Blood-brain barrier dysfunction following systemic infection v1.0
Research type
Research Study
Full title
Understanding the pathogenic mechanisms of infection-associated cognitive impairment – a multimodal study
IRAS ID
277598
Contact name
Jonathan Underwood
Contact email
Sponsor organisation
Cardiff and Vale University Health Board
Duration of Study in the UK
2 years, 8 months, 30 days
Research summary
Bloodstream infections (also known as 'septicaemia' or 'blood-poisoning') are common life-threatening infections affecting over 4,000 people in Wales (and over 50,000 in the UK) every year. They often cause sepsis which is a life-threatening condition with a 30-day mortality in excess of 15%. In those who survive, morbidity is significant with short term cognitive impairment, such as problems with memory or attention (known as delirium), frequently observed by doctors, patients and their families. Subsequent problems with memory and thinking are a frequent complaint of survivors of sepsis. Our understanding of why this happens is limited.
The global SARS-CoV2 pandemic has also shown how viral pathogens, associated with significant inflammation, are also frequently associated with delirium and other neurological conditions. Around 10% of patients are left with persistent symptoms more than three months after infection, including the sensation of ‘brain fog’. This syndrome is known as the post-COVID syndrome or ‘long COVID’. The pathophysiological mechanisms underlying this are unknown but may be mediated in a similar manner to bloodstream infections.
This project aims to investigate how bloodstream infections and COVID-19 affect the brain using detailed brain scans. Patients with bloodstream infections, COVID-19 and healthy controls will be recruited into a research study where they have a magnetic resonance imaging (MRI) scan near to the time of their infection and 12-18 months later. Disruption to the brain's usual protective mechanisms from infection (known as the blood-brain barrier) will be measured and analysed in conjunction with measures of cognitive function and the immune response in the blood.
Bloodstream infections, sepsis and COVID-19 are increasingly common conditions with a substantial mortality and long-term morbidity. This study has the potential to provide novel mechanistic insights into why systemic infections have such devastating long-term cognitive consequences and provide valuable data for devising therapeutic strategies in the future.
REC name
Wales REC 7
REC reference
21/WA/0202
Date of REC Opinion
28 Jun 2021
REC opinion
Favourable Opinion