Specific effects of SARS-CoV-2 infection on different subtypes of microglia and astrocytes in human brain

doi:10.16352/j.issn.1001-6325.2025.07.0933

Abstract

Abstract: Objective To investigate the impact of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infections on different phenotypes of microglia and astrocytes in the human brain and their role in neurological symptoms resulted from COVID-19 infection. Methods Fourteen human hippocampus-entorhinal cortex (HP-EC) samples were selected including 7 from COVID-19 patients and 7 from control donors. Multiplex immuno-histochemistry was used to detect markers of microglia and astrocytes followed by quantitative evaluation and statistical analysis. Results COVID-19 infection significantly changed density of microglia and astrocytes in HP-EC regions. It led to a decrease in quantity of neuro-protective, neurotoxic, and water-homeostasis-regulating astrocytes, while phagocytic microglia, chemotactic microglia and lipid-transporting astrocytes showed a region-specific density changes. Conclusions COVID-19 infection disrupts immune microenvironment of central nervous system, that may potentially contribute to the pathogenesis of COVID-19-related neurological symptoms as shown by changes of functional states of microglia and astrocytes.

Key words: SARS-CoV-2, microglia, astrocytes, multiplex immunohistochemistry

CLC Number:

R361.2

JIN Zhongman, WEI Hui. Specific effects of SARS-CoV-2 infection on different subtypes of microglia and astrocytes in human brain[J]. Basic & Clinical Medicine, 2025, 45(7): 933-938.

References 15

[1]	Agyeman AA, Chin KL, Landersdorfer CB, et al. Smell and taste dysfunction in patients with COVID-19: a systematic review and meta-analysis[J]. Mayo Clin Proc, 2020, 95: 1621-1631. doi:10.1016/j.mayocp.2020.05.030.
[2]	Merkler AE, Parikh NS, Mir S, et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza[J]. JAMA Neurol, 2020, 77: 1366-1372. doi:10.1001/jamaneurol.2020.2730.
[3]	Abenza Abildúa MJ, Atienza S, Carvalho Monteiro G, et al. Encephalopathy and encephalitis during acute SARS-CoV-2 infection. spanish society of neurology COVID-19 registry[J]. Neurologia, 2021, 36: 127-134. doi:10.1016/j.nrl.2020.11.013.
[4]	Zhao H, Shen D, Zhou H, et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence?[J]. Lancet Neurol, 2020, 19: 383-384. doi:10.1016/S1474-442230109-5.
[5]	Garland EF, Hartnell IJ, Boche D. Microglia and astrocyte function and communication: What do we know in humans?[J]. Front Neurosci, 2022, 16: 824888. doi:10.3389/fnins.2022.824888.
[6]	Patani R, Hardingham GE, Liddelow SA. Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration[J]. Nat Rev Neurol, 2023, 19: 395-409. doi:10.1038/s41582-023-00822-1.
[7]	Yang AC, Kern F, Losada PM, et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19[J]. Nature, 2021, 595: 565-571. doi:10.1038/s41586-021-03710-0.
[8]	Stein SR, Ramelli SC, Grazioli A, et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy[J]. Nature, 2022, 612: 758-763. doi:10.1038/s41586-022-05542-y.
[9]	Qiu W, Zhang H, Bao A, et al. Standardized operational protocol for human brain banking in China[J]. Neurosci Bull, 2019, 35: 270-276. doi:10.1007/s12264-018-0306-7.
[10]	World Medical Association. World medical association declaration of Helsinki: ethical principles for medical research involving human subjects[J]. JAMA, 2013, 310: 2191-2194. doi:10.1001/jama.2013.281053.
[11]	Fontes-Dantas FL, Fernandes GG, Gutman EG, et al. SARS-CoV-2 spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice[J]. Cell Rep, 2023, 42: 112189. doi:10.1016/j.celrep.2023.112189.
[12]	Copaescu A, Smibert O, Gibson A, et al. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection[J]. J Allergy Clin Immunol, 2020, 146: 518-534.e1. doi:10.1016/j.jaci.2020.07.001.
[13]	Zhang L, Zhou L, Bao L, et al. SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration[J]. Signal Transduct Target Ther, 2021, 6: 1-12. doi:10.1038/s41392-021-00719-9.
[14]	Villaseñor R, Kuennecke B, Ozmen L, et al. Region-specific permeability of the blood-brain barrier upon pericyte loss[J]. J Cereb Blood Flow Metab, 2017, 37: 3683-3694. doi:10.1177/0271678X17697340.
[15]	Hernández VS, Zetter MA, Guerra EC, et al. ACE2 expression in rat brain: implications for COVID-19 associated neurological manifestations[J]. Exp Neurol, 2021, 345: 113837. doi:10.1016/j.expneurol.2021.113837.