SARS-CoV-2 infection in brain tumors and the association with alterations in the tumor immune microenvironment

Objective: Recent clinical evidence indicates that persistent reservoirs of SARS-CoV-2 in human brain tissue are associated with various neurologic symptoms. While brain tumors have unique vascular abnormalities and immunosuppressive environments, it is unclear whether SARS-CoV-2 can infect brain tumors. Methods: Brain tumor samples were collected from a cohort of 72 COVID-19 patients during the SARS-CoV-2 BA.5 wave in Guangzhou. SARS-CoV-2 infection was confirmed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining. Immune cell infiltration within the tumor tissues was assessed using IHC. RNA-sequencing was performed to investigate virus-host interactions in the brain tumors. Results: Brain tumor samples from 72 COVID-19 patients were examined and SARS-CoV-2 RNA was detected in 11% of the samples, which included samples from craniopharyngiomas, pituitary neuroendocrine tumors (PitNETs), meningiomas, and gliomas. SARS-CoV-2 infection was present in tumor and endothelial cells within these brain tumors. SARS-CoV-2-positive tumors had greater immune cell infiltration, particularly an increase in CD8+ T cells in gliomas and pituitary PitNETs, along with the activation of innate signaling pathways. The transcriptomic analysis revealed that activation of the complement cascade within tumors may drive changes in the immune microenvironment of SARS-CoV-2-positive tumors. Conclusions: These findings provided evidence of SARS-CoV-2 infection in brain tumors and suggested a role in altering the tumor immunosuppressive microenvironment.