Almost 7 million people have died from COVID-19 since the deadly coronavirus began more than three years ago. And yet even after repeated infections, some people still do not experience a single symptom after contracting SARS-CoV-2.
An immune gene variant may explain why, paving the way for more effective vaccines and treatments.
Global research led by the University of California San Francisco (UCSF) found that one in five people who were asymptomatic after infection with the SARS-CoV-2 virus had the gene variant HLA-B*15:01.
In addition, UCSF neuroscientist Jill Hollenbach and colleagues found people with HLA-B*15:01 who had never been infected with the virus, had immune cells that reacted to SARS-CoV-2 protein fragments, suggesting that immunity had developed after exposure to other infections.
Research suggests at least 20 percent of SARS-CoV-2 infections are asymptomatic, so learning more about this could help scientists in the fight against the disease that continues to claim lives around the world.
“Most global efforts have focused on severe illness in COVID-19,” Hollenbach and team write in the paper they published.
“Examining asymptomatic infection provides a unique opportunity to assess 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, such as viruses, which present small fragments to help immune cells like ‘kill’ T cells identify and fight infection or disease.
“If you have an army that can identify the enemy early, that’s a huge advantage,” Hollenbach say; “It’s like having soldiers who are ready for battle and already know what to look for and can tell by the uniform that these are the bad guys.”
The researchers examined genetic data previously collected 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 a voluntary smartphone-based program that these donors participated in, tracking infection, symptoms and outcomes.
There were 1,428 unvaccinated donors who reported testing positive for SARS-CoV-2, of whom 136 said they had no symptoms.
One hint of a genetic link was the discovery that 20 percent of these infected but asymptomatic donors had at least one copy of these infected but asymptomatic donors. HLA-B*15:01 gene, compared to 9 percent of infected people who developed symptoms.
Have one copy of the defense HLA-B*15:01 double the likelihood that someone infected with COVID-19 would be symptom-free, while someone with two copies was eight times more likely to show no symptoms.
“Asymptomatic individuals may enable us to identify 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’ observed in individuals able to avoid COVID-19.”
Further analysis of T cells from people with HLA-B*15:01 who had never been exposed to SARS-CoV-2 (from blood donations collected before 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 could recognize different versions of COVID-19, including Omicron versions.
“So even if the bad guys changed the uniform, the army would still be able to identify them by their boots or maybe a tattoo on their arms,” explains University of North Carolina immunologist Danillo Augusto.
“That’s how our immunological memory works to keep us healthy.”
There are limitations to the study; symptoms were self-reported, and the analysis included only individuals who self-identified as White.
The IS HLA-B*15:01 the gene variant is common, seen in about 10 percent of Europeans, but may be less common in other populations, so larger and broader studies may provide more reliable conclusions.
However, these significant findings may lead to ways to manage this devastating disease.
“Our findings have important implications for understanding early infection and the mechanism underlying early viral clearance,” the team said. writes“and may lay the groundwork for fine-tuning the development of vaccines and therapeutic options for early disease.”
The peer-reviewed research is published in nature.