{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:43:26Z","timestamp":1782492206915,"version":"3.54.5"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Post-acute COVID syndrome (PACS) is a growing concern, given its impact on mental health and quality of life. However, its effects on cerebral white matter remain poorly understood, particularly in non-hospitalized cohorts. The goals of this cross-sectional, observational study were to examine (1) whether PACS was associated with distinct alterations in white matter microstructure, compared to symptom-matched non-COVID viral infection; and (2) whether microstructural alterations correlated with indices of post-COVID emotional health.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were collected for 54 symptomatic individuals who tested positive for COVID-19 (mean age 41\u2009\u00b1\u200912\u2009yrs., 36 female) and 14 controls who tested negative for COVID-19 (mean age 41\u2009\u00b1\u200914\u2009yrs., 8 female), with both groups assessed an average of 4\u20135\u2009months after COVID testing. Diffusion magnetic resonance imaging data were collected, and emotional health was assessed via the NIH emotion toolbox, with summary scores indexing social satisfaction, well-being and negative affect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Despite similar symptoms, the COVID-19 group had reduced mean and axial diffusivity, along with increased mean kurtosis and neurite dispersion, in deep white matter. After adjusting for social satisfaction, higher levels of negative affect in the COVID-19 group were also correlated with increased mean kurtosis and reduced free water in white matter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results provide preliminary evidence that indices of white matter microstructure distinguish PACS from symptomatic non-COVID infection. Moreover, white matter effects seen in PACS correlate with the severity of emotional sequelae, providing novel insights into this highly prevalent disorder.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1432450","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T04:46:23Z","timestamp":1722919583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of post-acute COVID-19 syndrome on cerebral white matter and emotional health among non-hospitalized individuals"],"prefix":"10.3389","volume":"15","author":[{"given":"Nathan W.","family":"Churchill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenie","family":"Roudaia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Jean","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Sekuler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqiang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Masellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivy","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Heyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E.","family":"Black","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley J.","family":"MacIntosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom A.","family":"Schweizer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1016\/S0140-6736(21)00847-3","article-title":"UK guidelines for managing long-term effects of COVID-19","volume":"397","author":"Shah","year":"2021","journal-title":"Lancet"},{"key":"ref3","year":"2021"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41591-021-01283-z","article-title":"Post-acute COVID-19 syndrome","volume":"27","author":"Nalbandian","year":"2021","journal-title":"Nat Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.cmi.2022.01.014","article-title":"Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: a systematic review and meta-analysis","volume":"28","author":"Alkodaymi","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1021\/acschemneuro.0c00122","article-title":"Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host\u2013virus interaction, and proposed neurotropic mechanisms","volume":"11","author":"Baig","year":"2020","journal-title":"ACS Chem Neurosci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.ejim.2021.06.009","article-title":"Prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized COVID-19 survivors: a systematic review and meta-analysis","volume":"92","author":"Fern\u00e1ndez-De-Las-Pe\u00f1as","year":"2021","journal-title":"Eur J Intern Med"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1148\/rg.2016160031","article-title":"White matter diseases with radiologic-pathologic correlation","volume":"36","author":"Sarbu","year":"2016","journal-title":"Radiographics"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1196\/annals.1444.017","article-title":"Cerebral white matter: neuroanatomy, clinical neurology, and neurobehavioral correlates","volume":"1142","author":"Schmahmann","year":"2008","journal-title":"Ann N Y Acad Sci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/jmri.10424","article-title":"Clinical applications of diffusion tensor imaging","volume":"19","author":"Dong","year":"2004","journal-title":"J Magnet Reson Imaging"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.3389\/fnins.2013.00031","article-title":"A hitchhiker's guide to diffusion tensor imaging","volume":"7","author":"Soares","year":"2013","journal-title":"Front Neurosci"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"W26","DOI":"10.2214\/AJR.13.11365","article-title":"Diffusion kurtosis imaging: an emerging technique for evaluating the microstructural environment of the brain","volume":"202","author":"Steven","year":"2014","journal-title":"Am J