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