Longitudinal Analysis of Respiratory Syncytial Virus in Children During and After COVID-19 Pandemic: Shifts in Seasonality and Disease Burden

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Methods In this hospital-based surveillance study, 21,744 children hospitalized with acute respiratory infections (ARI) were enrolled. RSV was detected via RT-PCR across three phases: pre-pandemic (2017–2019), NPIs implementation (2020–2022), and post-NPIs (2023–2024). Results RSV positivity varied significantly between phases ( p < 0.001), peaking at 37.83% (751/1,985) in 2021. Seasonal peaks shifted from winter (pre-pandemic) to spring (post-NPIs). The disease burden shifted toward infants aged 7–12 months (38.46%, 845/2,197 vs. 20.45%, 200/978 pre-pandemic; p < 0.001). Notably, mechanical ventilation was required in 8.00% (4/50) and 5.71% (2/35) of severe pneumonia cases aged 13–36 months during Phases II and III, respectively, whereas no cases were recorded pre-pandemic (0/14; p = 0.85). Conclusion NPIs fundamentally reshaped RSV epidemiology, inducing seasonal shifts and redirecting disease burden toward older infants experiencing delayed primary infection due to "immune debt." RSV COVID-19 epidemiology seasonality surveillance children immune debt Figures Figure 1 Figure 2 Figure 3 1 Background Respiratory Syncytial Virus (RSV) remains a significant public health concern due to its high transmissibility, particularly as a leading cause of morbidity and mortality among infants aged 1 month to 1 year [ 1 ]. Globally, RSV is estimated to cause 248 million annual cases of acute lower respiratory tract infections and 76,600 deaths in children under 5 years [ 2 ], imposing substantial disease burden on both young children and older adults (≥ 65 years) [ 2 ]. Respiratory viruses typically exhibit distinct seasonal patterns influenced by geographic regions and climatic conditions [ 3 ]. In temperate zones, viral respiratory infections peak during winter with reduced activity in summer [ 4 ]. The COVID-19 pandemic and associated non-pharmaceutical interventions (NPIs) have profoundly altered the epidemiology of common respiratory infections [ 5 ]. Measures to control SARS-CoV-2 transmission, combined with potential viral interference, have driven significant global declines in common respiratory infections [ 6 ]. However, as restrictions eased, respiratory viruses have demonstrated heterogeneous resurgence patterns [ 7 ]. These epidemiological shifts indicate that pandemic-induced behavioral modifications and interventions have fundamentally reshaped respiratory pathogen transmission dynamics. Crucially, current studies predominantly assess short-term NPI effects, lacking longitudinal observations on RSV epidemiological evolution post-policy adjustment. Accurate estimation of pediatric RSV incidence is essential for quantifying regional clinical/economic burdens and identifying populations benefiting from RSV therapeutics or prophylaxis. This study aims to quantify NPI-driven shifts in RSV seasonality and age-specific disease burden through longitudinal surveillance (2017–2024), with emphasis on implications for 'immune debt'. 2 Materials and methods 2.1 Study Population and Design This hospital-based cross-sectional study analyzed epidemiological data from children presenting with respiratory illnesses at Ganzhou Maternal and Child Health Hospital between January 2017 and December 2024. The investigation focused on patients with primary diagnosis of RSV infection, with study protocol approved by the Institutional Ethics Committee of Ganzhou Maternal and Child Health Hospital (Approval No:240127). Eligibility criteria included: 1) Hospitalized children < 18 years with pneumonia diagnosis; 2) Availability of RSV real-time polymerase chain reaction (PCR) test results. Exclusion criteria comprised: 1) Children with severe congenital anomalies (e.g., congenital heart disease, immunodeficiency disorders); 2) Patients with malignancy diagnoses or those receiving immunosuppressive therapy during hospitalization. Clinico-demographic variables included admission date, visit date, length of hospitalization, age, sex, clinical manifestations, and primary diagnosis. Disease classification followed International Classification of Diseases, Tenth Revision (ICD-10) criteria. Nasopharyngeal specimens were collected within 24 hours of admission using standardized viral transport media and processed for pathogen detection within 24 hours of collection. Age was categorized as: 0–3, 4–6, 7–12, 13–36, 37–72, and 73–180 months. Seasonal variation was analyzed using meteorological definitions: spring (March-May), summer (June-August), autumn (September-November), and winter (December-February). To assess pandemic impacts, the study period was divided into three phases based on China's COVID-19 policy adjustments: pre-pandemic (Phase I: 2017–2019), NPIs implementation (Phase II: 2020–2022), and post-NPIs (Phase III: 2023–2024). 