SARS-CoV-2 Brain Tropism Drives Spike RBD-Mediated Oncogenesis in Primary Glioma Cells

SARS-CoV-2, the agent of COVID-19, demonstrates notable neurotropic abilities extending beyond respiratory pathology. The virus penetrates the central nervous system through the olfactory route and by disrupting the blood-brain barrier, provoking diverse neuropathological outcomes. Glioma patients are particularly vulnerable to severe infection due to therapy-induced immune suppression. Transcriptomic studies using single-cell and bulk RNA sequencing indicate elevated expression of viral entry genes in glioma cells and microglia, accompanied by intensified cytokine secretion and marked upregulation of ANG2 and CXCR4. Time-course experiments with glioblastoma cells exposed to the spike protein receptor-binding domain reveal sequential activation of oncogenic cascades, including phosphorylation of Akt and Erk1/2. The MAPK pathway activates rapidly within 1 hour, followed by mTOR activation at 8 hours. These molecular events suggest that SARS-CoV-2 fosters oncogenic signaling and may accelerate glioma progression, emphasizing the clinical importance of vigilant management of brain cancer patients during the pandemic.