Structural Brain Abnormalities and Neuropsychiatric Symptoms in Post-COVID Condition

We aimed to cross-sectionally and longitudinally compare brain morphometry and neuropsychiatric symptoms, and evaluate their relationship, in participants with Post-Coronavirus Disease Condition (PCC) and healthy Controls.

At Baseline, 29 PCC (19 female; average age=42.4±12.2 years; 242±156 days since infection) and 25 Controls (14 female; 44.1±12.3 years) completed the NIH Toolbox Emotion, Motor and Cognition Batteries; Patient Reported Outcomes Measurement Information System (PROMIS); and structural brain MRI (thickness, areas, volumes). We compared neurobehavioral performance on the NIH Toolbox and PROMIS and structural brain morphometry for 34 cortical regions and 8 subcortical volumes, between PCC and matched Controls at Baseline (~8 months post-infection) and 11 PCC and 7 Controls at a Follow-Up Visit (~3 years post-infection).

At Baseline, PCC had significantly larger putamen and amygdala (FDR-corrected p=0.04; +5.3 and 5.9%) and a trend for larger hippocampus and accumbens (uncorrected-p=0.012 and 0.027, +5.1 and 12.9%) than Controls. PCC also tended to have 4 thicker cortices (p=0.010-0.049; +3.6-6.5%), 6 larger surface areas (p=0.009-0.023; +5.9-8.6%), and 9 larger cortical volumes (p=0.003-0.008; +4.2-10.7%). These abnormal measures were associated with more anxiety, depression, and pain (r=0.5-0.75; p=0.005-0.04). At Follow-Up, PCC had more sadness, fear, pain, and fatigue compared to Controls. However, group differences in morphometry diminished and PCC neurobehavioral performance tended to improve.

Structural abnormalities in PCC suggest compensatory processes such as enhanced myelination or neurogenesis, rather than neuroinflammation, which in turn may contribute to persistent neurobehavioral symptoms. However, these alterations and symptoms may improve three years after infection.