The genetics behind why some people get sicker with COVID-19 than others.

Norman Swan: One of the common questions that Tegan and I get about Covid is why there's so much variation in how people respond to the infection. One answer is in your genes, and there is a massive ongoing study into comparing people's genomes with how COVID-19 has affected them. Dr Gita Pathak is a team leader in what's called the COVID-19 Host Genetics Initiative. Gita is based at Yale University's School of Medicine in the United States.

Gita Pathak: Thank you for inviting me, I really appreciate it.

Norman Swan: So you're not mapping the virus here, you're mapping the people who were infected with the virus to see what happens to them and whether there are specific genes involved in their experience of the virus.

Gita Pathak: That is correct. The goal of the study is to understand human genetics response to the viral infection which we know as COVID-19. We wanted to look at three different outcomes of COVID-19, specifically people who were critically ill from Covid, then people who were hospitalised due to Covid, and people who tested positive for Covid, so the least severe of the three definitions, and which genes might be associated with these three outcomes.

Norman Swan: And how many genomes have you managed to test?

Gita Pathak: 60 studies from 25 countries, and that resulted in close to 3 million individuals' genetic profiles, and we found a total of 23 genes that show an association with COVID-19.

Norman Swan: So, let's take severity, and this is in a European population, by and large, a Caucasian population. Have you found any consistency in genes for severe disease?

Gita Pathak: Yes, so genetic ancestry is different than what someone may identify themselves as, like ethnically or geographically. Mostly we do have genetic ancestry of the European descent, but we also had people who are genetically South Asian, East Asian, African ancestry, and that separate from where they are geographically or what they identify as.

Norman Swan: So this is a bit like 23andMe or where you send off your genes and you find out that you are 50% Greek and you didn't think you were 50% Greek.

Gita Pathak: Correct. When we are looking at genetic profiles, it's really important to adjust for genetic ancestry and not specifically for what somebody identifies as. Some genetic variation is more common in one ancestry over others, and if we include people from these diverse ancestries, we can pick up these signals much more quickly…

Norman Swan: So, for example, it was said in the early part of the pandemic that people of South Asian origin had more severe disease and a higher risk of death. Did that pan out in your study?

Gita Pathak: We did find one of the genetic variants that was more common in South Asian populations relative to other populations, but that is just one variant. Genes tend to perform in a similar way across ancestries. They may vary based on their frequency in different ancestries, and that information helps us capture why one ancestry might be exhibiting a higher response or a softer response, but by and large all the genes we saw, they tend to have a similar effect across all ancestries.

Norman Swan: And what with these genes doing to increase your vulnerability to severe disease?

Gita Pathak: Some of the genes that we found were related to different lung functions. So, for example, we found something called SFTPD which is a lung surfactant protein, and it has already been known to be associated with different pulmonary functions, and there are other studies which have shown that this specific gene has been known with respiratory distress syndrome in different populations.

Norman Swan: And just to explain, surfactant is the fluid, if you like, that lines the tubes of your lungs and keeps them open, and it's what is deficient in premature babies, causing the respiratory disease of the premature baby. So, in other words, a deficiency of this in adults may predispose you, unsurprisingly, to severe disease. The question of course on everybody's lips now is why do some people not seem to catch COVID-19? There's a group of people who appear anecdotally to be resistant. Did you find COVID-19 resistance genes?

Gita Pathak: Not in our work. Depending on how we look at the variant, the varients we find are associated with the COVID-19 outcome, but if there are people who may be on the opposite spectrum of these, so let's say who are not carriers of this, they might be generally resistant to Covid but that specific study we haven't performed, but that's a good question for later.

Norman Swan: And just finally, any therapeutic insights that might direct people towards more effective medications to treat people who've got Covid, or prevent it getting worse?

Gita Pathak: One good thing that we understand from this work is that we now have a good number of genes to specifically focus our efforts into, and now this can lead to efforts of drug repurposing or drug development. Did we find a specific drug? No, but we definitely found several targets that now could be investigated for different drugs.

Norman Swan: Gita, thank you very much for joining us.

Gita Pathak: Thank you so much for having me, I really appreciate it.

Norman Swan: Dr Gita Pathak is a team leader in the COVID-19 Host Genetics Initiative at Yale University's School of Medicine.

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