Throughout the COVID-19 pandemic, it was clear that many people who became infected did not show any sign of illness. Now researchers have found that when they were infected, carriers of two copies of a specific genetic variant were eight times less likely to have symptoms from COVID-19, which is caused by the virus SARS-CoV-2. The findings have been reported in Nature.
The genetic variant appears in a gene that is part of the human leukocyte antigen (HLA) complex, which act as signals for the immune system. Carriers of the variant, called HLA-B*15:01 seem to be better able to identify the coronavirus even if they have not been exposed to SARS-CoV-2 before, because it does bear some resemblance to coronaviruses that cause the common cold. T cells in these carriers are thus primed to respond to SARS-CoV-2.
“If you have an army that’s able to recognize the enemy early, that’s a huge advantage,” noted lead study author and professor Jill Hollenbach, PhD, MPH, 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.”
About ten percent of the study participants carried the HLA-B*15:01 variant. About 20 percent of study volunteers who were asymptomatic while infected carried one or more copies of the HLA-B*15:01 variant, while about nine percent of those who had symptoms carried the variant. People with two copies of the variant were eight times more likely to be asymptomatic when infected than non-carriers.
The National Marrow Donor Program/Be The Match, which links those in need of a bone marrow transplant with donors, is the largest registry in the US that contains HLA data. The researchers suspected that HLA was related to asymptomatic cases. They were able to query the database, and match this with COVID-19 case outcomes with a mobile app - the COVID-19 Citizen Science Study.
Almost 30,000 bone marrow registry participants were tracked during the first year of the pandemic. There were just over 1,400 people who tested positive before vaccines were widely available, from February 2020 until the end of April 2021.
There were 136 people in that group who did not have symptoms in the two weeks before and after they had tested positive. Of HLA variants, only HLA-B*15:01 was strongly associated with asymptomatic COVID-19 infections. An analysis of two independent cohorts confirmed this conclusion.
Additional work showed that HLA-B*15:01 carrier T cells were reacting to a portion of SARS-CoV-2 called the NQK-Q8 peptide even though they had not been exposed to this virus before. Some seasonal coronaviruses appear to have taught the immune systems of these individuals to recognize SARS-CoV-2, which triggers a very rapid and effective response from their immune system. These findings could offer new insights into how to improve people's protection against this virus with new vaccines or drugs, the study authors noted.