This study explores the intricate molecular interactions between glioma and COVID-19, emphasizing the pivotal role of the PI3K-Akt signaling pathway and the immunomodulatory effects of vitamin D. Through extensive bioinformatics analyses—including enrichment, survival, and molecular docking assessments—we identified six key prognostic genes (MYBL2, RBM6, VEPH1, AHNAK2, GNG10, and DUSP14) that are differentially expressed in both glioma and COVID-19 contexts. This evidence concerns the gene AHNAK2 and central nervous system cancer.