Post-COVID Syndrome and Neurological Consequences:Diagnosis, Treatment, and Rehabilitation

Post-COVID syndrome, also known as long COVID, has emerged as a complex, multisystem condition that persists beyond the resolution of acute SARS-CoV-2 infection. Among its most debilitating manifestations are neurological and neuropsychiatric consequences, which can severely impair quality of life and functional independence. Patients commonly report symptoms such as cognitive dysfunction («brain fog»), chronic fatigue, sleep disturbances, anosmia, dysautonomia, headache, myalgia, and mood disorders, often occurring in combination and without clear correlation to the severity of the initial infection. The underlying mechanisms remain incompletely understood but likely involve a combination of chronic neuroinflammation, blood–brain barrier disruption, persistent immune activation, viral remnants, and dysregulation of the autonomic nervous system. Neuroimaging studies have shown structural and metabolic brain alterations, including reduced gray matter volume, microglial activation, and regional hypometabolism, particularly in frontal and temporal lobes. Diagnostic evaluation requires a comprehensive neurological and psychiatric assessment, exclusion of alternative diagnoses, and increasingly, the use of blood-based biomarkers such as neurofilament light chain, GFAP, and inflammatory cytokines. Treatment is largely supportive and symptom-driven, incorporating pharmacological approaches for pain, insomnia, depression, and orthostatic intolerance, alongside non-pharmacologic strategies such as cognitive training, graded physical therapy, breathing exercises, and neuropsychological rehabilitation. Multidisciplinary collaboration is essential to tailor interventions to the heterogeneous and evolving needs of patients. Rehabilitation strategies must address not only physical deficits but also cognitive and emotional resilience, with emphasis on patient education and pacing to avoid post-exertional symptom exacerbation. Emerging therapeutic avenues include vagus nerve stimulation, immune-modulatory therapies, and digital neurocognitive platforms. Longitudinal studies are urgently needed to define prognostic biomarkers, identify subtypes, and evaluate treatment efficacy. As the global burden of long COVID continues to rise, structured frameworks for early diagnosis, integrated care, and standardized rehabilitation protocols will be critical to mitigate long-term neurological disability and restore functional recovery.