Genetic Mutation Could Be Responsible for Why Some People Who Contracted COVID-19 Don’t Experience Symptoms [Study]

Genetic mutation plays a part in why some people don't get sick even after contracting COVID-19. According to a new study, they carry a particular gene variation that helps them fight the virus.

Genetic Mutation in Asymptomatic Cases of COVID-19

The so-called "super dodgers," who get COVID-19 but show no symptoms, may have a hereditary advantage. According to a recent study by experts at UC San Francisco, they are more than twice as likely to possess a particular gene variation that aids them in eliminating the virus as individuals who develop symptoms.

The new study provides the first proof that asymptomatic SARS-CoV-2 has a genetic foundation. The study unravels why some people can contract COVID-19 infection without ever becoming ill.

The human leukocyte antigen (HLA), or protein markers that alert the immune system, holds the key. It indicates that SARS-CoV-2 can be recognized and attacked by virus-killing T lymphocytes thanks to a mutation in one of the HLA genes. Because of the novel coronavirus' likeness to the seasonal cold viruses they are already familiar with, the T cells of specific individuals who carry this variety can recognize it even if they have never seen it before.

The finding suggests brand-new pharmacological and vaccination targets.

Jill Hollenbach, Ph.D., MPH, professor of neurology as well as epidemiology and biostatistics, and a member of the Weill Institute for Neurosciences at UCSF, said that having an army that can spot the enemy early is a significant advantage. It's comparable to having warriors ready to fight and aware that these are evil people.

In the research population, 10% of people have the HLA-B*15:01 mutation, which is relatively prevalent. It instead stops patients from experiencing any symptoms rather than stopping the virus from infecting cells—for example, a sore, scarcely perceptible throat or a runny nose.

The HLA-B*15:01 variant was discovered in at least one copy in 20% of study participants who remained asymptomatic following infection, compared to 9% of those who reported symptoms, according to UCSF researchers. Two copies of the variation significantly increased the likelihood of staying healthy by more than eight times.

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**HLA-B * 15 Gene in COVID-19**

Early on, researchers hypothesized that HLA was involved, and thankfully, the information they needed was available in a national registry. The National Marrow Donor Program/Be The Match connects donors with patients needing bone marrow transplants. It is the most extensive registry of HLA-typed volunteer donors in the United States.

According to Mark Pletcher, MD, MPH, a professor of epidemiology and biostatistics at UCSF, they didn't set out to study genetics. Still, they were thrilled to see this result from our multidisciplinary collaboration with Dr. Hollenbach and the National Marrow Donor Program.

Between February 2020 and the end of April 2021, before vaccines were widely available and when it still took several days to receive test results, researchers discovered 1,428 unvaccinated donors who tested positive.

One hundred thirty-six had no symptoms for at least two weeks before and after testing positive. Only one HLA variant, HLA-B*15:01, demonstrated a significant connection with asymptomatic COVID-19 infection, and this association was confirmed in two other cohorts.

Researchers from La Trobe University in Australia worked with Hollenbach's team to determine how HLA-B15 could stop the virus. They focused on T-cell memory, or how the immune system retains memories of prior infections.

When the researchers examined T cells from individuals who had HLA-B15 but had never been exposed to the SARS-CoV-2 virus, they discovered that these cells continued to react to the NQK-Q8 peptide, a component of the novel coronavirus. They concluded that exposure to some seasonal coronaviruses, which have a peptide that is strikingly similar to SARS-CoV-2 and is known as NQK-A8, allowed T cells in these people to detect SARS-CoV-2 swiftly and generate a quicker, more effective immune response.

According to Stephanie Gras, a professor and laboratory director at La Trobe University, examining their immune response could help them identify new ways of promoting resistant protection against COVID-19. Additionally, it will be helpful in the development of future vaccines and drugs.

The study was published in Nature.