The misunderstood link between SARS-CoV-2 and angiogenesis. A narrative review

Area of Science:

• Vascular Biology
• Infectious Diseases
• Pathophysiology

Background:

• COVID-19 causes multi-systemic issues, including circulatory problems like endothelial dysfunction and microangiopathic thrombosis.
• Intussusceptive angiogenesis, a form of blood vessel formation, is increasingly implicated in COVID-19 pathogenesis.

Purpose of the Study:

• To review and discuss splitting angiogenesis in COVID-19, covering its mechanisms, drivers, regulators, and roles.
• To examine the relevance of angiogenic features in COVID-19, including their impact on inflammation, endothelial dysfunction, and permeability.
• To assess the prognostic value and therapeutic potential of angiogenic mediators in COVID-19.

Main Methods:

• A narrative review was conducted following the SANRA guidelines.
• Data on splitting angiogenesis, its mechanisms, and its role in COVID-19 were systematically reviewed.
• Literature on angiogenic mediators as prognostic markers and therapeutic targets in COVID-19 was analyzed.

Main Results:

• Splitting angiogenesis in COVID-19 is driven by hypoxia, hypoxia-inducible factors, VEGF, angiopoietins, hyperinflammation, cytokine storm, and Renin-Angiotensin-Aldosterone System dysregulation.
• Elevated angiopoietins and VEGF in COVID-19 patients are associated with adverse outcomes, suggesting prognostic value.
• Limited data suggests potential therapeutic benefits of targeting angiogenic mediators, with bevacizumab showing promise as an add-on therapy.

Conclusions:

• Splitting angiogenesis is a key feature in COVID-19 pathophysiology, contributing to endothelial dysfunction and thrombosis.
• Angiogenic mediators like VEGF and angiopoietins serve as potential prognostic biomarkers for COVID-19 severity.
• Targeting angiogenic pathways may offer novel therapeutic strategies for managing severe COVID-19.