Genetic cheat code might explain why some people catch Covid but never get sick
What makes people able to clear SARS-CoV-2 out of their systems before it gains a foothold has been one of the enduring mysteries of the pandemic. Now, a group of scientists from the University of California, San Francisco, believes it has found an answer: It’s in their genes.
In a study published Wednesday in Nature, the team identified a mutation that increases a person’s chance of being asymptomatic by nearly tenfold. “It’s just one of these natural lucky breaks,” said immunogeneticist Jill Hollenbach, who led the research.
Hollenbach’s UCSF lab focuses on human leukocyte antigen, or HLA — a molecule that helps the immune system surveil every cell of the human body and is critical during the earliest stages of infection. HLA proteins are constantly grabbing bits of chopped-up proteins they find inside or around their cells and bringing them to the surface to display them to immune cells passing by.
Most of the time, these proteins are just harmless bits of healthy cells. Like a biometric scanner, the immune cells read this as “self” and ignore them. But sometimes, HLA molecules hold up something unrecognizable — a piece of a bacterial protein or a part of a virus. That should set off alarm bells in the immune system, mobilizing the production of antibodies and sending troops of T cells to storm the area.
But not all HLA molecules are created equal — some are better at grabbing different kinds of proteins than others. And HLA genes are some of the most diverse in the human genome. Hollenbach had a hunch that some of the variety in people’s immune responses to SARS-CoV-2 could be coming from their particular HLA. To find out if that was true, she turned to the National Marrow Donor Program, the largest database of people who have had their HLA genes decoded, totaling around 13 million individuals. (HLA genes are the ones that have to be matched for people receiving an organ or bone marrow transplant to not reject the foreign tissue.)
Hollenbach’s team was able to recruit about 30,000 people from that registry to be a part of The Covid-19 Citizen Science Study, a project launched by her UCSF colleagues Jeffrey Olgin, Mark Pletcher, and Gregory Marcus to track people’s Covid exposures, infections, and symptoms through a smartphone app. From the time they began tracking this data until April 2021 — when vaccines became widely available — more than 13,000 tested positive. Among that group, 10% remained completely symptom-free.