Assessing the endothelium's role in COVID-19 severity using the HUVEC model

Area of Science:

• Endocrinology and Metabolism
• Immunology
• Vascular Biology

Background:

• COVID-19 is linked to severe systemic inflammation, endothelial injury, and thrombosis.
• The impact of patient-derived factors on endothelial cells in COVID-19 is not fully understood.

Purpose of the Study:

• To investigate how serum from severe COVID-19 patients affects endothelial cell activation, inflammation, and oxidative stress.
• To use human umbilical vein endothelial cells (HUVEC) as an in vitro model to study these effects.

Main Methods:

• Collected serum from severe COVID-19 patients, convalescent patients, and healthy volunteers.
• Exposed HUVEC to 15% serum and analyzed gene expression (endothelial activation, thrombosis, inflammation, oxidative stress) via qPCR.
• Assessed endothelial secretory profiles using multiplex immunoassays and analyzed data with ANOVA, ROC curves, and regression analysis.

Main Results:

• Severe COVID-19 serum significantly increased expression of VCAM1, F3, IL6, and antioxidant genes in HUVEC.
• Elevated levels of adhesion molecules (sICAM-1, P-selectin), thrombotic factors (tissue factor), and cytokines (IL-6, TNF-α) were observed in HUVEC treated with severe COVID-19 serum.
• P-selectin and MIP-1β levels distinguished severe cases from healthy volunteers, while IL-10 and MIP-1β levels correlated with disease severity.

Conclusions:

• HUVEC can serve as a biological sensor for COVID-19 inflammatory responses.
• The endothelium plays a critical role in exacerbating the cytokine storm in severe COVID-19.
• Endothelial activation by circulating factors contributes to COVID-19 severity and mortality.