Unraveling the Link Between COVID-19 and Memory Deficits: The Role of Brain Microglia Activation

DOI record: { "DOI": "10.3390/neuroglia7010010", "ISSN": [ "2571-6980" ], "URL": "http://dx.doi.org/10.3390/neuroglia7010010", "abstract": "<jats:p>The coronavirus disease 2019 (COVID-19) pandemic has been associated with a wide range of neurological complications, among which persistent cognitive impairment and memory deficits are increasingly recognized as key symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID). Although clinical and epidemiological studies have documented these symptoms across diverse patient populations, the underlying neurobiological mechanisms remain incompletely understood. Growing evidence from human studies, neuropathological analyses, and experimental models indicates that neuroimmune and inflammatory processes plays a central role in COVID-19-associated cognitive dysfunction. As the brain’s resident immune cells, microglia are vital for synaptic health, neuroplasticity, and memory, yet these processes may be compromised after SARS-CoV-2 infection. Systemic inflammation, blood–brain barrier (BBB) disruption, endothelial injury, and cytokine signaling can induce sustained microglial activation and priming, leading to inflammasome activation, complement-mediated synaptic remodeling, oxidative stress, and impaired hippocampal neurogenesis. These processes collectively disrupt neural circuits involved in learning and memory and may underlie the persistent “brain fog” reported by COVID-19 survivors. This review synthesizes clinical, biomarker, neuroimaging, and mechanistic evidence linking SARS-CoV-2 infection to microglia-mediated neuroinflammation and memory impairment. In contrast to prior reviews that broadly describe neuroinflammation in COVID-19, we integrate multidimensional evidence into a microglia-centric immunovascular framework that highlights converging pathogenic pathways underlying cognitive symptoms. We further discuss emerging biomarkers of glial activation and evaluate current and prospective therapeutic strategies targeting microglial and neuroimmune pathways. Understanding the role of microglial dysregulation in post-COVID cognitive impairment may facilitate the development of targeted interventions to mitigate long-term neurological consequences of COVID-19.</jats:p>", "alternative-id": [ "neuroglia7010010" ], "author": [ { "ORCID": "https://orcid.org/0000-0003-1570-3588", "affiliation": [ { "name": "Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh" }, { "name": "Laboratory of Advanced Computational Biology, Biological Research on the Brain (BRB), Jashore 7408, Bangladesh" } ], "authenticated-orcid": false, "family": "Aktaruzzaman", "given": "Md.", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0003-3839-2145", "affiliation": [ { "name": "Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh" } ], "authenticated-orcid": false, "family": "Abid", "given": "Md. Ahsan", "sequence": "additional" }, { "ORCID": "https://orcid.org/0009-0008-4017-6963", "affiliation": [ { "name": "Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh" } ], "authenticated-orcid": false, "family": "Rakib", "given": "Md. Asaduzzaman", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, USA" } ], "family": "Islam", "given": "Md. Sazzadul", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Genetic Engineering and Biotechnology, Jagannath University, Dhaka 1100, Bangladesh" } ], "family": "Dona", "given": "Humayra Afroz", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-0503-101X", "affiliation": [ { "name": "Department of Genetic Engineering and Biotechnology, Jagannath University, Dhaka 1100, Bangladesh" } ], "authenticated-orcid": false, "family": "Tabassum", "given": "Afrida", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Pharmacy, Gono Bishwabidyalay, Savar, Dhaka 1344, Bangladesh" } ], "family": "Hossain", "given": "Nazmul", "sequence": "additional" }, { "ORCID": "https://orcid.org/0009-0007-2124-2251", "affiliation": [ { "name": "Department of Pharmacy, Gono Bishwabidyalay, Savar, Dhaka 1344, Bangladesh" } ], "authenticated-orcid": false, "family": "Sezin", "given": "Sabekun Nahar", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-8690-1058", "affiliation": [ { "name": "Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj, Dhaka 8100, Bangladesh" } ], "authenticated-orcid": false, "family": "Metu", "given": "Chowdhury Lutfun Nahar", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Pharmaceutical Sciences, College of Health Sciences and Pharmacy, Chicago State University, Chicago, IL 60628, USA" } ], "family": "Raihan", "given": "Md. Obayed", "sequence": "additional" } ], "container-title": "Neuroglia", "container-title-short": "Neuroglia", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2026, 3, 16 ] ], "date-time": "2026-03-16T08:41:26Z", "timestamp": 1773650486000 }, "deposited": { "date-parts": [ [ 2026, 3, 16 ] ], "date-time": "2026-03-16T09:30:09Z", "timestamp": 1773653409000 }, "indexed": { "date-parts": [ [ 2026, 3, 16 ] ], "date-time": "2026-03-16T10:08:32Z", "timestamp": 1773655712586, "version": "3.50.1" }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2026, 3, 16 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2026, 3 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 3, 16 ] ], "date-time": "2026-03-16T00:00:00Z", "timestamp": 1773619200000 } } ], "link": [ { "URL": "https://www.mdpi.com/2571-6980/7/1/10/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "10", "prefix": "10.3390", "published": { "date-parts": [ [ 2026, 3, 16 ] ] }, "published-online": { "date-parts": [ [ 2026, 3, 16 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1186/s12974-022-02579-8", "article-title": "COVID-19 and cognitive impairment: Neuroinvasive and blood-brain barrier dysfunction", "author": "Chen", "doi-asserted-by": "crossref", "first-page": "222", "journal-title": "J. 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