[en] Cohort studies that quantify volumetric brain data among individuals with different levels of COVID-19 severity are presently limited. It is still uncertain whether there exists a potential correlation between disease severity and the effects of COVID-19 on brain integrity. Our objective was to assess the potential impact of COVID-19 on measured brain volume in patients with asymptomatic/mild and severe disease after recovery from infection, compared with healthy controls, using artificial intelligence (AI)-based MRI volumetry. A total of 155 participants were prospectively enrolled in this IRB-approved analysis of three cohorts with a mild course of COVID-19 (n = 51, MILD), a severe hospitalised course (n = 48, SEV), and healthy controls (n = 56, CTL) all undergoing a standardised MRI protocol of the brain. Automated AI-based determination of various brain volumes in mL and calculation of normalised percentiles of brain volume was performed with mdbrain software, using a 3D T1-weighted magnetisation-prepared rapid gradient echo (MPRAGE) sequence. The automatically measured brain volumes and percentiles were analysed for differences between groups. The estimated influence of COVID-19 and demographic/clinical variables on brain volume was determined using multivariate analysis. There were statistically significant differences in measured brain volumes and percentiles of various brain regions among groups, even after the exclusion of patients undergoing intensive care, with significant volume reductions in COVID-19 patients, which increased with disease severity (SEV > MILD > CTL) and mainly affected the supratentorial grey matter, frontal and parietal lobes, and right thalamus. Severe COVID-19 infection, in addition to established demographic parameters such as age and sex, was a significant predictor of brain volume loss upon multivariate analysis. In conclusion, neocortical brain degeneration was detected in patients who had recovered from SARS-CoV-2 infection compared to healthy controls, worsening with greater initial COVID-19 severity and mainly affecting the fronto-parietal brain and right thalamus, regardless of ICU treatment. This suggests a direct link between COVID-19 infection and subsequent brain atrophy, which may have major implications for clinical management and future cognitive rehabilitation strategies.
Disciplines :
Neurology Immunology & infectious disease
Author, co-author :
Bendella, Zeynep; Department of Neuroradiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Widmann, Catherine Nichols ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Layer, Julian Philipp ; Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany ; Institute of Experimental Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
Layer, Yonah Lucas; Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
Haase, Robert ; Department of Neuroradiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, 53127 Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Sauer, Malte; Department of Neuroradiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Bieler, Luzie; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
Lehnen, Nils Christian; Department of Neuroradiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, 53127 Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Paech, Daniel ; Department of Neuroradiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, 53127 Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
HENEKA, Michael ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) ; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Radbruch, Alexander; Department of Neuroradiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, 53127 Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Schmeel, Frederic Carsten ; Department of Neuroradiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, 53127 Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Brain Volume Changes after COVID-19 Compared to Healthy Controls by Artificial Intelligence-Based MRI Volumetry.
Publication date :
12 May 2023
Journal title :
Diagnostics
ISSN :
2075-4418
eISSN :
2075-4418
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
the German Ministry of Health for the Umbrella Project COVIMMUNE—Untersuchungen zur Funktion des Immunsystems und dem Krankheitsverlauf von COVID-19
Funding text :
This research was funded by the German Ministry of Health for the Umbrella Project COVIMMUNE—Untersuchungen zur Funktion des Immunsystems und dem Krankheitsverlauf von COVID-19. Grant Number 01K/20343.
