New study using BioResource volunteer data brings us the latest insights into severe COVID and its impacts on the brain

Data from 351 COVID-19 BioResource volunteers under the COVID-CNS study, was used by researchers from the University of Liverpool, King's College London and the University of Cambridge, alongside the COVID-CNS Consortium in a new research study that discovered that 12-18 months after COVID-19 hospitalisation, patients exhibited worse cognitive function, elevated markers of brain injury and experienced reductions in grey matter volume. 

These changes, particularly in memory, processing speed, and executive function, led to cognitive deficits, equivalent to twenty years of normal ageing. Although the results of this study cannot and should not be too widely generalised to all people with lived experience of COVID, the scale of deficit, links to brain injury 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. 

Our role: COVID-CNS  

The COVID-19 Clinical Neuroscience Study (COVID-CNS) is part of our COVID-19 BioResource and is a UKRI-funded collaborative jointly led by experts in neuroscience and psychiatry based at the University of Liverpool and King’s College London. We recruited patients who were either: 

• Admitted to hospital with COVID-19 and had neurological or neuropsychiatric complications 

• Admitted to hospital but without experiencing these symptoms 

• Admitted to hospital with neurological or neuropsychiatric complications after receiving a COVID-19 vaccination 

• Or health control (without COVID-19) 

The aim of the study is to understand the biological causes and long-term outcomes of neurological and neuropsychiatric complications in hospitalised COVID-19 patients and to help develop strategies to prevent and treat them. 

COVID-19 BioResource 

At the start of the pandemic, we set up the  COVID-19 cohort to support cutting-edge research into the virus and the development and roll-out of vaccines. Researchers at the University of Cambridge began recruiting people who had tested positive for the virus into the cohort. These included asymptomatic healthcare staff identified via routine screening, through to patients admitted to hospital (via Cambridge University Hospitals NHS Foundation Trust), as well as some to its intensive care unit. 

Over the course of 2.5 years, we recruited different groups of participants, ranging from asymptomatic to hospitalised, who provided multiple blood samples over a period of time post-infection and filled out questionnaires. This created a rich data resource for researchers to carry out studies into the disease, in particular the effects of long COVID. 

Speaking on the findings from this research, Study author Dr. Greta Wood from the University of Liverpool said: 

“After hospitalisation 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 hospitalisation 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 hospitalisation with COVID-19 can lead to global, objectively measurable cognitive deficits that can be identified even 12-18 months after hospitalisation.

“These persistent cognitive deficits were present in those hospitalised 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 in 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.”

The paper, 'Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study of patients seen in hospital' is published in Nature Medicine. 

This publication was funded by the UK Research and Innovation (UKRI) grant COVID-CNS and is supported through the national NIHR BioResource and the NIHR Cambridge Biomedical Research Centre.