Revista da Sociedade Brasileira de Medicina TropicalOct 23, 2026

Changes in the Nervous System in People with Long COVID: A Systematic Review

Updated Oct 24, 2026

Abstract

Forty-two studies indicate heterogeneous alterations in the central nervous system of individuals with long COVID.

Persistent neurological and cognitive symptoms in long COVID may suggest central nervous system involvement beyond the acute phase of infection.
Observed alterations include impaired cortical excitability and abnormal brain activity across multiple frequency bands.
Changes in functional connectivity and structural abnormalities in neural networks were frequently reported.
Some studies noted imbalances in neurotransmission and biomarkers indicating neuroinflammation or axonal injury.
These neurophysiological changes are often associated with symptoms like fatigue, cognitive dysfunction, and brain fog.
Methodological issues such as variability in study design limit the strength of the conclusions drawn from the evidence.

Simplified

Long COVID (post-COVID-19 condition) has been associated with persistent neurological and cognitive symptoms, suggesting possible central nervous system involvement beyond the acute phase of severe acute respiratory syndrome coronavirus 2 infection. A systematic review of articles published up to April 2026 was conducted following the PRISMA guidelines, and observational studies evaluating neurophysiological, structural, and functional alterations in individuals with long COVID were analyzed. Forty-two studies with substantial variability in design and methods were included; thus, the findings were synthesized narratively. The evidence indicates heterogeneous yet recurrent alterations in the central nervous system of individuals with lonf COVID, including impaired cortical excitability, abnormal cerebral oscillatory activity across multiple frequency bands, changes in functional connectivity, and structural abnormalities in neural networks. Some studies also reported imbalances in excitatory-inhibitory neurotransmission and biomarkers suggestive of neuroinflammation or axonal injury. These neurophysiological and structural alterations were commonly associated with persistent fatigue, cognitive dysfunction, and brain fog. However, the available evidence is limited by important methodological issues, including substantial heterogeneity in study populations, assessment techniques, and reported outcomes; the observational design also limited the strength of the conclusions. Taken together, the current evidence suggests a persistent and multifactorial central nervous system dysfunction in long COVID. However, definitive conclusions remain limited, and well-designed prospective longitudinal studies using standardized methods are needed to clarify the mechanisms, duration, and clinical relevance of these alterations.

Changes in the Nervous System in People with Long COVID: A Systematic Review

Abstract

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