2.2 Specimen Collection and Detection RSV RNA was detected using a real-time qRT-PCR assay, targeting the conserved N gene. The assay was performed with the integrated Daan Gene kit (Guangzhou, China), which combines sample preparation, nucleic acid extraction, and amplification steps. Manufacturer validation indicates a sensitivity of 95% and specificity of 99%. Samples with cycle threshold values < 26 were defined as positive. The kit incorporates both a sample processing control and a probe inspection control to monitor sample processing adequacy and detect potential PCR inhibitors. Amplification and fluorescence detection were conducted on a Lepgen real-time PCR instrument (China) using specific primers and fluorescent probes. Results were determined by real-time monitoring of fluorescence signal changes during amplification. 2.3 Statistical Analysis Statistical analyses were performed using SPSS (version 26.0; IBM Corp.). RSV positive rates were calculated for the overall cohort and for age-stratified subgroups defined by gender, season, and the three distinct COVID-19 pandemic phases. Continuous variables (e.g., age, hospital length of stay) are presented as median and interquartile range [M (P25, P75)]. Categorical variables (e.g., gender, age group, season) are expressed as frequencies and percentages. Group comparisons employed the Kruskal-Wallis rank test for continuous variables and the Chi-squared test for categorical variables; a two-tailed P-value < 0.05 defined statistical significance. Temporal trends were analyzed using Joinpoint Regression (version 5.0.2; National Cancer Institute), with permutation tests to determine optimal joinpoints. Trends were quantified by calculating the annual percent change (APC) and associated 95% confidence interval (CI). 3 Result 3.1 Demographic characteristics of patients From January 2017 to December 2024, 21,744 children hospitalized with acute respiratory tract infections (ARTIs) were enrolled. RSV infection was confirmed in 4,819 cases, yielding an overall positivity rate of 22.16%. The median age of RSV-positive children was 8 months (IQR: 4–12 months), with a male predominance (male-to-female ratio: 1.86:1, 3,133/1,686). Following the COVID-19 outbreak, significant phase-dependent variations were observed in both annual ARTI hospitalization rates and RSV positivity rates (Table 1 ). Phase III had significantly higher mean annual ARTI hospitalizations compared to both Phase I and Phase II. RSV positivity rates differed substantially across phases (χ² = 86.78, p < 0.001). A significant increasing trend was observed from 2017 to 2021 (annual percent change [APC] = + 19.46%, p < 0.001), peaking at 37.83% (751/1,985) in 2021. Subsequently, a significant declining trend occurred (APC = -23.26%, p < 0.001; Fig. 1 ). Furthermore, age-specific analysis revealed marked differences in RSV positivity (χ2 = 563.79, p < 0.001). The vast majority (94.55%; 4,556/4,819) of RSV cases occurred in children under 36 months of age, with infants under 12 months accounting for 73.03% (3,519/4,819). The highest positivity rate was observed in the 4–6 months age group (27.8%, 816/2847), followed by a monotonic decrease with advancing age. Finally, no significant difference in RSV positivity rate was observed between males (22.36%, 3,133/14,012) and females (21.81%, 1.686/7.732; p > 0.05). Table 1 Demographic characteristics of paediatric patients with common respiratory infectious diseases. Category ARTI n = 21,744 (%) RSV n = 4,819 (%) Positive rate(%) H/χ2 p Male 14,012 (64.44) 3,133 (65.02) 22.36 0.89 0.35 Female 7,732 (35.56) 1,686 (34.98) 21.81 Phase I (SD) 1,642(104) 326(111) 19.85 86.78 <0.001 Phase II (SD) 1,853(364) 548(179) 29.57 Phase III (SD) 5,629(1035) 1099(234) 19.52 < 4 months 4,814 (22.14) 1,298 (26.94) 26.96 563.79 <0.001 4–6 months 2,847 (13.09) 816 (16.93) 28.66 7–12 months 5,914 (27.20) 1,405 (29.16) 23.76 13–36 months 4,790 (22.03) 1,037 (21.52) 21.65 37–72 months 2,436 (11.20) 232 (4.81) 9.52 73–180 months 943 (4.34) 31 (0.64) 3.29 3.2 Seasonal and Peak Pattern Evolution of RSV RSV seasonality exhibited significant phase-dependent variations (Fig. 2 ). Phase I was characterized by a typical winter peak (Dec-Feb). The highest positivity rate was observed in winter 2018 (43.22%, 376/870). Notably, the winter RSV positivity rate demonstrated