Genetics may explain why some don't get sick from Covid

While even mild Covid leaves people sick, some called super dodgers never have common symptoms like a runny nose or sore throat, even after testing positive for the deadly virus. Turns out their genetics may be at work, according to a team of researchers from the US and Australia.

According to the team at the University of California -San Francisco the people who contract Covid-19 but never develop symptoms are more than twice as likely as those who become symptomatic to carry a specific gene variation that helps them obliterate the virus.

The secret lies with the human leukocyte antigen (HLA), or protein markers that signal the immune system. A mutation in one of the genes coding for HLA appears to help virus-killing T cells identify SARS-CoV-2 and launch a lighting attack, reveals the study, published in the journal Nature.

The T cells of some people who carry this variant can identify the novel coronavirus, even if they have never encountered it before, thanks to its resemblance to the seasonal cold viruses they already know. The discovery points to new targets for drugs and vaccines.

“If you have an army that’s able to recognise the enemy early, that’s a huge advantage,” explained the study’s lead researcher Jill Hollenbach, Professor of neurology, as well as epidemiology and biostatistics, and a member of the Weill Institute for Neurosciences at UCSF.

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

In the study, first, 29,947 unvaccinated individuals were screened using a mobile app designed specifically to track Covid-19 symptoms, and 1,428 reported a positive test for the virus.

All individuals had their DNA previously sequenced to analyse their HLA genes. The researchers found that individuals having the genetic variant HLA-B*15:01 were much more likely to remain asymptomatic after infection.

The mutation — HLA-B*15:01 — is quite common, carried by about 10 per cent of the study’s population. It doesn’t prevent the virus from infecting cells but, rather, prevents people from developing any symptoms. That includes a runny nose or even a barely noticeable sore throat. 

The researchers found that 20 per cent of people in the study who remained asymptomatic after infection carried at least one copy of the HLA-B*15:01 variant, compared to 9 per cent of those who reported symptoms. Those who carried two copies of the variant were far more likely — more than eight times — to avoid feeling sick.

To figure out how HLA-B15 managed to quash the virus, Hollenbach’s team collaborated with researchers from La Trobe University in Australia. They homed in on the concept of T-cell memory, which is how the immune system remembers previous infections. 

 The researchers looked at T cells from people who carried HLA-B15 but had never been exposed to the SARS-CoV-2 virus, and found these cells still responded to a part of the novel coronavirus called the NQK-Q8 peptide.

They concluded that exposure to some seasonal coronaviruses, which have a very similar peptide, called NQK-A8, enabled T cells in these individuals to quickly recognise SARS-CoV-2 and mount a faster, more effective immune response. 

 “By studying their immune response, this might enable us to identify new ways of promoting immune protection against SARS-CoV-2 that could be used in future development of vaccines or drugs,” said Stephanie Gras, a professor and laboratory head at La Trobe University.