MRI evidence of gray matter loss in COVID-19 patients with cognitive and olfactory disorders

Objective: The aim of this study was to assess COVID-19-related gray matter (GM) structural alterations in two distinct groups of patients presenting with the prevailing and distinctive COVID-19-related neurological symptoms – isolated olfactory disorders as sole neurological manifestation (COVID-OD) and cognitive disorders (COVID-CD) – as compared to a control group of unaffected individuals. Methods: The study included 61 COVID-CD patients (57 [60–63] years, 62% females), 84 COVID-OD patients (49 [35–57] years, 60% females), and 17 controls (51 [41–52] years, 41% females). Region-based morphometry (RBM) and voxel-based morphometry (VBM) were performed on T1-weighted MRI scans to assess GM regional volume and voxel-wise density differences between COVID-19 patients and controls. Surface-based morphometry (SBM) was applied to investigate cortical thickness alterations. The statistical models built to assess GM structural differences among groups included total intracranial volume and age as nuisance variables. Results: The multi-morphometric analysis revealed statistically significant (p < 0.05 corrected for multiple comparisons) reduction in GM regional volumes, in voxel-wise GM density and in cortical thickness in both COVID-CD and COVID-OD patient groups as compared to controls. Across all three analyses, COVID-CD patients showed more distributed and severe GM loss than COVID-OD patients. The most prominently affected GM regions in the COVID-CD group included the hippocampus, putamen, cingulate gyrus, precuneus, precentral and postcentral gyri, amygdala, lingual gyrus, and caudate nucleus. Interpretation: Our MRI findings show that COVID-19-related olfactory and cognitive disorders both induce GM atrophy, although at different degrees of severity, likely indicative of neurodegeneration and neuroinflammation.