Scientists have recently discovered a gene variant that may explain why 20 percent of people who get COVID-19 never develop symptoms.
In a recent study published in Nature, researchers theorized that human leukocyte antigen (HLA) genes may be the reason some people are asymptomatic when they test positive for COVID-19.
According to the authors, HLA genes play a significant role in viral infections by helping the immune system recognize infected or foreign cells and are the most medically important region of the human genome.
To determine whether HLA gene variants are associated with asymptomatic COVID-19, researchers enrolled 24,947 bone marrow donors over a nine-month study period, as gene sequencing is a prerequisite for being a tissue or organ donor and recipient, and genetic information was already available.
Participants used a smartphone app to track positive COVID-19 tests and daily symptoms, including fever, chills, and mild symptoms such as scratchy throat or runny nose. Each week, volunteers noted whether they had taken a COVID-19 test, and each month reported whether hospitalization had occurred.
During the study period, 1,428 unvaccinated individuals reported a positive COVID-19 test, with 20 percent of individuals reporting no symptoms. Further analysis revealed a specific HLA-B*15:01 variant was “significantly overrepresented” in asymptomatic individuals compared to symptomatic individuals.
Those who carried two copies of the variant—one passed down by each parent—were more than eight times more likely to remain asymptomatic than those carrying other genotypes. Researchers confirmed their findings in two other groups of people.
The authors then examined the effect HLA-B*15:01 had on T cells—a type of white blood cell that helps the immune system recognize germs and fight disease, including SARS-CoV-2.
Analyzing T cells donated by HLA-B*15:01-positive people before the pandemic, researchers discovered that T cells in asymptomatic participants reacted to a specific piece of SARS-CoV-2 spike protein, enabling the virus to enter the cells as if they had previously encountered the virus. Additional experiments showed that T cells with the specific HLA variant responded aggressively to an almost identical spike protein fragment from two seasonal coronaviruses associated with common colds.
“The findings suggest that T cells in many people with HLA-B*15:01 could already recognize SARS-CoV-2 because of their prior exposure to seasonal coronaviruses,” according to the National Institutes of Health (NIH). This ability to recognize SARS-CoV-2 allowed their immune systems to respond rapidly to clear out the virus before it caused symptoms of infection.
“If you have an army that’s able to recognize the enemy early, that’s a huge advantage,” the study’s coauthor, Dr. Jill Hollenbach, a professor at the University of California–San Francisco’s departments of neurology and epidemiology and biostatistics, told the NIH. “It’s like having soldiers that are prepared for battle and already know what to look for, and that these are the bad guys.”
Although the study’s results may explain why some people don’t develop symptoms of COVID-19, the study had limited genetic data, relied on self-reporting, and consisted of participants who were white and mostly female.
Despite these limitations, the authors said their results “provide strong support” for the role HLA genes play in viral clearance causing asymptomatic SARS-CoV-2 infections and provide a framework for additional study treatments for COVID-19.