A newly discovered immune response may explain why some individuals have managed to dodge COVID-19 for over four years. In a study that involved intentionally infecting volunteers with the coronavirus, researchers found that those with elevated activity of a gene called HLA-DQA2 did not sustain an infection after exposure to SARS-CoV-2. This study provided a detailed view of the immune system’s response to the virus and how variations in this response could determine who gets sick and who doesn’t.
The challenge trial conducted during the 2021 pandemic exposed 36 young, healthy, unvaccinated individuals who had never had COVID-19 to the virus. The goal was to determine the minimal infectious dose required to cause an infection, but only six of the 16 participants tested further ended up getting sick. This unexpected outcome allowed researchers to closely examine how some individuals were able to fend off the virus despite exposure, offering valuable insights into early infection mechanisms that are rarely observed.
While challenge trials are controversial, as deliberately infecting participants raises ethical concerns, the information gathered from such studies is invaluable for understanding the immune response to pathogens. By tracking individuals from the moment they encounter the virus, researchers can gain insights into how the body reacts to the pathogen and potentially identify factors that contribute to successful infection avoidance.
Participants who did not get sick in the trial showed subtle changes in immune cells before exposure to the virus, with some mounting a rapid immune response in their noses within a day of exposure, preventing the infection from taking hold. Those who got sick took longer to mount the same response, allowing the virus time to replicate and cause illness. Surprisingly, participants who developed symptoms had interferon activity in their blood before their noses did, suggesting a swift systemic response to infection.
The study also identified a gene, HLA-DQA2, which was more active before exposure in individuals who did not get sick compared to those who did. This gene, which is involved in alerting the immune system to pathogens, may play a role in predicting susceptibility to COVID-19. While the study provides valuable insights, the current immunity landscape due to widespread infection and vaccination may alter immune responses in the general population, making diverse and large-scale studies critical for a more comprehensive understanding of immune responses to the virus.
Overall, the study sheds light on the complex interplay between genetics, the immune system, and viral infections. Understanding how certain immune responses can prevent infection can help guide future research and potentially lead to the development of predictive tools for identifying individuals at risk of severe illness. The study also highlights the unique opportunity challenge trials provide for studying early infection mechanisms and immune responses in controlled settings, offering valuable insights that may not be possible in other types of studies.
