Cortical and subcortical grey matter volume alterations in neuropsychiatric long-COVID syndrome episode

Introduction Neuropsychiatric symptoms are among the most common sequelae of long-COVID-19 and highly diminish the patient's quality of life. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it appears necessary to further investigate brain structural changes in relation to clinical long-COVID symptoms. Understanding the pathogenic processes in neuropsychiatric long-COVID will be vital to identify targeted therapy and to ease the months long-lasting symptoms. Methods The present cross-sectional study investigated 3T-MRI scans from long-COVID patients (n=30) with neuropsychiatric symptoms, and healthy controls matched for age and gender (n=20). Whole-brain comparison of grey matter volume (GMV) was conducted by voxel-based morphometry using the CAT12 software package. To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and / or initial severity of symptoms of COVID19 and time since onset of COVID-19, we performed multiple linear regression analysis. Results Enlarged GMV in long-COVID patients was present in several clusters (p<0.05, FWE- corr-ected) spanning frontotemporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres when compared to controls. Time since onset of COVID-19 was a significant regressor in three of these clusters (anatomically located in right inferior frontal gyrus, lateral and posterior orbital gyrus, anterior parts of the insula, left superior, middle and inferior temporal gyrus and left postcentral and precentral gyrus). Conclusion Grey matter alterations in limbic and secondary olfactory areas are present in neuropsychiatric long-COVID patients. Some GMV alterations were inversely associated with time elapsed since acute COVID-19, suggesting higher GMV with shorter time since onset of COVID-19. Detection of associations between GMV and clinical symptoms might be difficult, because of heterogenous clinical presentation. Larger samples and longitudinal data in neuropsychiatric long-COVID patients are required to further clarify the mediating mechanisms between COVID-19 and GMV.