physiological flow, SARS-CoV-2 spike protein induced sustained endothelial activation in both aortic and pulmonary microvascular endothelial cells, including prolonged adhesion molecule expression, cytokine/chemokine release, leukocyte binding, and a procoagulant state. Transcriptomics revealed persistent upregulation of antiviral, cytokine, pattern-recognition, complement, and coagulation pathways.

Key Findings

• SARS-CoV-2 spike triggered prolonged adhesion molecule expression in both HAoEC and HPMC, akin to TNF-α effects.
• Spike exposure led to cytokine/chemokine release, increased leukocyte binding, and a procoagulant endothelial state.
• Transcriptomics under flow showed persistent upregulation of antiviral, cytokine-mediated, pattern recognition, complement, and coagulation pathways.

Clinical Implications

Supports evaluating endothelial-protective and anticoagulant/anti-inflammatory strategies in COVID-19-related ARDS and post-acute sequelae. Biomarker development targeting endothelial activation pathways may aid risk stratification.

Limitations

• In vitro study without in vivo validation; clinical dosing/exposure not directly modeled
• Use of spike protein rather than whole virus; translation to clinical outcomes requires further study

Future Directions

Validate findings in in vivo models and patient samples; test endothelial-stabilizing interventions and link endothelial activation signatures with ARDS severity and long COVID outcomes.