The COVID-19 RNA vaccine Spikevax ^TM transfects human umbilical endothelial cells and induces Spike protein production, inflammation and leukocyte adhesion

Abstract Endothelial cell dysfunction plays a key role in the pathogenesis of severe and critical COVID-19, leading to a multi-systemic inflammatory disease, and results from the direct interaction of the SARS-CoV-2 Spike proteins with endothelial cells. COVID-19 RNA vaccines encode a recombinant SARS-CoV-2 Spike protein which undergoes systemic biodistribution. No information is however so far available on the direct effects of COVID-19 RNA vaccines on human endothelial cells. In the present study, we exposed cultured human umbilical venous endothelial cells (HUVEC) to the COVID-19 RNA vaccine Spikevax TM (Moderna, Inc.), and thereafter we measured the expression of the Spike protein, of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α, of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as the attachment of human leukocytes to HUVEC layers. We also assessed the effects of Spikevax TM on HUVEC viability. Exposure of HUVEC to the COVID-19 RNA vaccine Spikevax TM resulted in effective cell transfection, and subsequent production of the Spike protein, which was expressed in the cells and secreted in the culture medium. Spike protein production was accompanied by increased gene expression of IL-6 and TNF-α and of ICAM-1 and VCAM-1, as well as by increased attachment of leukocytes to HUVEC monolayers. Exposure to the COVID-19 RNA vaccine Spikevax TM did not affect HUVEC viability. Our results provide a mechanistic explanation to post-COVID-19 RNA vaccination pathologies resulting from endothelial dysfunction, such as during atherosclerosis, autoimmune inflammation, and systemic inflammatory conditions.