Influenza Vaccination and Protective Effectiveness Against Influenza Illness in Community‑Dwelling Children: A Prospective Cohort Study

Influenza Vaccination and Protective Effectiveness Against Influenza Illness in Community‑Dwelling Children: A Prospective Cohort Study | 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 Research Article Influenza Vaccination and Protective Effectiveness Against Influenza Illness in Community‑Dwelling Children: A Prospective Cohort Study Xiaoman Cai, Ailing Zhang, Shiyou Luo, Xiubin Ma, Bin Wang, Xueying Meng, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8466942/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Children are highly susceptible to influenza and face significant risks when infected, which makes vaccination a vital preventive measure. Still, there is limited real-world evidence, particularly from community-based studies, on whether the vaccine can reduce disease severity in children once they are diagnosed. Methods This prospective cohort study enrolled 388 children aged 6 months to 6 years diagnosed with influenza at the Longdong Community Health Service Center of Shenzhen Longgang Central Hospital between May 15, 2024, and October 16, 2025. Participants were categorized into vaccinated (n = 196) and unvaccinated (n = 192) groups based on vaccination history within the preceding year. Differences in clinical presentation, laboratory findings, healthcare resource utilization, and clinical outcomes were compared between the groups. Continuous variables were analyzed using the t-test or Mann-Whitney U test, and categorical variables were analyzed using the chi-square test. Results Compared to the unvaccinated group, vaccinated children had a lower body temperature (38.81 ± 0.58°C vs 39.03 ± 0.64°C), a shorter time to fever resolution (2.01 ± 1.21 days vs 2.45 ± 1.55 days), and lower incidences of myalgia (5.61% vs. 17.19%) and gastrointestinal symptoms (9.69% v. 20.83%) (all P < 0.01). Regarding medical outcomes, the vaccinated group had fewer outpatient visits (1.55 ± 0.82 vs.1.78 ± 0.91), lower outpatient costs (349.42 ± 201.23 vs 407.41 ± 337.44; P = 0.04), and lower rates of hospitalization (4.1% vs 21.9%) and antibiotic use (5.6% vs. 15.1%) ( P < 0.01). Conclusion Among community-dwelling children, while influenza vaccination may not completely prevent infection, it can alleviate clinical symptoms of breakthrough infections, reduce the risk of hospitalization and antibiotic use, and decrease healthcare burden. Influenza vaccine Children Community-acquired influenza Disease severity Hospitalization Retrospective cohort 1. Background Influenza remains a significant public health concern worldwide.[ 1 ] Studies indicate that in China, influenza is associated with approximately 201,000 excess respiratory deaths annually, imposing a substantial burden on society.[ 2 , 3 ]The threat of influenza is particularly pronounced among children. Statistics show that the incidence of influenza in children under five years of age in China ranks among the highest across all age groups, with outpatient/emergency visits and hospitalization rates reaching approximately 2,200 and 224 per 100,000 population, respectively.[ 4 , 5 ] Influenza infection in children can not only lead to severe symptoms such as high fever and systemic myalgia but also increases the risk of secondary complications like pneumonia, thereby imposing ongoing pressures on pediatric health, household economies, and healthcare system resources.[ 6 ] Vaccination remains the most cost-effective strategy for preventing influenza and its serious complications. However, it must be recognized that the protective efficacy of influenza vaccines is not absolute, influenced by factors such as viral strain variation and host immune response heterogeneity.[ 7 , 8 ] Some vaccinated individuals may still experience breakthrough infections. Consequently, the evaluation of vaccine value has shifted from solely focusing on “preventing infection” to also emphasizing its “disease-modifying effect”—namely, the critical role of vaccination in mitigating clinical severity, reducing hospitalization, and lowering mortality risk.[ 9 , 10 ] Although the disease-modifying effect of influenza vaccines is widely acknowledged in theory, empirical evidence based on community pediatric populations in China remains relatively scarce. Existing studies have primarily focused on estimating vaccine effectiveness against infection, while real-world data on the actual protective impact—among vaccinated children who nonetheless contract influenza—in terms of alleviating clinical symptoms, reducing complications, and conserving medical resources are still insufficient. Accordingly, this retrospective cohort study aims to evaluate the real-world effectiveness of influenza vaccination in pediatric patients by comparing disease severity, hospitalization rates, antibiotic use, and medical expenditures between vaccinated and unvaccinated children with confirmed influenza. The results intend to inform evidence-based strategies for childhood influenza prevention and clinical care. 2. Method 2.1 Research population This study employed a prospective cohort design and was conducted at the Longdong Community Health Service Center of Shenzhen Longgang Central Hospital between May 15, 2024, and October 16, 2025. The study participants were children aged 6 months to 6 years who were clinically diagnosed with influenza at the center. The diagnosis of influenza was strictly based on the criteria outlined in the Expert Consensus on Diagnosis and Treatment of Influenza in Children (2020 Edition) . Written informed consent was obtained from the guardians of all enrolled children, and the study protocol was approved by the Institutional Ethics Committee. The following exclusion criteria were applied: (1) presence of other acute non‑influenza‑related illnesses at the time of visit; (2) underlying chronic conditions that could affect the course or severity of influenza, including chronic respiratory, cardiovascular, immunodeficiency, hematologic, renal, hepatic, neurological, neuromuscular, metabolic, or endocrine diseases, or immunosuppressed status; (3) refusal by guardians to participate in telephone or community follow‑up required for the study; and (4) incomplete key clinical data. Finally, a total of 388 children with community‑acquired influenza who met all eligibility criteria were included in the final analysis. 