A recently published study in the journal Nature has found a genetic variant that explains why some individuals infected with the virus that causes COVID-19 experience no symptoms. The study revealed that people with a specific gene variant associated with immunity to prior seasonal cold viruses are more likely to remain asymptomatic after contracting COVID-19.
When the COVID-19 pandemic began, researchers noticed that many infected individuals did not develop any symptoms. However, studying the genetics of asymptomatic infections proved challenging since these individuals were unlikely to seek medical help. To overcome this obstacle, the researchers utilized existing genetic data from the Be The Match U.S. bone marrow donor registry.
Volunteers registered as donors were invited to track their COVID-19 experiences using a smartphone app developed by the COVID-19 Citizen Science Study. By analyzing the genetic information of nearly 30,000 individuals without collecting biological samples, the researchers were able to identify COVID-19 positive individuals who remained asymptomatic.
The study focused on analyzing the variation of a gene called HLA, which plays a crucial role in the immune system. The gene encodes proteins that display viral particles recognized by T cells, a group of immune system cells crucial for fighting infections. Given the importance and variability of HLA molecules, the researchers suspected they might play a role in COVID-19.
By analyzing data from 1,428 unvaccinated individuals who tested positive for COVID-19, the researchers identified a common variant of the HLA gene called HLA-B*15:01 that was associated with asymptomatic infection. This gene variant is present in approximately 10% of the population with European ancestry.
The researchers found that individuals carrying the HLA-B*15:01 variant were more than twice as likely to remain asymptomatic after being infected with COVID-19. Furthermore, those carrying two copies of this variant were over eight times more likely to experience no symptoms.
To investigate the preexisting immunity to the virus that causes COVID-19 among individuals with the HLA variant, researchers used blood cells donated by these individuals several years before the pandemic. The study revealed that those who had never been exposed to COVID-19 had memory T cells that were effective against a specific viral particle. These T cells triggered a robust immune response against COVID-19. Additionally, the viral particle bound to HLA closely resembled fragments of seasonal coronaviruses recognized by T cells.
The findings of this study suggest that prior exposure to seasonal cold viruses enabled individuals with the HLA-B*15:01 variant to develop an effective immune memory, which aided in quickly eliminating the virus before symptoms appeared.
Understanding the genetic factors associated with COVID-19 infection and symptom development is crucial for comprehending differential responses to the virus and other viral diseases. The focus on asymptomatic infections also sheds light on the early stages of infection and the mechanisms by which the immune system combats COVID-19.
While existing vaccines provide protection against severe COVID-19 symptoms, the discovery of viral fragments responsible for asymptomatic infections like the one found in this study can contribute towards developing more targeted vaccines and therapies for the disease.
Although the genetic association identified in this study is strong, the immune system is complex, and it is still unclear what other mechanisms govern asymptomatic infections or why not all individuals carrying this specific variant remain asymptomatic.
Future research aims to investigate whether the genetic variant identified is present in individuals from different ancestral backgrounds. This exploration will aid in understanding the relevance of specific genetic variants among diverse populations who experience asymptomatic COVID-19. Furthermore, researchers hope to unravel what makes the cross-reactive T cells found in individuals with the HLA-B*15:01 variant so remarkably effective in preventing COVID-19 symptoms.
By unraveling the genetic basis of asymptomatic COVID-19 and enhancing our understanding of immune responses, researchers are paving the way for more effective strategies to combat the virus and other infectious diseases.
