Genetic variation associated with the absence of symptoms of COVID-19

At least 20% of people infected with SARS-CoV-2, the virus that causes COVID-19, have shown no symptoms. These asymptomatic infections can provide clues as to how quickly the virus can be cleared from the body. Genetic factors may be involved. However, the majority of studies on the genetics and consequences of COVID-19 to date have focused on severe disease.

An NIH-funded study looked at genetic variants associated with asymptomatic SARS-CoV-2 infection. The researchers examined how these differences affect the function of T cells, a part of the immune system that is key in fighting viral infections. The results came from within Nature on July 19, 2023.

The team focused on a group of genes called the human leukocyte antigen (HLA) complex. The proteins encoded by these genes help the immune system recognize infected or foreign cells by displaying fragments of viruses that trigger T cells to recognize. HLA genes vary greatly between people.

To find HLA variants associated with asymptomatic COVID-19, researchers recruited nearly 30,000 bone marrow donors. Since then HLA genes determine the compatibility of tissue or organ donors and recipients, these people already have HLA genes respectively. Study participants used a smartphone app to track symptoms of COVID-19 and report a positive SARS-CoV-2 test. Nearly 1,500 unvaccinated participants reported a positive test.

Analysis of HLA genes among this group showed that one is different, called HLA-B*15:01, was more common in asymptomatic participants (20%) than symptomatic participants (9%). The result was confirmed in two other groups of people.

The team next explored the road HLA-B*15:01 affected the ability of T cells to recognize SARS-CoV-2. They studied T cells from four people HLA-B*15:01 which was given before the COVID-19 pandemic. These T cells, they found, responded to a particular piece of SARS-CoV-2 as if they had been exposed to it before. Further tests showed that the T cells that recognize this fragment of SARS-CoV-2 also recognize the same fragment of the coronavirus that causes the seasonal cold. Both fragments bind to the HLA-B*15:01 protein in the same way. This suggests that T cells that have encountered and learned to recognize seasonal coronaviruses can also recognize SARS-CoV-2.

The results show that T cells in many people four HLA-B*15:01 they already know SARS-CoV-2 because of their previous exposure to seasonal coronaviruses. This allowed the immune system to respond quickly and eliminate the virus before it caused any symptoms.

Dr. Jill Hollenbach of the University of California, San Francisco says: “If you have an army that can spot the enemy early, that’s a huge advantage.” “It’s like having soldiers ready for battle who already know what to look for, and they become bad people.”

These findings may help guide the development of better vaccines or drugs to prevent and treat COVID-19.

—by Brian Doctrow, Ph.D.