If you’ve made it this far without ever getting sick from Covid, you may have your genes to thank.
A study published Wednesday in the journal Nature found that people who have a specific genetic variation of a protein in the body may be more likely to never develop Covid symptoms — even if they are infected with the virus.
The protein in question is called human leukocyte antigen, or HLA. It’s found on the surface of cells and helps flag down the body’s immune system if something goes wrong — say, its cell becomes infected with the coronavirus.
But the proteins aren’t identical to those of siblings, family members or friends, thanks to tiny differences on the genetic level that make each person’s HLA proteins unique.
“These are highly variable immune system molecules that sit on the surface of all the cells in the body and are very different in everyone,” said Jill Hollenbach, a professor of neurology at the University of California, San Francisco, who led the new research.
In fact, HLAs are the most variable part of the human genome — which is by design.
“Genetic diversity is very important for the immune response,” said Neville Sanjana, an associate professor of biology at New York University and core faculty of the New York Genome Center, who was not involved with the study. “When there are diverse pathogens that we are exposed to, not all people’s immune systems are going to respond to pathogens in the same way.”
In the new study, Hollenbach and her team turned to a national bone marrow donor database. People in the database had already had their HLA genetically sequenced. The researchers used this existing data to understand each person’s HLA proteins. The participants had also reported whether they had tested positive for Covid from February 2020 through April 2021 and if they developed symptoms. All were unvaccinated.
The researchers noted that the study only included people who identify as white, because they didn’t have enough data from other races and ethnicities. However, they said that the gene variant identified in the study does appear to be linked to a lower likelihood of not developing symptoms in Black individuals, though its effect is unclear in Asian, Hispanic and American Indian/Alaska Native populations.
The study included almost 1,500 people, all of whom were unvaccinated. Of these, 136 tested positive but never had symptoms — not even a slightly runny nose or a tickle in their throat.
The genetic code that tells cells how to construct HLA proteins can carry many small mutations that lead to different variants of the protein. Each person is born with two copies of the HLA gene, one from each parent.
The study found that 20% of people who never developed Covid symptoms had at least one copy of a variant called HLA-B*15:01, compared to just 9% of those who had symptoms. People who carried two copies of this variant were more than eight times more likely than those who didn’t to test positive for Covid but remain asymptomatic.
But HLA proteins are just one piece of the puzzle, the researchers found.
People with the HLA-B*15:01 variation also had T-cells that were able to better spot the virus that causes Covid, because they remembered previous coronavirus infections. (SARS-CoV-2, which causes Covid, isn’t the only coronavirus that infects humans — several coronaviruses can cause common colds.) The viruses were similar enough to allow the T-cells to take quick action once SARS-CoV-2 infected the body.
In general, to clear viruses from a person’s cells, T-cells work in tandem with the HLA proteins.
When a virus infects a cell, the HLA protein will take a snippet of the virus and hold it up on the cell’s surface. This acts as a sort of signal that flags down T-cells that are able to recognize the threat. When one comes along that does, it attacks and kills the infected cell.
In the case of people with the HLA-B*15:01 variant, this process seemed more effective than usual, allowing the T-cells to work more quickly to kill cells infected with the virus before symptoms have time to develop.
Hollenbach said the findings could help researchers develop better drugs and vaccines for Covid.
Experts note that the discovery is just one of the many factors that determine whether a person will get sick from Covid.
“It’s a complex symptom at play here, it’s not the one thing that answers everything,” said Genevieve Wojcik, an assistant professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, who specializes in genetics. “Genetics are usually only part of the puzzle and just one variant is an even smaller part of the puzzle.”
She noted that the study had limitations: because data was also only collected from white people, it leaves huge gaps in our understanding of how genes play a role in the communities of color that were most burdened by Covid.
“The HLA is one of the most diverse parts of the human genome,” Wojcik said. “We really need more diversity on a global scale if we want it to be applicable to every group.”
This article was originally published on NBCNews.com
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