Recent rhinovirus infection was tied to a markedly lower risk of SARS-CoV-2 infection and reduced viral load among those who did become infected, according to recently published findings.
The analysis, based on case-cohort and case-control methods, drew on 10,493 nasal swabs from 1,156 participants in the Human Epidemiology and Response to SARS-CoV-2 cohort, which tested for 21 respiratory pathogens. Participants with a rhinovirus infection in the past 30 days were 48% less likely to contract SARS-CoV-2 than those without. Among SARS-CoV-2–positive participants, recent rhinovirus infection was linked to a nearly tenfold reduction in viral load. No benefit was seen when both viruses were detected at the same time.
Gene expression data offered a potential explanation. Researchers identified 57 genes whose preinfection activity was inversely associated with SARS-CoV-2 viral load, including 24 with established antiviral roles such as DDX58 (RIG-I), IFIH1 (MDA5), IFIT1, IFIT3, and OASL induced during rhinovirus infection, increasing nearly twofold in vivo (mean, 1.82-fold) and up to more than 200-fold in infected airway epithelial cultures.
Children demonstrated stronger innate defenses than adults, with higher baseline expression of protective genes. Expression of 13 of the 22 rhinovirus-inducible genes declined with age, and children were more than twice as likely to experience rhinovirus infections, suggesting both increased viral exposure and enhanced gene activity may contribute to reduced SARS-CoV-2 viral loads and milder illness.
Limitations included the biweekly sampling schedule, which may have underestimated infections, the absence of quantitative rhinovirus load data, and RNA sequencing restricted to a subset of samples.
“Nevertheless, our findings show that recent HRV infections are associated with an airway gene expression profile that may limit SARS-CoV-2 infections,” said Camille M. Moore, PhD, Departments of Immunology and Genomic Medicine and Biostatistics and Informatics, National Jewish Health and University of Colorado, Denver, Colorado, and colleagues. “Understanding these viral interactions may improve the management and forecasting of future pandemics.”
Full disclosures can be found in the published study.