Employing genetic polymorphisms in ageing signalling pathways to predict individual risk of severe Covid-19 disease.
Age is the major risk factor for death and serious illness following SARS-CoV-2 infection. Understanding what happens to our organs and cells as we age may provide a clue as to why older people are more susceptible to severe COVID-19 disease. In recent years, scientists have identified several proteins inside cells that appear to control the rate at which animals age. Many of these proteins are also involved in generating an immune response that helps fight infections. As we age this immune response malfunctions, and the body begins to show signs of inflammation.
One of the proteins involved in the ageing process is called Nrf2. This protein protects the cell from damage, and also plays a role in the immune system. We have previously shown that the levels of this protein are lower in older people compared to younger individuals. We also found that some individuals, who have a slightly different DNA code for this protein, are at greater risk of developing certain characteristics of ageing, such as frailty at an earlier age. We therefore ask if individuals that differ at this gene may be at greater risk of severe COVID-19 disease. As well as this particular gene, we are also interested in finding out whether differences in other genes that code for proteins involved in the ageing process are related to severe forms of this infection.
Our project will involve looking at genetic material from patients who were admitted to hospital with COVID-19 disease and comparing the frequencies of the different forms of these genes with the frequencies found in the general population. We will also look at whether certain forms of the gene are more prevalent in hospitalised patients who die with COVID-19, compared to those who stabilise. The value in this research is that it could help us understand more about the role ageing plays in the progression of this disease, and identify targets for drug treatment. Importantly, it may help us to identify individuals who should be targeted for shielding, and early vaccination, should one become available. As this project will only involve reanalysis of existing data, we expect the project duration to be a period of months.