{"doi":"10.3389/fmicb.2024.1404312","title":"Impact of age and sex on neuroinflammation following SARS-CoV-2 infection in a murine model","abstract":"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is known to infect people of all ages and both sexes. Senior populations have the greatest risk of severe COVID-19, and sexual dimorphism in clinical outcomes has been reported. Neurological symptoms are widely observed in COVID-19 patients, with many survivors exhibiting persistent neurological and cognitive impairment. The present study aims to investigate the impact of age and sex on the neuroinflammatory response to SARS-CoV-2 infection using a mouse model. Wild-type C57BL/6J mice were intranasally inoculated with SARS-CoV-2 lineage B.1.351, a variant known to infect mice. Older male mice exhibited a significantly greater weight loss and higher viral loads in the lung at 3 days post infection. Notably, no viral RNA was detected in the brains of infected mice. Nevertheless, expression of IL-6, TNF-α, and CCL-2 in the lung and brain increased with viral infection. RNA-seq transcriptomic analysis of brains showed that SARS-CoV-2 infection caused significant changes in gene expression profiles, implicating innate immunity, defense response to virus, and cerebrovascular and neuronal functions. These findings demonstrate that SARS-CoV-2 infection triggers a neuroinflammatory response, despite the lack of detectable virus in the brain. Aberrant activation of innate immune response, disruption of blood-brain barrier and endothelial cell integrity, and suppression of neuronal activity and axonogenesis underlie the impact of SARS-CoV-2 infection on the brain. Understanding the role of these affected pathways in SARS-CoV-2 pathogenesis helps identify appropriate points of therapeutic interventions to alleviate neurological dysfunction observed during COVID-19.","journal":"Frontiers in Microbiology","year":2024,"id":434207,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1172678,"name":"Allison Chang","orcid":"0000-0003-4194-2304","position":1,"is_corresponding":false},{"id":655228,"name":"Holly Korthas","orcid":"0000-0003-0153-3549","position":2,"is_corresponding":false},{"id":1108582,"name":"Susanna R. Var","orcid":"0000-0002-5494-4248","position":3,"is_corresponding":false},{"id":337450,"name":"Davis Seelig","orcid":"0000-0002-1733-8177","position":4,"is_corresponding":false},{"id":337787,"name":"Walter C. Low","orcid":"0000-0001-8593-0175","position":5,"is_corresponding":false},{"id":20492,"name":" Ling Li","orcid":"0000-0002-9245-7387","position":6,"is_corresponding":false},{"id":500956,"name":"Maxim C.‐J. Cheeran","orcid":"0000-0002-5331-4746","position":7,"is_corresponding":false},{"id":500953,"name":"Venkatramana D. Krishna","orcid":"0000-0002-1980-5525","position":0,"is_corresponding":true}],"reference_count":112,"raw_metadata":null,"created_at":"2026-07-19T01:59:53.957667Z","pmid":"39077737","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}