Preprint No evidence for the association between COVID-19 and neuroinflammation: A diffusion basis spectrum imaging study., 2023, Zhang et al.

No evidence for the association between COVID-19 and neuroinflammation: A diffusion basis spectrum imaging study.
Wei Zhang; Aaron J Gorelik; Qing Wang; Sara A Norton; Tamara Hershey; Janine D Bijsterbosch; Ryan Bogdan

COVID continues to be a major international public health concern, the underlying mechanisms of which are not fully understood. Recent studies suggest that COVID may cause prolonged inflammation within the central nervous system. However, the evidence so far has been limited to few small-scale case studies.

To address this, this study leveraged a longitudinal dataset from the UK Biobank that included neuroimaging data prior to and following COVID testing (analytic N=416 including n=224 COVID-positive cases) and applied a novel and non-invasive Diffusion Basis Spectrum Imaging (DBSI) technique to derive putative indices of neuroinflammation (i.e., restricted fraction; DBSI-RF) for gray matter structures and white matter tracts in the brain. We hypothesized that SARS-CoV-2 infection would be associated with elevated DBSI markers of putative neuroinflammation and conducted linear regression analyses with adjustment for age, sex, race, body mass index, smoking frequency, and data acquisition interval.

After multiple testing correction using false discovery rate, we found no evidence that COVID is associated with variability in neuroinflammation. Several brain regions showed nominally significant differences in DBSI-RF between COVID cases and controls including psychopathology-related regions linked that are either part of (i.e., orbitofrontal cortex) or functionally connected to the olfactory network (e.g., amygdala, caudate).

It remains possible that there are acute and transitory neuroinflammatory effects associated with COVID that were not observed in our study due to potential resolution of COVID prior to the scan. Future research is warranted to examine whether neuroinflammation is associated with SARS-CoV-2 infection in a timeand/or symptom-dependent manner.

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