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

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.