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Microglial Inflammatory Responses to SARS‐CoV‐2 Infection: A Comprehensive Review

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Abstract

Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease causing a worldwide pandemic in the year of 2019. SARS‐CoV‐2 is an enveloped, positive-stranded RNA virus that could invade the host through spike protein and exhibits multi-organ effects. The Brain was considered to be a potential target for SARS‐CoV‐2 infection. Although neuropsychiatric symptoms and cognitive impairments were observed in COVID-19 patients even after recovery the mechanism of action is not well documented. In this review, the contribution of microglia in response to SARS‐CoV‐2 infection was discussed aiming to design a therapeutic regimen for the management of neuroinflammation and psycho-behavioral alterations. Priming of microglia facilitates the hyper-activation state when it interacts with SARS-CoV-2 known as the ‘second hit’. Moreover, the microgliosis produces reactive free radicals and pro-inflammatory cytokines like IL-1β, IFN-γ, and IL-6 which ultimately contribute to a ‘cytokine storm’, thereby increasing the occurrence of cognitive and neurological dysfunction. It was reported that elevated CCL11 may be responsible for psychiatric disorders and ROS/RNS-induced oxidative stress could promote major depressive disorder (MDD) and phenotypic switching. Additionally, during SARS-CoV-2 infection microglia-CD8+ T cell interaction may have a significant role in neuronal cell death. This cytokine-mediated cellular cross-talking plays a crucial role in pro-inflammatory and anti-inflammatory balance within the COVID-19 patient’s brain. Therefore, all these aspects will be taken into consideration for developing novel therapeutic strategies to combat SARS-CoV-2-induced neuroinflammation.

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Acknowledgements

The authors are highly thankful to the Department of Medical Laboratory Technology, Swami Vivekananda University, Barrackpore and Immunology Laboratory, Department of Physiology, University of Calcutta. The authors also declare that no funds or grants were received during the preparation of this article.

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No funds were received for this review work.

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RD participated in the conception of the study. RD participated in literature searches and extraction. RD wrote the manuscript and BB approved the article for submission to this journal.

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Correspondence to Rajen Dey.

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Dey, R., Bishayi, B. Microglial Inflammatory Responses to SARS‐CoV‐2 Infection: A Comprehensive Review. Cell Mol Neurobiol 44, 2 (2024). https://doi.org/10.1007/s10571-023-01444-3

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  • DOI: https://doi.org/10.1007/s10571-023-01444-3

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