NEUROCOGNITIVE AND NEUROLOGICAL DISORDERS ASSOCIATED WITH COVID-19: A REVIEW OF PATHOPHYSIOLOGY, DIAGNOSIS, AND TREATMENT
Abstract
Relevance. Post-COVID syndrome (PCS), especially its neurological and neurocognitive manifestations, has become one of the main challenges for global health after the COVID-19 pandemic. Affecting 10% to 30% of people who have had even mild forms of the disease, post-COVID syndrome places a significant burden on the healthcare system and causes socio-economic losses due to the prolonged incapacity of millions of people.
Objective. To systematize and summarize current data on clinical manifestations, pathophysiological mechanisms, and means of diagnosis and treatment of neurological and neurocognitive disorders in post-COVID syndrome.
Materials and methods. A review of the literature was conducted. Publications were searched for in English in the PubMed, Cochrane Library, and Scopus databases for the period 2020–2025. Key terms were used: post-COVID syndrome, neurocognitive disorders, brain fog, pathophysiology of brain fog in COVID-19. The analysis included randomized controlled trials, systematic reviews, meta-analyses, and large cohort studies. Studies with a high risk of bias were excluded from further consideration.
Results. Post-COVID syndrome is considered a complex multisystem condition characterized by brain fog, persistent headache, post-COVID neuropathies, psychiatric disorders, and dysautonomia (e.g., POTS). The leading clinical manifestation remains “brain fog” - a complex of cognitive impairments such as decreased attention, memory, and executive functions. The pathophysiology is multifactorial and includes: direct neurotropic effects of SARS-CoV-2 (via the olfactory bulb or hematogenous route), chronic systemic inflammation, neuroinflammation with microglial activation, endothelial dysfunction, microthrombosis, and autoimmune reactions. Diagnosis is based on clinical history, neuropsychological testing (MoCA, MMSE scales), and instrumental studies (MRI, fMRI, PET), which can reveal structural, functional, and metabolic changes. There is no standardized treatment. The therapeutic approach should be individualized and multidisciplinary, with an emphasis on non-pharmacological measures (cognitive rehabilitation, gradual physical activity) and symptomatic pharmacotherapy.
Conclusions. Post-COVID syndrome is a global medical and socioeconomic problem diagnosed in 10% to 30% of patients after COVID-19, even in mild cases. Neurological consequences include brain fog, persistent headaches, post-COVID neuropathies, psychiatric disorders, and dysautonomia (e.g., postural orthostatic tachycardia syndrome, POTS). Cognitive impairment in PCS is multifactorial in nature, caused by the synergy of the direct neurotropic effect of SARS-CoV-2, chronic neuroinflammation with cytokine activation of microglia and endothelial dysfunction with microthrombosis, as well as mechanisms of tau protein dysregulation common to Alzheimer's disease. Diagnosis of PCS is complicated by the lack of a universal biomarker and the variety of symptoms. Treatment is currently not standardized and is based on an individual approach. It includes cognitive rehabilitation, physical activity with consideration of the risk of post-exertional malaise, psycho-emotional support, and symptomatic pharmacotherapy.
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