Alterações do sistema nervoso central na Covid longa: uma revisão sistemática

Abstract

Background: Long COVID has been associated with persistent neurological and cognitive symptoms, suggesting central nervous system (CNS) involvement beyond the acute phase of viral infection. Objective: To identify the main neurophysiological changes in the CNS in long COVID, their clinical symptoms, and duration. Methods: A systematic review conducted according to PRISMA guidelines, with searches performed from April 2025 at April 2026 across PubMed, Embase, LILACS, SciELO, and Cochrane Library databases. Two independent reviewers performed study selection and data extraction. Observational studies on CNS changes in individuals with long COVID were included. Methodological quality was assessed using JBI tools, and a narrative synthesis was performed. Results: Forty-two studies were included (39 in adults, 3 in children). The most frequent structural changes included reduced limbic and olfactory cortical thickness, decreased hippocampal volume, and white matter abnormalities lasting up to two years. Functional findings involved frontal compensatory activation, neural hypoexcitation, reduced posterior alpha activity and beta power, increased P300 latency, and lower prefrontal activation during gait. Biomarkers such as NfL, GFAP, and sCD163 were elevated, with GFAP associated with cognitive impairment. Fatigue, olfactory dysfunction, and brain fog correlated with altered connectivity and cortical excitability. Conclusion: Long COVID is associated with persistent CNS dysfunction involving structural, metabolic, and connectivity changes. However, methodological heterogeneity limits definitive conclusions.