Neurological Impact of SARS-CoV-2 Changing Variants: A 4-Year DW-MRI Study on Olfactory and Taste-Related Brain Regions

Abstract

Neurological symptoms such as impaired smell and taste have been recognized as hallmark manifestations of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. This study investigates and quantifies microstructural changes in the white matter of the olfactory bulb and taste-related brain regions (frontal operculum, insular cortex and parietal operculum) using diffusion-weighted magnetic resonance imaging (DW-MRI). Apparent diffusion coefficient (ADC) values were measured in patients with confirmed coronavirus disease of 2019 (COVID-19) at the onset of anosmia and ageusia (24 patients, scanned between March and December 2020), 1 month post-infection (20 subjects) and 36 months post-infection (20 participants). ADC values were analyzed over time and compared to normal white matter ADC ranges (calculated retrospectively from 979 pre-pandemic patients) and to those from patients infected with the 2024 strain of SARS-CoV-2 (27 patients). The results revealed significantly elevated ADC values in the white matter of the targeted brain regions, with a peak at the time of infection, followed by a decline 1 month post-infection, and a return to near-normal levels 3 years later. In contrast, the 2024 COVID-19 variant demonstrated reduced virus-related alterations in brain microstructure compared to the 2020 strain. These findings highlight the potential of DWI as a non-invasive tool for elucidating the molecular mechanisms underlying olfactory and taste dysfunction in COVID-19 patients.

Keywords: COVID-19 neurological involvement; apparent diffusion coefficient; diffusion-weighted MRI; olfactory and gustatory dysfunction; white matter microstructural changes.

Figure 1

Theoretical placing of ROIs in the following areas: olfactory bulbs (yellow), insular cortex (blue), frontal operculum (green), parietal operculum (red).

Figure 2

ROIs in the following areas: olfactory bulbs, insular cortex, frontal operculum, and parietal operculum for the normal cohort (1st row), those in the acute stage of 2020 variant (2nd row), individuals 1 month after infection (3rd row), individuals 36 months after infection (4th row), those in the acute stage of 2024 variant (5th row), and individuals 1 month post-infection (6th row).