Brain connectivity and microstructure in COVID-19 patients with cognitive or olfactory dysfunction.

Poster No:

1529 

Submission Type:

Abstract Submission 

Authors:

Alberto Arrigoni1, Mattia Previtali1, Sara Bosticardo2, Giulio Pezzetti3, Sofia Poloni1, Serena Capelli1, Angela Napolitano3, Andrea Remuzzi4, Rosalia Zangari3, Ferdinando Lorini3, Maria Sessa3, Alessandro Daducci2, Anna Caroli1, Simonetta Gerevini3

Institutions:

1Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy, 2University of Verona, Verona, Italy, 3ASST Papa Giovanni XXIII, Bergamo, Italy, 4University of Bergamo, Bergamo, Italy

First Author:

Alberto Arrigoni  
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Bergamo, Italy

Co-Author(s):

Mattia Previtali  
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Bergamo, Italy
Sara Bosticardo  
University of Verona
Verona, Italy
Giulio Pezzetti  
ASST Papa Giovanni XXIII
Bergamo, Italy
Sofia Poloni  
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Bergamo, Italy
Serena Capelli  
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Bergamo, Italy
Angela Napolitano  
ASST Papa Giovanni XXIII
Bergamo, Italy
Andrea Remuzzi  
University of Bergamo
Bergamo, Italy
Rosalia Zangari  
ASST Papa Giovanni XXIII
Bergamo, Italy
Ferdinando Lorini  
ASST Papa Giovanni XXIII
Bergamo, Italy
Maria Sessa  
ASST Papa Giovanni XXIII
Bergamo, Italy
Alessandro Daducci  
University of Verona
Verona, Italy
Anna Caroli  
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Bergamo, Italy
Simonetta Gerevini  
ASST Papa Giovanni XXIII
Bergamo, Italy

Introduction:

The global impact of the COVID-19 pandemic has resulted in mortality and multi-organ morbidity affecting millions of individuals. Notably, significant neurological complications, such as cognitive impairment and the most common olfaction disorder, have been reported. While previous MRI studies have identified structural changes in the brains of COVID-19 patients, there is still a limited comprehension of alterations in brain microstructure and connectivity [Davis et al., 2021; Guo et al., 2022]. This study aimed to examine changes in brain structure, microstructure, and connectivity in individuals with COVID-19-related neurological issues using multi-directional diffusion-weighted MRI (DW-MRI).

Methods:

The study included 16 COVID-19 patients with cognitive and memory deficits (COVID-CM, 56[51-61] years, 69% females), 35 COVID-19 patients with olfaction disorder (COVID-OD, 40[31-53] years, 71% females), and 14 normal controls (62[45-70] years old, 57% females). All patients underwent a T1-weighted MRI scan and a 32-direction DW-MRI scan at 264[208-313] days after the disease onset. A state-of-the-art processing pipeline was developed for this study. This pipeline first involved MRI pre-processing to address potential issues such as noise, artifacts, and distortions. Subsequently, the corrected DW-MRI scan was employed to compute the diffusion tensor image with the pertinent mean diffusivity (MD) and fractional anisotropy (FA) maps, offering insights into the brain microstructure's condition. The application of constrained spherical deconvolution (CSD) generated the fiber-orientation distribution image (FOD), which allowed the whole brain tractography via a probabilistic algorithm (iFOD2). The COMMIT2 filtering model was employed to enhance the biological accuracy of the reconstructed fibers before evaluating connectivity.
The process also involved registering the pre-processed T1 scan to the DWI-b0 scan and brain segmentation into gray matter (GM) and white matter (WM). Brain tissue masks were combined with GM and WM anatomical atlases to classify the brain into distinct tissues and areas, allowing regional investigation.

Results:

Compared to controls, COVID-CM patients showed overall gray matter atrophy (age and sex corrected p=0.004), and both COVID-19 patient groups showed regional atrophy and cortical thinning (corrected p<0.001). Both groups showed a significant increase in gray matter mean diffusivity (corrected p=0.001), and COVID-CM patients also showed an overall increase in white matter diffusivity (p=0.022) and a decrease in white matter anisotropy (corrected p=0.038). Graph-based analysis revealed reduced network modularity in both groups (corrected p=0.024 and p=0.010, respectively), with an extensive pattern of connectivity increase in conjunction with a more localized reduction in a few connections, mainly located in the left hemisphere. In both groups, connection impairment mainly involved the left cingulate, anterior cingulate, and insula. In COVID-CM patients, the left postcentral cortex and the right frontal and anterior cingulate cortex were also affected, while in COVID-OD patients, the left nucleus accumbens and the frontal, supramarginal, and occipital left cortex were further concerned.

Conclusions:

In line with earlier findings [Douaud et al., 2022; Kas et al., 2021], this study revealed notable changes in the brain's structure, microstructure, and connectivity among individuals with COVID-19 who experienced either olfactory or cognitive disorders. Current findings indicate possible underlying neurodegeneration and neuroinflammation alongside compensatory mechanisms. It would be crucial to perform additional longitudinal studies to provide definitive evidence of brain changes in response to COVID-19 pathology, explore brain impairment evolution over time, and ultimately determine its temporary or permanent nature.

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural) 1
Diffusion MRI Modeling and Analysis 2
Segmentation and Parcellation

Neuroinformatics and Data Sharing:

Brain Atlases

Perception, Attention and Motor Behavior:

Chemical Senses: Olfaction, Taste

Keywords:

Cognition
Data analysis
MRI
Smell
Tractography
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - COVID-19, Microstructure, Connectivity, Neuroinflammation, Neurodegeneration

1|2Indicates the priority used for review

Provide references using author date format

Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re’em Y, Redfield S, Austin JP, Akrami A (2021): Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. eClinicalMedicine 38. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00299-6/fulltext.
Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JLR, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM (2022): SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature 604:697–707.
Guo P, Benito Ballesteros A, Yeung SP, Liu R, Saha A, Curtis L, Kaser M, Haggard MP, Cheke LG (2022): COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study. Frontiers in Aging Neuroscience 14. https://www.frontiersin.org/articles/10.3389/fnagi.2022.804937.
Kas A, Soret M, Pyatigoskaya N, Habert M-O, Hesters A, Le Guennec L, Paccoud O, Bombois S, Delorme C, on the behalf of CoCo-Neurosciences study group and COVID SMIT PSL study group (2021): The cerebral network of COVID-19-related encephalopathy: a longitudinal voxel-based 18F-FDG-PET study. Eur J Nucl Med Mol Imaging 48:2543–2557.