Genetic Advantage: Unveiling the Secrets of COVID-19 "Super Evaders"

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Genetic Advantage: Unveiling the Secrets of COVID-19 “Super Evaders”

Genetic Advantage: Unveiling the Secrets of COVID-19 “Super Evaders”

Researchers at the University of California, San Francisco, have discovered that individuals who remain asymptomatic after COVID-19 infection often carry the HLA-B*15:01 gene mutation.

This genetic mutation enhances the immune response against the virus, providing insights into the genetic basis of asymptomatic COVID-19 and offering potential avenues for vaccine and drug development.

Scientists have identified a genetic variation, HLA-B*15:01, associated with cases of asymptomatic COVID-19, paving the way for new therapeutic approaches and vaccine development.

Individuals who become infected with the COVID-19 virus but never show symptoms—referred to as “super evaders”—may possess a genetic trump card. According to a recent study led by researchers at the University of California, San Francisco, they are more than twice as likely to carry a specific genetic variation, which aids in the elimination of the virus, compared to symptomatic individuals.

Published in the journal “Nature,” this paper is the first to demonstrate the genetic basis of asymptomatic SARS-CoV-2. The research contributes to unraveling the mystery of why some people can contract COVID-19 without developing symptoms.

Genetic Advantage: Unveiling the Secrets of COVID-19 "Super Evaders"

Role of HLA Gene Variations

The key lies in Human Leukocyte Antigen (HLA), proteins that signal the immune system. A gene encoding HLA undergoes a mutation that appears to assist T cells in recognizing SARS-CoV-2 and launching a rapid attack. Some individuals carrying this mutated gene can recognize the novel coronavirus, even if they have never encountered it before, thanks to its similarity to seasonal flu viruses they are already familiar with. This discovery opens up new targets for drug and vaccine development.

The chief investigator of the study, Dr. Jill Hollenbach, a professor of Neurology, Epidemiology, and Biostatistics at the Weill Institute for Neurosciences at the University of California, San Francisco, explains, “If you have an army that can identify the enemy early, that’s a huge advantage. It’s like having soldiers prepared for battle who already know what to look for, knowing these are the bad guys.”

Prevalence and Impact of HLA-B*15:01 Mutation

The HLA-B*15:01 mutation is relatively common, present in about 10% of the study population. It doesn’t prevent the virus from infecting cells but rather prevents individuals from displaying any symptoms. This includes mild symptoms like a runny nose or even almost imperceptible throat discomfort.

Researchers at the University of California, San Francisco, found that in a study population with asymptomatic COVID-19 cases, 20% carried at least one copy of the HLA-B*15:01 variant, while in the symptomatic group, this proportion was only 9%. Individuals with two copies of the variant had a much greater chance of avoiding illness, more than eight times that of carriers.

The study utilized data from the National Marrow Donor Program/Be The Match, the largest HLA-typing volunteer registry in the United States, which facilitates connections between donors and those in need of bone marrow transplants.

However, the study’s primary research group was limited to those who self-identified as white, as there weren’t enough individuals from other ethnic and racial groups in the final cohort for analysis.

Study Results and Sample Limitations

The researchers identified 1,428 unvaccinated donors who tested positive for COVID-19 between February 2020 and the end of April 2021 when vaccines were not widely available, and test results took days to come back.

Among these, 136 individuals had no symptoms at least two weeks before and after testing positive. Only one HLA variant—HLA-B*15:01—showed a strong correlation with asymptomatic COVID-19 infection, and this finding was confirmed in two independent cohorts. Risk factors for severe COVID-19 infections, such as older age, obesity, and chronic diseases like diabetes, appeared unrelated to asymptomatic infections.

Martin Maiers, Vice President of Research at the National Marrow Donor Program/Be The Match, expressed, “We are honored to collaborate on this research, which has the potential to leverage the long-term public investment in establishing a national registry to help treat diseases and enhance our ability to avoid future pandemics.”

Understanding Immune Responses

To understand how HLA-B15 eliminates the virus, Dr. Hollenbach’s team collaborated with researchers at La Trobe University in Australia. They explored the concept of T-cell memory, investigating how the immune system remembers previous infections.

The researchers observed T cells in individuals carrying HLA-B15 but who had never been exposed to the SARS-CoV-2 virus. They found that these cells still responded to a portion of the novel coronavirus called the NQK-Q8 peptide. The conclusion drawn was that T cells in individuals who had encountered some seasonal coronaviruses (which have a very similar peptide called NQK-A8) could quickly recognize the SARS-CoV-2 virus and mount a faster, more effective immune response.

Professor Stephanie Gras, Laboratory Director and Professor at La Trobe University, stated, “By studying their immune responses, this may help us identify new approaches to promote immune protection against SARS-CoV-2 for future vaccine or drug development.”