Multisystem Endothelial Inflammation: A Key Driver of Adverse Events Following mRNA-Containing COVID-19 Vaccines

Area of Science:

• Immunology
• Vaccinology
• Cell Biology

Background:

• mRNA lipid nanoparticle (LNP) vaccines like Comirnaty and Spikevax have been instrumental in controlling the COVID-19 pandemic.
• A notable concern is the occurrence of post-vaccination syndrome (PVS), characterized by a broad spectrum of adverse events (AEs).
• Despite low reported rates, the extensive use of these vaccines has led to a significant number of reported vaccine-related injuries.

Purpose of the Study:

• To investigate the role of endothelial cells in the microcirculation as primary sites for mRNA-LNP transfection and subsequent PVS.
• To explore how anatomical variations in microcirculation influence symptom variability in PVS.
• To examine the molecular and cellular mechanisms driving toxic and autoimmune processes following mRNA-LNP exposure.

Main Methods:

• Narrative review focusing on endothelial cell responses to mRNA-LNP.
• Analysis of microcirculatory anatomy and its relation to PVS symptom presentation.
• Examination of molecular and cellular pathways involved in vaccine-induced inflammation and autoimmunity.

Main Results:

• Endothelial cells in microcirculatory networks are identified as key sites of mRNA-LNP transfection.
• Anatomical variations in microcirculation contribute to the diverse clinical manifestations of PVS.
• Specific molecular and cellular pathways are implicated in sustained toxic and autoimmune reactions post-vaccination.

Conclusions:

• mRNA-LNP transfection of endothelial cells is a central mechanism in PVS development.
• Understanding these cellular-level interactions is vital for mitigating vaccine-related adverse events.
• This knowledge is critical for enhancing the safety of current and future mRNA-based therapeutics.