Brain cortical alterations in COVID-19 patients with neurological symptoms

Abstract

BackgroundGrowing evidence suggests that the central nervous system is affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), since infected patients suffer from acute and long-term neurological sequelae. Nevertheless, it is currently unknown whether the virus affects the brain cortex. The purpose of this study was to assess the cortical gray matter volume, the cortical thickness, and the cortical surface area in a group of SARS-CoV-2 infected patients with neurological symptoms compared to healthy control subjects. Additionally, we analyzed the cortical features and the association with inflammatory biomarkers in the cerebrospinal fluid (CSF) and plasma.Materials and methodsThirty-three patients were selected from a prospective cross-sectional study cohort during the ongoing pandemic (August 2020–April 2021) at the university hospitals of Basel and Zurich (Switzerland). The group included patients with different neurological symptom severity (Class I: nearly asymptomatic/mild symptoms, II: moderate symptoms, III: severe symptoms). Thirty-three healthy age and sex-matched subjects that underwent the same MRI protocol served as controls. For each anatomical T1w MPRAGE image, regional cortical gray matter volume, thickness, and surface area were computed with FreeSurfer. Using a linear regression model, cortical measures were compared between groups (patients vs. controls; Class I vs. II–III), with age, sex, MRI magnetic field strength, and total intracranial volume/mean thickness/total surface area as covariates. In a subgroup of patients, the association between cortical features and clinical parameters was assessed using partial correlation adjusting for the same covariates. P-values were corrected using a false discovery rate (FDR).ResultsOur findings revealed a lower cortical volume in COVID-19 patients’ orbitofrontal, frontal, and cingulate regions than in controls (p < 0.05). Regional gray matter volume and thickness decreases were negatively associated with CSF total protein levels, the CSF/blood-albumin ratio, and CSF EN-RAGE levels.ConclusionOur data suggest that viral-triggered inflammation leads to neurotoxic damage in some cortical areas during the acute phase of a COVID-19 infection in patients with neurological symptoms.

Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”

“…A further report identified decreases in cortical thickness and subcortical volumes mainly in the left frontal and limbic systems in patients with both mild and severe infections, despite having no neurologic manifestations during their acute phase [36]. Sanabria-Diaz and colleagues describe findings in 33 selected patients with different levels of post COVID-19 infection severity and identified lower cortical volumes in orbitofrontal and cingulate regions than in controls [37]. In addition, cortical reconstruction using Freesurfer 3D morphometry showed lower GM volumes in frontal, limbic, parietal and temporal brain regions [37].…”

“…Sanabria-Diaz and colleagues describe findings in 33 selected patients with different levels of post COVID-19 infection severity and identified lower cortical volumes in orbitofrontal and cingulate regions than in controls [37]. In addition, cortical reconstruction using Freesurfer 3D morphometry showed lower GM volumes in frontal, limbic, parietal and temporal brain regions [37]. Duan et al analyzed a series of 58 acutely ill COVID patients using Computer Tomographic (CT) source-based morphometry (SBM) to assess GM changes as compared to 62 non-COVID controls [35].…”

Overcoming Infections Including COVID-19, by Maintaining Circulating 25(OH)D Concentrations Above 50 ng/mL

“…14,15 These manifest as diverse syndromes, predominantly related to the central nervous system, 16 with a high likelihood of dormant viruses. 17 This post-COVID syndrome, also known as long-COVID, affects multiple systems and is a chronic process. 16 Evidence suggests that those with low circulating 25(OH)D have a higher risk of acquiring post-COVID syndrome.…”

Increased neurovirulence of omicron BA.5 and XBB variants over BA.1 in K18-hACE2 mice and human brain organoids

“…There is strong evidence for brain abnormalities in COVID-19 patients [20][21][22][23] . Encephalitis is well documented, usually in hospitalized COVID-19 patients with severe disease, with encephalitis predisposing to poor outcomes and a higher risk of mortality 9,[24][25][26] .…”