In a landmark paper published in the leading journal Nature Immunology, the consortium of scientists 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.

Throughout history, infectious diseases have imposed a strong evolutionary pressure on humans. Viruses, particularly, seem to have been dominant drivers of genetic change as adaptations have arisen that protect individuals from infection or from serious illness during infection.

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

Now the COVIDHGE consortium wants to find the genes responsible for why some people are resistant to COVID-19. The effort to uncover natural resistance to COVID-19 is being led by András Spaan of the Rockefeller University in New York.

Global strategy and the Irish project

The collaborating COVIDHGE scientists will, over the next 12 months, seek people who seem to be naturally resistant to COVID-19 (having been exposed, in close quarters, and for significant time to an infected person) and compare their genetic – and other biological – profiles with those of non-resistant people who become infected.

In doing so, they will hunt – in a targeted manner – for genetic answers that could explain why some people are resistant and others not, and by extension, make a global impact in fighting the virus.

The Irish group, led by Cliona O’Farrelly, Professor of Comparative Immunology at Trinity, has been a member of COVIDHGE since June 2020 and is now supported by Science Foundation Ireland to contribute to the global effort, via the DIRECTS: Detecting Innate pRotECTion against SARS-CoV2 project.

Professor O’Farrelly, whose team is based in the Trinity Biomedical Sciences Institute and who collaborates with clinicians and scientists in St James’s Hospital, said:

“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.”

Jamie Sugrue, PhD Candidate in Professor O’Farrelly’s team, added:“We have recruited 30 ‘resistors’ from St James’ Hospital – people who remained COVID-negative while living with someone who was infected – and have DNA and serum samples ready to be analyzed. 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.”

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