Abstract / Summary
BackgroundCoronavirus disease 2019 (COVID-19) may be associated with persistent subjective cognitive complaints, including difficulties with attention, memory, and executive function, in some individuals with post-acute sequelae of SARS-CoV-2 infection (PASC, “long COVID”). Inter-individual variability raises the possibility that host genetic factors contribute to susceptibility. This study explored the relationship between dementia-related polygenic risk scores (PRS) and subjective cognitive burden after COVID-19.MethodsGenome-wide genotype data from 60 individuals with a history of COVID-19 were merged with 915 South Asian population reference samples (total N = 975). Dementia-related PRS were generated using PRSice-2 across prespecified GWAS p-value thresholds. A subset of 15 participants completed a structured, study-specific self-report questionnaire assessing perceived cognitive difficulties across multiple domains 24–30 months after infection. Principal component analysis (PCA) summarized shared variance across cognitive domains. Associations between PRS and cognitive scores were examined using Spearman’s rank correlation. All analyses were considered exploratory because no independent validation cohort was available.ResultsCOVID-19–affected individuals aged 18–52 years showed a modest rightward shift in dementia-related PRS compared with population reference samples, with substantial overlap between groups (mean standardized PRS 0.24 vs. − 0.01; Mann–Whitney U = 29,504.5, p = 0.065; Cohen’s d = 0.25). Memory-related difficulties contributed most strongly to the shared variance across cognitive domains, with PC1 explaining 52.5% of the variance. Among the 15 participants with cognitive assessment, PRS showed a positive but uncertain association with subjective cognitive burden (Spearman’s r = 0.51, 95% CI − 0.02 to 0.82, p = 0.054).ConclusionThis hypothesis-generating study identified a possible relationship between dementia-related genetic liability and subjective cognitive burden after COVID-19. The PRS group comparison was descriptive and should not be interpreted as evidence of increased dementia risk. The phenotype–genotype finding is severely limited by the small subgroup, possible selection bias, non-validated subjective assessment, lack of multivariable adjustment, and cross-sectional design. Validation in larger, ancestry-matched, longitudinal cohorts is required.