Genetic basis found for asymptomatic COVID-19 infection

US and Australian scientists have uncovered a genetic basis for strong immunity against COVID-19 in a large study on people with asymptomatic cases of the disease, opening the way for better vaccines and treatment.

The research, published in the journal Nature, shows that a person who carries one copy of the protective HLA-B15 gene is twice as likely to remain asymptomatic, while someone who carries two copies of the gene is eight times more likely to show no symptoms. The research is part of a global study led by the University of California San Francisco (UCSF).

The study investigates the genetics and COVID-19 symptoms of almost 30,000 registered bone marrow donors, who were involved in a voluntary program to track COVID-19 infection and symptoms. The researchers found that of 1428 unvaccinated donors with positive test results for SARS-CoV-2, 136 had no symptoms. A high proportion of these asymptomatic donors were carrying the HLA-B15 gene, which was the first evidence of a genetic link.

In collaboration with UCSF, La Trobe University’s Professor Stephanie Gras, Dr Dimitra Chatzileontiadou and Lawton Murdolo found that the killer T cells, which help our bodies fight infection, had a strong immune response to SARS-CoV-2 and seasonal coronaviruses in those people with the HLA-B15 gene. These killer T cells also had the capacity to recognise COVID-19 and its different variants, including the current Omicron variants.

“Using the Australian Synchrotron facility, we were able to show at the atomic level how HLA-B15 individuals activate T cells upon SARS-CoV-2 exposure in the same manner as some seasonal coronaviruses, providing the mechanism for this pre-existing immunity,” Murdolo said. This enables them to mount a faster and stronger immune response after infection, and to eliminate the virus more quickly, Chatzileontiadou added.

Gras said the results might enable scientists to “identify new ways of promoting protection against SARS-CoV-2 infection by mimicking this immune ‘shield’ observed in individuals that can dodge COVID-19”. This was reiterated by study leader Professor Jill Hollenbach, from UCSF, who said that understanding how asymptomatic cases occur is a tremendous advantage in fighting a disease which has killed almost 7 million people worldwide.

“If you have an army that’s able to recognise the enemy early, that’s a huge advantage,” Hollenbach said.

“It’s like having soldiers that are prepared for battle and already know what to look for and can tell by the uniform that these are the bad guys.”

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