Large Study Offers Latest Insights into After-Effects of Severe COVID-19 on the Brain

In the U.K.'s largest study to date, researchers have come to a better understanding of the immediate and long-term impacts of COVID-19 on the brain.

Published in Nature Medicine, the study from researchers led by the University of Liverpool alongside King's College London and the University of Cambridge as part of the COVID-CNS Consortium shows that 12–18 months after hospitalization due to COVID-19, patients have worse cognitive function than matched control participants.

Importantly, these findings correlate with reduced brain volume in key areas on MRI scans as well as evidence of abnormally high levels of brain injury proteins in the blood.

Strikingly, the post-COVID cognitive deficits seen in this study were equivalent to 20 years of normal aging. It is important to emphasize that these were patients who had experienced COVID, requiring hospitalization, and these results shouldn't be too widely generalized to all people with lived experience of COVID.

However, the scale of deficit in all the cognitive skills tested, and the links to brain injury in the brain scans and blood tests, provide the clearest evidence to date that COVID can have significant impacts on brain and mind health long after recovery from respiratory problems.

The work forms part of the University of Liverpool's COVID-19 Clinical Neuroscience Study (COVID-CNS), which addresses the critical need to understand the biological causes and long-term outcomes of neurological and neuropsychiatric complications in hospitalized COVID-19 patients.

Study author Dr. Greta Wood from the University of Liverpool said, "After hospitalization with COVID-19 many people report ongoing cognitive symptoms often termed 'brain fog.'

"However, it has been unclear as to whether there is objective evidence of cognitive impairment and, if so, is there any biological evidence of brain injury; and most importantly if patients recover over time.

"In this latest research, we studied 351 COVID-19 patients who required hospitalization with and without new neurological complications. We found that both those with and without acute neurological complications of COVID-19 had worse cognition than would be expected for their age, sex and level of education, 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 condition simply of the lung. Often, those patients who are most severely affected are the ones who have brain complications.

"These findings indicate that hospitalization with COVID-19 can lead to global, objectively measurable cognitive deficits that can be identified even 12–18 months after hospitalization.

"These persistent cognitive deficits were present in those hospitalized both with and without clinical neurological complications, indicating that COVID-19 alone can cause cognitive impairment without a neurological diagnosis having been made.

"The association with brain cell injury biomarkers in blood and reduced volume of brain regions on MRI indicates that there may be measurable biological mechanisms underpinning this.

"Now our group is working to understand whether the mechanisms that we have identified in COVID-19 may also be responsible for similar findings in other severe infections, such as influenza."

Professor Gerome Breen from King's College London said, "Long term research is now vital to determine how these patients recover or who might worsen and to establish if this is unique to COVID-19 or a common brain injury with other infections.

"Significantly, our work can help guide the development of both similar studies in those with long COVID who often have much milder respiratory symptoms and also report cognitive symptoms such as 'brain fog' and also to develop therapeutic strategies."