The common cold is associated with protection from SARS-CoV-2 Infections

Camille M. Moore, Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
Elizabeth A. Secor, Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
Jamie L. Everman, Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
Ana Fairbanks-Mahnke, Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
Nathan Jackson, Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
Elmar Pruesse, Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
Katrina Diener, Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
Andrew Morin, Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
Samuel J. Arbes, Rho, Inc., Chapel Hill, NC, USA.
Leonard B. Bacharier, Monroe Carell Jr. Children's Hospital at Vanderbilt University Medical Center, Nashville, TN, USA.
Casper G. Bendixsen, National Farm Medicine Center, Marshfield Clinic Research Institute, Marshfield, WI, USA.
Agustin Calatroni, Rho, Inc., Chapel Hill, NC, USA.
William D. Dupont, Vanderbilt University Medical Center, Nashville, TN, USA.
Glenn T. Furuta, Digestive Health Institute, Children's Hospital Colorado and Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, University of Colorado School of Medicine, Aurora, CO, USA.
Tebeb Gebretsadik, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
Rebecca S. Gruchalla, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ruchi S. Gupta, Ann & Robert H. Lurie Hospital of Chicago & Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Gurjit K. Khurana Hershey, Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Meyer Kattan, Columbia University Medical Center New York, NY, USA.
Andrew H. Liu, Digestive Health Institute, Children's Hospital Colorado and Section of Pediatric Gastroenterology, Hepatology and Nutrition, Gastrointestinal Eosinophilic Diseases Program, University of Colorado School of Medicine, Aurora, CO, USA.
Stephanie J. Lussier, Rho, Inc., Chapel Hill, NC, USA.
Liza Bronner Murrison, Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Mari Numata, Department of Medicine, National Jewish Health, Denver, CO, USA.
George T. O'Connor, Pulmonary Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
Katherine River-Spoljaric, Washington University School of Medicine; St. Louis, MO, USA.
Wanda Phipatanakul, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Marc E. Rothenberg, Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Christine M. Seroogy, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Edward M. Zoratti, Henry Ford Health, Detroit, MI, USA.
Sharon Castina, Rho, Inc., Chapel Hill, NC, USA.
Daniel J. Jackson, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Carlos A. Camargo, Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Document Type

Journal Article

Publication Date

8-11-2025

Journal

The Journal of infectious diseases

DOI

10.1093/infdis/jiaf374

Keywords

COVID-19; Rhinovirus; SARS-CoV-2; epidemiology; viral interference

Abstract

BACKGROUND: Adults and children often respond differently to SARS-CoV-2 infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children's protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses. METHODS: Using case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved. We tested 10,493 longitudinal nasal swabs from 1,156 participants for 21 respiratory pathogens. We performed RNA-sequencing on 147 swabs (N=144 participants) collected prior SARS-CoV-2 infection and 391 swabs (N=165 participants) during and before rhinovirus infection. RESULTS: Participants with rhinovirus infection in the previous 30 days were at 48% lower risk of SARS-CoV-2 infection (aHR:0.52, p=0.034). Among participants with SARS-CoV-2 infection, recent rhinovirus infection was associated with 9.6-fold lower SARS-CoV-2 viral load (p=0.0031). Higher pre-infection expression of 57 genes was associated with lower SARS-CoV-2 viral load, including 24 antiviral defense genes; 22 of these were induced by rhinovirus infections. Relative to adults, children expressed higher levels of the antiviral gene signature (p=0.014) and were at 2.2-fold increased risk for rhinovirus infections. CONCLUSIONS: Rhinovirus infections, which trigger increased expression of antiviral airway genes, are linked to a lower risk of SARS-CoV-2 infection. Frequent rhinovirus infections may enhance this protective gene profile, partially explaining why children experience milder SARS-CoV-2 infections compared to adults. TRIAL REGISTRATION NUMBER: NCT04375761.

Department

Pediatrics

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