COVID-19 has left a profound impact on millions worldwide, leading some to require hospitalization, others needing extended bed rest and a significant number who lost their lives. However, there exists a group of individuals who contracted the contagious virus but didn’t experience a single symptom.
Researchers may have unraveled the reason behind this phenomenon: the human leukocyte antigen (HLA), a molecule that assists the immune system during early infections.
A mutated HLA gene could explain why some people never develop symptoms from SARS-CoV-2, the virus that causes COVID-19, even if they were infected.
A study published Wednesday in Nature found that people with the mutated gene, HLA-B*15:01, are more than twice as likely to not get sick from the virus. And those who had two copies of the gene were more than eight times more likely to remain asymptomatic.
“We found that HLA-B*15:01 was significantly overrepresented in asymptomatic individuals relative to symptomatic individuals,” the researchers stated.
“If you have an army that’s able to recognize the enemy early, that’s a huge advantage,” Jill Hollenbach, the study’s lead author and professor of neurology at the University of California San Francisco, said in a media release Wednesday.
“It’s like having soldiers that are prepared for battle and already know what to look for, and that these are the bad guys.”
The gene variant does not stop the virus from entering the body, but it prevents people from developing symptoms like a runny nose, fever or a sore throat.
In order to find people with asymptomatic infections, the authors used a database of bone-marrow donors and enrolled nearly 30,000 people.
Participants self-reported any positive tests for SARS-CoV-2 and any symptoms during the study (between February 2020 and April 2021) — which was conducted before vaccines were widely available. Of the 1,400 participants who tested positive during this period, 136 remained asymptomatic, the researchers said.
The researchers then looked for potential connections between individuals who had asymptomatic infections and variations in their HLA genes.
They found a link in around 10 per cent of the study’s population. This group had T-cells that recognized COVID-19, even if they were not previously exposed to the virus, the researcher stated.
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A potential explanation for this lies in the variant’s exposure to other seasonal coronaviruses, such as those responsible for causing the common cold, explained Colin Furness, an infection control epidemiologist and assistant professor at the University of Toronto.
“All coronaviruses are similar in the same way we are to chimpanzees, around 98 or 99 per cent … yet we all look really different. So all coronaviruses to you your immune system are about 98 to 99 per cent similar,” he said.
The mutated gene functions similarly to a person with exceptional facial recognition skills, Furness said. It provides T-cells with extra talent and adaptability, enabling them to recognize pathogens effectively, even if they haven’t encountered them before.
“If you have this particular gene mutation, it’s essentially a fisherman with a really wide net,” he said.
Asymptomatic but still contagious
The symptoms of being sick, such as fever, coughing and sneezing, are often the result of the body’s immune response to an infection, Furness noted.
For example, a fever can be a natural response to help the body create an inhospitable environment for the pathogens while coughing and sneezing help to expel the pathogens from the respiratory tract.
Feeling unwell also alerts someone to stay away from others until they recover and are no longer contagious, preventing the spread of the infection, he said.
The asymptomatic people in the study may have effectively swatted down the infection, but the virus was still in their bodies. Furness warned that this does not make someone invulnerable like “Superman” – in fact, it could pose a risk to others around them.
“If you’re not being alerted by your immune system that you’re infected … you can go ahead and infect other people,” he said.
Furness hopes that studies like the one published in Nature will bring to light the fact that being asymptomatic does not mean you are not contagious.
He believes that gaining more knowledge about the genes involved in combating COVID-19 could pave the way for future diagnostic tests or therapeutic advancements.
The study’s authors agree.
“Understanding the biological underpinning of asymptomatic infection with SARS-CoV-2 has important implications for public health measures, vaccine design and therapeutic development,” they stated.