2.2 Data collection 2.21 Collection of Baseline Data : At the time of the child's visit, baseline data were collected through medical record review and face-to-face interviews. Information gathered included general demographics (age, sex, and preschool education history), clinical manifestations (body temperature, and symptoms such as cough, nasal congestion, rhinorrhea, sore throat, myalgia, and gastrointestinal symptoms), and laboratory test results based on peripheral blood samples. Laboratory parameters comprised white blood cell count, the percentage and absolute counts of neutrophils and lymphocytes, hemoglobin level, platelet count, and C-reactive protein (CRP) level, with a CRP level >10 mg/L defined as abnormal. Additionally, influenza vaccination history (where children vaccinated within the year prior to the visit were classified as the “vaccinated group” and others as the “unvaccinated group”), use of antibiotics, as well as the number of medical visits and total outpatient expenses during the current illness episode were recorded. 2.22 Collection of Follow-up Data: Follow-up was conducted 7–10 days after the initial visit via telephone or at the community health service center to collect additional information on disease course and outcomes. Data included time to fever resolution (from illness onset to complete normalization of body temperature), time to cough resolution, occurrence of influenza-related hospitalization, antibiotic use, complications, total number of medical visits, and direct medical costs related to the illness. To ensure accuracy, all data were entered and verified independently by two uniformly trained researchers. 2.3 Statistical analysis All statistical analyses in this study were performed using SPSS 30.0 and R language (version 4.4.3). Normality of continuous variables was assessed using the Shapiro–Wilk test. Normally distributed data are presented as mean ± standard deviation (Mean ± SD) and compared between groups using the independent samples t-test. Non-normally distributed data are expressed as median (interquartile range) [M (IQR)] and analyzed with the nonparametric Mann–Whitney U test. Categorical variables are summarized as frequency (percentage) [n (%)] and compared using the chi-square test. All tests were two‑sided, and a P ‑value < 0.05 was considered statistically significant. 3. Result 3.1 Demographic Characteristics A total of 388 pediatric patients were enrolled in this study, with 196 assigned to the vaccinated group and 192 to the unvaccinated group. No statistically significant differences were observed between the two groups in terms of age, sex, or education level (all P > 0.05), indicating comparability at baseline(Table1). 3.2 Comparison of Clinical Symptom Severity A comparison of clinical symptoms between the two groups is presented in Table 2. Compared with the unvaccinated group, children in the vaccinated group had lower body temperature (38.81 ± 0.58 °C vs 39.03 ± 0.64 °C, P < 0.01), shorter time to fever resolution (2.01 ± 1.21 days vs 2.45 ± 1.55 days, P < 0.01), and lower incidence of myalgia (5.61% vs 17.19%, P < 0.01) and gastrointestinal symptoms (9.69% vs 20.83%, P 0.05). 3.3 Laboratory Findings Baseline laboratory results are presented in Table 3. No statistically significant differences were observed between the two groups in white blood cell count, neutrophil or lymphocyte count (or their percentages), hemoglobin level, or platelet count (all P > 0.05). Although the proportion of patients with elevated C‑reactive protein was higher in the unvaccinated group, this difference did not reach statistical significance ( P = 0.06). 3.4 Clinical Outcomes and Healthcare Utilization Clinical outcomes and healthcare resource utilization are summarized in Table 4. Compared with the unvaccinated group, children in the vaccinated group had fewer average medical visits (1.55 ± 0.82 vs 1.78 ± 0.91, P < 0.01), lower outpatient costs (349.42 ± 201.23 vs 407.41 ± 337.44, P = 0.04), and significantly lower rates of hospitalization (4.1% vs 21.9%, P < 0.01) and antibiotic use (5.6% vs 15.1%, P < 0.01). 4. Discussion This study analyzed the clinical data of 388 children aged 6 months to 6 years diagnosed with influenza at a community health service center. The results demonstrated that, among confirmed influenza cases, children who had received influenza vaccination within the preceding year exhibited milder clinical manifestations—including lower body temperature, faster fever resolution, and reduced incidence of myalgia and gastrointestinal symptoms—compared to their unvaccinated counterparts. Furthermore, vaccinated children experienced better clinical outcomes, such as a lower risk of hospitalization, fewer medical visits and lower outpatient costs. Collectively, these real-world evidence support that influenza vaccination in children offers clinical benefits,encompassing both infection prevention and disease-modifying outcomes. The core findings of this study align with global evidence on the clinical value of influenza vaccination and further provide localized empirical data from a community-based pediatric population in China. Consistent with the fundamental expectation that influenza vaccination mitigates disease severity, vaccinated children in our cohort presented with lower body temperature and milder systemic symptoms. A systematic review of real-world effectiveness studies in children (1995–2023) concluded that influenza vaccines provide protection and reduce disease burden following infection, a finding our study supports with specific, quantifiable clinical evidence.[ 11 ] The observed reductions in hospitalization (4.1% vs. 21.9%) and antibiotic use (5.6% vs. 15.1%) in the vaccinated group indicates public health significance, reflecting the vaccine's role in preventing serious clinical consequences. Multiple studies have protective effects of influenza vaccination against pediatric hospitalization, severe illness, and mortality.[ 10 , 12 ]Furthermore, a 2022 study on influenza vaccine coverage and antibiotic use in children highlighted that vaccination reduces both antibiotic prescribing rates and the risk of requiring antibiotic treatment, an effect our data confirm among community-managed pediatric influenza patients.[ 13 ]From a health economics perspective, the decreases in medical visits and outpatient costs in the vaccinated group are consistent with other reports demonstrating that influenza vaccination lowers healthcare resource utilization.