Astrocyte-mediated hippocampal damage in the pathogenesis of dysexecutive syndrome following COVID-19: A narrative review

SARS-CoV-2 infection has been implicated in hippocampal damage, contributing to the pathogenesis of dysexecutive syndrome observed in post-COVID-19 patients. Given the growing prevalence of long-COVID worldwide, understanding how SARS-CoV-2 affects hippocampal structure and function has become an urgent scientific and clinical priority. The hippocampus-crucial for memory, emotional regulation, and executive functioning-is especially susceptible to viral-driven neuroinflammatory cascades. SARS-CoV-2 triggers astrocyte and microglia activation, disrupts blood-brain barrier integrity, and induces cytokine-mediated neurotoxicity, ultimately impairing neuroplasticity and neurogenesis. These mechanisms converge to produce cognitive and affective disturbances-most notably fatigue, apathy, low mood, and executive dysfunction-that typify dysexecutive syndrome in long-COVID. This review synthesizes current evidence from clinical and experimental studies, integrating findings on viral neurotropism, hippocampal hypometabolism, and astrocyte-mediated neurodegeneration. Distinctions between depressive symptoms driven by neuroinflammation and classical depressive disorders are clarified to improve diagnostic accuracy and guide personalized treatment. Emerging data on the neuroprotective role of COVID-19 vaccination-particularly its capacity to modulate microglial activation and support hippocampal neurogenesis-are also examined. Overall, the findings underscore the need for targeted therapeutic strategies aimed at modulating neuroinflammation and supporting hippocampal plasticity, including cognitive rehabilitation approaches. Longitudinal studies are essential to elucidate the enduring impact of SARS-CoV-2 on hippocampal function and to inform effective clinical interventions.