Dr. Ellen Foxman can still vividly recall the fear she felt watching her young son struggle to breathe during a severe asthma attack. For any parent, it’s a terrifying experience. For Foxman, a scientist as well as a mother, that moment planted a question that would later drive groundbreaking research.
She already knew her son had asthma. She also understood that rhinovirus — the most common cause of the common cold — often triggers wheezing and breathing problems in people with asthma.
“In fact, rhinovirus infection is the most common trigger of asthma attacks,” said Foxman, an associate professor of laboratory medicine and immunobiology at Yale School of Medicine.
What truly puzzled her, however, was why the very same virus could cause life-threatening breathing problems in some people, while in others it barely caused a runny nose.
“This is a virus that, in many people, causes no symptoms at all,” Foxman explained. “Some people just get a cold in their nose. But in certain groups, it can trigger serious, even life-threatening breathing difficulties. That contrast makes it a really fascinating virus.”
Why do some people suffer worse from the same cold virus? The nose might know why.
Foxman and her team at Yale discovered that a major reason lies in how quickly a person’s nasal cells respond when the virus first arrives.
Their research showed that the body’s early immune defense — known as the interferon response — plays a crucial role. Interferons are proteins that help stop viruses from spreading. But not everyone’s interferon response kicks in at the same speed or strength.
When that response is delayed or suppressed, the result can be excessive mucus production and inflammation, according to the team’s study published in January in the journal Cell Press Blue.
“It’s really the body’s response that determines how severe the disease becomes,” Foxman said, noting that she was a lead author of the study.
Recreating the Nose in a Lab
To reach these conclusions, Foxman and her colleagues grew nasal cells from healthy adults in the laboratory. Over four weeks, the cells developed into complex tissues that closely resembled the lining of the human nose and airways.
“They’re real human cells,” Foxman said. “When you grow them with air exposure, they organize themselves into tissue that looks just like what you’d find in the nose or lungs.”
The researchers then infected these lab-grown nasal tissues with rhinovirus and observed how thousands of individual cells reacted at the same time. This allowed them to track how infected cells — and nearby “bystander” cells — activated their defenses.
Fast Defenses vs. Runaway Infection
When the interferon response activated quickly, the virus was contained remarkably well. Fewer than 2% of nasal cells became infected. In real life, that kind of response might mean no symptoms at all — or just a few mild sniffles.
But when researchers blocked the early interferon response to mimic what happens in some people, the results changed dramatically.
“Instead of only about 1% of the cells being infected, roughly 30% became infected,” Foxman said. Those cells also began producing large amounts of mucus and showed signs of inflammation — hallmarks of a miserable cold or a dangerous asthma flare-up.
In other words, the team was able to model both extremes: a mild, contained infection and a severe, inflammatory one.
What Weakens the Immune Response?
One major question remains unanswered: why do some people have a weaker or delayed interferon response in the first place?
Foxman believes that studies involving real-life patients could help uncover the answer. For now, she views the research as an important first step toward understanding what happens inside the nose during a rhinovirus infection.
In the future, this knowledge could help guide new treatments aimed at reducing inflammation and mucus rather than targeting the virus alone.
Expert Perspectives
Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, called the study “very informative,” though he emphasized the need for confirmation in real-world patients.
“People may have different levels of interferon response,” Barouch said. “Those with a strong early response might recover quickly with minimal symptoms, while others may develop a more widespread infection. What’s still unclear is how someone could boost that response.”
He also noted that interferon is likely not the only factor involved.
Dr. Larry Anderson, a professor of pediatric infectious diseases at Emory University School of Medicine, agreed. He explained that differences in how people experience viral infections are common across medicine.
Other factors — such as genetics, underlying health conditions, bacteria in the airways, and prior exposure to the virus — may all shape how sick someone becomes.
“You see this with many infections,” Anderson said. “Influenza, RSV, parainfluenza, coronavirus — the same virus can lead to very different outcomes in different people.”
A Step Toward Understanding the Common Cold
While the common cold is often dismissed as minor, Foxman’s work highlights just how complex it can be — and why it’s anything but harmless for some people.
Understanding how the nose and immune system respond in those first critical moments could eventually help explain why one person shrugs off a virus, while another ends up struggling to breathe.
