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

Camille M Moore^{1

2

3}, Elizabeth A Secor¹, Jamie L Everman¹, Ana Fairbanks-Mahnke¹, Nathan Jackson¹, Elmar Pruesse¹, Katrina Diener¹, Andrew Morin¹, Samuel J Arbes⁴, Leonard B Bacharier⁵, Casper G Bendixsen⁶, Agustin Calatroni⁴, William D Dupont^{7

8}, Glenn T Furuta⁹, Tebeb Gebretsadik⁸, Rebecca S Gruchalla¹⁰, Ruchi S Gupta¹¹, Gurjit K Khurana Hershey^{12

13}, Meyer Kattan¹⁴, Andrew H Liu^{9

15}, Stephanie J Lussier⁴, Liza Bronner Murrison¹², Mari Numata¹⁶, George T O'Connor¹⁷, Katherine River-Spoljaric¹⁸, Wanda Phipatanakul¹⁹, Marc E Rothenberg²⁰, Christine M Seroogy²¹, Edward M Zoratti²², Sharon Castina⁴, Daniel J Jackson²¹, Carlos A Camargo Jr²³, Christine C Johnson²², Rachel Ethridge⁴, Sima Ramratnam²¹, Lia Stelzig⁴, Stephen J Teach²⁴, Alkis G Togias²⁵, Patricia C Fulkerson²⁵, Tina V Hartert^{5

7}, Max A Seibold^{1

26

27}

Affiliations

¹ Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
² Department of Immunology and Genomic Medicine, National Jewish Health; Denver, CO, USA.
³ Department of Biostatistics and Informatics, University of Colorado; Denver, CO, USA.
⁴ Rho, Inc., Chapel Hill, NC, USA.
⁵ Monroe Carell Jr. Children's Hospital at Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ National Farm Medicine Center, Marshfield Clinic Research Institute, Marshfield, WI, USA.
⁷ Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁹ 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.
¹⁰ University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹¹ Ann & Robert H. Lurie Hospital of Chicago & Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹² Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹³ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹⁴ Columbia University Medical Center New York, NY, USA.
¹⁵ Breathing Institute, Children's Hospital Colorado and Section of Pediatric Pulmonary & Sleep Medicine, University of Colorado School of Medicine, Aurora CO, USA.
¹⁶ Department of Medicine, National Jewish Health, Denver, CO, USA.
¹⁷ Pulmonary Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
¹⁸ Washington University School of Medicine; St. Louis, MO, USA.
¹⁹ Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
²⁰ Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²¹ University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²² Henry Ford Health, Detroit, MI, USA.
²³ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
²⁴ Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
²⁵ National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.
²⁶ Department of Pediatrics, National Jewish Health; Denver, CO, USA.
²⁷ Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine; Aurora, CO, USA.

PMID: 40795882
DOI: 10.1093/infdis/jiaf374

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

Camille M Moore et al. J Infect Dis. 2025.

. 2025 Aug 11:jiaf374.

doi: 10.1093/infdis/jiaf374. Online ahead of print.

Authors

Affiliations

¹ Center for Genes, Environment, and Health, National Jewish Health; Denver, CO, USA.
² Department of Immunology and Genomic Medicine, National Jewish Health; Denver, CO, USA.
³ Department of Biostatistics and Informatics, University of Colorado; Denver, CO, USA.
⁴ Rho, Inc., Chapel Hill, NC, USA.
⁵ Monroe Carell Jr. Children's Hospital at Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ National Farm Medicine Center, Marshfield Clinic Research Institute, Marshfield, WI, USA.
⁷ Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁹ 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.
¹⁰ University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹¹ Ann & Robert H. Lurie Hospital of Chicago & Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹² Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹³ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹⁴ Columbia University Medical Center New York, NY, USA.
¹⁵ Breathing Institute, Children's Hospital Colorado and Section of Pediatric Pulmonary & Sleep Medicine, University of Colorado School of Medicine, Aurora CO, USA.
¹⁶ Department of Medicine, National Jewish Health, Denver, CO, USA.
¹⁷ Pulmonary Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
¹⁸ Washington University School of Medicine; St. Louis, MO, USA.
¹⁹ Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
²⁰ Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
²¹ University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²² Henry Ford Health, Detroit, MI, USA.
²³ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
²⁴ Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
²⁵ National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.
²⁶ Department of Pediatrics, National Jewish Health; Denver, CO, USA.
²⁷ Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine; Aurora, CO, USA.

PMID: 40795882
DOI: 10.1093/infdis/jiaf374

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.

Keywords: COVID-19; Rhinovirus; SARS-CoV-2; epidemiology; viral interference.

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

Affiliations

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

Authors

Affiliations

Abstract

Associated data

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous