A strange gene mutation helps some people avoid COVID-19

In the midst of the COVID-19 pandemic, scientists are working tirelessly to unravel the mysteries of the virus and understand why some people show no symptoms even after infection. A recent study led by the University of California, San Francisco (UCSF) has shed light on this phenomenon, revealing that a specific genetic mutation known as HLA may be responsible for the resistance of these individuals, dubbed “superuklonists.”

The study, published in Nature on July 19, 2023, marks a significant breakthrough in our understanding of how genetics influences the body’s response to SARS-CoV-2, the virus that causes COVID-19. By focusing on human leukocyte antigen (HLA), a protein marker that serves as the immune system’s “smoke signal,” researchers were able to uncover the role of this genetic mutation in preventing disease symptoms.

HLA plays a key role in the immune system’s defense against pathogens. It allows virus-destroying T-cells to quickly recognize SARS-CoV-2, triggering a lightning-fast attack. This ability is akin to if an army is well prepared for battle and already knows what to look for. T-cells recognize the virus due to its similarity to common cold viruses they have encountered before. This discovery opens up new possibilities for drug and vaccine development.

Dr. Jill Hollenbach, lead researcher of the study, explains the significance of this genetic mutation, “If you have an army that can recognize the enemy at an early stage, that’s a huge advantage. It’s like having soldiers who are ready to fight and already know what to look for and that they are the bad guys.”

A specific genetic mutation known as HLA-B*15:01 is relatively common, occurring in about 10 percent of study participants. While carriers of this mutation do not avoid contracting the virus, they can avoid symptoms commonly associated with it, such as a runny nose or a slight sore throat.

The study found that 20% of participants who were symptom-free after contracting the virus had at least one copy of the HLA-B*15:01 variant. While only 9% of those with symptoms were carriers of this mutation. Interestingly, the likelihood of being symptom-free was more than eight times greater in participants who carried two copies of this variant.

To collect data for their study, the scientists turned to the National Marrow Donor Program/Be The Match, an existing national registry that matches bone marrow donors and recipients for transplants. They analyzed information on nearly 30,000 people in the bone marrow archive and tracked their COVID-19 infection during the first year of the pandemic, when vaccines were not yet available and routine testing was common.

“We did not set out to study genetics, but we are very pleased that this result is the result of our interdisciplinary collaboration with Dr. Hollenbach and the National Marrow Donor Program,” said Dr. Mark Pletcher, professor of epidemiology and biostatistics at UCSF.

This groundbreaking research not only provides insight into why some people remain asymptomatic after infection with COVID-19, but also highlights the critical role genetics plays in determining the body’s response to this virus. By understanding these genetic factors, scientists can develop targeted treatments and interventions that improve our immune system’s ability to fight the virus.

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