METABRONA [COVID-19]
Research type
Research Study
Full title
Metabolic approaches to abolishing cytokine storm in COVID-19
IRAS ID
285084
Contact name
Cathy Thornton
Contact email
Sponsor organisation
Swansea University
Duration of Study in the UK
0 years, 10 months, 0 days
Research summary
Hyperinflammation is a feature of severe COVID-19 and is underpinned by dysfunction of a key inflammatory cell type called mononuclear phagocytes (MNPs). Highly inflammatory blood MNPs traffic to the airways and supplant reparative local MNPs to cause lung damage; similarly, they travel to the heart, kidneys and other tissues and damage those organs too. Continuous high levels of multiple inflammatory protein mediators called cytokines contribute to auto-amplification of inflammation, changes to blood, organ failure and death. Why cytokine storm occurs is unknown. We propose that cellular metabolic adaptation - the way the cells use fuels such as glucose to power their function- drive the hyperactivated MNP phenotype and offer targets for therapeutic intervention to abolish production of multiple cytokines and provide better outcomes for more patients. This is based on our own data that depriving human blood MNPs of glucose leads to hallmarks of hyperinflammation. To address this, we propose to use blood and airways MNPs from mechanically ventilated COVID-19 patients to investigate the link between metabolic maladaptation and cytokine hyperproduction. Patients who are mechanically ventilated for other reasons will serve as controls. The airways sample will be bronchial secretions that are a natural waste product of routine physiotherapy care of mechanically ventilated patients and blood will be from the arterial line that is inserted as part of routine clinical care. These samples will be used to undertake detailed analysis of the phenotype and functions of MNPs and identify ways of limiting their cytokine production that can be translated to patient benefit.
REC name
North West - Greater Manchester East Research Ethics Committee
REC reference
20/NW/0452
Date of REC Opinion
23 Nov 2020
REC opinion
Favourable Opinion