Single-Cell and Mendelian Randomization Analyses Identify Key Genes Common to COVID-19 and Multiple Sclerosis

The pathophysiology of multiple sclerosis (MS) bears notable similarities to the dysregulated inflammatory response occurring during coronavirus disease 2019 (COVID-19) infection. B cells play a pivotal role among immune cells in the pathogenesis of both these diseases. Consequently, clarifying the molecular mechanism underlying B cell function in COVID-19 and MS is of great significance for formulating more efficient treatment strategies. A comprehensive analysis integrating single-cell RNA sequencing (scRNA-seq), genome-wide association study, and expression quantitative trait locus data from patients with COVID-19 and MS was performed. Gene set enrichment analysis revealed pathways and functional roles associated with the key genes, while pseudotime analysis tracked their expression patterns across different B cell developmental trajectories. The results of scRNA-seq analysis showed that, in comparison with the healthy control group, the proportion of B cells rose in patients with COVID-19 and those with MS. Through differential expression analysis and Mendelian randomization analysis, DR1 , IKZF3 , and RUVBL2 were identified as risk factors for both COVID-19 and MS, whereas ANAPC5 was characterized as a protective factor against these two conditions. The findings of the pseudotime analysis indicated that only IKZF3 had differential expression across different branches of B cells. IKZF3 ’s role in promoting immune inflammation and inhibiting metabolism could potentially be linked to the onset and comorbidity of COVID-19 and MS. This emphasizes not only the possible interaction mechanisms between these two diseases but also their clinical significance.