Patients with severe COVID-19 experience long-lasting effects on their cognitive function, a breakthrough study shows, likening their post-recovery state to accelerated aging. Newly discovered sequelae include reduced brain volume and an increase in brain-damaging proteins, underscoring the virus's severe and lasting impact on brain health.
The UK's largest study to date takes a new step towards better understanding the immediate and long-term effects of COVID-19 on the brain.
The scope, pathophysiology, and recovery trajectories of persistent cognitive deficits after COVID-19 are unknown, limiting our ability to develop prevention and treatment strategies. Researchers report one-year cognitive, serum biomarker, and neuroimaging results from a prospective national cognitive study that compared 351 COVID-19 patients requiring hospitalization with 2,927 norm-matched controls. Cognitive impairment was global and associated with elevated brain injury markers and reduced anterior cingulate cortex volume one year after COVID-19. The severity of the initial infectious injury, postacute psychiatric symptoms, and history of encephalopathy were associated with the greatest cognitive deficits. There is strong agreement between subjective and objective cognitive deficits. Longitudinal follow-up of 106 patients showed a trend toward recovery. Together, these findings support the hypothesis that moderate to severe COVID-19 brain injury may be immune-mediated and provide guidance for the development of treatment strategies.
Results published on September 23 in the journal Nature Medicine by researchers from the COVID-CNS Consortium, led by the University of Liverpool and involving King's College London and the University of Cambridge, showed that 12-18 months after hospitalization for COVID-19, patients had worse cognitive function than matched control patients. Importantly, these findings correlate with evidence of reduced brain volume in key areas on MRI scans and abnormally high levels of brain-damage proteins in the blood.
Shockingly, the post-COVID cognitive impairment found in this study was equivalent to two decades of normal aging. It is important to emphasize that these patients all experienced COVID and required hospitalization, so these results should not be generalized too broadly to everyone who has experienced COVID. However, the extent of the deficit in all cognitive skills tested, and the link to brain damage in brain scans and blood tests, provide the clearest evidence yet that COVID can have significant impacts on the brain and mental health long after recovery from respiratory problems.
The study is part of the University of Liverpool's COVID-19 Clinical Neuroscience Study (COVID-CNS), which aims to understand the biological causes and long-term outcomes of neurological and psychiatric complications in hospitalized patients with COVID-19.
Study author Dr Greta Wood from the University of Liverpool said: "Many people develop persistent cognitive symptoms after hospitalization with COVID-19, often referred to as 'brain fog'."
However, it is unclear whether there is objective evidence of cognitive impairment and, if so, whether there is biological evidence of brain damage; and, most importantly, whether patients will recover over time. In this latest study, we looked at 351 COVID-19 patients who required hospitalization, either with or without new neurological complications. The study found that patients with and without acute neurological complications of COVID-19 had worse cognitive abilities than expected given their age, gender and education level, based on 3,000 control subjects.
Corresponding author Professor Benedict Michael, Professor of Neuroscience at the University of Liverpool, said: "COVID-19 is not a purely pulmonary disease. Typically, the most severely affected patients develop brain complications. These findings suggest that hospitalization with COVID-19 can lead to global, objectively measurable cognitive impairment that can be detected even 12-18 months after hospitalization. These persistent cognitive impairments are present in both hospitalized patients with clinical neurological complications, "It is also present in hospitalized patients without clinical neurological complications, suggesting that COVID-19 can independently cause cognitive impairment in the absence of a neurological diagnosis. The association of biomarkers of brain cell damage in the blood with reduced brain area size on MRI suggests that there may be a measurable biological mechanism for this. Now, our research team is working to understand whether the mechanisms we discovered in COVID-19 may also be responsible for similar findings in other serious infections, such as influenza."
Professor Gerome Breen, of King's College London, said: "Long-term studies will be crucial to determine how well these patients recover or which patients are likely to worsen, and to establish whether this condition is unique to COVID-19 or is a brain injury common to other infections. Notably, our work could help guide similar studies in Long-COVID patients, who often have much milder respiratory symptoms and also experience cognitive symptoms such as 'brain fog', as well as help develop treatment strategies."
Compiled from/SciTechDaily
DOI:10.1038/s41591-024-03309-8