The true prevalence would be much higher than the test only picks up about 80 percent of the COVID-related antibodies.
But why do some people get very ill from COVID-19, others experience little or no symptoms, and some do not get infected at all?
“That is the puzzle we are trying to crack,” says Professor Stuart Tangye, an immunologist from the Garvan Institute of Medical Research who leads the Oceania hub of the COVID Human Genetic Effort.
Rather than luck, the consortium of scientists believes the answer lies in our genes.
It is investigating the DNA of people from all over the world who either suffered from a severe life-threatening case of COVID-19, experienced an asymptomatic infection or are possibly resistant to infection or disease.
“Our mission is to find out why and how our genes affect our immunity against coronavirus, and how and why immunity can also be affected by other, non-genetic causes,” the COVID Human Genetic Effort says on its website.
In late 2020, the COVID Human Genetic Effort made some major discoveries, revealing why some otherwise healthy people end up in intensive care units following SARS-CoV2 infection.
About 15-20 per cent of people with severe COVID develop antibodies that neutralize a key component of our own immune system which prevents us from attacking the invading virus. Another 3.5 per cent were found to have genetic mutations which impaired their immune response to certain viruses, including SARS-CoV2.
“People who were missing a key protein – interferon – essential for immunity in the first few days of infection, were left really vulnerable to critical disease,” says Dr Vanessa Bryant, an immunologist from WEHI, Australia’s oldest medical research institute. Bryant is leading part of the Australian First Few X (FFX) study that is investigating COVID-19 transmission in households.
“That can give us insight into new antiviral therapies and different ways to shape and boost our immune system.”
While the work on severe COVID is ongoing, Tangye says the global consortium has now evolved to answering the more difficult questions.
“What’s become obvious is that there’s been a number of people who not only are not symptomatic, they’re actually not infected, or they exhibit some type of resistance,” he says.
“The next plank is to identify genes that could be essentially giving you a bit of protection or ‘forcefield’, or whatever you want to call it, that stops you from either getting infected, or stops you getting really sick if you do get infected .”
This has been a little bit trickier, Tangye says, because asymptomatic and healthy people are not showing up in doctor’s clinics.
“So you’re trying to pull them out of the woodwork to go, you know what, there’s some people here who seem to have a superpower of resistance, and they’re not succumbing to infection or disease, or even symptoms.”
Last November, a study of UK health care workers during the first wave of the pandemic found some were able to clear their bodies of the virus before producing COVID antibodies.
It was hypothesized that exposure to other human coronaviruses – such as those that cause the common cold – had helped them fight off infection.
“There can be elements of cross reactivity,” Bryant says. “But the impact of that is still unknown and somewhat controversial, like, is it just providing an extra bump in our protection? We certainly don’t think that it is a main driver in protecting people from severe disease.”
At this point in the pandemic, it is difficult to unpick whether people are not getting sick due to vaccines and boosters, a past undiagnosed COVID infection, or something else.
“It could boil down to a combination of cross-immunity against some other infection that they previously had, but that is offering some kind of protection,” says the Murdoch Children’s Research Institute’s Professor John Christodoulou, who is also involved with the COVID Human Genetic effort
“Or it could be environmental factors like being very diligent with mask wearing or physical distancing. Or it could just be blind luck.”
The COVID Human Genetic Effort is also researching whether – in extremely rare cases – some people carry a mutation that makes them resistant to SARS-CoV2 infection and severe COVID-19.
Almost 30 years ago, researchers discovered a genetic mutation which means about 1 per cent of people descended from Northern Europeans are immune to HIV infection. This led to scientists developing HIV-blocking drugs.
Christodoulou hypothesizes that if there were mutations in the body’s ACE2 receptors – essential for the COVID-19 virus getting into our cells – it could prevent people being infected.
“And so that’s certainly one of the genes that people are looking at amongst that very small proportion of individuals who seem to have been hyperexposed, this is, those who have had multiple family members affected with COVID, yet they remain COVID-free.”
But ACE2 receptors also regulate blood pressure and inflammation and Bryant warns that a mutation probably comes with another health cost.
“But identifying those gene changes really gives us an amazing opportunity to develop better drugs or hone our vaccine targets and, at the other end of the spectrum, identify people who are most vulnerable to severe disease.”
On Wednesday, Holmes and Alderton met with Tangye, and offered to contribute to the COVID Human Genetic Effort study.
Tangye says it is possible that Alderton has had the virus but was asymptomatic. To find out, they would screen his blood to look for antibodies and T-cells that are specific for the virus and not in the vaccines.
A study coordinator will then recruit Alderton and Holmes and, after taking a blood sample, sequence their entire DNA in their cells.
“We will see if there are any differences in some key genes in Tom, that may offer a suggestion as to why he was resistant or why he was uninfected despite proximity and an opportunity.”
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