Why do some people have no symptoms from a Covid-19 infection, and others quickly become septic, develop respiratory failure, and die? We’ve had only a few clues—age, gender, and weight are crude predictors of trouble.
A new multicenter study from the UK sheds more light and brings the promise of new treatments. Dr Kenneth Baillie, a critical care specialist at the University of Edinburgh’s Roslin Institute, is the project’s chief investigator.
Using genetics can help find targeted new therapies. In this case, they found five genes (called LZTFL1, OAS1, DPP9, TYK2, and IFNAR2) that were markedly different between ICU patients and volunteers who did not have Covid-19. He continues, “Your DNA is a long code, which we represent as the letters A, C, T and G. There are 3,000,000,000 letters in the code to make a human.Dr. Kenneth Baillie, a critical care specialist at the University of Edinburgh’s Roslin Institute, is the project’s chief investigator.
At this one position, if you have a “T” instead of a “C”, then your odds of life-threatening Covid-19 are 1.3x greater.
Doesn’t sound like much, and compared to the effect of age on risk, it isn’t. But that’s not why it matters.
That one change makes a difference to how much of the TYK2 gene you make. So we can ask, if you make more TYK2, are you more at risk?
The answer is yes. Less TYK2 is associated with lower risk. That suggests that a drug that inhibits TYK2 might make people less likely to develop life-threatening Covid-19. The good news is that we have a whole class of drugs that do this (JAK inhibitors).
The other genes we find suggest other treatments, which we discuss in the paper. We already know that genetic evidence doubles the chance that a drug will be successful.
This demonstrates the beauty of genetics for drug target discovery. Faced with a new disease, that we didn’t understand at all, we can look across the *entire* code that makes our immune system, to find the exact points we need to target with drugs, in order to save lives.”
This thread is a stellar example of effective science communication.
This multi-centre study is also remarkable for having been done within only six months and for the sheer number of collaborating centres. There were 208 ICUs across the UK which already have enrolled 2700 critically ill patients in this study to examine their genes.