Neuroinflammation as a Mechanism in Long COVID

Long COVID is recognized as a chronic post-viral condition characterized by fatigue, cognitive impairment, mood changes, and other neuropsychiatric symptoms that go beyond the acute phase of COVID-19. More research is now suggesting that neuroinflammation processes, involving microglial reactivity, altered cytokine signaling, and increased permeability of the blood-brain barrier, may contribute to the persistence of these symptoms. This paper provides a critical review of four recent empirical studies that directly examined neuroinflammatory mechanisms in individuals with long COVID using functional neuroimaging, biomarker analysis, and structural MRI measures. Across studies, converging evidence shows persistent central and peripheral immune activation linked to deficits in memory, attention, and mood regulation. Despite promising findings, the literature is limited by small sample sizes, inconsistent diagnostic criteria, and primarily cross-sectional designs, which limit conclusions about causality. Differences in imaging techniques and biomarker measurement approaches hinder direct comparison and synthesis of results. Future research should prioritize longitudinal, multimodal designs that integrate neuroimaging with immune and behavioral markers to clarify the trajectory and clinical relevance of neuroinflammation in long COVID. Overall, the evidence suggests that neuroinflammation plays a significant role in long COVID related cognitive and mood disturbances and emphasizes the need for biologically guided and consistent clinical approaches.