This narrative review provides a critical synthesis of current literature regarding the clinical presentations, potential mechanisms, and biomarkers associated with neurological involvement in Long COVID and helps define disease heterogeneity, support patient stratification, and guide future personalized therapeutic approaches.
Abstract
Six years after the onset of the COVID-19 pandemic, many individuals continue to experience persistent neurological symptoms that extend beyond the acute phase of infection, affecting daily life, work, and overall functioning, thereby representing a substantial long-term health burden. Cognitive impairment, fatigue, headache, and autonomic dysfunction are among the most frequently reported neurological features, often persisting despite the absence of clear diagnostic findings. Although Long COVID is recognized as a distinct clinical entity, the underlying pathophysiological mechanisms remain incompletely understood. This narrative review provides a critical synthesis of current literature regarding the clinical presentations, potential mechanisms, and biomarkers associated with neurological involvement in Long COVID. Reflecting the high heterogeneity of the available evidence, it is important to note that no neurological biomarker or disease-modifying therapy has yet been clinically validated. Ultimately, characterizing these pathways may help define disease heterogeneity, support patient stratification, and guide future personalized therapeutic approaches.
Context: Long COVID has emerged as a major cause of persistent respiratory symptoms and functional impairment after acute SARS-CoV-2 infection. Pulmonary involvement is among the most common long-term manifestations and may affect both previously hospitalized and non-hospitalized individuals. However, the clinical pres...
Amin Shahverdi, Shadi Kamali, Ehsan Shahverdi· International Journal of Inf...· 0 citations
Background: Long COVID is a heterogeneous multisystem condition associated with fatigue, cognitive difficulties, sleep disturbance, depression, anxiety, and post-traumatic symptoms.
Methods: This narrative review examined PubMed/MEDLINE literature published between January 2020 and July 2026, supplemented by major rev...
Sandra Kołodziejczyk, Bartłomiej Wiak, Monika Łapot et al.· African Journal of Biomedica...· 0 citations
The conclusion that routine CSF abnormalities largely do not seem to reflect mechanisms specific to PCS is argued against routine CSF diagnostics as a source of disease-specific biomarkers in unselected PCS patients and support future studies focusing on alternative mechanisms underlying persistent neurological symptom...
D. Erhart, L. Balz, I. Giotaki et al.· medRxiv· 0 citations
Cognitive dysfunction represents a prevalent and long-lasting non-respiratory symptom following a protracted course of coronavirus infection, yet its molecular basis remains inadequately characterized. This review aims to present a comprehensive and systematic examination of the pathogenic mechanisms underlying cogniti...
I. Shirolapov, A. Zakharov, D. P. Kurmaev et al.· Zhurnal Nevrologii i Psikhia...· 0 citations
Long COVID, also referred to in the literature as postacute sequelae of SARS-CoV-2 infection (PASC) or postacute COVID-19 syndrome (PACS), is a chronic and heterogeneous multisystem condition persisting beyond acute COVID-19. For consistency, this review uses the term “Long COVID” throughout; PASC and PACS are noted on...
Akhilesh Koli, Ayush Khangar, Sharmilla Khatri et al.· Infectious Diseases in Clini...· 0 citations
Respiratory viral infections (RVIs) affect millions annually, yet long-term consequences outside COVID-19 are poorly defined. Post-acute sequelae, encompassing persistent or new physical, cognitive, and mental health impairments, are increasingly recognised as clinically important. We systematically reviewed evidence o...
Esther Hui-En Chong, I. Wee, J. G. Low et al.· Respirology (Carlton South....· 1 citation
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