Some people never develop COVID symptoms. Scientists may have figured out why
COVID-19 symptoms fall on a wide spectrum of severity. Some people may experience a life-threatening illness while most feel mildly sick.
Then there are folks who never feel a thing.
To understand why, scientists turn to genetics. Genes contain the information to specify biological traits, like how a body responds to an infection.
Every person has two copies of each gene, one inherited from each parent, according to the National Library of Medicine. Most genes are the same in all people, but a small number vary from person to person.
By studying genetic variations, researchers can pinpoint how genetics contribute to human disease.
While most researchers trying to understand the genetics involved in COVID-19 infections focus on severe disease, a team of scientists from the United States, Brazil and Australia has discovered a gene that might explain why some individuals with a COVID-19 infection never develop symptoms.
These are known as asymptomatic infections.
Studying asymptomatic infections is important because these individuals can still transmit the virus to others. Additionally, it can help scientists understand how immune systems fight the virus in its earliest stages and potentially develop a better vaccine.
The search begins
The team started by analyzing the most medically relevant group of genes in the human genome — the human leukocyte antigen, or HLA, genes.
Variations in HLA genes have been associated with many illnesses, including human immunodeficiency virus, hepatitis B and hepatitis C.
HLA genes hold the information needed to build molecules that present toxins to the surface of our cells.
These toxins are usually recognized by T-cells, which initiate an immune response against the virus.
The T-cells start a cascade of immune responses to kill the infected cells. This process helps the immune system develop a memory of that toxin, so the second time the toxin is presented, the response will be faster.
Researchers have found an HLA genetic variant shared among asymptomatic individuals with COVID-19 that tells T-cells how to kill infected cells faster.
Finding the common variant
The scientists studied how variations in HLA genes might affect this process.
The team used a smartphone-based study designed to track COVID-19 symptoms and outcomes to find 1,428 individuals who reported a positive test for an active COVID infection and who self-identified as white, due to insufficient numbers for analysis in other groups.
They found that the genetic variant, known as HLA-B*15:03, was strongly associated with a lack of developing symptoms.
Individuals carrying two copies of HLA-B*15:01 were more than eight times more likely to remain asymptomatic than individuals carrying other kinds of HLA genes.
“When we have a genetic association, most of the time we can’t explain them,” said Danillo Augusto, first author of the paper and assistant professor at the University of North Carolina Charlotte. “But then we were able to reproduce the same association in different samples and that was like very, very amazing.”
The team was able to explain the association by showing that pre-pandemic T-cells from individuals with the HLA-B*15:01 variant were able to fight off COVID.
A familiar foe
The researchers believe that some asymptomatic individuals had a cold before — a cold caused by a related, seasonal coronavirus, explained Mary Carrington, director of the Basic Science Program at the Frederick National Laboratory, in a phone interview.
The team identified a little piece of Sars-CoV-2 that fits in the groove of HLA-B*15:01.
That little piece of Sars-CoV-2, or peptide, is nearly identical to a peptide found in common, seasonal coronaviruses.
The first time a T-cell sees that peptide it initiates an immune response to kill the cell.
The second time T-cells meet that peptide, they initiate a stronger and faster response. This is similar to how vaccines work.
If a person’s immune system can kill infected cells quickly enough, it can prevent the virus from spreading and causing more problems, said Carrington.
Researchers believe this is why individuals with the genetic variant HLA-B*15:01 remain asymptomatic.
Since this previously seen peptide fits in the groove of HLA-B*15:01, the cells of individuals with this variant can initiate a better immune response and kill infected cells before the virus spreads and symptoms arise.
Carrington believes that if more familiar peptides from previous coronaviruses are found in SARS-CoV-2, a vaccine could be designed that results in asymptomatic infection.
With the SARS-CoV-2 vaccines we have right now, many people still get infected with a mild disease.
“These vaccines are great,” Carrington said. “But maybe we can improve them.”
The next steps
One limitation of the study was that the team’s sample population was biased toward European Americans, said Augusto.
Augusto said he would be interested to see if the association between HLA-B*15:01 and asymptomatic COVID-19 infection is seen in other populations of people.
Because they didn’t have enough numbers of non-European Americans, they weren’t able to test for this association.
