Causal association of long COVID with brain structure changes: Findings from a 2-sample Mendelian randomization study.

Nearly 7.5% U.S. adults have long COVID. Recent epidemiological studies indicated that long COVID, is significantly associated with subsequent brain structure changes. However, it remains unknown if long COVID is causally associated with brain structure change. Here we applied two Mendelian Randomization (MR) methods - Inverse Variance Weighting MR method (IVW) for correlated instrument variables and Component analysis-based Generalized Method of Moments (PC-GMM) - to examine the potential causal relationships from long COVID to brain structure changes. The MR study was based on an instrumental variable analysis of data from a recent long COVID genome-wide association study (GWAS) (3,018 cases and 994,582 controls), the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) (Global and regional cortical measures, N = 33,709; combined hemispheric subcortical volumes, N = 38,851), and UK Biobank (left/right subcortical volumes, N = 19,629). We found no significant causal relationship between long COVID and brain structure changes. As we gain more insights into long COVID and its long-term health outcomes, future works are necessary to validate our findings and understand the mechanisms underlying the observed associations, though not causal, of long COVID with subsequent brain structure changes.