Irish scientists are looking for people who tested negative for Covid-19, and were in close-proximity to someone who tested positive, for a study into genetic resistance to the virus.
In a landmark paper published in leading journal Nature Immunology, the consortium sets out a strategy for answering one of the pandemic’s greatest questions: why do some people not get Covid-19?
The Covid-19 Human Genome Effort (COVIDHGE) is being led by Jean Laurent Casanova of the Rockefeller Institute in New York and Helen Su of the National Institutes of Health in the US. It involves teams from over 50 countries, including one from Trinity.
The Irish group is led by Cliona O’Farrelly, Professor of Comparative Immunology at Trinity College Dublin.
Prof O'Farrelly has been researching innate immune system responses for some time, having previously done research on people exposed to hepatitis C who did not become infected.
Prof O'Farrelly told BreakingNews.ie: "The criteria we’re setting is we’re looking for people who have shared a bedroom with someone who was PCR-positive for at least three days. We need to be really sure they were in the environment of the virus, because otherwise people would say they didn’t get infected because they didn’t get the virus.
"They need to have shared a bedroom with the person for three days, for the other person to be PCR-positive, and they have to have a documented negative PCR test for the same time.
"Anecdotally loads of your friends will be saying, 'they all got it in my house, but I didn’t'. Then, when you probe a bit you discover that person was out every night or something, so not really exposed, that’s what is challenging, to make sure the people we are studying have been exposed to the virus and remained PCR-negative."
Antibodies
"Then we have to check their antibodies, we get serum samples from them and check that the antibodies which mark infection, we can tell the difference between people who are infected and those who have made antibodies because of vaccination," she explained.
"The people who have been vaccinated will only have antibodies against the spike, the protein on the surface of the virus, whereas people who have been infected will have antibodies against spike but also antibodies against what we call the nucleoproteins, proteins inside the virus."
Prof O'Farrelly said some people will have avoided the virus due to their adaptive immune system, however, this study is looking for people who did not need this immune defence.
"If a person who volunteers for our study didn’t get the virus even though they were with somebody who was PCR positive, and we discover that they have antibodies, that means their adaptive immune system got rid of the virus and that’s interesting in itself, but we’re not studying that. We’re looking for people that kept the virus away without having to use their adaptive immune system.
"Adaptive means you’ve become immune, innate is what you’re born with. Your vaccine teaches your immune system about the virus."
Prof O'Farrelly explained that the immune system includes a range of "complex mechanisms".
Immune diversity
"Those mechanisms are hugely variable across humans and this explains why you have this huge diversity of response to any infection, some people who get really sick, some who get a bit sick, some who don’t get sick at all, and some who don’t get infected at all. That is a reflection of this huge diversity in the human immune repertoire. All those mechanisms are controlled by genes and so the variability in those genes, the code for those mechanisms that account for the huge variability."
She added: "What we’re looking for is the variation in the genes that code for the innate immune system, we think that some people have a genetic variation in some of those innate anti-viral mechanisms that makes them able to respond quicker and better, so they get rid of the virus before ever needing to use these other mechanisms."
Prof O'Farrelly said successful findings in the research could have a number of impacts. These include explaining better how the body responds to viruses, aiding in the development of "better vaccines, and drugs" to fight Covid and future viruses.
"What we would go on to test would be whether people who are resistant to Covid, are they resistant to other viruses? This would be hugely powerful information to have for the next pandemic."
"Even if it was only a few people, wouldn’t it be amazing for doctors, nurses, healthcare workers, if you were able to identify people who were resistant it would be hugely beneficial when responding to another pandemic," she added.
Prof O'Farrelly said samples from the first 26 Irish people involved in the study have been sent for further analysis, with data expected back soon.
The study will look at 4,500 people in total across 50 countries.
"There will be two elements to the study, one will be part of the big consortium, and we ourselves in Ireland will study our own.
"In addition to the genetic study we’re also carrying out biological analysis. So those people will be invited back to give a blood sample, so we can study how their innate immune response acts, so we can correlate the biology of the genetics."
Prof O'Farrelly is currently broadening the criteria to look for people who appear to be resistant to the Omicron and Delta variants of the virus, she said: "I definitely think there are people out there [who are resistant to both variants]".
Getting people who are eligible for the study can be challenging, but Prof O'Farrelly is hopeful more people who fit the criteria will register.
"If people have been vaccinated you can’t be sure it wasn’t their vaccine that has protected them, so we need evidence of exposure even before the vaccine. Some people will remember and have their PCR tests.
"Because not everyone was being PCR tested at the beginning, it’s difficult, but hopefully the antibodies will tell me.
"Whatever we discover will help to inform equivalent studies next time. Now lots of people understand the idea of viral resistance. When I first started studying resistance to hepatitis C people were sceptical.
"Antibodies and T cells are really important, but that doesn’t take away from the likelihood that the innate immune system is also really important.
"Most of us when we get exposed to viruses our innate immune system clears most infections, because we’re constantly getting exposed to viruses. It’s great for Ireland to be involved in an international study like this, it’s such a privilege."
Anybody who may be eligible for the study can find more information at viralresistanceproject.com.