[ 4 , 14 , 15 ]This further supports the cost-effectiveness of childhood influenza vaccination in terms of reduced economic burden. The clinical pattern observed among vaccinated children—characterized by milder symptoms, prevention of severe disease, and fewer complications—is rooted in the rapid and effective response of vaccine-induced pre-existing immunity to viral infection. Following vaccination, the body generates specific antibodies and memory immune cells (memory B cells and T cells). In the event of a breakthrough infection, these pre-existing immune components are quickly activated.[ 16 , 17 ] Memory B cells rapidly proliferate and produce large quantities of high-affinity antibodies to neutralize the virus, while memory T cells—particularly cytotoxic T cells—promptly recognize and eliminate virus-infected host cells. This accelerated immune response enables viral replication to be controlled at an earlier stage and at a lower level, thereby directly reducing the degree of viremia and limiting tissue damage.[ 18 , 19 ] This mechanism provides a plausible explanation for the findings in our study: vaccinated children exhibited lower peak body temperature, shorter time to fever resolution, and fewer systemic inflammatory symptoms such as myalgia. Furthermore, influenza virus infection can compromise the respiratory mucosal barrier and suppress innate immunity, increasing the risk of secondary bacterial complications such as pneumonia and otitis media.[ 20 – 23 ] By curbing viral replication, alleviating epithelial damage, and mitigating inflammatory cytokine release, vaccination helps preserve the defensive function of the respiratory tract, thereby lowering the risk of secondary bacterial infection. This offers a coherent pathophysiological explanation for the observed reductions in antibiotic use and hospitalization rates in the vaccinated group. This study has several limitations. As a observational study, unmeasured confounding factors may exist. For instance, families who chose vaccination might generally exhibit stronger health awareness or have a lower baseline risk of illness—a phenomenon often described as the “healthy vaccinee bias.” Furthermore, vaccination history and past medical information for some children could be subject to recall bias. Finally, the data were derived from a single community health service center with a relatively limited sample size, which may affect the generalizability of the findings. Future multi‑center, large‑sample prospective studies are warranted to validate these results. 5. Conclusion This study demonstrates that influenza vaccination can alleviate clinical symptoms, reduce the risks of hospitalization and antibiotic use, and decrease healthcare resource consumption among children with community-acquired influenza. These findings strongly support the ongoing public health strategy of promoting and expanding influenza vaccination in children as a key measure for seasonal influenza prevention and control. Abbreviations WBC White Blood Cell count Ne Per Neutrophil Percentage Lym Per Lymphocyte Percentage Ne Neutrophil count Lym Lymphocyte count HB Hemoglobin Plt Platelet count CRP C-Reactive Protein Declarations Acknowledgements Not applicable. Author contributions Yaoting Su and Xiaoman Cai wrote the main text of the manuscript, the data collection, and analysis.Ailing Zhang , Shiyou Luo and Xiubin Ma were involved in the conceptualization of the study's design and the manuscript's writing. Bin Wang and Xueying Meng were involved in the analysis and writing the manuscript. All the authors have read and approved the final manuscript. Funding This work was supported by the Medical and Health Science and Technology Planning Project of Longgang District, Shenzhen City (grant number: LGWJ2023-7). Non-Funding Projects of Shenzhen City Data availability Data can be obtained from the corresponding author upon reasonable request. Ethics approval and consent to participate This study was approved by the Ethics Committee of Longgang Central Hospital, Shenzhen. All procedures were conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from the guardians of all participants prior to enrollment. (Clinical Trials ID: 2024ECPJ026) Consent for publication Not applicable. Competing interests The authors have no conflict of interests. References Minozzi S, Lytras T, Gianola S, Gonzalez-Lorenzo M, Castellini G, Galli C, Cereda D, Bonovas S, Pariani E, Moja L: Comparative efficacy and safety of vaccines to prevent seasonal influenza: A systematic review and network meta-analysis . eClinicalMedicine 2022, 46 . Li L, Liu Y, Wu P, Peng Z, Wang X, Chen T, Wong JY, Yang J, Bond HS, Wang L: Influenza-associated excess respiratory mortality in China, 2010 –15: a population-based study . The Lancet Public Health 2019, 4 (9):e473-e481. Li J, Chen Y, Wang X, Yu H: Influenza-associated disease burden in mainland China: a systematic review and meta-analysis . Sci Rep 2021, 11 (1):2886. Feng L, Feng S, Chen T, Yang J, Lau YC, Peng Z, Li L, Wang X, Wong JY, Qin Y: Burden of influenza ‐associated outpatient influenza ‐like illness consultations in China, 2006 ‐2015: a population ‐based study . Influenza and other respiratory viruses 2020, 14 (2):162-172. Control CCfD, Prevention: 中国流感疫苗预防接种技术指南(2023 —2024) . 中国病毒病杂志 2024, 14 (01):1-19. Wang X, Li Y, O'brien KL, Madhi SA, Widdowson M-A, Byass P, Omer SB, Abbas Q, Ali A, Amu A: Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study . The Lancet Global Health 2020, 8 (4):e497-e510. Osterholm MT, Kelley NS, Sommer A, Belongia EA: Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis . The Lancet infectious diseases 2012, 12 (1):36-44. Trombetta CM, Kistner O, Montomoli E, Viviani S, Marchi S: Influenza Viruses and Vaccines: The Role of Vaccine Effectiveness Studies for Evaluation of the Benefits of Influenza Vaccines . Vaccines 2022, 10 (5):714. Arriola CS, Anderson EJ, Baumbach J, Bennett N, Bohm S, Hill M, Lindegren ML, Lung K, Meek J, Mermel E: Does influenza vaccination modify influenza severity? Data on older adults hospitalized with influenza during the 2012− 2013 season in the United States . The Journal of Infectious Diseases 2015, 212 (8):1200-1208. Boddington NL, Pearson I, Whitaker H, Mangtani P, Pebody RG: Effectiveness of Influenza Vaccination in Preventing Hospitalization Due to Influenza in Children: A Systematic