Chandelier
Established Member (Voting Rights)
Abstract
BackgroundAdults and children often respond differently to severe acute respiratory syndrome coronavirus 2 (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 1156 participants for 21 respiratory pathogens. We performed RNA sequencing on 147 swabs (n = 144 participants) collected prior to 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 (adjusted hazard ratio, 0.52; P = .034). Among participants with SARS-CoV-2 infection, recent rhinovirus infection was associated with 9.6-fold lower SARS-CoV-2 viral load (P = .0031). Higher preinfection 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 = .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.
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, Jr, Christine C Johnson , Rachel Ethridge, Sima Ramratnam, Lia Stelzig , Stephen J Teach, Alkis G Togias , Patricia C Fulkerson, Tina V Hartert, Max A Seibold
C. C. J., C. M. M., G. K. H., and W. D. D. report grant funding from National Institutes of Health (NIH). A. H. L. reports grant funding from NIH, ResMed, and OM Pharma; contracts with ThermoFisher Scientific; and data safety monitoring board (DSMB) participation for AstraZeneca and OM Pharma. L. B. B. reports grant funding from National Heart, Lung, and Blood Institute (NHLBI); royalties from Elsevier; consulting fees from Sanofi, Regeneron, Genentech, GlaxoSmithKline, DBV Technologies, Teva, Medscape, Kinaset, OM Pharma, AstraZeneca, and Recludix; and DSMB participation for DBV Technologies, AstraZeneca, Vertex, and Aravax. C. M. S. reports grant funding from NIH; and royalties from UpToDate. D. J. J. reports grant funding from NHLBI, NIH Office of Director, and Regeneron; consulting fees from AstraZeneca, Avillion, Areteia, Genentech, GlaxoSmithKline, Regeneron, Sanofi, Chiesi, and Apogee; and DSMB participation for AstraZeneca, Upstream Bio, and Pfizer. K. R. S. reports honoraria from Sanofi-Genzyme. M. A. S. reports grant funding from the NIH and Department of Defense; and consulting fees from Escient Pharmaceuticals. M. E. R. reports grant funding from NIH, Astra Zeneca, Regeneron/Sanofi, GlaxoSmithKline, CURED Foundation, Food Allergy Fund, US-Israel Binational Grant; royalties from UptoDate, Ception Therapeutics (Reslizumab), and Mapi Trust (PEESS instrument); consulting fees from Bristol Myers Squibb, Santa Ana bio, Regeneron/Sanofi, Enzen Therapeutics, Astra Zeneca, Pfizer, Nexstone One, GlaxoSmithKline, Celldex, Revolo Biotherapeutics, and Guidepoint; and stocks/stock options from Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nextstone One, Santa Ana Bio, and Enzen Therapeutics. R. S. Gu. reports grant funding from NIH, Food Allergy Research and Education (FARE), Sunshine Charitable Foundation, Genentech, Novartis, Abbott Laboratories; consulting fees from FARE, Genentech, Novartis, OWYN, Kaléo, Bryn Pharma, Kenvue, ARS Pharmaceuticals, Oracle Life Sciences, Alpina Biotechnology; and ownership interest in Yobee Care, Inc. S. J. L. reports stocks from Moderna. S. J. T. reports grant funding from NIH, EJF Philanthropies, Novartis, DC Health; and royalties from UptoDate. S. K. R. reports consulting fees from Sanofi; and DSMB participation for University of Wisconsin-Madison Institute for Clinical and Translational Research. T. V. H. reports grant funding from NIH; payments from AAAAI and UpToDate; and DSMB participation for Pfizer. All other authors report no potential conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.