Neurological Sequelae of Long COVID: Mechanisms, Clinical Impact and Emerging Therapeutic Insights

The COVID-19 pandemic has demonstrated that its effects go far beyond the initial respiratory illness, with many survivors experiencing lasting neurological problems. Some patients develop a condition known as Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), which includes current issues such as reduced cognitive function, chronic headaches, depression, neuropathic pain, and sensory disturbances. These symptoms can severely disrupt daily life and overall well-being. In this narrative review, we provide an overview of current understanding regarding the neurological effects of COVID-19, with a focus on Long COVID. We discuss possible underlying mechanisms, including direct viral invasion of the nervous system, immune-related damage, and vascular complications. We also summarize findings from cohort studies and meta-analyses that explore the causes, symptom patterns, and frequency of these neurological issues. Approximately one-third of people who have had COVID-19 report neurological symptoms, especially those who experienced severe illness or were infected with pre-Omicron variants. Emerging research has identified potential biomarkers such as neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) that may help in diagnosis. Treatment approaches under investigation include antiviral medications, nutraceuticals, and comprehensive rehabilitation programs. Factors like older age, existing health conditions, and genetic differences in ACE2 and TMPRSS2 genes may affect an individual’s risk. To effectively address these challenges, current research is essential to improve diagnostic methods, develop targeted treatments, and enhance rehabilitation strategies. Ultimately, a coordinated, multidisciplinary effort is crucial to reduce the neurological impact of Long COVID and support better recovery for patients.