Scientists may have found the reason behind asymptomatic Covid infections: Genetic variation in immune system

Variation in genes encoding proteins involved in immune responses could be behind why some people remain asymptomatic following SARS-CoV-2 infection. Human leukocyte antigen (HLA) genes encode these proteins used by the immune system in identifying and distinguishing healthy cells in the body from infected ones.

Research has shown at least 20 % of Covid-infected do not develop symptoms, or remain asymptomatic.

Critical to one’s immunity and highly varied among individuals, the HLA system might have specific variants rendering them more protected against or vulnerable to Covid, the researchers in this US-Australia collaborative study wondered.

Studying asymptomatic infection may improve our understanding of the features of the immune system that promote rapid clearance of the virus, the study published in the journal Nature said.

To understand if an HLA variation might predispose some people to asymptomatic Covid infection, the researchers enrolled 29,947 individuals to participate in a smartphone-based study designed to track COVID-19 symptoms and outcomes. All of them were DNA sequenced for their HLA genetic profiling.

A total of 1,428 unvaccinated individuals reported a positive test for infection with SARS-CoV-2 and 136 of them reported having no symptoms.

One in five individuals who remained asymptomatic after infection were found to carry a common variant of HLA called HLA-B*15:01. People carrying two copies of this variant were more than eight times likely to remain asymptomatic than those carrying other versions of HLA, the study found.

“We hypothesised that their immune system could react so fast and powerfully that the virus was eliminated before causing any symptoms. It’s like having an army that already knows what to look for and can tell by the uniform that these are the bad guys,” according to Jill Hollenbach, professor at the University of California San Francisco, US.

In a separate arm of the study, the researchers found that individuals carrying HLA-B*15:01 with no prior exposure to SARS-CoV-2 had T cells (a type of immune cell) that were reactive to SARS-CoV-2 protein fragments sharing some genetic sequences with other seasonal coronaviruses.

This finding indicated that people carrying HLA-B*15:01 and previously exposed to seasonal cold viruses had pre-existing immunity to SARS-CoV-2 and could rapidly eliminate the virus before symptoms could present.

The researchers analysed this to be because the T cells from pre-pandemic individuals, that could identify viral particles from past coronaviruses, created an immunological memory from the previous coronaviruses.

These memory T cells recognise SARS-CoV-2, owing to its high similarities with those coronaviruses, and kill it very quickly.

“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. That is how our immunological memory works to keep us healthy,” said Danillo Augusto, assistant professor at the University of North Carolina at Charlotte, US.