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Updated: Jul 26, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
White matter integrity in hospitalized COVID-19 patients is not associated with short- and long-term clinical
Theresa J van Lith1, Hao Li1, Marte W van der Wijk1
1Department of Neurology, Donders Center for Medical Neurosciences, Radboud University Medical Center, Nijmegen, Netherlands.
Objectives:
SARS-CoV-2 infection is associated with a decline in functional outcomes; many patients experience persistent symptoms, while the underlying pathophysiology remains unclear. This study investigated white matter (WM) integrity on brain MRI in hospitalized COVID-19 patients and its associations with clinical outcomes, including long COVID.
Materials And Methods:
We included hospitalized COVID-19 patients and controls from CORONavirus and Ischemic Stroke (CORONIS), an observational cohort study, who underwent MRI-DWI imaging at baseline shortly after discharge (<3 months after positive PCR) and 3 months after baseline scanning. We assessed WM integrity using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) and performed comparisons between groups and within patients. Clinical assessment was conducted at 3 and 12 months with functional outcomes such as modified Rankin Scale (mRS), Post-COVID-19 Functional Status scale (PCFS), Visual Analogue Scale (VAS), and long COVID, cognitive assessment was conducted by the Modified Telephone Interview for Cognitive Status (TICS-M), and the Hospital Anxiety and Depression Scale (HADS) was used to assess mood disorder. Associations between WM integrity and clinical outcomes were evaluated using logistic regression and linear regression.
Results:
A total of 49 patients (mean age 59.5 years) showed higher overall peak width of skeletonized mean diffusivity (PSMD) (p = 0.030) and lower neurite density index (NDI) in several WM regions compared with 25 controls at the baseline (p < 0.05; FWE-corrected) but did not remain statistically significant after adjusting for WM hyperintensities. Orientation dispersion index (ODI) increased after 3-month follow-up in several WM regions within patients (p < 0.05), which remained significant after correction for changes in WMH volume. Patients exhibited worse clinical outcomes compared with controls. Low NDI at baseline was associated with worse performance on the Post-COVID-19 Functional Status scale after 12 months (p = 0.018).
Conclusion:
After adjusting for WMH, hospitalized COVID-19 patients no longer exhibited lower WM integrity compared with controls. WM integrity was generally not associated with clinical assessments as measured shortly after discharge, suggesting that factors other than underlying WM integrity play a role in worse clinical outcomes or long COVID.
Insights
COVID-19 patients showed altered white matter integrity post-infection, but this was not linked to long COVID symptoms after accounting for white matter hyperintensities. Other factors likely influence persistent symptoms.
Area of Science:
- Neuroimaging
- Infectious Diseases
- Neurology
Background:
- SARS-CoV-2 infection can lead to persistent symptoms and functional decline, with unclear underlying pathophysiology.
- White matter (WM) integrity changes in the brain are suspected but not fully understood in COVID-19 patients.
Purpose of the Study:
- To investigate white matter (WM) integrity using advanced MRI techniques in hospitalized COVID-19 patients.
- To explore the association between WM integrity and clinical outcomes, including long COVID, cognitive function, and mood disorders.
Main Methods:
- Utilized diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) on MRI scans of COVID-19 patients and controls.
- Assessed clinical outcomes including functional status (mRS, PCFS), cognitive function (TICS-M), and mood (HADS) at 3 and 12 months post-discharge.
Main Results:
- COVID-19 patients initially showed differences in WM integrity (higher PSMD, lower NDI) compared to controls, but these were not significant after adjusting for WM hyperintensities (WMH).
- Orientation dispersion index (ODI) increased in patients over 3 months, independent of WMH volume changes.
- Low neurite density index (NDI) at baseline correlated with poorer functional status (PCFS) at 12 months.
Conclusions:
- Adjusting for WMH eliminated significant differences in WM integrity between COVID-19 patients and controls.
- WM integrity shortly after discharge did not strongly correlate with clinical outcomes or long COVID, suggesting other factors are involved.
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