Review and Meta-analysis . Clinical Infectious Diseases 2021, 73 (9):1722-1732. Wang X, Li Y, O'Brien KL, Madhi SA, Widdowson M-A, Byass P, Omer SB, Abbas Q, Ali A, Amu A et al : Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study . The Lancet Global Health 2020, 8 (4):e497-e510. Diseases CoI: Recommendations for prevention and control of influenza in children, 2022 –2023 . Pediatrics 2022, 150 (4):e2022059275. Younas M, Royer J, Winders HR, Weissman SB, Bookstaver PB, Ann Justo J, Waites KS, Bell L, Al-Hasan MN: Temporal Association between Influenza Vaccination Coverage and Ambulatory Antibiotic Use in Children . The Pediatric Infectious Disease Journal 2022, 41 (7):600-602. Lai X, Rong H, Ma X, Hou Z, Li S, Jing R, Zhang H, Lyu Y, Wang J, Feng H et al : The Economic Burden of Influenza-Like Illness among Children, Chronic Disease Patients, and the Elderly in China: A National Cross-Sectional Survey . Int J Environ Res Public Health 2021, 18 (12):6277. Calabrò GE, D’Ambrosio F, Fallani E, Ricciardi W: Influenza Vaccination Assessment according to a Value-Based Health Care Approach . Vaccines 2022, 10 (10):1675. Sridhar S, Brokstad K, Cox R: Influenza vaccination strategies: comparing inactivated and live attenuated influenza vaccines. Vaccines (Basel) 3: 373 –389 . In . ; 2015. Wild K, Smits M, Killmer S, Strohmeier S, Neumann-Haefelin C, Bengsch B, Krammer F, Schwemmle M, Hofmann M, Thimme R: Pre-existing immunity and vaccine history determine hemagglutinin-specific CD4 T cell and IgG response following seasonal influenza vaccination . Nat Commun 2021, 12 (1):6720. Janssens Y, Joye J, Waerlop G, Clement F, Leroux-Roels G, Leroux-Roels I: The role of cell-mediated immunity against influenza and its implications for vaccine evaluation . Front Immunol 2022, 13 :959379. Becker T, Elbahesh H, Reperant LA, Rimmelzwaan GF, Osterhaus ADME: Influenza Vaccines: Successes and Continuing Challenges . The Journal of Infectious Diseases 2021, 224 (Supplement_4):S405-S419. McCullers JA: The co-pathogenesis of influenza viruses with bacteria in the lung . Nature Reviews Microbiology 2014, 12 (4):252-262. Lalbiaktluangi C, Yadav MK, Singh PK, Singh A, Iyer M, Vellingiri B, Zomuansangi R, Zothanpuia, Ram H: A cooperativity between virus and bacteria during respiratory infections . Front Microbiol 2023, 14 :1279159. Klomp M, Ghosh S, Mohammed S, Nadeem Khan M: From virus to inflammation, how influenza promotes lung damage . Journal of Leukocyte Biology 2021, 110 (1):115-122. Sumitomo T, Kawabata S: Respiratory tract barrier dysfunction in viral-bacterial co-infection cases . Japanese Dental Science Review 2024, 60 :44-52. Tables Tables 1 to 4 are available in the supplementary files section Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Posted 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. 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Background","content":"\u003cp\u003eInfluenza remains a significant public health concern worldwide.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Studies indicate that in China, influenza is associated with approximately 201,000 excess respiratory deaths annually, imposing a substantial burden on society.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]The threat of influenza is particularly pronounced among children. Statistics show that the incidence of influenza in children under five years of age in China ranks among the highest across all age groups, with outpatient/emergency visits and hospitalization rates reaching approximately 2,200 and 224 per 100,000 population, respectively.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eInfluenza infection in children can not only lead to severe symptoms such as high fever and systemic myalgia but also increases the risk of secondary complications like pneumonia, thereby imposing ongoing pressures on pediatric health, household economies, and healthcare system resources.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Vaccination remains the most cost-effective strategy for preventing influenza and its serious complications. However, it must be recognized that the protective efficacy of influenza vaccines is not absolute, influenced by factors such as viral strain variation and host immune response heterogeneity.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Some vaccinated individuals may still experience breakthrough infections. Consequently, the evaluation of vaccine value has shifted from solely focusing on \u0026ldquo;preventing infection\u0026rdquo; to also emphasizing its \u0026ldquo;disease-modifying effect\u0026rdquo;\u0026mdash;namely, the critical role of vaccination in mitigating clinical severity, reducing hospitalization, and lowering mortality risk.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Although the disease-modifying effect of influenza vaccines is widely acknowledged in theory, empirical evidence based on community pediatric populations in China remains relatively scarce. Existing studies have primarily focused on estimating vaccine effectiveness against infection, while real-world data on the actual protective impact\u0026mdash;among vaccinated children who nonetheless contract influenza\u0026mdash;in terms of alleviating clinical symptoms, reducing complications, and conserving medical resources are still insufficient.\u003c/p\u003e \u003cp\u003eAccordingly, this retrospective cohort study aims to evaluate the real-world effectiveness of influenza vaccination in pediatric patients by comparing disease severity, hospitalization rates, antibiotic use, and medical expenditures between vaccinated and unvaccinated children with confirmed influenza. The results intend to inform evidence-based strategies for childhood influenza prevention and clinical care.