A new study conducted by researchers from UC San Francisco reveals that people who contract COVID-19 but remain asymptomatic, often referred to as "super dodgers," may have a hereditary advantage. These individuals are more than twice as likely as those who develop symptoms to carry a specific gene variation that aids in eradicating the virus.
Published in Nature on July 19, 2023, the study provides the first evidence that there is a genetic basis for asymptomatic SARS-CoV-2 infection.
This research sheds light on the mystery of why some people can be infected with the virus without ever experiencing symptoms of COVID-19.
The key lies in the human leukocyte antigen (HLA), a protein marker that signals the immune system. A mutation in one of the genes coding for HLA seems to assist virus-fighting T cells in identifying SARS-CoV-2 and launching a rapid attack. T cells of individuals carrying this variant can recognize the novel coronavirus, even without previous exposure, as it resembles the seasonal cold viruses they are already familiar with. This discovery opens up new possibilities for drug and vaccine targets.
Lead researcher Jill Hollenbach, PhD, MPH, a professor of neurology, epidemiology, and biostatistics, and a member of the Weill Institute for Neurosciences at UCSF, explained, "If you have an army that's able to recognize the enemy early, that's a huge advantage. It's like having soldiers that are prepared for battle and already know what to look for, and that these are the bad guys."
The identified mutation, HLA-B*15:01, is quite common and is carried by approximately 10% of the study's population. While it doesn't prevent the virus from infecting cells, it does prevent people from developing any symptoms, including even a mild sore throat or runny nose.
The researchers from UCSF found that 20% of asymptomatic individuals in the study carried at least one copy of the HLA-B*15:01 variant, compared to only 9% of those who experienced symptoms. Those who carried two copies of the variant were more than eight times more likely to avoid falling sick.
To conduct the study, researchers leveraged data from the National Marrow Donor Program/Be The Match, which houses the largest registry of HLA-typed volunteer donors in the US. They also employed a mobile app called the COVID-19 Citizen Science Study, developed at UCSF, and recruited nearly 30,000 people from the bone marrow registry. These participants were tracked throughout the first year of the pandemic, before vaccines were widely available, and underwent routine COVID testing for work or potential exposure.
The study primarily focused on those who self-identified as white due to insufficient representation from other ethnic and racial groups to analyze in the final set of respondents.
Among 1,428 unvaccinated donors who tested positive between February 2020 and the end of April 2021, the researchers identified 136 individuals who remained asymptomatic for at least two weeks before and after testing positive. HLA-B*15:01 was the only HLA variant strongly associated with asymptomatic COVID-19 infection, and this was confirmed in two independent cohorts. Factors such as age, weight, and chronic diseases like diabetes did not appear to play a role in who remained asymptomatic.
The researchers collaborated with scientists from La Trobe University in Australia to understand how HLA-B15:01 managed to suppress the virus. They focused on T-cell memory, which is how the immune system remembers past infections. T cells from individuals carrying HLA-B15:01, despite never being exposed to the SARS-CoV-2 virus, still responded to a part of the novel coronavirus called the NQK-Q8 peptide. The exposure to some seasonal coronaviruses, which have a similar peptide, NQK-A8, enabled T cells in these individuals to quickly recognize SARS-CoV-2 and mount a faster, more effective immune response.
Stephanie Gras, a professor and laboratory head at La Trobe University, stated, "By studying their immune response, this might enable us to identify new ways of promoting immune protection against SARS-CoV-2 that could be used in future development of vaccine or drugs."
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