Why do some coronavirus patients experience no symptoms or suffer a rare form of the illness, whereas others require hospitalisation, ventilation and in some cases die from the disease? The answer to this question is likely, in part, to lie in our genes; indeed, recent research has highlighted links between certain genes and coronavirus disease severity. The first part of this project will aim to confirm these genetic links in UK Biobank participants. Although important in its own right, further work is needed to explain such genetic associations if we are to help patients whose DNA unfortunately puts them at higher risk of suffering serious consequences of the disease. By “explaining” here, we mean finding what biological consequences of these genetic factors go on to affect disease severity. The biological “consequences” of genetic factors are the levels of a range of biomarkers in our bodies. Knowing which of these biomarkers, affected by the genes, go on to play an important role in coronavirus disease severity is potentially very useful, since the majority of drugs act by changing the levels of particular biomarkers in our bodies. Therefore, knowing which are the problematic biomarkers involved in coronavirus disease severity could lead us to existing or new drugs that could help to treat the disease in those patients who contract a severe form of the illness.
There are considerable statistical challenges involved in addressing these aims. Genetic and protein data are highly complex, first because there are so many different genes and protein levels measured, second because there are close relationships between the levels of one protein and another, and third because there are environmental factors (BMI, smoking status, chronic conditions such as diabetes) and demographic factors (age, sex, ethnicity) that likely affect, for example, both the levels of certain proteins and coronavirus disease severity. Thus, for the proteins aspect of the research, we will make use of flexible state-of-the-art statistical methods recently developed for this purpose.
We will start working on this as soon as we obtain access to the data, potentially obtaining results on the important proteins within a matter of weeks. We would then pass these results on to colleagues at Cardiff Univerity’s Medicines Discovery Institute who will investigate the druggability of these proteins using existing databases of drugs and proteins. The potential Public Health impact will come from the suggestion of existing/new drug therapies.