Does mRNA-based COVID-19 vaccination in the subacute phase lead to microstructural brain changes? A prospective pilot...

Messenger ribonucleic acid (mRNA)-based vaccines delivered via lipid nanoparticles (LNP) were pivotal in managing the severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic. While mild systemic reactions are common after vaccination, rare neurological complications have raised concerns about potential structural cerebral changes. This prospective pilot study tested the hypothesis that LNP-mRNA-based SARS-CoV-2 vaccination does not induce significant microstructural cerebral changes in healthy adults. Dedicated 3 Tesla brain MRI was performed at three time points: up to one month before the first vaccination (t1), and 1-2 weeks (t2) and 2-3 months (t3) after the second dose of either BNT162b2 or mRNA-1273. Across 85 MRI scans from 29 initially SARS-CoV-2-seronegative adults, 2D T2-weighted fluid-attenuated inversion recovery, synthetic 3D T1 magnetization prepared rapid acquisition of gradient echoes and 3D quantitative T1 mapping were analyzed. Changes in w matter hyperintensities (WMH) were evaluated visually (Prins scale) and semiquantitatively (Longitudinal Brain Imaging). Microstructural changes of deep and cortical gray matter and white matter were analyzed using qT1 values via paired t-tests or Wilcoxon signed-rank tests. No new or progressive WMH nor significant intraindividual qT1 changes were observed. QT1% deviations were small (mean 0.1%, SD 0.9%; maximum 2.08%) and remained within established scan-rescan variability limits at 3 T. Apart from a 1 mm decrease of a preexisting WMH in one participant, no visually detectable structural brain alterations were observed. Our findings provide no evidence for WMH progression or microstructural cerebral changes after LNP-mRNA-based SARS-CoV-2 vaccination in healthy adults in the subacute phase.