NYMC Faculty Publications
Multisystem Endothelial Inflammation: A Key Driver of Adverse Events Following Mrna-Containing COVID-19 Vaccines
Author Type(s)
Faculty
DOI
10.3390/vaccines13080855
Journal Title
Vaccines
Document Type
Article
Publication Date
8-1-2025
Department
Physiology
Keywords
adaptive immunity, adverse events (AEs), autoimmunity, comirnaty, complement activation, COVID-19, endothelial inflammation, endothelitis, functional mimicry, immune response, inflammatory signaling, innate immunity, ionizable lipids, lipid nanoparticles (LNPs), microcirculation, mRNA vaccines, multisystem inflammatory response syndrome (MIS), post-vaccination syndrome (PVS), spike protein, spikevax, systemic transfection, vaccine-induced pathology, vasculitis
Disciplines
Medicine and Health Sciences
Abstract
mRNA-LNP-based COVID-19 vaccines, namely Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax, were successfully deployed to help control the SARS-CoV-2 pandemic, and their updated formulations continue to be recommended, albeit only for high-risk populations. One widely discussed aspect of these vaccines is their uniquely broad spectrum and increased incidence of adverse events (AEs), collectively referred to as post-vaccination syndrome (PVS). Although the reported PVS rate is low, the high number of administered doses among healthy individuals has resulted in a substantial number of reported vaccine-related injuries. A prominent manifestation of PVS is multisystem inflammation, hypothesized to result from the systemic transfection of organ cells with genetic instructions for a toxin, the spike protein, delivered with lipid nanoparticles (LNPs). In this narrative review, we focus on endothelial cells in the microcirculatory networks of various organs as primary sites of transfection with mRNA-LNP and consequent PVS. We outline the anatomical variations in the microcirculation contributing to the individual variability of symptoms and examine the molecular and cellular responses to vaccine nanoparticle exposure at the endothelial cell level with a focus on the pathways of a sustained cascade of toxic and autoimmune processes. A deeper understanding of the mechanisms underlying mRNA-LNP-induced AEs and PVS at the organ and cellular levels is critical for improving the safety of future vaccines and other therapeutic applications of this groundbreaking technology.
Recommended Citation
Szebeni, J., & Koller, A. (2025). Multisystem Endothelial Inflammation: A Key Driver of Adverse Events Following Mrna-Containing COVID-19 Vaccines. Vaccines, 13 (8). https://doi.org/10.3390/vaccines13080855
