A cold today helps keep the COVID away

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Protective Role of Rhinovirus Infections Against SARS-CoV-2: Insights into Age-Dependent Immunity

Cough and cold by rhinovirus.
Credit: Photo by Andy Vult on Unsplash

Introduction
Adults are more likely than children to develop symptomatic and severe COVID-19. One hypothesis suggests that frequent respiratory viral infections in children prime antiviral defenses, offering protection against SARS-CoV-2. This study investigates whether prior respiratory infections, particularly rhinovirus, influence SARS-CoV-2 susceptibility and severity.

Methods
Within the Human Epidemiology and Response to SARS-CoV-2 cohort, 10,493 nasal swabs from 1,156 participants were analyzed for 21 respiratory pathogens. Case-cohort and case-control approaches were used. RNA sequencing was performed on 538 swabs to identify molecular mechanisms underlying observed protection.

Results
Participants with rhinovirus infection in the preceding 30 days had a 48% lower risk of SARS-CoV-2 infection (adjusted hazard ratio, 0.52; P = .034). Among those infected, prior rhinovirus exposure was linked to a 9.6-fold reduction in SARS-CoV-2 viral load (P = .0031). Transcriptomic analysis identified 57 genes associated with lower viral load, including 24 antiviral defense genes; 22 were strongly induced by rhinovirus. Children displayed higher baseline expression of this antiviral signature (P = .014) and a greater likelihood of rhinovirus infection compared to adults.

Conclusion
Frequent rhinovirus infections enhance airway antiviral gene expression, lowering both SARS-CoV-2 risk and viral load. This innate immune priming may explain children’s relative resilience to severe COVID-19 and offers insights for developing preventive strategies.

Citation:
Camille M Moore, Elizabeth A Secor, Jamie L Everman, Ana Fairbanks-Mahnke, Nathan Jackson, Elmar Pruesse, Katrina Diener, Andrew Morin, Samuel J Arbes, Leonard B Bacharier, Casper G Bendixsen, Agustin Calatroni, William D Dupont, Glenn T Furuta, Tebeb Gebretsadik, Rebecca S Gruchalla, Ruchi S Gupta, Gurjit K Khurana Hershey, Meyer Kattan, Andrew H Liu, Stephanie J Lussier, Liza Bronner Murrison, Mari Numata, George T O’Connor, Katherine Rivera-Spoljaric, Wanda Phipatanakul, Marc E Rothenberg, Christine M Seroogy, Edward M Zoratti, Sharon Castina, Daniel J Jackson, Carlos A Camargo, Christine C Johnson, Rachel Ethridge, Sima Ramratnam, Lia Stelzig, Stephen J Teach, Alkis G Togias, Patricia C Fulkerson, Tina V Hartert, Max A Seibold, on behalf of the HEROS study team, The Common Cold Is Associated With Protection From SARS-CoV-2 Infections, The Journal of Infectious Diseases, 2025;, jiaf374, https://doi.org/10.1093/infdis/jiaf374

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