"Super-dodgers" who don’t get sick from COVID-19 may have special HLA genetic mutation

It’s not magic, it’s science. Recent research led by the University of California, San Francisco (UCSF) reveals that individuals who contract COVID-19 but remain symptom-free – dubbed as ‘super dodgers’ – may owe their resilience to a specific genetic mutation known as HLA.

According to the study, carriers of this gene variant are more than twice as likely to be asymptomatic. This, compared to those who experience symptoms after contracting the virus.

This study, published in Nature on July 19, 2023, represents a significant step in understanding the genetic influence on our body’s response to SARS-CoV-2, the virus that causes COVID-19. The research provides a possible explanation for why some people contract the virus but never fall ill.

Human leukocyte antigen (HLA)

The researchers centered their attention on the human leukocyte antigen (HLA), protein markers that are the immune system’s smoke signal. A genetic mutation in one of the genes encoding the HLA allows virus-killing T cells to recognize SARS-CoV-2 rapidly, akin to triggering a lightning-fast attack.

It’s as if these T cells, even when encountering the virus for the first time, can recognize it due to its similarity to the common cold viruses they’ve already combated. This important discovery could open up new paths for drug and vaccine development.

Jill Hollenbach, PhD, MPH, the study’s lead researcher, explained it this way: “If you have an army that’s able to recognize the enemy early, that’s a huge advantage. It’s like having soldiers that are prepared for battle and already know what to look for, and that these are the bad guys.”

The genetic mutation, known as HLA-B*15:01, is relatively common, being present in about 10% of the study’s participants. Carriers of this mutation don’t avoid the virus itself, but they do sidestep the symptoms – from a runny nose to a slightly sore throat.

Hollenbach’s team discovered that 20% of participants who remained symptom-free after contracting the virus carried at least one copy of the HLA-B*15:01 variant.

In comparison, only 9% of symptomatic individuals were carriers. Interestingly, the likelihood of remaining symptom-free increased more than eightfold for participants carrying two copies of the variant.

Studying the COVID-19 genetic mutation

The researchers believed from the outset that the HLA might play a critical role in this context. They found the necessary data in an existing national registry.

The National Marrow Donor Program/Be The Match, which matches donors with bone marrow transplant recipients. However, they needed further information on how these donors fared against COVID-19.

To gather this information, they turned to the COVID-19 Citizen Science Study, a mobile app developed at UCSF.

They tracked nearly 30,000 people in the bone marrow archive through the first year of the pandemic, a period when vaccines were still unavailable and routine COVID-19 testing was prevalent.

“We did not set out to study genetics, but we were thrilled to see this result come from our multidisciplinary collaboration with Dr. Hollenbach and the National Marrow Donor Program,” stated Mark Pletcher, MD, MPH, a professor of epidemiology and biostatistics at UCSF.

What the researchers learned about HLA

Researchers identified 1,428 unvaccinated donors who tested positive between February 2020 and April 2021. Of these, 136 individuals showed no symptoms for at least two weeks before and after testing positive. Only the HLA-B*15:01 genetic mutation showed a robust association with asymptomatic COVID-19 infection.

Notably, the common risk factors for severe COVID-19, such as older age, obesity, or chronic conditions like diabetes, didn’t seem to influence who remained asymptomatic.

Martin Maiers, vice president of research at the National Marrow Donor Program/Be The Match, said, “We are proud to partner on research that has the potential to leverage a long-term public investment in building the national archive to help cure diseases and improve our ability to avoid future pandemics.”

To understand how the HLA-B15:01 variant works, Hollenbach’s team collaborated with La Trobe University scientists in Australia. They focused on the concept of T-cell memory, the immune system’s way of “remembering” past infections.

The team found that T cells from individuals carrying the HLA-B15:01 variant, even those never exposed to SARS-CoV-2, still responded to a part of the novel coronavirus named NQK-Q8 peptide.

This suggests that exposure to seasonal coronaviruses, carrying a very similar peptide, NQK-A8, enabled these T cells to quickly recognize and mount an effective response against SARS-CoV-2.

“By studying their immune response, this might enable us to identify new ways of promoting immune protection against SARS-CoV-2 that could be used in future development of vaccines or drugs,” noted Stephanie Gras, a professor and laboratory head at La Trobe University.

This study, hence, unveils the genetic chess game at play in the fight against COVID-19, providing a pathway for future research and potential therapeutic developments.

More about COVID-19 and genetic mutations

The novel coronavirus, known as SARS-CoV-2, causes the infectious disease COVID-19. It was first identified in Wuhan, China, in December 2019, and since then, it has led to a global pandemic.

The virus has infected millions of people worldwide and caused millions of deaths. Here is a more in-depth explanation of what is known about COVID-19:

Symptoms

COVID-19 symptoms vary, but the most common include fever, cough, shortness of breath, loss of taste or smell, muscle or body aches, headache, sore throat, fatigue, and sometimes gastrointestinal problems like diarrhea.

While some people may remain asymptomatic, others can become seriously ill and develop complications like pneumonia, acute respiratory distress syndrome, or other organ problems.

Transmission

COVID-19 primarily spreads through the air when an infected person coughs, sneezes, talks, or breathes.

It can also spread by touching a surface contaminated by the virus and then touching the face, although this is less common. Individuals who are symptomatic, asymptomatic, or pre-symptomatic can transmit the virus.

Prevention

Preventive measures include wearing masks, maintaining physical distance from others, avoiding large gatherings, washing hands frequently, and getting vaccinated.

Vaccines developed by companies such as Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca have received emergency use authorization in various countries around the world.

Also, as we learned above, COVID-19 patients show show no symptoms often have a genetic mutation called HLA.

Treatment

Treatments include antiviral drugs like Remdesivir, the steroid dexamethasone for severe cases, monoclonal antibodies, and supportive care to help relieve symptoms.

Additionally, the anticoagulant heparin is often used due to the increased risk of blood clots in severe cases. Research and trials are ongoing to develop more effective treatments.

Impact

Beyond its health impacts, COVID-19 has also led to significant economic, social, and psychological disruption worldwide, including job losses, increased mental health issues, and interruptions to education.

Variants

Several variants of SARS-CoV-2 have emerged since the start of the pandemic, some of which are more transmissible or potentially more virulent.

These include the Alpha, Beta, Gamma, and Delta variants. Ongoing surveillance of these variants is crucial to public health efforts to control the spread of the virus.

Long COVID

Some people experience prolonged symptoms or long-term effects after their acute infection has resolved, a condition sometimes referred to as “long COVID” or “Post-Acute Sequelae of SARS-CoV-2 infection” (PASC).

Symptoms can include fatigue, brain fog, breathlessness, and a host of other problems. Research is ongoing to understand why this occurs and how to treat it.

For the most accurate and up-to-date information, please refer to reputable health organizations such as the World Health Organization (WHO) or the Centers for Disease Control and Prevention (CDC).