4 Minutes
Researchers have identified a plausible biological mechanism that helps explain why children—who experience more frequent common colds—are often less susceptible to symptomatic SARS‑CoV‑2 infection. New analysis of data from a large national cohort suggests that recent rhinovirus infections can transiently “prime” airway antiviral defenses, reducing the likelihood that SARS‑CoV‑2 will establish an infection.
Study design and scientific background
The findings derive from the Human Epidemiology and Response to SARS‑CoV‑2 (HEROS) study, a prospective national project that collected thousands of self‑administered nasal swabs from more than 4,100 participants in 1,394 U.S. households between May 2020 and February 2021. Investigators screened those samples for SARS‑CoV‑2 and for other respiratory pathogens—including rhinoviruses, the primary cause of the common cold—and profiled gene expression in airway samples to measure antiviral responses.
Rhinoviruses stimulate production of interferons, a family of signaling proteins that form an early, nonspecific antiviral defense in the respiratory tract. This rapid interferon response can reduce replication of other viruses arriving shortly afterward, a phenomenon known as heterologous viral interference. While laboratory studies and retrospective observations previously suggested such interference among respiratory viruses, this report represents a prospective, population‑scale look at how recent cold infections correlated with subsequent SARS‑CoV‑2 detection.
Key findings and implications
Analysis showed that individuals—particularly children—who tested positive for rhinovirus in the weeks before were less likely to test positive for SARS‑CoV‑2 during follow‑up. Children also displayed higher baseline expression of interferon‑related genes in airway samples compared with adults, providing a molecular explanation for their stronger immediate antiviral state.
"Our findings suggest that the immune boost from a recent cold may give the body an early advantage in fighting SARS‑CoV‑2 before it has a chance to take hold," said Max Seibold, PhD, Director of the Regenerative Medicine and Genome Editing Program (REGEN) at National Jewish Health and senior author of the study. The work complements earlier HEROS results indicating that children are substantially less likely than adults to develop symptomatic COVID‑19.
Lead author Camille Moore, PhD, emphasized caution: "This doesn’t mean people should intentionally try to catch a cold. But understanding how one virus can affect the body’s response to another could help us develop new prevention strategies, especially for vulnerable populations." The results point toward potential public‑health and clinical strategies that could harness innate immune activation—for example, targeted interferon therapies or timing of prophylactic measures—without exposing people to pathogenic viruses.
Gene expression and methods
Using high‑throughput molecular assays on the nasal swabs, investigators quantified expression of interferon‑stimulated genes and other immune markers. The study’s prospective design and dense sampling allowed temporal associations between recent rhinovirus detection and subsequent SARS‑CoV‑2 outcomes, strengthening evidence for causality compared with cross‑sectional snapshots.
Expert Insight
Dr. Elena Vargas, fictional pediatric immunologist and science communicator, notes: "These results nicely link molecular immunology to real‑world epidemiology. Children’s airways are often in a heightened antiviral state because of frequent mild infections. Translating that natural protection into safe, short‑acting interventions could be valuable for protecting high‑risk adults during respiratory virus seasons."
Broader significance and future directions
This study reinforces that innate immune dynamics and recent viral exposures shape population susceptibility to novel pathogens like SARS‑CoV‑2. Future research should test whether controlled, safe activation of airway interferon responses can reduce infection risk in vulnerable groups, and evaluate how viral interference interacts with vaccination, viral variants, and seasonal patterns.
Conclusion
Prospective data from the HEROS study indicate that recent rhinovirus infections may transiently lower the risk of subsequent SARS‑CoV‑2 infection—especially in children—by inducing a strong interferon‑mediated antiviral state in the airways. While not a reason to seek infection, these findings shed light on age‑related differences in COVID‑19 susceptibility and suggest new avenues for preventive research and therapies.
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