Relationship between body mass index, gray matter volume and peripheral inflammation in patients with post-COVID condition, 2025, Claaß et al.

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Relationship between body mass index, gray matter volume and peripheral inflammation in patients with post-COVID condition
Claaß; Schick; Rocktäschel; Garza; Gaser; Reuken; Stallmach; Finke; Thanarajah; Walter; Dunay; Besteher; Opel

BACKGROUND
Obesity, a condition associated with low-grade peripheral inflammation, is an independent risk factor for severe COVID-19 and has been linked to structural brain alterations. Given that post-COVID condition (PCC) is also associated with structural brain abnormalities and lingering immunological alterations, this study aimed to assess whether obesity contributes to these neural and immunological differences in PCC patients.

METHODS
We investigated a previously established cohort of PCC patients (n = 61), recruited between April 2021 and June 2022. Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry (VBM). Obesity, as measured by body mass index (BMI), as well as age, sex, and total intracranial volume (TIV), were included as regressors in a linear model. Signature immunological markers were quantified in 50 participants using a LEGENDplex™ multiplex bead-based assay.

RESULTS
A significant negative association was found between BMI and GMV in the right thalamus (p(FWE) = 0.039, k = 209, TFCE = 1037.97, x = 18, y = −21, z = 8). Moreover, BMI and thalamic GMV were significantly associated with immunological markers in PCC. Specifically, BMI was positively associated with Interleukin-6 (p = 0.021) and negatively with Interleukin-7 (p = 0.021), while GMV showed positive associations with Interleukin-8 (p = 0.05).

CONCLUSION
The results suggest that BMI contributes to GMV alterations in PCC patients, with both BMI and GMV demonstrating correlations with peripheral immunological markers. These findings indicate that converging mechanisms involving inflammation and structural brain alterations may contribute to obesity and PCC.

HIGHLIGHTS
• Higher body mass index is linked to lower gray matter volume in post-COVID patients.

• Brain structural alterations and body mass index link to immunological changes.

• These changes are most pronounced in patients with cognitive deficits.

• Obesity and post-COVID condition may share converging pathomechanisms.

Web | DOI | Brain, Behavior, & Immunity - Health | Open Access
 
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To further investigate the relationship between immunological marker levels and brain structure, we extracted GMV data using the eigenvariate function in SPM12. The eigenvariate values of the cluster in the right thalamus showed a positive correlation with IL-8 (p = 0.050). However, this correlation did not remain significant after adjusting for multiple comparisons using the Benjamini-Hochberg procedure.

This analysis revealed varying relationships among immunological markers, BMI, and GMV. In participants with reduced cognitive function, BMI was positively linked to IL-6 and negatively linked to Interferon-γ and TNF-α. However, after adjusting for multiple comparisons, only a trend-level effect for IL-6 remained.

In participants with normal cognitive functioning, BMI and GMV were both differently associated with sTREM-1, although these effects did not remain significant after correction for multiple testing.

While our finding of GMV reductions aligns with previous findings, the pattern of regional distribution differs from most previous studies.

Given the cross-sectional design of the current study, conclusions regarding causal relationships must be drawn with utmost caution.
 
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