{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:38:11Z","timestamp":1773920291463,"version":"3.50.1"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Advancing Translational Sciences of the National Institutes of Health","award":["UL1TR000114"],"award-info":[{"award-number":["UL1TR000114"]}]},{"name":"Institutional Center Cores for Advanced Neuroimaging","award":["S10 OD017974"],"award-info":[{"award-number":["S10 OD017974"]}]},{"name":"Institutional Center Cores for Advanced Neuroimaging","award":["P30 NS076408"],"award-info":[{"award-number":["P30 NS076408"]}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["P41 EB027061"],"award-info":[{"award-number":["P41 EB027061"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health","award":["R01 NS124065-02S1"],"award-info":[{"award-number":["R01 NS124065-02S1"]}]},{"name":"National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health","award":["R01 NS124065"],"award-info":[{"award-number":["R01 NS124065"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Hum. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neurological post-acute sequelae of COVID-19 (neuroPASC) are associated with persistent cognitive dysfunction and quality-of-life decline. We aimed to identify clinical, behavioral and sociodemographic factors associated with neuroPASC symptom burden two years after COVID-19 among individuals without prior neurological disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this prospective, observational study, individuals with neuroPASC (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f102) and controls without symptomatic COVID-19 (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f74), all without prior neurological, psychiatric, or post-viral conditions, were enrolled between February 2022 and June 2024 across five academic sites. An unsupervised algorithm identified clusters with differing self-reported neurological symptom burden within the neuroPASC group. Functional differences between clusters were evaluated using quality-of-life, neurological and cognitive evaluations. Demographics, behavioral history, comorbidities, and blood biomarkers were compared across clusters and controls. Multivariable logistic regression assessed predictors of neuroPASC severity, including demographics, body-mass-index, Charlson Comorbidity Index, Framingham Risk Score, pre-existing endocrine\/metabolic and\/or gastrointestinal\/hepatobiliary conditions, COVID-19 vaccination prior to infection, hospitalization during acute infection, and cumulative alcohol use.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two clusters emerged based on neurological symptom burden, labeled \u201chigh-burden\u201d and \u201clow-burden\u201d neuroPASC, reflecting differences in the number and frequency of symptoms. Both clusters had deficits in quality-of-life and cognitive function compared to controls, with greater impairment in high-burden than low-burden neuroPASC. The clusters did not differ by sex, education, tobacco and cannabis use, blood pressure, body-mass-index, HbA1C, days since infection, hospitalization during COVID-19, pre-COVID vaccination rate, antibody-positivity, inflammation, and neurodegeneration biomarkers. The high-burden cluster was older and exhibited higher comorbidity burden and greater cumulative alcohol use compared with the low-burden cluster and controls. Pre-existing endocrine\/metabolic and gastrointestinal\/hepatobiliary conditions were more common in high-burden (63%) than in low-burden neuroPASC (35%). After adjusting for clinical and demographic factors, these pre-existing conditions remained the only independent predictor of severity, conferring a 3.5-fold increase in the odds of high-burden versus low-burden neuroPASC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Older age, higher comorbidity burden, greater cumulative alcohol use, and endocrine\/metabolic and gastrointestinal conditions, rather than acute COVID-19 severity, were observed in the high-burden neuroPASC cluster. After multivariable adjustment, only pre-existing endocrine\/metabolic and\/or gastrointestinal\/hepatobiliary conditions remained independently associated with high-burden neuroPASC, conferring a 3.5-fold increase in odds and highlighting the need for targeted post-infection monitoring in at-risk patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnhum.2026.1754342","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:50:46Z","timestamp":1773903046000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Factors associated with severe neurological sequelae of COVID-19: findings from the multicenter COVID-BRAIN imaging cohort"],"prefix":"10.3389","volume":"20","author":[{"given":"Ana I.","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keenan Christopher","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. 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