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

tetano

Editor, Senior Moderator
Viral Immunol


. 2026 Mar 17:8828245261426986.
doi: 10.1177/08828245261426986. Online ahead of print.
Single-Cell and Mendelian Randomization Analyses Identify Key Genes Common to COVID-19 and Multiple Sclerosis

Shuping Chen[SUP] 1 [/SUP], Jun Ruan[SUP] 1 [/SUP], Sikai Cheng[SUP] 2 [/SUP], Huifang Zheng[SUP] 1 [/SUP], Tianyu Chang[SUP] 3 [/SUP], Guichun Bao[SUP] 1 [/SUP], Zijing Zhu[SUP] 1 [/SUP], Xinglin Li[SUP] 1 [/SUP], Wei Zhao[SUP] 4 [/SUP], Kunwen Zheng[SUP] 1 [/SUP]


Affiliations
Abstract

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.

Keywords: B cells; Mendelian randomization; coronavirus disease; multiple sclerosis; single-cell RNA sequencing.

 
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