“By looking at resistance, we can basically understand how to clear an infection,” said Samira Asghari, assistant professor of genetics and genomics at Icahn School of Medicine in Mount Sinai, who was not involved in the study.
To figure out how some people are avoiding COVID-19 symptoms, researchers looked to: human leukocyte antigen (HLA) genes play an important role in our body’s ability to recognize and fight pathogens. These gene warriors are “the most medically important regions of the genome,” said Jill Hollenbach, a professor in the Department of Neurology and Epidemiology at the University of California, San Francisco.
for their study Published Wednesday in NatureHollenbach and her team enrolled 29,947 volunteer bone marrow donors because high-quality genetic data were already available for this group. They asked volunteers to use their smartphones every day to track their own coronavirus infections and associated symptoms such as runny noses, rashes in the throat, fevers and chills. Participants were asked to record whether they had been tested for coronavirus each week and whether they had been hospitalized monthly.
During the nine-month study period, 1,428 unvaccinated individuals tested positive for coronavirus, of whom 136 had no symptoms. Among the asymptomatic participants, 20% carried a common HLA variant called HLA-B*15:01. Those who carried her two copies of this variant (one her from each parent) were more than eight times more likely to remain asymptomatic than those carrying other her HLA variants.
The researchers also used volunteer data to model whether non-genetic factors influence a volunteer’s likelihood of asymptomatic infection.
“There are many factors that increase the likelihood of developing serious illness, including various comorbidities, weight, age and gender,” Hollenbach said. “None of these things seem to matter in this case, especially when it comes to asymptomatic consequences. It seems to be driven primarily by genetics.”
T cells and pre-existing immunity
To better understand the role of genetics in asymptomatic cases, researchers examined samples of people carrying HLA-B*15:01 collected before the coronavirus pandemic. They found that these people possess immune cells called T cells that respond to proteins common to SARS-CoV-2 and other seasonal coronaviruses. This suggests that carriers exposed to seasonal cold viruses may have acquired pre-existing immunity to the novel coronavirus.
This result may explain why some asymptomatic infections occur, but this study was limited to genetic data that already existed from previous studies. The study group was also highly homogenous, with all participants self-identifying as white and 81% self-identifying as female.
“In terms of variability, these results cannot be extended to all populations, as we know, based on epidemiological reports, that COVID-19 symptoms vary from population to population,” Asgari said.
Despite its limitations, the study is an important step in understanding why asymptomatic infections occur, with potential implications for public health, vaccine design and treatment development, the researchers said.
“As we’ve all learned, preventing COVID-19 has turned out to be more difficult than we expected,” said Hollenbach. “It may not stop the infection, but if we could design a vaccine that would deal with the infection quickly and not cause symptoms, I would be personally very happy.”
