Evidences of neurological injury caused by COVID‐19 from glioma tissues and glioma organoids

Abstract

IntroductionDespite the extensive neurological symptoms induced by COVID‐19 and the identification of SARS‐CoV‐2 in post‐mortem brain samples from COVID‐19 patients months after death, the precise mechanisms of SARS‐CoV‐2 invasion into the central nervous system remain unclear due to the lack of research models.MethodsWe collected glioma tissue samples from glioma patients who had a recent history of COVID‐19 and examined the presence of the SARS‐CoV‐2 spike protein. Subsequently, spatial transcriptomic analyses were conducted on normal brain tissues, glioma tissues, and glioma tissues from glioma patients with recent COVID‐19 history. Additionally, single‐cell sequencing data from both glioma tissues and glioma organoids were collected and analyzed. Glioma organoids were utilized to evaluate the efficacy of potential COVID‐19 blocking agents.ResultsGlioma tissues from glioma patients with recent COVID‐19 history exhibited the presence of the SARS‐CoV‐2 spike protein. Differences between glioma tissues from glioma patients who had a recent history of COVID‐19 and healthy brain tissues primarily manifested in neuronal cells. Notably, neuronal cells within glioma tissues of COVID‐19 history demonstrated heightened susceptibility to Alzheimer's disease, depression, and synaptic dysfunction, indicative of neuronal aberrations. Expressions of SARS‐CoV‐2 entry factors were confirmed in both glioma tissues and glioma organoids. Moreover, glioma organoids were susceptible to pseudo‐SARS‐CoV‐2 infection and the infections could be partly blocked by the potential COVID‐19 drugs.ConclusionsGliomas had inherent traits that render them susceptible to SARS‐CoV‐2 infection, leading to their representability of COVID‐19 neurological symptoms. This established a biological foundation for the rationality and feasibility of utilization of glioma organoids as research and blocking drug testing model in SARS‐CoV‐2 infection within the central nervous system.