Cortical morphology alterations in non-COVID-19 post-infectious olfactory dysfunction

While COVID-19-associated olfactory dysfunction leads to gray matter (GM) structural alterations, it remains unclear whether these structural GM alterations are specific to COVID-19. To address this, we investigated GM changes in patients with post-infectious olfactory dysfunction (PIOD) who tested negative for SARS-CoV-2 infection. This study included 65 patients with PIOD who were SARS-CoV-2 negative and 65 healthy controls. Olfactory function was assessed using the Sniffin’ Sticks test and olfactory event-related potentials (OERPs). T1-weighted MRI scans were analyzed using three complementary approaches: region-based morphometry (RBM) to assess regional GM volume, voxel-based morphometry (VBM) to examine voxel-wise GM density differences between PIOD patients and controls, and surface-based morphometry (SBM) to investigate cortical thickness alterations. Compared to controls, patients with PIOD exhibited significant reductions in GM volume, voxel-based GM density, and cortical thickness. Regions demonstrating GM volume/thickness reductions across these three morphological analyses included the orbitofrontal cortex, insula, fusiform gyrus, superior frontal cortex, and hippocampus. Further region-of-interest (ROI) analyses revealed that reduced cortical thickness in the orbitofrontal cortex was negatively correlated with the duration of olfactory dysfunction and positively correlated with olfactory performance. Our findings indicate brain structural alterations also occurs in SARS-CoV-2-negative PIOD patients.