Background: Long COVID is a heterogeneous post-viral condition in which persistent neurological, autonomic, cognitive, and psychometric symptoms often occur without clear isolated biomarker abnormalities. This mismatch suggests that disease persistence may be driven not only by changes in individual markers, but by longitudinal reorganization of biological and clinical interactions. Materials and Methods: This observational longitudinal study evaluated patients with persistent symptoms after confirmed SARS-CoV-2 infection at 3 and 6 months. Clinical assessment included neurological examination, Hospital Anxiety and Depression Scale, Beck Depression Inventory, and COMPASS-31. Biomarkers representing hypoxia signaling, oxidative/redox stress, endothelial and renin–angiotensin system activity, glycation-related processes, and complement regulation were analyzed. Correlation analysis, association-level biomarker–clinical network modeling, and complementary Graphical LASSO-based sparse network estimation were used to compare network density, community organization, centrality, and edge rewiring between time points. Results: Conventional paired analysis identified HIF-1$\alpha$ as the only continuous variable with a statistically significant longitudinal change (Wilcoxon statistic = 610.0, $p=0.000350$), whereas association-level network analysis revealed a broader systems-level signal. The association-level biomarker–clinical network preserved a similar global size at 3 and 6 months, with 16 nodes, 27 versus 26 edges, and densities of 0.225 versus 0.217. However, this apparent stability concealed substantial rewiring: 19 edges were shared, 8 were lost, and 7 emerged. Complementary Graphical LASSO analysis with 1000 bootstrap resamples supported this pattern by identifying a conservative sparse conditional-dependency core, including seven shared conditional-dependency edges across time points and selective weakening of four early conditional dependencies. The C3–C4 relationship reversed from negative to positive correlation ($r=-0.618$ to $r=0.618$), indicating marked remodeling of complement-associated regulation. A psychometric–autonomic module involving Beck, HADS I, HADS II, and COMPASS-31 remained stable across both assessments. Conclusions: Long COVID progression was characterized by dynamic remodeling of immune, endothelial/RAS, oxidative-redox, hypoxia-related, autonomic, and psychometric interactions. Longitudinal network analysis identified a systems-level interaction structure that was not captured by isolated biomarker comparisons alone and that was further supported by complementary sparse conditional-dependency analysis.

In the acute period of COVID-19, more than 1/3 patients develop neurological symptoms, 25% of which can be attributed to direct damage to the central nervous system. Most often, all these complications arise due to the penetration of the virus into the systemic circulation, its dissemination and damage to the vascular endothelium. All clinical manifestations associated with the penetration of COVID-19 into the nervous tissue can be divided into several groups:1) signs of damage to the central nervous system, including headache, impaired consciousness, encephalitis, cerebrovascular diseases, seizures and ataxia; 2) signs of damage to the peripheral nervous system, such as anosmia/hyposmia, dysgeusia, visual disturbances, neuralgia and Guillain-Barre syndrome; and 3) signs of damage to the musculoskeletal system, such as myopathy, myalgia and fatigue.The aim of the review was to identify the main sources and mechanisms of nerve tissue damage in COVID-19 disease.Literature search was conducted in the Web of Science, PubMed and Scopus databases. The search was carried out by the following keywords: «COVID-19», «nerve tissue», «endothelial dysfunction», «oxidative stress», «neuroinflammation». The literature search yielded 329 results, of which 234 articles.As a result of the analysis of the articles, 2 main groups of studies were identified: descriptive and experimental. The pathogenesis of damage to the nervous system by the COVID-19 virus has two sources: by infecting nerve endings, such as olfactory sensory neurons, and retrograde penetration of the virus into the brain.