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Original Article | Open Access

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

Weikang Chen1,2,*Haojie Bai2,*Maoling Tian1,*Yanxia Huang3,*Depei Li1Luyao Wu1Wei Li2Lei Zhou2Wange Lu2Xiaoxing Li2 ( )Linyi Liu4 ( )Xiaobing Jiang1 ( )
Department of Neurosurgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China
Department of Neurosurgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China
Department of Neurosurgery, Northeast Yunnan Central Hospital, Zhaotong 657000, China

*These authors contributed equally to this work.

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Abstract

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.

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Cancer Biology & Medicine
Pages 769-784

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Cite this article:
Chen W, Bai H, Tian M, et al. SARS-CoV-2 infection in brain tumors and the association with alterations in the tumor immune microenvironment. Cancer Biology & Medicine, 2026, 23(5): 769-784. https://doi.org/10.20892/j.issn.2095-3941.2025.0468

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Received: 15 August 2025
Accepted: 06 January 2026
Published: 16 February 2026
©2026 The Authors.

Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)