\u003c/p\u003e"},{"header":"2. Method","content":"\u003cp\u003e\u003cstrong\u003e2.1 Research population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study employed a prospective cohort design and was conducted at the Longdong Community Health Service Center of Shenzhen Longgang Central Hospital between May 15, 2024, and October 16, 2025. The study participants were children aged 6 months to 6 years who were clinically diagnosed with influenza at the center. The diagnosis of influenza was strictly based on the criteria outlined in the \u003cem\u003eExpert Consensus on Diagnosis and Treatment of Influenza in Children (2020 Edition)\u003c/em\u003e. Written informed consent was obtained from the guardians of all enrolled children, and the study protocol was approved by the Institutional Ethics Committee. The following exclusion criteria were applied: (1) presence of other acute non‑influenza‑related illnesses at the time of visit; (2) underlying chronic conditions that could affect the course or severity of influenza, including chronic respiratory, cardiovascular, immunodeficiency, hematologic, renal, hepatic, neurological, neuromuscular, metabolic, or endocrine diseases, or immunosuppressed status; (3) refusal by guardians to participate in telephone or community follow‑up required for the study; and (4) incomplete key clinical data. Finally, a total of 388 children with community‑acquired influenza who met all eligibility criteria were included in the final analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2\u003c/strong\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.21 Collection of Baseline Data\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eAt the time of the child's visit, baseline data were collected through medical record review and face-to-face interviews. Information gathered included general demographics (age, sex, and preschool education history), clinical manifestations (body temperature, and symptoms such as cough, nasal congestion, rhinorrhea, sore throat, myalgia, and gastrointestinal symptoms), and laboratory test results based on peripheral blood samples. Laboratory parameters comprised white blood cell count, the percentage and absolute counts of neutrophils and lymphocytes, hemoglobin level, platelet count, and C-reactive protein (CRP) level, with a CRP level \u0026gt;10 mg/L defined as abnormal. Additionally, influenza vaccination history (where children vaccinated within the year prior to the visit were classified as the “vaccinated group” and others as the “unvaccinated group”), use of antibiotics, as well as the number of medical visits and total outpatient expenses during the current illness episode were recorded.\u003cbr\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003cstrong\u003e\u0026nbsp;2.22 Collection of Follow-up Data:\u0026nbsp;\u003c/strong\u003eFollow-up was conducted 7–10 days after the initial visit via telephone or at the community health service center to collect additional information on disease course and outcomes. Data included time to fever resolution (from illness onset to complete normalization of body temperature), time to cough resolution, occurrence of influenza-related hospitalization, antibiotic use, complications, total number of medical visits, and direct medical costs related to the illness. To ensure accuracy, all data were entered and verified independently by two uniformly trained researchers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses in this study were performed using SPSS 30.0 and R language (version 4.4.3). Normality of continuous variables was assessed using the Shapiro–Wilk test. Normally distributed data are presented as mean ± standard deviation (Mean ± SD) and compared between groups using the independent samples t-test. Non-normally distributed data are expressed as median (interquartile range) [M (IQR)] and analyzed with the nonparametric Mann–Whitney U test. Categorical variables are summarized as frequency (percentage) [n (%)] and compared using the chi-square test. All tests were two‑sided, and a \u003cem\u003eP\u003c/em\u003e‑value \u0026lt; 0.05 was considered statistically significant. \u0026nbsp;\u003c/p\u003e"},{"header":"3. Result","content":"\u003cp\u003e\u003cstrong\u003e3.1 Demographic Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;A total of 388 pediatric patients were enrolled in this study, with 196 assigned to the vaccinated group and 192 to the unvaccinated group. No statistically significant differences were observed between the two groups in terms of age, sex, or education level (all\u003cem\u003e\u0026nbsp;P\u003c/em\u003e \u0026gt; 0.05), indicating comparability at baseline(Table1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Comparison of Clinical Symptom Severity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA comparison of clinical symptoms between the two groups is presented in Table 2. Compared with the unvaccinated group, children in the vaccinated group had lower body temperature (38.81 \u0026plusmn; 0.58 \u0026deg;C vs 39.03 \u0026plusmn; 0.64 \u0026deg;C, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01), shorter time to fever resolution (2.01 \u0026plusmn; 1.21 days vs 2.45 \u0026plusmn; 1.55 days, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01), and lower incidence of myalgia (5.61% vs 17.19%, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01) and gastrointestinal symptoms (9.69% vs 20.83%, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01). No significant differences were observed in the incidence of cough, nasal congestion, rhinorrhea, or sore throat (all \u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Laboratory Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBaseline laboratory results are presented in Table 3. No statistically significant differences were observed between the two groups in white blood cell count, neutrophil or lymphocyte count (or their percentages), hemoglobin level, or platelet count (all \u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05). Although the proportion of patients with elevated C‑reactive protein was higher in the unvaccinated group, this difference did not reach statistical significance (\u003cem\u003eP\u003c/em\u003e = 0.06).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Clinical Outcomes and Healthcare Utilization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical outcomes and healthcare resource utilization are summarized in Table 4. Compared with the unvaccinated group, children in the vaccinated group had fewer average medical visits (1.55 \u0026plusmn; 0.82 vs 1.78 \u0026plusmn; 0.91, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01), lower outpatient costs (349.42 \u0026plusmn; 201.23 vs 407.41 \u0026plusmn; 337.44, \u003cem\u003eP\u003c/em\u003e = 0.04), and significantly lower rates of hospitalization (4.1% vs 21.9%, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01) and antibiotic use (5.6% vs 15.1%, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study analyzed the clinical data of 388 children aged 6 months to 6 years diagnosed with influenza at a community health service center. The results demonstrated that, among confirmed influenza cases, children who had received influenza vaccination within the preceding year exhibited milder clinical manifestations\u0026mdash;including lower body temperature, faster fever resolution, and reduced incidence of myalgia and gastrointestinal symptoms\u0026mdash;compared to their unvaccinated counterparts. Furthermore, vaccinated children experienced better clinical outcomes, such as a lower risk of hospitalization, fewer medical visits and lower outpatient costs. Collectively, these real-world evidence support that influenza vaccination in children offers clinical benefits,encompassing both infection prevention and disease-modifying outcomes.