By Aidin Vaziri

About 1 in 5 people who contract the coronavirus exhibit no symptoms.

Now, researchers at UCSF have uncovered a genetic mutation potentially responsible for the phenomenon of coronavirus super dodgers.

The study, identifies a variant in a gene that enhances early detection and response to SARS-CoV-2 — the virus that causes COVID-19 — mitigating common symptoms like a runny nose, scratchy throat, or fever and chills. The speedy reaction appears to derive from previous exposure to other coronaviruses, such as those that cause the common cold.

Jill Hollenbach, the lead author and a professor of neurology at UCSF, likens this advantage to having a well-briefed army inside the body anticipating the enemy’s tactics.

“It’s like having soldiers that are prepared for battle and already know what to look for and that these are the bad guys,” she said.

The genetic quirk in the human leukocyte antigen gene, scientifically known as HLA-B*15:01, does not hinder viral infection but rather swiftly recognizes SARS-CoV-2, allowing the body to launch an immune attack before symptoms manifest.

“We found people that have this version of the gene are twice as likely to be asymptomatic because they have some pre-existing immunity due to the common cold,” Hollenbach said.

The study, conducted in partnership with researchers from La Trobe University in Australia, delved into the role of T-cell memory and how the HLA-B*15:01 mutation enables virus-killing cells to draw on their experience from battling other coronaviruses to mount a potent immune response against SARS-CoV-2. T-cells are the body’s first line of defense against infections.

The genetic anomaly was present in about 20% of asymptomatic participants, compared to 9% of individuals who showed symptoms. Those carrying two copies of the variant were more than eight times more likely to remain asymptomatic after testing positive for the virus. However, it remains unclear why the remaining 80% of asymptomatic people who did not have the mutation also showed no signs of illness.

“This explains some aspects of asymptomatic COVID, but it doesn’t explain the entire phenomenon,” Hollenbach said.

The study was conducted during the early stages of the pandemic, before widespread vaccination, utilizing about 30,000 volunteer bone marrow donors with high-quality genetic data. Participants recorded their daily coronavirus infections and symptoms for a year using UCSF’s COVID-19 Citizen Science Study smartphone app while reporting testing frequency and hospitalization.

“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,” said Dr. Mark Pletcher, a professor of epidemiology and biostatistics at UCSF.

While the research results don’t entirely explain resistance to symptoms, the HLA variant may explain why about 25% of the U.S. population has never been diagnosed with COVID-19 even three years into the pandemic.

The findings could also help pave the way for next-generation vaccines and treatments that block symptoms from developing even in those without the mutation.

“We might consider designing vaccines that don’t necessarily prevent infection but think about a vaccine aimed toward eliminating symptoms,” Hollenbach said. “This gives us some insight into what immunological conditions are necessary for people to manage infections without any ill effects.”