Neurological Manifestations of Post-Viral Syndromes and Long COVID: Clinical Spectrum and Pathophysiological Mechanisms (Qualitative Systematic Review)

Introduction: Post-viral syndromes are characterized by the persistence of symptoms following acute viral infection. In the context of the SARS-CoV-2 pandemic, Long COVID—also known as post-acute sequelae of SARS-CoV-2 infection (PASC)—has emerged as a clinically relevant condition with prominent neurological manifestations. Objective: To describe the neurological manifestations of post-viral syndrome and Long COVID, and to analyze the pathophysiological mechanisms proposed to underlie these neurological symptoms in adult and pediatric populations. Methods: A qualitative systematic review was conducted following PRISMA guidelines. Searches were performed in PubMed, Scopus, Web of Science, and SciELO for articles published between January 2020 and May 2025. Observational studies, clinical trials, systematic reviews, and consensus guidelines addressing neurological manifestations of post-viral syndrome or Long COVID were included. A total of 23 studies met inclusion criteria and were synthesized qualitatively. Results: The most consistently reported neurological manifestations included persistent fatigue and post-exertional symptom exacerbation, cognitive dysfunction (“brain fog”), headache, sleep disturbances, dysautonomia, sensory abnormalities, and neuropathic symptoms. Mechanistic domains most frequently implicated across studies included immune dysregulation and neuroinflammation, endothelial and microvascular dysfunction, mitochondrial and metabolic impairment, autonomic nervous system disruption, and possible viral persistence or immune-mediated injury. Pediatric studies reported a similar symptom spectrum, with particular impact on cognitive performance, headache, fatigue, and mood or behavioral disturbances. Conclusions: Neurological manifestations represent a core component of Long COVID and related post-viral syndromes. Current evidence supports a multifactorial pathophysiology involving immune, vascular, metabolic, and autonomic mechanisms. Improved mechanistic understanding and standardized phenotyping are essential to guide future diagnostic and therapeutic strategies, particularly in pediatric populations.