Neuroinflammation-Linked Neuropsychiatric Symptoms in COVID-19 and Other Inflammatory States: A Mechanistic Hypothesis

Neurological and neuropsychiatric symptoms are common in acute and post-acute COVID-19. Evidence from dynamic contrast–enhanced MRI, TSPO-PET, FDG-PET, cerebrospinal fluid analysis, and neuropathology indicates that these symptoms arise primarily from neuroinflammation, microglial activation, and neurovascular dysfunction rather than direct viral neuro-invasion. Affected regions consistently include frontal and temporal cortices, limbic structures, the anterior cingulate cortex, basal ganglia, thalamus, brainstem, cerebellum, and olfactory pathways. These patterns correspond closely to impairments in executive function, emotional regulation, motivation, threat processing, sensory integration, and autonomic control. Parallels with established inflammatory and autoimmune disorders support a transdiagnostic mechanism in which systemic inflammation alters CNS circuits via glial activation and blood– brain barrier vulnerability. Within this context, the theoretical possibility that modulation of peripheral inflammation—such as through NSAIDs or selected plant-derived compounds—could influence neuroinflammation-linked symptoms warrants controlled investigation, though no therapeutic efficacy is established. This paper synthesises current evidence and outlines a research framework for empirically testing these mechanisms.