a significant decreasing trend during this phase (Annual Percent Change [APC] = -39.38%, p = 0.02), while Summer (Jun-Aug) rates remained low. Phase II displayed a disrupted seasonal pattern. A significant seasonality joinpoint occurred in 2019, triggering an autumn (Sep-Nov) 2020 shift to anomalous "low winter/high summer" pattern. Summer positivity surged significantly (2017–2021: APC = + 68.91%), peaking at 57.30% (357/623) in summer 2021 the highest rate observed in the study. This inverted pattern followed a spring (Mar-May) 2020 joinpoint marking the onset of rising summer trends (2020–2021: APC = + 60.65%). Phase III exhibited spring-peak dominance. Spring 2023 reached 38.25% (757/1,979), significantly exceeding Phase I spring rates ( p < 0.01). Winter rates rebounded after a 2022 joinpoint (2022–2024: APC = + 53.14%), while summer rates declined sharply (2021–2024: APC = -43.36%). Autumn showed relative stability (2019–2024: APC = -0.14%). Overall, the seasonal peak of RSV incidence sequentially shifted across phases. Initiating in winter (Phase I), transitioning to summer (Phase II), and ultimately establishing in spring (Phase III). Correspondingly, winter positivity declined significantly (AAPC = -21.01%, 95% CI: -39.82 to -10.80, p < 0.001) while spring positivity increased (AAPC = + 13.27%, 95% CI: -13.81 to 47.92) across the study period. 3.3 Age Stratification and Disease Severity in RSV Infections Across Pandemic Phases Significant phase-dependent restructuring of the age distribution among RSV-positive children was observed (χ²=304.09, p < 0.001; Fig. 3 A), characterized by three distinct patterns: 1. A progressive decrease in infants aged < 4 months (phase I: 39.16%, 383/978; phase II: 28.16%, 463/1644; phase III: 20.57%, 452/2197; p < 0.001). 2. A significant increase in the proportion of infants aged 7–12 months, which became predominant in phase III (38.46%, 845/2197) compared to phase I (20.45%, 200/978) and phase II (21.90%,360/1644; p < 0.001). 3. A transient peak in children aged 13–36 months during phase II (27.98%, 460/1644 vs. 15.13%, 148/978 in phase I and 19.53% (429/2197) in phase III; p < 0.001). Concurrently, progression to severe pneumonia showed no phase-dependent variation for 4-6-month ( p = 0.25) or 37–72 months groups ( p = 0.69), though 4–6 months severe cases exhibited significantly prolonged hospitalization in Phase III (median 19 days vs. 14 days in both Phase I [ p = 0.007] and Phase II [ p = 0.023]; Fig. 3 C). Further analysis revealed divergent mechanical ventilation trajectories: Infants < 4 months showed a numerical decrease from 39.29%(11/28)in phase I to 20.59%(7/34) in phase III ( p = 0.26). Infants aged 4–6 months consistently had the highest numerical rates across phases (phase I: 43.33%, 13/30; phase III: 31.37%, 16/51; p = 0.56). Children aged 13–36 months had no need for ventilation in phase I, but exhibited low rates (8%, 4/50) in phases II and III ( p = 0.85). 4 Discussion This study demonstrates the impact of COVID-19 NPIs on the epidemic characteristics and seasonality of Respiratory Syncytial Virus (RSV) among hospitalized children at the Maternal and Child Health Hospital of Ganzhou from 2017 to 2024. NPIs significantly altered the seasonal epidemic pattern of RSV, resulting in enhanced transmission during non-epidemic seasons. Prior to NPI implementation, RSV in the Ganzhou region exhibited a typical winter epidemic peak. NPIs markedly disrupted this pattern, consistent with observations in countries like Japan [ 7 ] and Italy [ 8 ] where summer-autumn peaks replaced winter peaks. The characteristic reversal in 2020 (winter trough-summer peak), culminating in the peak positivity rate (57.3%) in summer 2021, indicates that stringent NPIs effectively suppressed winter RSV transmission. This suppression resulted in an accumulation of population susceptibility, termed "immunity debt" [ 9 ], triggering an explosive off-season epidemic peak upon NPI relaxation [ 10 , 11 ]. Furthermore, a study in Southwest China [ 12 ] suggested a potential competitive suppression dynamic between RSV and influenza viruses. The synchronous suppression of influenza by NPIs may have conferred a seasonal transmission advantage to RSV. Viral evolution also likely contributed to atypical transmission. A P376S mutation in the F protein emerged within the RSV-A subtype circulating during NPIs, potentially enhancing viral membrane fusion efficiency and immune evasion capabilities [ 13 ]. This mutation could underlie the anomalous off-season transmission observed in Phase II (summer 2021 peak), although validation through more comprehensive regional