A massive international collaborative effort has begun investigating whether specific genetic characteristics can make someone resistant to SARS-CoV-2 infection. The project is called the COVID Human Genetic Effort, and the goal is to understand why some people seem naturally immune to this new virus while others suffer severe infections.
In the late 1970s, a partner of New York artist Stephen Crohn tragically died from a disease that was soon to be known as AIDS. Over the subsequent years a number of Crohn’s friends and partners were struck with the disease, yet Crohn never got sick.
In 1994, a team of scientists started investigating subjects with potential genetic resistance to HIV infection and Crohn, who suspected he had some kind of unexplained protection, enthusiastically took part in the project. After plenty of hard work the researchers homed in on a single genetic mutation that seemed to be the cause of Crohn’s unusual protection.
This single genetic mutation prevented the HIV virus from infecting Crohn’s cells. And the discovery ultimately led to the development of antiviral drugs now used to treat the condition.
One of the most striking characteristics of SARS-CoV-2, the novel coronavirus responsible for this global pandemic, is just how unpredictable its effects are from person to person. Researchers have developed a reasonably consistent picture of who is most at risk of severe disease, however, there are countless stories of young, healthy people succumbing to COVID-19. And, at the other end of the spectrum, plenty of anecdotes of couples where one member suffers from severe COVID-19 while the other experiences no ill-effects whatsoever.
Some researchers suspect unique genetic characteristics could explain why some people seem to resist SARS-CoV-2 infection despite significant exposure to the virus. But ... identifying people with potential genetic immunity to COVID-19 is difficult.
It isn’t exactly ethical to expose someone to the virus to see if they get infected. So researchers rely on tracking down individuals who are likely to have been highly exposed, yet didn’t experience any signs of disease.
Household contacts of positive cases are good candidates but those in intimate relationships are even better. Known as discordant couples, these are couples where one member is symptomatic while the other not only is asymptomatic but is confirmed seronegative through a COVID-19 PCR test. These are not simply asymptomatic cases, but cases where someone has not even been infected with the virus in the first place, despite extraordinary exposure to a positive case.
A new perspective article published in the journal Nature Immunology, is proposing a strategy for “identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.” The article, co-authored by dozens of researchers involved in the COVID Human Genetic Effort consortium, argues prior research into genetic resistance to HIV infection has led to the development of significant new therapies and it is reasonable to think this could be possible for COVID-19.
“No specific drug effective against COVID-19 has been discovered since the start of the pandemic,” the researchers write in the article. “Lessons learned from experiments of nature could potentially guide us toward such specific treatments for COVID-19.”
A preliminary study, yet to be published in a peer-reviewed journal but available as a preprint, reports on initial investigations of a cohort of 86 discordant couples. The findings suggest there may be no single gene variant that confers resistance to COVID-19, but instead it could be a collection of gene variants related to particular immune cell activity.
The ongoing project has already enrolled more than 400 people. Anyone interested in participating in the project can get involved through the website COVID Human Genetic Effort.
The new article was published in the journal Nature Immunology.