\u003c/p\u003e \u003cp\u003eThe core findings of this study align with global evidence on the clinical value of influenza vaccination and further provide localized empirical data from a community-based pediatric population in China. Consistent with the fundamental expectation that influenza vaccination mitigates disease severity, vaccinated children in our cohort presented with lower body temperature and milder systemic symptoms. A systematic review of real-world effectiveness studies in children (1995\u0026ndash;2023) concluded that influenza vaccines provide protection and reduce disease burden following infection, a finding our study supports with specific, quantifiable clinical evidence.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] The observed reductions in hospitalization (4.1% vs. 21.9%) and antibiotic use (5.6% vs. 15.1%) in the vaccinated group indicates public health significance, reflecting the vaccine's role in preventing serious clinical consequences. Multiple studies have protective effects of influenza vaccination against pediatric hospitalization, severe illness, and mortality.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]Furthermore, a 2022 study on influenza vaccine coverage and antibiotic use in children highlighted that vaccination reduces both antibiotic prescribing rates and the risk of requiring antibiotic treatment, an effect our data confirm among community-managed pediatric influenza patients.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]From a health economics perspective, the decreases in medical visits and outpatient costs in the vaccinated group are consistent with other reports demonstrating that influenza vaccination lowers healthcare resource utilization.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]This further supports the cost-effectiveness of childhood influenza vaccination in terms of reduced economic burden.\u003c/p\u003e \u003cp\u003eThe clinical pattern observed among vaccinated children\u0026mdash;characterized by milder symptoms, prevention of severe disease, and fewer complications\u0026mdash;is rooted in the rapid and effective response of vaccine-induced pre-existing immunity to viral infection. Following vaccination, the body generates specific antibodies and memory immune cells (memory B cells and T cells). In the event of a breakthrough infection, these pre-existing immune components are quickly activated.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Memory B cells rapidly proliferate and produce large quantities of high-affinity antibodies to neutralize the virus, while memory T cells\u0026mdash;particularly cytotoxic T cells\u0026mdash;promptly recognize and eliminate virus-infected host cells. This accelerated immune response enables viral replication to be controlled at an earlier stage and at a lower level, thereby directly reducing the degree of viremia and limiting tissue damage.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] This mechanism provides a plausible explanation for the findings in our study: vaccinated children exhibited lower peak body temperature, shorter time to fever resolution, and fewer systemic inflammatory symptoms such as myalgia. Furthermore, influenza virus infection can compromise the respiratory mucosal barrier and suppress innate immunity, increasing the risk of secondary bacterial complications such as pneumonia and otitis media.[\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] By curbing viral replication, alleviating epithelial damage, and mitigating inflammatory cytokine release, vaccination helps preserve the defensive function of the respiratory tract, thereby lowering the risk of secondary bacterial infection. This offers a coherent pathophysiological explanation for the observed reductions in antibiotic use and hospitalization rates in the vaccinated group.\u003c/p\u003e \u003cp\u003eThis study has several limitations. As a observational study, unmeasured confounding factors may exist. For instance, families who chose vaccination might generally exhibit stronger health awareness or have a lower baseline risk of illness\u0026mdash;a phenomenon often described as the \u0026ldquo;healthy vaccinee bias.\u0026rdquo; Furthermore, vaccination history and past medical information for some children could be subject to recall bias. Finally, the data were derived from a single community health service center with a relatively limited sample size, which may affect the generalizability of the findings. Future multi‑center, large‑sample prospective studies are warranted to validate these results.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis study demonstrates that influenza vaccination can alleviate clinical symptoms, reduce the risks of hospitalization and antibiotic use, and decrease healthcare resource consumption among children with community-acquired influenza. These findings strongly support the ongoing public health strategy of promoting and expanding influenza vaccination in children as a key measure for seasonal influenza prevention and control.