Direct and Indirect Effects of Influenza Vaccination on the Risk of Infection with Multiple Respiratory Pathogens in Children

Direct and Indirect Effects of Influenza Vaccination on the Risk of Infection with Multiple Respiratory Pathogens in Children | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Direct and Indirect Effects of Influenza Vaccination on the Risk of Infection with Multiple Respiratory Pathogens in Children Hao Lei, Shuyi Ji, Linli Wang, Weibo Tang, Hanqing He, Shi Zhao, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8260906/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract The interaction between influenza virus and other respiratory pathogens is increasingly recognized, yet the extent to which influenza vaccination alters the dynamics remains to be fully elucidated. Here we evaluate the associations between influenza vaccination and subsequent infection risk of 11 respiratory pathogens using a test-negative case-control study. Additionally, a dynamic “SVIRS×SIRS” model considering both direct and indirect pathways was constructed to explore the primary mechanisms underlying the observed associations. Among the 52,725 paediatric patients included, 11,895 (22.6%) had been vaccinated against influenza within 2 years of the test date. We identified robust associations between influenza vaccination and subsequent infection with influenza A virus (OR 0.52, 95% CI 0.47–0.58), influenza B virus (OR 0.22, 95% CI 0.19–0.26), and Mycoplasma pneumoniae (MP) (OR 1.24, 95% CI 1.20–1.27). The potential increase in human adenovirus and human metapneumovirus infection risk following influenza vaccination, in contrast to the decreased risk of human coronavirus and human respiratory syncytial virus, necessitates further research. No statistically significant associations were detected for the other four pathogens: chlamydia, human rhinovirus, human parainfluenza, and human bocavirus. Simulations using the dynamic model indicated that associations on MP was predominantly mediated by indirect pathway, i.e., the suppression of the influenza virus leaves a void for MP, rather than the direct side effect of the vaccine. These findings underscore that distinguishing between the direct and indirect impacts of vaccination is extremely important considering the currently fragile global confidence in vaccines. Furthermore, understanding these vaccine-pathogen interactions helps strengthen integrated prevention systems for multiple respiratory infectious diseases. Health sciences/Diseases/Infectious diseases/Viral infection Biological sciences/Immunology/Vaccines Influenza vaccination Respiratory pathogens Test-negative case-control study Dynamic model Paediatric population Full Text Additional Declarations There is NO Competing Interest. This study was approved by the Institutional Review Board and Human Research Ethics Committee of the Children’s Hospital, Zhejiang University School of Medicine (No. 2025-IRB-0006-P-01). The need for written informed consent was waived by the Ethics Committee due to the retrospective nature of the study, and all data were analyzed anonymously. All the participate consented to participate in the study. Supplementary Files SupplementFinalNATHEALTHA02012.pdf Supplementary Information Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8260906","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":554821801,"identity":"dfa53aab-9cbc-4673-9177-7706b7532bb2","order_by":0,"name":"Hao 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