Aghagoli G. Gallo Marin B. Katchur N.J. Chaves-Sell F. Asaad W.F. Murphy S.A. Neurological Involvement in COVID-19 and Potential Mechanisms: A Review Neurocritcal Care 2021 34 1062 1071 10.1007/s12028-020-01049-4
Lechien J.R. Chiesa-Estomba C.M. De Siati D.R. Horoi M. Le Bon S.D. Rodriguez A. Dequanter D. Blecic S. El Afia F. Distinguin L. et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study Eur. Arch. Otorhinolaryngol. 2020 277 2251 2261 10.1007/s00405-020-05965-1 32253535
Ortelli P. Ferrazzoli D. Sebastianelli L. Engl M. Romanello R. Nardone R. Bonini I. Koch G. Saltuari L. Quartarone A. et al. Neuropsychological and neurophysiological correlates of fatigue in post-acute patients with neurological manifestations of COVID-19: Insights into a challenging symptom J. Neurol. Sci. 2021 420 117271 10.1016/j.jns.2020.117271
Romagnolo A. Balestrino R. Imbalzano G. Ciccone G. Riccardini F. Artusi C.A. Bozzali M. Ferrero B. Montalenti E. Montanaro E. et al. Neurological comorbidity and severity of COVID-19 J. Neurol. 2021 268 762 769 10.1007/s00415-020-10123-y 32749601
Herman C. Mayer K. Sarwal A. Scoping review of prevalence of neurologic comorbidities in patients hospitalized for COVID-19 Neurology 2020 95 77 84 10.1212/WNL.0000000000009673
Heneka M.T. Golenbock D. Latz E. Morgan D. Brown R. Immediate and long-term consequences of COVID-19 infections for the development of neurological disease Alzheimer’s Res. Ther. 2020 12 69 10.1186/s13195-020-00640-3
Mao L. Jin H. Wang M. Hu Y. Chen S. He Q. Chang J. Hong C. Zhou Y. Wang D. et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China JAMA Neurol. 2020 77 683 690 10.1001/jamaneurol.2020.1127
Helms J. Kremer S. Merdji H. Clere-Jehl R. Schenck M. Kummerlen C. Collange O. Boulay C. Fafi-Kremer S. Ohana M. et al. Neurologic Features in Severe SARS-CoV-2 Infection N. Engl. J. Med. 2020 382 2268 2270 10.1056/NEJMc2008597
Paterson R.W. Brown R.L. Benjamin L. Nortley R. Wiethoff S. Bharucha T. Jayaseelan D.L. Kumar G. Raftopoulos R.E. Zambreanu L. et al. The emerging spectrum of COVID-19 neurology: Clinical, radiological and laboratory findings Brain 2020 143 3104 3120 10.1093/brain/awaa240
Widmann C.N. Wieberneit M. Bieler L. Bernsen S. Grafenkamper R. Brosseron F. Schmeel C. Tacik P. Skowasch D. Radbruch A. et al. Longitudinal Neurocognitive and Pulmonological Profile of Long COVID-19: Protocol for the COVIMMUNE-Clin Study JMIR Res. Protoc. 2021 10 e30259 10.2196/30259 34559059
Dieckmeyer M. Roy A.G. Senapati J. Wachinger C. Grundl L. Dopfert J. Bertran P.F. Lemke A. Zimmer C. Kirschke J.S. et al. Effect of MRI acquisition acceleration via compressed sensing and parallel imaging on brain volumetry Magn. Reson. Mater. Phys. Biol. Med. 2021 34 487 497 10.1007/s10334-020-00906-9 33502667
Suchyta M.R. Jephson A. Hopkins R.O. Neurologic changes during critical illness: Brain imaging findings and neurobehavioral outcomes Brain Imaging Behav. 2010 4 22 34 10.1007/s11682-009-9082-3
Gunther M.L. Morandi A. Krauskopf E. Pandharipande P. Girard T.D. Jackson J.C. Thompson J. Shintani A.K. Geevarghese S. Miller R.R. 3rd et al. The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: The VISIONS cohort magnetic resonance imaging study* Crit. Care Med. 2012 40 2022 2032 10.1097/CCM.0b013e318250acc0 22710202