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eWBC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;White Blood Cell count\u003c/p\u003e\n\u003cp\u003eNe Per \u0026nbsp; \u0026nbsp; \u0026nbsp;Neutrophil Percentage\u003c/p\u003e\n\u003cp\u003eLym Per \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Lymphocyte Percentage\u003c/p\u003e\n\u003cp\u003eNe \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Neutrophil count\u003c/p\u003e\n\u003cp\u003eLym \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Lymphocyte count\u003c/p\u003e\n\u003cp\u003eHB \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Hemoglobin\u003c/p\u003e\n\u003cp\u003ePlt \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Platelet count\u003c/p\u003e\n\u003cp\u003eCRP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;C-Reactive Protein\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYaoting Su and Xiaoman Cai wrote the main text of the manuscript, the data collection, and analysis.Ailing Zhang , Shiyou Luo and Xiubin Ma were involved in the conceptualization of the study\u0026apos;s design and the manuscript\u0026apos;s writing. Bin Wang \u0026nbsp;and Xueying Meng were involved in the analysis and writing the manuscript. All the authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Medical and Health Science and Technology Planning Project of Longgang District, Shenzhen City (grant number: LGWJ2023-7). Non-Funding Projects of Shenzhen City\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData can be obtained from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Longgang Central Hospital, Shenzhen. All procedures were conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from the guardians of all participants prior to enrollment.\u0026nbsp;(Clinical Trials ID: 2024ECPJ026)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflict of interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMinozzi S, Lytras T, Gianola S, Gonzalez-Lorenzo M, Castellini G, Galli C, Cereda D, Bonovas S, Pariani E, Moja L: \u003cstrong\u003eComparative efficacy and safety of vaccines to prevent seasonal influenza: A systematic review and network meta-analysis\u003c/strong\u003e. \u003cem\u003eeClinicalMedicine \u003c/em\u003e2022, \u003cstrong\u003e46\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eLi L, Liu Y, Wu P, Peng Z, Wang X, Chen T, Wong JY, Yang J, Bond HS, Wang L: \u003cstrong\u003eInfluenza-associated excess respiratory mortality in China, 2010\u003c/strong\u003e\u003cstrong\u003e\u0026ndash;15: a population-based study\u003c/strong\u003e. \u003cem\u003eThe Lancet Public Health \u003c/em\u003e2019, \u003cstrong\u003e4\u003c/strong\u003e(9):e473-e481.\u003c/li\u003e\n\u003cli\u003eLi J, Chen Y, Wang X, Yu H: \u003cstrong\u003eInfluenza-associated disease burden in mainland China: a systematic review and meta-analysis\u003c/strong\u003e. \u003cem\u003eSci Rep \u003c/em\u003e2021, \u003cstrong\u003e11\u003c/strong\u003e(1):2886.\u003c/li\u003e\n\u003cli\u003eFeng L, Feng S, Chen T, Yang J, Lau YC, Peng Z, Li L, Wang X, Wong JY, Qin Y: \u003cstrong\u003eBurden of influenza\u003c/strong\u003e\u003cstrong\u003e‐associated outpatient influenza\u003c/strong\u003e\u003cstrong\u003e‐like illness consultations in China, 2006\u003c/strong\u003e\u003cstrong\u003e‐2015: a population\u003c/strong\u003e\u003cstrong\u003e‐based study\u003c/strong\u003e. \u003cem\u003eInfluenza and other respiratory viruses \u003c/em\u003e2020, \u003cstrong\u003e14\u003c/strong\u003e(2):162-172.\u003c/li\u003e\n\u003cli\u003eControl CCfD, Prevention: \u003cstrong\u003e中国流感疫苗预防接种技术指南(2023\u003c/strong\u003e\u003cstrong\u003e\u0026mdash;2024)\u003c/strong\u003e. \u003cem\u003e中国病毒病杂志 \u003c/em\u003e2024, \u003cstrong\u003e14\u003c/strong\u003e(01):1-19.\u003c/li\u003e\n\u003cli\u003eWang X, Li Y, O\u0026apos;brien KL, Madhi SA, Widdowson M-A, Byass P, Omer SB, Abbas Q, Ali A, Amu A: \u003cstrong\u003eGlobal burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study\u003c/strong\u003e. \u003cem\u003eThe Lancet Global Health \u003c/em\u003e2020, \u003cstrong\u003e8\u003c/strong\u003e(4):e497-e510.\u003c/li\u003e\n\u003cli\u003eOsterholm MT, Kelley NS, Sommer A, Belongia EA: \u003cstrong\u003eEfficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis\u003c/strong\u003e. \u003cem\u003eThe Lancet infectious diseases \u003c/em\u003e2012, \u003cstrong\u003e12\u003c/strong\u003e(1):36-44.\u003c/li\u003e\n\u003cli\u003eTrombetta CM, Kistner O, Montomoli E, Viviani S, Marchi S: \u003cstrong\u003eInfluenza Viruses and Vaccines: The Role of Vaccine Effectiveness Studies for Evaluation of the Benefits of Influenza Vaccines\u003c/strong\u003e. \u003cem\u003eVaccines \u003c/em\u003e2022, \u003cstrong\u003e10\u003c/strong\u003e(5):714.\u003c/li\u003e\n\u003cli\u003eArriola CS, Anderson EJ, Baumbach J, Bennett N, Bohm S, Hill M, Lindegren ML, Lung K, Meek J, Mermel E: \u003cstrong\u003eDoes influenza vaccination modify influenza severity? Data on older adults hospitalized with influenza during the 2012\u0026minus; 2013 season in the United States\u003c/strong\u003e. \u003cem\u003eThe Journal of Infectious Diseases \u003c/em\u003e2015, \u003cstrong\u003e212\u003c/strong\u003e(8):1200-1208.\u003c/li\u003e\n\u003cli\u003eBoddington NL, Pearson I, Whitaker H, Mangtani P, Pebody RG: \u003cstrong\u003eEffectiveness of Influenza Vaccination in Preventing Hospitalization Due to Influenza in Children: A Systematic Review and Meta-analysis\u003c/strong\u003e. \u003cem\u003eClinical Infectious Diseases \u003c/em\u003e2021, \u003cstrong\u003e73\u003c/strong\u003e(9):1722-1732.\u003c/li\u003e\n\u003cli\u003eWang X, Li Y, O\u0026apos;Brien KL, Madhi SA, Widdowson M-A, Byass P, Omer SB, Abbas Q, Ali A, Amu A\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eGlobal burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study\u003c/strong\u003e. \u003cem\u003eThe Lancet Global Health \u003c/em\u003e2020, \u003cstrong\u003e8\u003c/strong\u003e(4):e497-e510.\u003c/li\u003e\n\u003cli\u003eDiseases CoI: \u003cstrong\u003eRecommendations for prevention and control of influenza in children, 2022\u003c/strong\u003e\u003cstrong\u003e\u0026ndash;2023\u003c/strong\u003e. \u003cem\u003ePediatrics \u003c/em\u003e2022, \u003cstrong\u003e150\u003c/strong\u003e(4):e2022059275.\u003c/li\u003e\n\u003cli\u003eYounas M, Royer J, Winders HR, Weissman SB, Bookstaver PB, Ann Justo J, Waites KS, Bell L, Al-Hasan MN: \u003cstrong\u003eTemporal Association between Influenza Vaccination Coverage and Ambulatory Antibiotic Use in Children\u003c/strong\u003e. \u003cem\u003eThe Pediatric Infectious Disease Journal \u003c/em\u003e2022, \u003cstrong\u003e41\u003c/strong\u003e(7):600-602.\u003c/li\u003e\n\u003cli\u003eLai X, Rong H, Ma X, Hou Z, Li S, Jing R, Zhang H, Lyu Y, Wang J, Feng H\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eThe Economic Burden of Influenza-Like Illness among Children, Chronic Disease Patients, and the Elderly in China: A National Cross-Sectional Survey\u003c/strong\u003e. \u003cem\u003eInt J Environ Res Public Health \u003c/em\u003e2021, \u003cstrong\u003e18\u003c/strong\u003e(12):6277.