New research clarifies why the common cold ranges from mild discomfort to severe illness in different people, revealing that the body’s own immune response, rather than the virus itself, is often the key factor. Scientists at Yale University have grown miniature human nasal passages in laboratory dishes – dubbed “noses-in-a-dish” – to dissect how cells react to rhinovirus infection. The findings, published January 19 in Cell Press Blue, suggest that the severity of a cold isn’t just about exposure, but about how well the immune system manages the threat.
The Immune Response: A Double-Edged Sword
For most, rhinoviruses cause little more than a runny nose and cough. However, in smokers, asthmatics, and others, infection can escalate to life-threatening breathing difficulties. The new study reveals this disparity stems from how effectively nasal cells activate immune defenses. When the immune system works too well, it can overreact, causing more harm than the virus itself.
Researchers used single-cell RNA sequencing to analyze the molecular signals within infected nasal cells. They found that a key regulator, interferon, is critical in controlling the response. Interferons are the body’s first line of defense, but their absence triggers runaway inflammation. Without interferon signaling, over 30% of nasal cells become infected, leading to a surge in inflammatory molecules and mucus production.
NF-κB: The Overactive Immune Conductor
The study pinpointed nuclear factor kappa B (NF-κB) as the protein driving this overreaction. When NF-κB runs unchecked, it mimics the severe inflammation seen in vulnerable patients. Some individuals may have genetic defects affecting interferon production, making them more susceptible to this exaggerated response. This explains why the same virus variant can cause wildly different outcomes.
Antiviral Strategies and Future Treatments
The research suggests that drugs suppressing the immune response, such as the experimental rupintrivir, could help manage severe cases, particularly in COPD patients. However, experts caution that blocking inflammation entirely could hinder effective infection fighting. A more precise approach may involve targeting the virus directly.
Rhinoviruses evolve rapidly, making treatment challenging. The study underscores the need to understand why colds make us sick, not just how to kill the virus. As Emory Vaccine Center professor Mehul Suthar put it, “It’s obviously very challenging. Otherwise, we’d have drugs for every virus out there.”
The findings are a critical step toward developing more effective treatments for the common cold, but finding the right balance between immune control and viral suppression remains a major hurdle.
