Neurological Manifestations of COVID-19

The neurological sequelae of COVID-19 encompass a broad spectrum of central and peripheral nervous system involvement, ranging from mild sensory disturbances to life-threatening syndromes. Early in the pandemic, encephalopathy and delirium were frequently observed in severely ill patients, often reversible with supportive care. Inflammatory processes may trigger acute disseminated encephalomyelitis–like lesions, while vascular complications, including ischaemic stroke and microhaemorrhages, reflect a prothrombotic state. Peripheral neuropathies such as Guillain–Barré syndrome have emerged as post-infectious complications. Autopsy studies reveal blood–brain barrier disruption, neuroglial activation and immune-mediated injury driven by monocyte and lymphocyte infiltration. Biomarker analyses detect elevated neurofilament light chain and glial fibrillary acidic protein, indicating neuronal and astrocytic damage both during acute infection and into convalescence. Together, these findings underscore multifactorial mechanisms—direct viral effects, neuroimmune dysregulation and vascular injury—underpinning the global burden of COVID-19-related neurological disease and highlighting the necessity of longitudinal follow-up and targeted neuroprotective strategies.

Research from Nature Portfolio

Recent investigations have demonstrated persistent markers of neuroglial injury in patients with COVID-19 who developed neurological complications. In a cohort study comparing acute and convalescent sera, concentrations of tau protein, neurofilament light chain and glial fibrillary acidic protein were elevated acutely and remained raised in convalescence among those with central nervous system involvement. Concurrent profiling of cytokines and autoantibodies revealed associations between altered consciousness and innate immune mediators, with autoantibodies targeting neuronal antigens more frequent in severely affected individuals. These results indicate that para-infectious brain injury persists beyond viral clearance and is linked to dysregulated innate and adaptive responses, suggesting potential avenues for immunomodulatory intervention.

Neurological Manifestations of COVID-19 publication trend

The graph below shows the total number of articles in neurological manifestations of covid-19 across all publications each year (not limited to Nature Index journals).

Technical terms

Encephalopathy: A diffuse dysfunction of the brain presenting with altered consciousness or cognition.

Microglia: Resident immune cells of the central nervous system that mediate inflammatory responses.

Glial fibrillary acidic protein (GFAP): An intermediate filament protein expressed by astrocytes, serving as a marker of astroglial injury.

Neurofilament light chain (NfL): A structural axonal protein released into cerebrospinal fluid and blood upon neuronal damage.

Cytokine: A signalling protein released by immune cells that modulates inflammation and intercellular communication.

References

1. COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy. Signal Transduction and Targeted Therapy (2023).
2. Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses. Nature Communications (2023).
3. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain (2020).
4. Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathologica (2020).
5. Stroke in COVID-19: A systematic review and meta-analysis. International Journal of Stroke (2020).
6. Guillain–Barré syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases. Journal of Neurology (2020).