Decreased functional connectivity in post-COVID syndrome patients with high neuroinflammatory activity

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INTRODUCTION: Previous research suggests some post-COVID patients with neurocognitive complaints (NCC) show neuroinflammation. Like in inflammatory diseases, this may affect network connectivity. This study aimed to compare resting-state functional connectivity in individuals with and without i) neuroinflammation and ii) persistent post-COVID NCC. METHODS: F]DPA-714 PET scan with arterial sampling for neuroinflammation, and 3T MRI scan for resting-state functional connectivity. Twenty resting-state networks (RSNs) were identified using independent component analysis. Group differences in within-RSN connectivity were analyzed using general linear models. Differences in subcortico-cortical between-RSN connectivity-between brainstem or thalamus and cortical RSNs-were assessed using interaction models. RESULTS: F]DPA-714 binding in participants with NCC. Lastly, thalamic-somatomotor and brainstem-control network connectivity (between-RSN) was altered in both individuals with persistent NCC and those with neuroinflammation, with thalamic-somatomotor changes mainly driven by NCC and brainstem-control changes by neuroinflammation. CONCLUSION: Our results suggest that neuroinflammation in individuals with persistent NCC after SARS-CoV-2 infection is linked to altered functional connectivity in RSNs central to higher-order cognitive functions.