Gray Matter Changes Following Mild COVID-19: An MR Morphometric Study in Healthy Young People

Abstract

Background: Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings.

Purpose: To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination.

Study type: Prospective.

Population: Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23).

Field strength/sequence: Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo.

Assessment: MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire.

Statistical tests: Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance.

Results: In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η² _p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η² _p = 0.101), lower subcortical gray matter (57881 ± 3998 mm³ vs. 60470 ± 5211 mm³, η² _p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm³ vs. 60.98 ± 15.8 mm³, η² _p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η² = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η² = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η² _p = 0.112).

Data conclusion: Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume.

Level of evidence: 2 TECHNICAL EFFICACY: Stage 3.

Keywords: SARS‐CoV‐2; brain; cortical thickness; morphometry.