\u003c/li\u003e\n\u003cli\u003eCalabr\u0026ograve; GE, D\u0026rsquo;Ambrosio F, Fallani E, Ricciardi W: \u003cstrong\u003eInfluenza Vaccination Assessment according to a Value-Based Health Care Approach\u003c/strong\u003e. \u003cem\u003eVaccines \u003c/em\u003e2022, \u003cstrong\u003e10\u003c/strong\u003e(10):1675.\u003c/li\u003e\n\u003cli\u003eSridhar S, Brokstad K, Cox R: \u003cstrong\u003eInfluenza vaccination strategies: comparing inactivated and live attenuated influenza vaccines. Vaccines (Basel) 3: 373\u003c/strong\u003e\u003cstrong\u003e\u0026ndash;389\u003c/strong\u003e. In\u003cem\u003e.\u003c/em\u003e; 2015.\u003c/li\u003e\n\u003cli\u003eWild K, Smits M, Killmer S, Strohmeier S, Neumann-Haefelin C, Bengsch B, Krammer F, Schwemmle M, Hofmann M, Thimme R: \u003cstrong\u003ePre-existing immunity and vaccine history determine hemagglutinin-specific CD4 T cell and IgG response following seasonal influenza vaccination\u003c/strong\u003e. \u003cem\u003eNat Commun \u003c/em\u003e2021, \u003cstrong\u003e12\u003c/strong\u003e(1):6720.\u003c/li\u003e\n\u003cli\u003eJanssens Y, Joye J, Waerlop G, Clement F, Leroux-Roels G, Leroux-Roels I: \u003cstrong\u003eThe role of cell-mediated immunity against influenza and its implications for vaccine evaluation\u003c/strong\u003e. \u003cem\u003eFront Immunol \u003c/em\u003e2022, \u003cstrong\u003e13\u003c/strong\u003e:959379.\u003c/li\u003e\n\u003cli\u003eBecker T, Elbahesh H, Reperant LA, Rimmelzwaan GF, Osterhaus ADME: \u003cstrong\u003eInfluenza Vaccines: Successes and Continuing Challenges\u003c/strong\u003e. \u003cem\u003eThe Journal of Infectious Diseases \u003c/em\u003e2021, \u003cstrong\u003e224\u003c/strong\u003e(Supplement_4):S405-S419.\u003c/li\u003e\n\u003cli\u003eMcCullers JA: \u003cstrong\u003eThe co-pathogenesis of influenza viruses with bacteria in the lung\u003c/strong\u003e. \u003cem\u003eNature Reviews Microbiology \u003c/em\u003e2014, \u003cstrong\u003e12\u003c/strong\u003e(4):252-262.\u003c/li\u003e\n\u003cli\u003eLalbiaktluangi C, Yadav MK, Singh PK, Singh A, Iyer M, Vellingiri B, Zomuansangi R, Zothanpuia, Ram H: \u003cstrong\u003eA cooperativity between virus and bacteria during respiratory infections\u003c/strong\u003e. \u003cem\u003eFront Microbiol \u003c/em\u003e2023, \u003cstrong\u003e14\u003c/strong\u003e:1279159.\u003c/li\u003e\n\u003cli\u003eKlomp M, Ghosh S, Mohammed S, Nadeem Khan M: \u003cstrong\u003eFrom virus to inflammation, how influenza promotes lung damage\u003c/strong\u003e. \u003cem\u003eJournal of Leukocyte Biology \u003c/em\u003e2021, \u003cstrong\u003e110\u003c/strong\u003e(1):115-122.\u003c/li\u003e\n\u003cli\u003eSumitomo T, Kawabata S: \u003cstrong\u003eRespiratory tract barrier dysfunction in viral-bacterial co-infection cases\u003c/strong\u003e. \u003cem\u003eJapanese Dental Science Review \u003c/em\u003e2024, \u003cstrong\u003e60\u003c/strong\u003e:44-52.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the supplementary files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Influenza vaccine, Children, Community-acquired influenza, Disease severity, Hospitalization, Retrospective cohort","lastPublishedDoi":"10.21203/rs.3.rs-8466942/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8466942/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChildren are highly susceptible to influenza and face significant risks when infected, which makes vaccination a vital preventive measure. Still, there is limited real-world evidence, particularly from community-based studies, on whether the vaccine can reduce disease severity in children once they are diagnosed.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective cohort study enrolled 388 children aged 6 months to 6 years diagnosed with influenza at the Longdong Community Health Service Center of Shenzhen Longgang Central Hospital between May 15, 2024, and October 16, 2025. Participants were categorized into vaccinated (n\u0026thinsp;=\u0026thinsp;196) and unvaccinated (n\u0026thinsp;=\u0026thinsp;192) groups based on vaccination history within the preceding year. Differences in clinical presentation, laboratory findings, healthcare resource utilization, and clinical outcomes were compared between the groups. Continuous variables were analyzed using the t-test or Mann-Whitney U test, and categorical variables were analyzed using the chi-square test.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCompared to the unvaccinated group, vaccinated children had a lower body temperature (38.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u0026deg;C vs 39.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u0026deg;C), a shorter time to fever resolution (2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21 days vs 2.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.55 days), and lower incidences of myalgia (5.61% vs. 17.19%) and gastrointestinal symptoms (9.69% v. 20.83%) (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Regarding medical outcomes, the vaccinated group had fewer outpatient visits (1.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82 vs.1.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91), lower outpatient costs (349.42\u0026thinsp;\u0026plusmn;\u0026thinsp;201.23 vs 407.41\u0026thinsp;\u0026plusmn;\u0026thinsp;337.44; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04), and lower rates of hospitalization (4.1% vs 21.9%) and antibiotic use (5.6% vs. 15.1%) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eAmong community-dwelling children, while influenza vaccination may not completely prevent infection, it can alleviate clinical symptoms of breakthrough infections, reduce the risk of hospitalization and antibiotic use, and decrease healthcare burden.\u003c/p\u003e","manuscriptTitle":"Influenza Vaccination and Protective Effectiveness Against Influenza Illness in Community‑Dwelling Children: A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-14 13:58:16","doi":"10.21203/rs.3.rs-8466942/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e3229825-cadb-486f-99da-ee1e503e4e0d","owner":[],"postedDate":"January 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-11T14:12:45+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-14 13:58:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8466942","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8466942","identity":"rs-8466942","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}