Have you ever wondered why some people get really sick with COVID while others have hardly a sniffle, or are completely asymptomatic when exposed to the disease? The answer lies in their genetics. Researchers have uncovered that the key to avoiding illness is carrying a version of a particular immune system gene called human leukocyte antigen (HLA), which encodes proteins that help the body fight off pathogens. In a nutshell, HLA proteins on a cell’s surface display pieces of the invader’s proteins, which alerts the immune system. The body’s T cells (the cells that help your immune system fight germs and protect you from disease) quickly recognize the pathogens and then kill the infected cells, thereby short-circuiting a virus’ replication capabilities.
During the pandemic, researchers came up with a contact-free procedure for data analysis: they enlisted a group of nearly 30,000 people who had signed up to donate bone marrow and thus had already undergone tests to determine their HLA genes. The participants downloaded a smartphone app and used it to record any COVID symptoms, even mild ones like a runny nose or scratchy throat, that persisted for at least 3 days. The researchers found that 20% of people in the study who remained asymptomatic after infection carried at least one copy of an HLA variant (called HLA-B*15:01). Those who carried two copies of the variant were far more likely — more than eight times — to avoid feeling sick.
In their research, the scientists also studied blood samples collected from people before the pandemic. They discovered that, when exposed to the SARS-CoV-2 spike protein, the T cells in 75% of blood donors with the HLA-B*15:01 variant recognized a snippet of the spike protein, which enables the virus to enter cells. The T cells were raring to fight SARS-CoV-2 — even though the virus had never been encountered before! How can this be explained? The blood donors probably had been infected by seasonal coronaviruses, which are widespread relatives of SARS-CoV-2 that give us colds. The researchers discovered that T cells from blood donors with the HLA-B*15:01 variant reacted aggressively not only to a fragment of the spike protein from a few seasonal coronaviruses that they tested, but to SARS-CoV-2 as well. Thus, in people with this HLA variant, their body’s T cells “remembered” and “recognized” a multitude of coronavirus pathogens, additionally helping protect these people against COVID-19.
The importance of this research is that scientists may be able to identify new ways of promoting immune protection against SARS-CoV-2, including how to rapidly clear the virus, that could be used in future development of vaccines or drugs.

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