Approved Research

Unravelling heterogeneity of host related outcomes and sequelae: from mild infection to septic shock.

Lay summary

When people suffer from an infection, they usually only become known to a healthcare professional once they are symptomatic, by which time many biological protective pathways have been activated and downstream effects underway. This has been clearly demonstrated by the current COVID-19 pandemic, where some patients present in a cytokine storm (an overexuberant response of the body against infection), whilst others have various degrees of milder infection. The syndrome in which the body's own response to fighting an infection results in organ damage is known as sepsis. Recently the worldwide burden of sepsis has been estimated to be 48.9million cases annually, with at least 20% mortality. However, no specific treatment yet exists for this severe manifestation of infection outside antibiotics and supportive care. Furthermore, by understanding the biological systems in our bodies that alter the disease course a patient takes will help us to increase the chances of finding specific targets to shift outcomes.

The main focus of our research questions will be:

-To establish what role variation in our genes play on determining susceptibility and outcomes from infections.

-Try to understand why some patients develop severe disease (and die) whereas others only mild symptoms, despite similar pathogens and other risk factors.

-Develop new predictive methods to allow a precision medicine approach to better target individual therapy rather than a one-size-fits-all approach that we currently use.

To date, only few studies have focused on how genetic variability affects susceptibility to severity of infection. By utilising population-wide collections of human genome and health data such as the UK Biobank we will increase our chances in making new discoveries and advancing healthcare. We expect to carry out this work over a 24-month period.