{"doi":"10.1093/infdis/jiad309","title":"Neuronal and Glial Metabolite Abnormalities in Participants With Persistent Neuropsychiatric Symptoms After COVID-19: A Brain Proton Magnetic Resonance Spectroscopy Study","abstract":"BACKGROUND: The aim of this study was to determine whether neurometabolite abnormalities indicating neuroinflammation and neuronal injury are detectable in individuals post-coronavirus disease 2019 (COVID-19) with persistent neuropsychiatric symptoms. METHODS: All participants were studied with proton magnetic resonance spectroscopy at 3 T to assess neurometabolite concentrations (point-resolved spectroscopy, relaxation time/echo time = 3000/30 ms) in frontal white matter (FWM) and anterior cingulate cortex-gray matter (ACC-GM). Participants also completed the National Institutes of Health Toolbox cognition and motor batteries and selected modules from the Patient-Reported Outcomes Measurement Information System. RESULTS: Fifty-four participants were evaluated: 29 post-COVID-19 (mean ± SD age, 42.4 ± 12.3 years; approximately 8 months from COVID-19 diagnosis; 19 women) and 25 controls (age, 44.1 ± 12.3 years; 14 women). When compared with controls, the post-COVID-19 group had lower total N-acetyl compounds (tNAA; ACC-GM: -5.0%, P = .015; FWM: -4.4%, P = .13), FWM glutamate + glutamine (-9.5%, P = .001), and ACC-GM myo-inositol (-6.2%, P = .024). Additionally, only hospitalized patients post-COVID-19 showed age-related increases in myo-inositol, choline compounds, and total creatine (interaction P = .029 to <.001). Across all participants, lower FWM tNAA and higher ACC-GM myo-inositol predicted poorer performance on several cognitive measures (P = .001-.009), while lower ACC-GM tNAA predicted lower endurance on the 2-minute walk (P = .005). CONCLUSIONS: In participants post-COVID-19 with persistent neuropsychiatric symptoms, the lower-than-normal tNAA and glutamate + glutamine indicate neuronal injury, while the lower-than-normal myo-inositol reflects glial dysfunction, possibly related to mitochondrial dysfunction and oxidative stress in Post-COVID participants with persistent neuropsychiatric symptoms.","journal":"The Journal of Infectious Diseases","year":2023,"id":325875,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":285283,"name":"Meghann C. Ryan","orcid":"0000-0003-3822-423X","position":1,"is_corresponding":false},{"id":578578,"name":"Huajun Liang","orcid":"0000-0002-3118-6296","position":2,"is_corresponding":false},{"id":10636,"name":"J. Wang","orcid":"0000-0002-5246-5497","position":3,"is_corresponding":false},{"id":356979,"name":"Eric Cunningham","orcid":"0000-0001-8705-3620","position":4,"is_corresponding":false},{"id":238013,"name":"Muhammad G. Saleh","orcid":"0000-0001-6921-112X","position":5,"is_corresponding":false},{"id":269403,"name":"Shyamasundaran Kottilil","orcid":null,"position":6,"is_corresponding":false},{"id":69435,"name":"Linda Chang","orcid":"0000-0002-1267-0699","position":7,"is_corresponding":false},{"id":387897,"name":"Thomas Ernst","orcid":"0000-0003-1211-7655","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:08:28.266998Z","pmid":"37540098","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":[]}