New research led by UC San Francisco scientists has uncovered a genetic basis for asymptomatic COVID-19 cases, shedding light on why some individuals can contract the virus without developing any symptoms. The study, published in the journal Nature on July 19, 2023, reveals that individuals who remain asymptomatic after infection are more than twice as likely to carry a specific gene variation, known as HLA-B*15:01, which aids in obliterating the virus.
The secret lies in the human leukocyte antigen (HLA), protein markers that signal the immune system. The HLA-B*15:01 mutation helps virus-killing T cells recognize and attack the SARS-CoV-2 virus, even if the individual has not encountered it before. This is possible due to the resemblance of the novel coronavirus to seasonal cold viruses that these T cells are already familiar with. The research provides the first evidence of a genetic basis for asymptomatic COVID-19 and opens up new avenues for drug and vaccine development.
Lead researcher Jill Hollenbach, a professor at UCSF, compared this immune response to having an “army that’s able to recognize the enemy early,” giving individuals a significant advantage in defending against the virus. The HLA-B*15:01 mutation is common, present in about 10% of the study’s population, and while it doesn’t prevent the virus from infecting cells, it prevents people from experiencing symptoms, even mild ones.
The study examined nearly 30,000 individuals using data from the National Marrow Donor Program/Be The Match, which matches donors with bone marrow transplant recipients. The researchers also utilized the UCSF-developed COVID-19 Citizen Science Study app to track COVID-19 cases. Among the unvaccinated individuals who tested positive for the virus, 136 remained asymptomatic for at least two weeks, and HLA-B*15:01 was found to be strongly associated with asymptomatic infection.
To understand how HLA-B15:01 suppressed the virus, the researchers collaborated with La Trobe University in Australia. They discovered that T cells from individuals carrying the HLA-B15:01 mutation responded to a part of the novel coronavirus called the NQK-Q8 peptide, despite never being exposed to SARS-CoV-2. Exposure to seasonal coronaviruses with a similar peptide, NQK-A8, enabled T cells in these individuals to recognize and mount a more effective immune response against the novel coronavirus.
This breakthrough research highlights the role of genetics in influencing COVID-19 outcomes and could potentially pave the way for the development of vaccines and drugs that enhance immune protection against the virus. Understanding how certain genetic variations impact COVID-19 responses may contribute to better treatment strategies and future pandemic preparedness.
Story Source:
Materials provided by University of California – San Francisco. Original written by Victoria Colliver. Note: Content may be edited for style and length.
Journal Reference:
- Augusto, D.G., Murdolo, L.D., Chatzileontiadou, D.S.M. et al. A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection. Nature, 2023 DOI: 10.1038/s41586-023-06331-x