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Abstract #3925

Neurite orientation dispersion mediates effects of chronic inflammation on executive function in long-COVID.

Ana Isabel Silva1, James M Joers1, Keenan Chirstopher Byrne2, Lauren Pollak2, Katherine Gundry1, Alfredo Lorente1, Jeromy Thotland1, Dinesh K. Deelchand1, Young Woo Park1, Xiufeng Li1, Georgios E Manousakis3, Abby I Metzler3, Christophe Lenglet1, Lynn Eberly1,4, Hamza Farooq1, June Kendall-Thomas5, Arvin Forganian-Arani5, Michel Toledano5, Orhun H Kantarci5, Merve Atik5, Matthew L Senjem5, Burcu Zeydan5, Meher R Juttukonda2,6, David H Salat2, Janet C Sherman2, Shibani Mukerji2, G. Kyle Harrold2, Sevil Yasar7, Mehreen Nabi7, Sana Rehman7, Christof Karmonik8, Syed A Gillani8, Valerie Flores8, Rachel Davis8, Tetsuo Ashizawa8, Peter B Barker7, Eva M Ratai2, Kejal Kantarci5, and Gülin Öz1
1CMRR, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, 2Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States, 3Department of Neurology, University of Minnesota, Minneapolis, MN, United States, 4School of Public Health, Division of Biostatistics and Health Data Science, University of Minnesota, Minneapolis, MN, United States, 5Mayo Clinic Rochester, Rochester, MN, United States, 6Department of Radiology, Harvard Medical School, Charlestown, MA, United States, 7Johns Hopkins University, Baltimore, MD, United States, 8The Houston Methodist Research Institute, Houston, TX, United States

Synopsis

Keywords: Infectious Disease, COVID-19, NODDI, neuroinflammation, cognitive deficits, long-COVID, mediation analysis

Motivation: Chronic inflammation is believed to be one of the causes underlying long-COVID.

Goal(s): To investigate the link between inflammation, white matter integrity and cognition in long-COVID.

Approach: We assessed white matter microstructure in long-COVID using DTI and NODDI, and examined associations with cognition and a blood marker for inflammation (hsCRP).

Results: Compared to controls, participants with long-COVID showed 1) higher hsCRP concentration, 2) white matter microstructural differences that correlated with hsCRP, and 3) cognitive deficits ~2 years after infection. Mediation analysis suggests that deficits in response inhibition may be partly caused by white matter alterations, potentially triggered by inflammation.

Impact: Our findings suggest SARS-CoV-2 infection may lead to inflammatory changes in the brain, present ~2 years after infection, which may drive cognitive deficits in long-COVID. These findings may trigger the development of therapeutic strategies targeting persistent inflammation after SARS-CoV-2 infection.

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Abstract

Keywords