Question: The other day, I listened to a BBC report on genetic studies relating to who gets very sick with COVID. The study identified a gene that supposedly could indicate if a COVID patient will get worse or better. At least this is how I understood the reporting. The study only focused on COVID positive cases so this is not about natural gene immunity to COVID. I was wondering if you have seen similar studies or heard of them and what is your opinion and how it could be used to determine whether positivity will result in hospitalization. Right now we are looking at positivity to implement restrictions but if we were able to narrow the percentage of those positive who will end up in hospitals, wouldn’t that be useful as a measurement?
Answer: I think the BBC report you’re referring to is this one, Covid: Genes hold clues to why some people get severely ill, which is reporting on a study published a few days ago in Nature, Genetic mechanisms of critical illness in Covid-19. The study findings are especially useful for identifying potential therapeutic advances. Since we’re not at the stage of gene-based personalized medicine, this type of study is *not* useful for identifying whether a given individual is at risk of severe COVID. Read on for more background and a brief description of the study.
The Strangeness of COVID-19: During a CSIS event yesterday, Dr. Fauci described SARS-CoV-2as “one of the most, if not the most, unusual virus that any of us have ever dealt with. Certainly in my 36 years as director of the institute I have not seen anything where you have a virus that in the – in 40 percent of the people has no symptoms. Then those who have symptoms, 80 percent have very mild to moderate symptoms that don’t require any significant medical intervention. And then you have 20 to 25 percent of people who are devastated, at attests the almost 300,000 deaths. There’s something very strange about a virus that in most people barely bothers them and in others it kills them. We still don’t understand why that’s the case right now.”
Genetic Susceptibility to Severe Illness: Genetic susceptibility is one of the theories to account for the strangeness of COVID-19, in terms of both susceptibility to viral infection and propensity to develop severe illness (e.g. harmful lung inflammation). As described and well referenced in the background section of the Nature paper, “Susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable. In particular, susceptibility to respiratory viruses such as influenza is heritable and known to be associated with specific genetic variants. In Covid-19, one genetic locus, in 3p21.31, has been repeatedly associated with hospitalisation.”
Study Purpose: If we can identify the genes connected with severe illness, we can find therapies to improve immune response and save lives!
Study Methods: The GenOMICC (Genetics Of Mortality In Critical Care, genomicc.org) study has been recruiting patients with critical illness syndromes, including influenza, sepsis, and emerging infections, for 5 years. Researchers performed a genome-wide association study comparing critically ill patients with Covid-19 with controls from population genetic studies in the UK. The analysis included 2244 individuals with severe COVID-19. These individuals were matched with controls based on common ancestry (5 controls to 1 case). Controls were excluded if they had a known positive test for the novel coronavirus.
Study Findings: Findings reveal that COVID-19 critical illness “is related to at least two biological mechanisms: innate antiviral defences, which are known to be important early in disease (IFNAR2 and OAS genes), and host-driven inflammatory lung injury, which is a key mechanism of late, life-threatening Covid-19 (DPP9, TYK2 and CCR2).” Study authors go on to describe how these findings relate to various therapeutics.
Other Genetic Studies: There are a number of other studies that have looked at the relationship of various genes to susceptibility to infection and to severe illness. One set of studies we’ve talked about in the past is about the relationship of blood type and susceptibility (see Q&A of 10/15). Interestingly, this latest study’s findings indicate that the ABO locus (genetic basis for blood type) may be associated with susceptibility to infection, but is not associated with critical illness.