Almost 7 million people died of COVID-19 since the outbreak of the deadly coronavirus more than three years ago. And yet, even after repeated infections, a number of individuals have not experienced any symptoms after contracting SARS-CoV-2.
A variant in an immune response gene may explain why, paving the way for more effective vaccines and treatments.
Global research led by the University of California San Francisco (UCSF) found one in five people were asymptomatic after being infected with the SARS-CoV-2 virus carrying the gene variant HLA-B*15:01.
In addition, UCSF neurologist Jill Hollenbach and colleagues found people with HLA-B*15:01 those who had never been infected with the virus had immune cells that responded to SARS-CoV-2 protein fragments, suggesting that immunity developed after exposure to other infections.
Research suggests at least 20 percent of SARS-CoV-2 infections are asymptomatic, so learning more could help scientists fight the disease that continues to claim lives around the world.
“Most global efforts have focused on serious illness in COVID-19,” Hollenbach and team write in their published paper.
“Exploring asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance.”
Human leukocyte antigen (HLA) genes produce proteins that support the immune system and some HLA molecules are found on cell surfaces. They name and shame foreign invaders e.g. viruses presenting miniature fragments to help immune cells like ‘killer’ T cells recognizing and fighting infection or disease.
“Having an army that can spot the enemy early is a huge advantage,” Hollenbach said say; “It’s like having soldiers who are prepared for battle and already know what to look for and can tell from the uniform that these are the bad guys.”
The researchers examined previously collected genetic data from 29,947 registered bone marrow donors to see if HLA variation could predispose people to asymptomatic infection with SARS-CoV-2. The COVID-19 data came from a voluntary smartphone-based program in which these donors participated, tracking infection, symptoms and outcomes.
There were 1,428 unvaccinated donors who reported testing positive for SARS-CoV-2, of which 136 said they had no symptoms.
An indication of a genetic connection was the discovery that 20 percent of these infected but asymptomatic donors had at least one copy of the HLA-B*15:01 gene, compared to 9 percent of infected people who developed symptoms.
Having a copy of the protective HLA-B*15:01 variant doubled a person’s chance of being symptom-free when infected with COVID-19, and someone with two copies was eight times more likely to be symptom-free.
“Asymptomatic people may allow us to find new ways to promote protection against SARS-CoV-2 infection,” say biochemist Stephanie Gras of La Trobe University in Australia, “by mimicking this immune ‘shield’ seen in individuals who can evade COVID-19.”
Further analysis found T cells from people with HLA-B*15:01 who had never been exposed to SARS-CoV-2 (from blood donations collected prior to the pandemic) had a strong immune response to SARS-CoV-2 protein fragments.
These fragments shared genetic sequences with other seasonal coronaviruses that cause the common cold. Their T cells were able to recognize several COVID-19 variants, including Omicron variants.
“So even if the bad guys changed the uniform, the military would still be able to identify them by their boots or maybe a tattoo on their arms.” explains Immunologist Danillo Augusto of the University of North Carolina.
“This is how our immunological memory works to keep us healthy.”
The study has limitations; symptoms were self-reported and the analysis included only individuals who self-identified as white.
The HLA-B*15:01 gene variant is quite common, occurring in about 10 percent of Europeans, but it may be less common in other populations, so larger and broader studies may provide more reliable conclusions.
Nevertheless, these important findings may lead to ways to manage this still devastating disease.
“Our results have important implications for understanding early infection and the mechanism underlying early viral clearance,” the team said. writes“and may lay the foundation for refinement of vaccine development and therapeutic options in early disease.”
The peer-reviewed study was published in Nature.
