Potential implications of lipid nanoparticles in the pathogenesis of myocarditis associated with the use of mRNA vaccines against SARS-CoV-2

Although mRNA-based vaccines BNT162b2 and mRNA-1273 exhibit a remarkable efficacy and effectiveness in preventing particularly severe Covid-19 with an overall favorable adverse event profile, their use has been associated with rare cases of acute myocarditis. These occur most commonly after the second dose, with the highest incidence among young male recipients. This complication has not been frequently observed among adenoviral vector vaccine receivers, and its clinical, laboratory and imaging features resemble those of other common causes of acute myocarditis. The pathogenesis of mRNA-vaccine associated myocarditis has not yet been elucidated, although a number of mechanisms have been proposed, typically implicating the administered S-protein mRNA and likely mediated through an autoimmune mechanism. Nonetheless, other mechanisms may be implicated given the fact that myocarditis cases are very rarely observed among recipients of non mRNA vaccines. The recent observation of a similar adverse event in a recipient of the non-mRNA, peptide-based NVX-CoV2373 in the frame of a phase III clinical trial with 7020 participants in the active treatment arm raises the question whether the lipid nanoparticle sheath, which is a common structural component of these platforms could be implicated in the pathogenesis of vaccine-induced myocarditis.