DOI record: { "DOI": "10.21203/rs.3.rs-10638786/v1", "URL": "http://dx.doi.org/10.21203/rs.3.rs-10638786/v1", "abstract": "<title>Abstract</title>\n <p>Cognitive impairment in long COVID has been linked to hippocampal neuroinflammation and elevated levels of CCL11, a chemokine associated with microgliosis and neuronal dysfunction. Vitamin B12 has emerged as a potential modulator of neuroinflammation, including through the inhibition of CCL11 transcription. Adult golden Syrian hamsters were intranasally infected with the SARS-CoV-2 Omicron variant and treated with vitamin B12 beginning three days after infection. Body weight and food intake were monitored throughout the study. At 15 days post infection, hippocampal transcriptomic alterations were investigated by RNA-Seq; microglial density and morphology were assessed by Iba1 immunohistochemistry; and NeuN-expressing postmitotic neuron density and alpha-synuclein levels were evaluated by immunofluorescence in the CA1 and CA3 hippocampal subregions. Plasma vitamin B12 and CCL11 concentrations, as well as hippocampal CCL11 levels, were quantified by ELISA. SARS-CoV-2 infection caused weight loss and reduced food intake during the acute phase and subsequently increased hippocampal CCL11 levels, reduced NeuN+ neuron density, induced sex- and subregion-dependent microglial alterations, and, in females, promoted hippocampal transcriptional reprogramming involving neurodegeneration-related pathways. Vitamin B12 modestly attenuated weight loss, prevented inappetence, and mitigated the increase in hippocampal CCL11 levels. It also preserved NeuN+ neuron density and modulated microglial and transcriptomic alterations in a sex-dependent manner. These findings support a role for CCL11 in hippocampal dysfunction associated with post-acute COVID-19 and suggest that early vitamin B12 treatment may mitigate neuroinflammatory and neuronal alterations, highlighting its potential as an adjuvant therapy for the neurological complications of this disease.</p>", "accepted": { "date-parts": [ [ 2026, 8, 8 ] ] }, "author": [ { "affiliation": [ { "name": "Neurogenômica, Instituto René Rachou (IRR), Fundação Oswaldo Cruz (Fiocruz)" } ], "family": "Oliveira", "given": "Marina da Silva", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "first" }, { "affiliation": [ { "name": "Neurogenômica, Instituto René Rachou (IRR), Fundação Oswaldo Cruz (Fiocruz)" } ], "family": "Silva-Contigli", "given": "Leonardo", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Instituto René Rachou (IRR), Fundação Oswaldo Cruz (Fiocruz)" } ], "family": "Salim", "given": "Anna Cristina Matos", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Neurogenômica, Instituto René Rachou (IRR), Fundação Oswaldo Cruz (Fiocruz)" } ], "family": "de Souza", "given": "Dayane Lorena Naves", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Neurogenômica, Instituto René Rachou (IRR), Fundação Oswaldo Cruz (Fiocruz)" } ], "family": "de Souza", "given": "Natália Satchiko Hojo", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Universidade Federal de Minas Gerais" } ], "family": "Romano-Silva", "given": "Marco Aurélio", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Neurogenômica, Instituto René Rachou (IRR), Fundação Oswaldo Cruz (Fiocruz)" } ], "family": "Coimbra", "given": "Roney Santos", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2026, 11, 5 ] ], "date-time": "2026-11-05T17:07:39Z", "timestamp": 1793898459000 }, "deposited": { "date-parts": [ [ 2026, 11, 5 ] ], "date-time": "2026-11-05T17:07:44Z", "timestamp": 1793898464000 }, "group-title": "In Review", "indexed": { "date-parts": [ [ 2026, 11, 5 ] ], "date-time": "2026-11-05T17:28:25Z", "timestamp": 1793899705692, "version": "4.8.0" }, "institution": [ { "name": "Research Square" } ], "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2026, 11, 5 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "unspecified", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 11, 5 ] ], "date-time": "2026-11-05T00:00:00Z", "timestamp": 1793836800000 } } ], "link": [ { "URL": "https://www.researchsquare.com/article/rs-10638786/v1", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.researchsquare.com/article/rs-10638786/v1.html", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "posted": { "date-parts": [ [ 2026, 11, 5 ] ] }, "prefix": "10.21203", "published": { "date-parts": [ [ 2026, 11, 5 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1007/s13205-025-04468-2", "article-title": "Implicating neuroinflammation in hippocampus, prefrontal cortex and amygdala with cognitive deficit: a narrative review", "author": "Blossom V", "doi-asserted-by": "publisher", "first-page": "320", "issue": "9", "journal-title": "3 Biotech", "key": "ref1", "unstructured": "Blossom V, Ullal SD, D’Souza MM, Ranade AV, Kumar NA, Rai R (2025) Implicating neuroinflammation in hippocampus, prefrontal cortex and amygdala with cognitive deficit: a narrative review. 3 Biotech 15(9):320. https://doi.org/10.1007/s13205-025-04468-2", "volume": "15", "year": "2025" }, { "DOI": "10.1093/bioinformatics/btu170", "article-title": "Trimmomatic: a flexible trimmer for Illumina sequence data", "author": "Bolger AM", "doi-asserted-by": "publisher", "first-page": "2114", "issue": "15", "journal-title": "Bioinformatics", "key": "ref2", "unstructured": "Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. 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