Neurological Manifestations of SARS-CoV-2

Abstract

Neurocognitive symptoms have emerged as notable sequelae of SARS-CoV-2 infection (COVID-19). Although primarily a respiratory virus, SARS-CoV-2 has been associated with central nervous system (CNS) changes observed in both clinical and experimental settings. To better understand these effects and their pathological mechanisms, we conducted a systematic literature search of published studies and employed a qualitative, analytical approach to identify and synthesize key findings from peer-reviewed studies, including large-scale retrospective clinical cohorts, human autopsy reports, animal models (murine, non-human primate), and in vitro brain organoid systems. While viral components were detected in post mortem central nervous system tissues, COVID-19 neuropathology appears to stem primarily from immune-mediated inflammation and vascular injury rather than direct CNS infection. Persistent glial activation and BBB disruption may underlie the long-term neurological symptoms reported in long COVID-19. Although animal models offer mechanistic insight, species-specific differences necessitate cautious extrapolation to human pathology. Further investigation into the chronic effects of SARS-CoV-2 on the brain is essential to guide long-term clinical management and therapeutic development.