Have you ever wondered why some people get severe COVID-19 infections, while others test positive but have no symptoms at all? This range of effects is due in large part to the natural genetic variation between people- specifically, variation between their immune systems. A new study shows that a common variant of an HLA protein may be responsible for asymptomatic infections, providing insight into the immunological processes that can protect from SARS CoV-2.
Examining Asymptomatic COVID-19 Infections
As of this month, there have been almost 800 million confirmed cases of COVID-19, with the actual tally likely much higher. A pandemic of that scale produces a huge variation in observed responses, namely the severity of infections. Many studies have searched for genetic variants that predispose people to unusually severe disease, hoping to find ways to protect that population from infection.
This far into the pandemic, with highly effective vaccines and a variety of treatment options available, it is worthwhile to investigate the genetic variants that may be behind asymptomatic COVID-19 infections. Understanding the molecular mechanisms of especially effective immune systems can help us in the long-term to design new therapies against SARS CoV-2 and potentially against many other types of viruses.
A Common HLA Variant May be Protective from Symptomatic Infections
Around 20% of SARS CoV-2 infections are asymptomatic. In a recent Nature paper, Augusto et al. from UCSF used bone marrow samples from 1,428 unvaccinated individuals to look for a genetic basis of asymptomatic infections.
When cells are infected with a virus, a protein complex called the human leukocyte antigen (HLA) complex displays fragments of the virus on the surface of the cell. This allows T cells to recognize, bind to, and eliminate the infected cell. The authors found a strong association between an HLA variant (HLA-B*15:01) and asymptomatic infection. People with one copy of the variant were more than twice as likely to remain asymptomatic after infection than those without it, while people with two copies of the variants were over eight times as likely to be asymptomatic.
What could cause this? The authors examined the efficacy of T cells in patients with the HLA variant from samples collected prior to the pandemic – meaning those T cells had never been exposed to SARS CoV-2. In vitro, those cells were still highly effective at targeting SARS CoV-2, suggesting that individuals with the HLA variant may also have T cells with strong immunological memory of infections by related coronaviruses, like those that cause the flu. The authors theorize that the HLA variant may be particularly good at presenting the viral fragments such that related coronavirus fragments more closely resemble one another to the T cells.
Applications for Public Health
The presence of the HLA variant, while strongly associated with asymptomatic infections, is not a guarantee that an individual will remain symptom free. The authors clearly note that this variant is one of many genes interacting in the complex immunological response to the virus.
However, better understanding the genetic factors that influence differing responses to viruses between people is a huge step forward for public health and potentially, for precision medicine. New treatments and vaccines can be designed to be maximally protective for groups with varying vulnerabilities, especially if the underlying causes are known.
Outsourcing Bioinformatics Analysis: How Bridge Informatics Can Help
Groundbreaking studies like these are made possible by technological advances making biological data generation, storage and analysis faster and more accessible than ever before. From pipeline development and software engineering to deploying existing bioinformatics tools, Bridge Informatics can help you on every step of your research journey.
As experts across data types from leading sequencing platforms, we can help you tackle the challenging computational tasks of storing, analyzing and interpreting genomic and transcriptomic data. Bridge Informatics’ bioinformaticians are trained bench biologists, so they understand the biological questions driving your computational analysis. Click here to schedule a free introductory call with a member of our team.
Jane Cook, Biochemist & Content Writer, Bridge Informatics
Jane Cook, the leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas. While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email [email protected] or [email protected].