Why Some Get Hit Harder by COVID: uncovering the Immune System’s Hidden Control
Why does COVID-19 leave some people gasping for breath while others experience mild symptoms? The answer lies hidden within our own immune system, specifically in a critical pathway that sends out alarm signals against invaders like viruses.
Scientists have long known the importance of the interferon pathway – a cellular communication network that sounds the alarm when our cells detect infections. When functioning properly, it triggers the release of interferon, a protein that tells other cells to prepare for battle. But disruptions in this delicate balance can lead to devastating consequences.
For years, glitches in the interferon pathway have been linked to severe COVID cases and long COVID, as well as autoimmune diseases and even cancer.
Now, a groundbreaking study from the University of colorado Boulder has pinpointed a crucial factor that fine-tunes this complex immune response: a tiny genetic variation that arose millions of years ago.
“We’ve uncovered a whole class of underappreciated protein variants that can have a profound impact on how our immune system functions,” explains Ed Chuong, the study’s lead author and an assistant professor in the Department of Molecular, Cellular and Developmental Biology.
His team focused on a specific variant of a protein called IFNAR2. This protein acts as a cellular antenna, receiving interferon’s distress signals and initiating a cascade of immune defenses. The variant they discovered acts like a "tuning dial," dampening the signal and modulating the immune response.
Intriguingly, this variant was found to be prevalent in all cells, frequently enough outnumbering the standard IFNAR2 protein. This suggested it plays a notable role in shaping our immune response, possibly tailoring it to individual needs.
Laboratory experiments revealed that cells lacking this variant became hyper-responsive to interferon, mounting a more potent defense against viruses like SARS-CoV-2 and dengue.
This discovery sheds light on why some individuals are more susceptible to severe infections, while others experience chronic inflammation, autoimmune disorders, or long-term consequences from infections like COVID.
"Think of it as an immune dimmer switch," says Chuong. "Variations in this dimmer switch can explain why some people experience stronger immune reactions than others."
The CU boulder team has filed for a patent and is actively developing therapies to target this newfound "tuning dial." Their work opens up exciting possibilities for personalized medicine, allowing us to fine-tune immune responses to treat a wide range of conditions.
This groundbreaking research suggests that thes ancient genetic quirks, once dismissed as "junk DNA," hold the key to unlocking the secrets of our complex immune system, paving the way for a new era of personalized health care.
How can understanding the interferon pathway improve personalized medicine strategies?
Interview: Uncovering the Immune System’s Hidden Control in COVID Responses
Time.news Editor (TNE): Welcome, Ed Chuong, assistant professor at the University of Colorado Boulder and lead author of the groundbreaking study on the immune response to COVID-19. Thank you for joining us today.
Ed Chuong (EC): Thank you for having me. It’s a pleasure to discuss our findings.
TNE: Your research delves into why some individuals experience severe COVID-19 symptoms while others remain largely unaffected. What is the pivotal role of the interferon pathway in this context?
EC: The interferon pathway is essential for our immune response. It acts as a dialog network, alerting our cells about infections and triggering the release of interferon—a crucial protein that prepares our cells to combat invaders like viruses.When this pathway functions properly, it can prevent severe disease. Though, disruptions can lead to serious outcomes, including severe COVID cases and other immune-related issues.
TNE: Fascinating! You mentioned a specific genetic variant linked to the interferon pathway. Can you elaborate on the significance of this finding?
EC: Yes, we identified a genetic variation in the protein IFNAR2, which acts as a receptor for interferon signals. This variant functions like a “tuning dial,” modulating the immune response. Interestingly, this variant is prevalent across different cells and often outnumbers the standard IFNAR2, suggesting it plays a crucial role in customizing the immune response to individual needs.
TNE: So, this variant can impact how effectively our bodies respond to COVID-19?
EC: Exactly! In our laboratory experiments, cells without this variant displayed an exaggerated immune response to interferon signals, leading to a stronger defense against viruses like SARS-CoV-2. This shows how the presence or absence of such variants can explain the differences in how individuals experience COVID-19.
TNE: What are the implications of your research for personalized medicine?
EC: Our findings open exciting avenues for personalized healthcare. By understanding these genetic variations and their roles in the immune system, we can possibly develop therapies that target these “tuning dials,” allowing us to fine-tune immune responses. This could lead to innovative treatments for various conditions, including COVID-19, autoimmune diseases, and chronic inflammation.
TNE: you mentioned that these genetic quirks were once considered “junk DNA.” How has this perspective changed through your research?
EC: Historically, many genetic variations were overlooked, deemed nonfunctional or insignificant. However, our study demonstrates that these seemingly trivial variations can have profound effects on immune function. This shift in perspective encourages more research into similar genetic quirks that might influence health and disease.
TNE: For our readers, what practical advice can you offer regarding COVID-19 and immune health?
EC: It’s essential to understand that our immune systems are uniquely tailored to us. Factors such as genetics, lifestyle, and overall health play significant roles in how we respond to infections. Maintaining a healthy lifestyle, including a balanced diet, regular exercise, and proper stress management, can enhance immune function. Additionally, staying informed about vaccines and recommended health measures can help us better prepare for diseases like COVID-19.
TNE: Thank you, Ed. It’s clear that your research could considerably impact our understanding of immune responses and pave the way for future health innovations.
EC: Thank you for having me. I’m excited about the potential of our findings and the future of personalized medicine.