Roentgenol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1016\/j.neuroimage.2012.03.072","article-title":"NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain","volume":"61","author":"Zhang","year":"2012","journal-title":"NeuroImage"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1038\/s41586-022-04569-5","article-title":"SARS-CoV-2 is associated with changes in brain structure in UK biobank","volume":"604","author":"Douaud","year":"2022","journal-title":"Nature"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1093\/brain\/awab435","article-title":"Persistent white matter changes in recovered COVID-19 patients at the 1-year follow-up","volume":"145","author":"Huang","year":"2022","journal-title":"Brain"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"100484","DOI":"10.1016\/j.eclinm.2020.100484","article-title":"Cerebral micro-structural changes in COVID-19 patients\u2013an MRI-based 3-month follow-up study","volume":"25","author":"Lu","year":"2020","journal-title":"EClinicalMed"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"175628642211119","DOI":"10.1177\/17562864221111995","article-title":"Mid-term MRI evaluation reveals microstructural white matter alterations in COVID-19 fully recovered subjects with anosmia presentation","volume":"15","author":"Pelizzari","year":"2022","journal-title":"Ther Adv Neurol Disord"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e147329","DOI":"10.1172\/JCI147329","article-title":"Long-term microstructure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations","volume":"131","author":"Qin","year":"2021","journal-title":"J Clin Invest"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1515\/nipt-2022-0016","article-title":"Abnormal brain diffusivity in participants with persistent neuropsychiatric symptoms after COVID-19","author":"Liang","year":"2023","journal-title":"Neuroimmune Pharmacol Ther"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/nrn2297","article-title":"From inflammation to sickness and depression: when the immune system subjugates the brain","volume":"9","author":"Dantzer","year":"2008","journal-title":"Nat Rev Neurosci"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/S0166-2236(00)02088-9","article-title":"Cytokine-induced sickness behaviour: mechanisms and implications","volume":"25","author":"Konsman","year":"2002","journal-title":"Trends Neurosci"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/S1474-4422(09)70335-7","article-title":"Assessment of neurological and behavioural function: the NIH toolbox","volume":"9","author":"Gershon","year":"2010","journal-title":"Lancet Neurol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1093\/brain\/awac384","article-title":"Multimodal neuroimaging in post-COVID syndrome and correlation with cognition","volume":"146","author":"D\u00edez-Cirarda","year":"2023","journal-title":"Brain"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e1114","DOI":"10.9778\/cmajo.20210023","article-title":"Brain structure and function in people recovering from COVID-19 after hospital discharge or self-isolation: a longitudinal observational study protocol","volume":"9","author":"Macintosh","year":"2021","journal-title":"Can Med Assoc Open Access J"},{"key":"ref25","year":"2021"},{"key":"ref26","volume-title":"Ontario dashboard: percentage of cases caused by different variants in Ontario","year":"2022"},{"key":"ref27","volume-title":"Ontario moving to phase two of COVID-19 vaccine distribution plan","year":"2021"},{"key":"ref28","article-title":"Investigating the role of ICBM-space human brain diffusion tensor templates in inter-subject spatial normalization","volume":"344","author":"Zhang","year":"2011","journal-title":"Proc Intl Soc Mag Reson Med"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"S76","DOI":"10.1212\/WNL.0b013e3182872e11","article-title":"Emotion assessment using the NIH toolbox","volume":"80","author":"Salsman","year":"2013","journal-title":"Neurology"},{"key":"ref30","doi-asserted-by":"crossref","DOI":"10.1201\/9780429246593","volume-title":"An introduction to the bootstrap","author":"Efron","year":"1994"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1080\/03610926.2011.625486","article-title":"A parametric bootstrap approach for one-way ANCOVA with unequal variances","volume":"42","author":"Sadooghi-Alvandi","year":"2013","journal-title":"Commun Stat Theory Methods"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.neuroimage.2015.12.033","article-title":"Age effects and sex differences in human brain white matter of young to middle-aged adults: a DTI, NODDI, and q-space study","volume":"128","author":"Kodiweera","year":"2016","journal-title":"NeuroImage"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/B978-0-12-374709-9.00010-9","article-title":"DTI in development and aging","volume":"1","author":"Salat","year":"2009","journal-title":"Diffusion MRI"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.1097\/00001756-200312190-00035","article-title":"Sex differences in frontal lobe white matter microstructure: a DTI study","volume":"14","author":"Szeszko","year":"2003","journal-title":"Neuroreport"},{"key":"ref35","first-page":"10","volume-title":"Model selection and multi-model inference","author":"Anderson","year":"2004"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1016\/j.neuroimage.2003.07.005","article-title":"Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia","volume":"20","author":"Song","year":"2003","journal-title":"Neuroimage"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.neuroimage.2005.01.028","article-title":"Demyelination increases radial diffusivity in corpus callosum of mouse brain","volume":"26","author":"Song","year":"2005","journal-title":"Neuroimage"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1017\/S0033291720000999","article-title":"Posttraumatic stress symptoms and attitude toward crisis mental health services among clinically stable patients with COVID-19 in China","volume":"51","author":"Bo","year":"2021","journal-title":"Psychol Med"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41398-020-01039-2","article-title":"A quantitative and qualitative study on the neuropsychiatric sequelae of acutely ill COVID-19 inpatients in isolation facilities","volume":"10","author":"Hao","year":"2020","journal-title":"Transl Psychiatry"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1016\/j.nurpra.2021.05.003","article-title":"Recognizing the clinical sequelae of COVID-19 in adults: COVID-19 long-haulers","volume":"17","author":"Leviner","year":"2021","journal-title":"J Nurse Pract"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.bbi.2020.07.037","article-title":"Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors","volume":"89","author":"Mazza","year":"2020","journal-title":"Brain Behav Immun"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"9097","DOI":"10.3390\/ijerph17239097","article-title":"The impact of social support on public anxiety amidst the COVID-19 pandemic in China","volume":"17","author":"Ao","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1111\/famp.12618","article-title":"Stress-buffering role of social support during COVID-19","volume":"60","author":"Szkody","year":"2021","journal-title":"Fam Process"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e923549-41","DOI":"10.12659\/MSM.923549","article-title":"The effects of social support on sleep quality of medical staff treating patients with coronavirus disease 2019 (COVID-19) in January and February 2020 in China","volume":"26","author":"Xiao","year":"2020","journal-title":"Med Sci Monitor"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1002\/acn3.445","article-title":"Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?","volume":"4","author":"Grussu","year":"2017","journal-title":"Ann Clin Trans Neurol"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1007\/s00234-019-02249-2","article-title":"Microstructural characterization of corticospinal tract in subacute and chronic stroke patients with distal lesions by means of advanced diffusion MRI","volume":"61","author":"Mastropietro","year":"2019","journal-title":"Neuroradiology"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1002\/hbm.24500","article-title":"White matter during concussion recovery: comparing diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI)","volume":"40","author":"Churchill","year":"2019","journal-title":"Hum Brain Mapp"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1152\/physrev.00027.2007","article-title":"Diffusion in brain extracellular space","volume":"88","author":"Sykov\u00e1","year":"2008","journal-title":"Physiol Rev"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1093\/schbul\/sbaa134","article-title":"Large-scale evidence for an association between peripheral inflammation and white matter free water in schizophrenia and healthy individuals","volume":"47","author":"Di Biase","year":"2021","journal-title":"Schizophr Bull"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.schres.2015.05.034","article-title":"In vivo imaging of neuroinflammation in schizophrenia","volume":"173","author":"Pasternak","year":"2016","journal-title":"Schizophr Res"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"e13706","DOI":"10.1111\/eci.13706","article-title":"Estimate false-negative RT-PCR rates for SARS-CoV-2. A systematic review and meta-analysis","volume":"52","author":"Pecoraro","year":"2022","journal-title":"Eur J Clin Investig"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"e120","DOI":"10.1056\/NEJMp2025631","article-title":"Rethinking Covid-19 test sensitivity\u2014a strategy for containment","volume":"383","author":"Mina","year":"2020","journal-title":"N Engl J Med"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1093\/infdis\/jiad309","article-title":"Neuronal and glial metabolite abnormalities in participants with persistent neuropsychiatric symptoms after COVID-19: a brain proton magnetic resonance spectroscopy study","volume":"228","author":"Ernst","year":"2023","journal-title":"J Infect Dis"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"e2409","DOI":"10.1212\/WNL.0000000000207309","article-title":"Changes in brain activation patterns during working memory tasks in people with post-COVID condition and persistent neuropsychiatric symptoms","volume":"100","author":"Chang","year":"2023","journal-title":"Neurology"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/jmri.28555","article-title":"MRI assessment of cerebral blood flow in nonhospitalized adults who self-isolated due to COVID-19","volume":"58","author":"Kim","year":"2023","journal-title":"J Magn Reson Imaging"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1002\/mrm.26575","article-title":"Analysis of the effects of noise, DWI sampling, and value of assumed parameters in diffusion MRI models","volume":"78","author":"Hutchinson","year":"2017","journal-title":"Magn Reson Med"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1432450\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T04:46:28Z","timestamp":1722919588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1432450\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":56,"alternative-id":["10.3389\/fneur.2024.1432450"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2024.1432450","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]},"article-number":"1432450"}}