An international group of scientists, which includes a team from Trinity College Dublin (TCD), is looking for a genetic explanation as to why some people experience life-threatening Covid symptoms, while others appear resistant to the virus.

The group, known as the Covid-19 Human Genome Effort (COVIDHGE) consortium, has published a landmark paper in the journal, Nature Immunology, which sets out a strategy for answering the question – why do some people not get Covid-19?

The scientists note that throughout history, infectious diseases have always put strong evolutionary pressure on humans. In particular, viruses appear to have been dominant drivers of genetic change as adaptations have arisen that protect people from infection or from serious illness during infection.

Over the years, scientists have discovered genetic factors that partly explain why infections such as HIV, hepatitis C and malaria affect some people more than others.

The COVIDHGE consortium has already discovered how variation in some immune genes contributes to severe Covid infection (for more on this, click here). It now wants to find the genes responsible for why some people are resistant to the Covid virus.

Over the next 12 months, the consortium will look for people who seem to be naturally resistant to Covid-19, i.e. those who have been exposed in close quarters and for a significant amount of time to an infected person. Their genetic and other biological profiles will be compared to people who became infected with the Covid virus.

This will allow them to seek genetic answers in a targeted manner and could explain why some people are resistant.

The Irish group, which is based in the Trinity Biomedical Sciences Institute, is led by Prof Cliona O’Farrelly, a professor of comparative immunology at TCD. It is collaborating with scientists and clinicians in St James’s Hospital in Dublin.

“There is a growing awareness that many people seem to have innate immune-mediated resistance to viral infections. My team and I have been highlighting this for a number of years since our discovery that around one-third of Rhesus-negative Irish women exposed to hepatitis C-contaminated anti-D in 1977-79 did not ever show symptoms of the virus.

“Because of that work, and growing information regarding the wildly variable responses that people have to COVID-19 exposure, we are convinced that a proportion of the population is resistant to the virus,” Prof O’Farrelly said.

Jamie Sugrue, a PhD candidate on Prof O’Farrelly’s team explained that they have recruited 30 “resistors” from St James’s Hospital – people who remained Covid-negative while living with someone who was infected. These people’s DNA and serum samples are ready to be analysed.

“Over the next 12 months, we will collect more biological material from the resistors and their virus susceptible living partners to compare their innate immune responses and identify biological hallmarks of resistance to Covid-19.

“We hope by combining the genetic, biological and serological data, we will identify a biomarker signature of resistance to Covid-19. This signature could then be used to find out, with great accuracy, how many people are resistant to Covid-19 and may help inform novel antiviral therapies,” Mr Sugrue said.

For more information on the Irish group’s work, click here. COVIDHGE involves teams from over 50 countries. For more information on it, click here.