Manca R. De Marco M. Ince P.G. Venneri A. Heterogeneity in Regional Damage Detected by Neuroimaging and Neuropathological Studies in Older Adults With COVID-19: A Cognitive-Neuroscience Systematic Review to Inform the Long-Term Impact of the Virus on Neurocognitive Trajectories Front. Aging Neurosci. 2021 13 646908 10.3389/fnagi.2021.646908
Douaud G. Lee S. Alfaro-Almagro F. Arthofer C. Wang C. McCarthy P. Lange F. Andersson J.L.R. Griffanti L. Duff E. et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank Nature 2022 604 697 707 10.1038/s41586-022-04569-5 35255491
Hosp J.A. Dressing A. Blazhenets G. Bormann T. Rau A. Schwabenland M. Thurow J. Wagner D. Waller C. Niesen W.D. et al. Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19 Brain 2021 144 1263 1276 10.1093/brain/awab009
Guedj E. Million M. Dudouet P. Tissot-Dupont H. Bregeon F. Cammilleri S. Raoult D. (18)F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: Substrate for persistent/delayed disorders? Eur. J. Nucl. Med. Mol. Imaging 2021 48 592 595 10.1007/s00259-020-04973-x 32728799
Duan K. Premi E. Pilotto A. Cristillo V. Benussi A. Libri I. Giunta M. Bockholt H.J. Liu J. Campora R. et al. Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19 Neurobiol. Stress 2021 14 100326 10.1016/j.ynstr.2021.100326
Griffanti L. Raman B. Alfaro-Almagro F. Filippini N. Cassar M.P. Sheerin F. Okell T.W. Kennedy McConnell F.A. Chappell M.A. Wang C. et al. Adapting the UK Biobank Brain Imaging Protocol and Analysis Pipeline for the C-MORE Multi-Organ Study of COVID-19 Survivors Front. Neurol. 2021 12 753284 10.3389/fneur.2021.753284
Lee M.H. Perl D.P. Nair G. Li W. Maric D. Murray H. Dodd S.J. Koretsky A.P. Watts J.A. Cheung V. et al. Microvascular Injury in the Brains of Patients with COVID-19 N. Engl. J. Med. 2021 384 481 483 10.1056/NEJMc2033369
Sanabria-Diaz G. Etter M.M. Melie-Garcia L. Lieb J.M. Psychogios M.N. Hutter G. Granziera C. Brain cortical alterations in COVID-19 patients with neurological symptoms Front. Neurosci. 2022 16 992165 10.3389/fnins.2022.992165 36340780
Kandemirli S.G. Dogan L. Sarikaya Z.T. Kara S. Akinci C. Kaya D. Kaya Y. Yildirim D. Tuzuner F. Yildirim M.S. et al. Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection Radiology 2020 297 E232 E235 10.1148/radiol.2020201697 32384020
Bougakov D. Podell K. Goldberg E. Multiple Neuroinvasive Pathways in COVID-19 Mol. Neurobiol. 2021 58 564 575 10.1007/s12035-020-02152-5
Romoli M. Jelcic I. Bernard-Valnet R. Garcia Azorin D. Mancinelli L. Akhvlediani T. Monaco S. Taba P. Sellner J. Infectious Disease Panel of the European Academy of Neurology A systematic review of neurological manifestations of SARS-CoV-2 infection: The devil is hidden in the details Eur. J. Neurol. 2020 27 1712 1726 10.1111/ene.14382 32503088
Calsavara A.J.C. Nobre V. Barichello T. Teixeira A.L. Post-sepsis cognitive impairment and associated risk factors: A systematic review Aust. Crit. Care 2018 31 242 253 10.1016/j.aucc.2017.06.001
