The common cold is associated with protection from SARS-CoV-2 Infections.
Recommended Citation
Moore CM, Secor EA, Everman JL, Fairbanks-Mahnke A, Jackson N, Pruesse E, Diener K, Morin A, Arbes SJ, Bacharier LB, Bendixsen CG, Calatroni A, Dupont WD, Furuta GT, Gebretsadik T, Gruchalla RS, Gupta RS, Khurana Hershey GK, Kattan M, Liu AH, Lussier SJ, Murrison LB, Numata M, O'Connor GT, River-Spoljaric K, Phipatanakul W, Rothenberg ME, Seroogy CM, Zoratti EM, Castina S, Jackson DJ, Camargo CA, Jr., Johnson CC, Ethridge R, Ramratnam S, Stelzig L, Teach SJ, Togias AG, Fulkerson PC, Hartert TV, and Seibold MA. The common cold is associated with protection from SARS-CoV-2 Infections. J Infect Dis 2025.
Document Type
Article
Publication Date
8-11-2025
Publication Title
The Journal of infectious diseases
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.
Medical Subject Headings
Covid-19; Rhinovirus; SARS-CoV-2; epidemiology; viral interference
PubMed ID
40795882
ePublication
ePub ahead of print