Jackson J.C. Pandharipande P.P. Girard T.D. Brummel N.E. Thompson J.L. Hughes C.G. Pun B.T. Vasilevskis E.E. Morandi A. Shintani A.K. et al. Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: A longitudinal cohort study Lancet Respir. Med. 2014 2 369 379 10.1016/S2213-2600(14)70051-7
Julayanont P. Tangwongchai S. Hemrungrojn S. Tunvirachaisakul C. Phanthumchinda K. Hongsawat J. Suwichanarakul P. Thanasirorat S. Nasreddine Z.S. The Montreal Cognitive Assessment-Basic: A Screening Tool for Mild Cognitive Impairment in Illiterate and Low-Educated Elderly Adults J. Am. Geriatr. Soc. 2015 63 2550 2554 10.1111/jgs.13820
Ibi K. Fujii K. Kobayashi H. Senda M. Kitazawa K. Honda A. Anterior cingulate cortex involvement in non-paraneoplastic limbic encephalitis Brain Dev. 2019 41 735 739 10.1016/j.braindev.2019.04.006
Lu Y. Li X. Geng D. Mei N. Wu P.Y. Huang C.C. Jia T. Zhao Y. Wang D. Xiao A. et al. Cerebral Micro-Structural Changes in COVID-19 Patients—An MRI-based 3-month Follow-up Study EClinicalMedicine 2020 25 100484 10.1016/j.eclinm.2020.100484
Seidenberg M. Hermann B. Pulsipher D. Morton J. Parrish J. Geary E. Guidotti L. Thalamic atrophy and cognition in unilateral temporal lobe epilepsy J. Int. Neuropsychol. Soc. 2008 14 384 393 10.1017/S1355617708080399
Yang A.C. Kern F. Losada P.M. Agam M.R. Maat C.A. Schmartz G.P. Fehlmann T. Stein J.A. Schaum N. Lee D.P. et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19 Nature 2021 595 565 571 10.1038/s41586-021-03710-0 34153974
de Erausquin G.A. Snyder H. Carrillo M. Hosseini A.A. Brugha T.S. Seshadri S. CNS SARS-CoV-2 Consortium The chronic neuropsychiatric sequelae of COVID-19: The need for a prospective study of viral impact on brain functioning Alzheimer’s Dement. 2021 17 1056 1065 10.1002/alz.12255
Meinhardt J. Radke J. Dittmayer C. Franz J. Thomas C. Mothes R. Laue M. Schneider J. Brunink S. Greuel S. et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19 Nat. Neurosci. 2021 24 168 175 10.1038/s41593-020-00758-5 33257876
Butowt R. Meunier N. Bryche B. von Bartheld C.S. The olfactory nerve is not a likely route to brain infection in COVID-19: A critical review of data from humans and animal models Acta Neuropathol. 2021 141 809 822 10.1007/s00401-021-02314-2 33903954
Butowt R. Bilinska K. von Bartheld C.S. Olfactory dysfunction in COVID-19: New insights into the underlying mechanisms Trends Neurosci. 2023 46 75 90 10.1016/j.tins.2022.11.003
Postma E.M. Smeets P.A.M. Boek W.M. Boesveldt S. Investigating morphological changes in the brain in relation to etiology and duration of olfactory dysfunction with voxel-based morphometry Sci. Rep. 2021 11 12704 10.1038/s41598-021-92224-w
Zhang H. Wang X. Lin J. Sun Y. Huang Y. Yang T. Zheng S. Fan M. Zhang J. Reduced regional gray matter volume in patients with chronic obstructive pulmonary disease: A voxel-based morphometry study AJNR Am. J. Neuroradiol. 2013 34 334 339 10.3174/ajnr.A3235
Harch P.G. Fogarty E.F. Subacute normobaric oxygen and hyperbaric oxygen therapy in drowning, reversal of brain volume loss: A case report Med. Gas Res. 2017 7 144 149 10.4103/2045-9912.208521
Wilcox M.E. Brummel N.E. Archer K. Ely E.W. Jackson J.C. Hopkins R.O. Cognitive dysfunction in ICU patients: Risk factors, predictors, and rehabilitation interventions Crit. Care Med. 2013 41 S81 S98 10.1097/CCM.0b013e3182a16946