genomic surveillance is required [ 14 ]. In the post-NPI period, the RSV positivity rate in 2023 (25.81%), while lower than the Phase II peak, remained significantly elevated above the pre-pandemic baseline, indicating persistently elevated transmission. Rebuilding population immunity may have partially mitigated this resurgence [ 15 ]. Throughout the study period, the RSV seasonal peak progressively shifted earlier: from winter in Phase I, to autumn (2020) and summer (2021) in Phase II, and stabilizing in spring (2023–2024) during Phase III. These findings suggest that a multi-year "recalibration period" is required for the restoration of baseline seasonal patterns, highlighting the necessity for prolonged RSV surveillance. Consequently, extending immunoprophylaxis strategies to cover the spring season is a critical priority for high-risk infant populations [ 16 ]. Significant shifts in the age distribution of RSV-infected patients across phases reflect transformations in the immunological landscape. The proportion of infants aged < 4 months decreased substantially from 39.16% in Phase I to 28.16% in Phase II and 20.57% in Phase III. Concurrently, older infants (particularly 7–12 months) experienced an "immune debt" due to the lack of natural infection during NPIs. This resulted in this group becoming the primary drivers of infection in Phase III (constituting 38.46%), strongly supporting the "immune debt" hypothesis [ 17 ]. Furthermore, differences in disease severity across age groups reveal complex interactions between immune maturity and prior viral exposure history. For infants < 4 months, the mechanical ventilation rate decreased from 39.29% in Phase I to 20.59% in Phase III, potentially attributable to improved prevention and treatment strategies for high-risk groups [ 18 , 19 ]. Conversely, infants aged 4–6 months in Phase III exhibited prolonged hospital stays, suggesting underlying pathophysiological alterations; for instance, activation of the Wnt-CstF64-MRJ signaling axis might extend tissue repair cycles [ 20 ]. Of particular note, the mechanical ventilation rate for severe pneumonia among toddlers aged 13–36 months increased to 8% in Phase II. As "immunologically naïve" individuals whose first RSV exposure was delayed by NPIs, their primary infection may result in higher viral loads and more severe lower respiratory tract disease [ 11 ], warranting consideration for expanded monoclonal antibody coverage in this age group to prevent severe outcomes [ 21 ]. This heightened severity aligns with reports that among otherwise healthy young children (< 5 years) with RSV requiring mechanical ventilation, a substantial proportion (up to 87%) present with non-bronchiolitis complications [ 22 ], a phenotype potentially amplified in populations experiencing delayed first exposure due to an immune debt. The single-hospital design of this study may underestimate the true community-level transmission intensity. Furthermore, the lack of systematic viral genotyping data limits our ability to perform in-depth analysis of the transmission dynamics and pathogenicity of specific strains. 5 Conclusion NPIs shifted RSV epidemics in Ganzhou from winter to spring and redirected disease burden toward infants aged 7–12 months. We recommend extending immunoprophylaxis to cover spring seasons and enhancing surveillance for older infants with delayed primary infections. Declarations Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author Contributions QYG drafted this manuscript. GHL performed the analysis. ZYL collected the raw data. GZL conducted Conception. The authors have accepted responsibility for the entire content of this manuscript and approved its submission. Funding This study was supported by the Ganzhou Guiding Science and Technology Program under grant number GZ2024YLJ208. Acknowledgments We thank all the participating patients and their families, as well as the clinical staff involved in patient care and sample collection. Clinical trial number Not applicable. Ethics approval and consent to participate This study protocol was reviewed and approved by the Institutional Ethics Committee of Ganzhou Maternal and Child Health Hospital (Approval No: 240127). Consent for publication All authors (Qiying Gu, Guihua Lai, Zhiyong Lai, Guanzhen Lai) have read and approved the final version of this manuscript and consent to its publication. Acknowledgements We thank all the participating patients and their families, as well as the clinical staff involved in patient care and sample collection. References Shi T, McLean K, Campbell H, Nair H. Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta-analysis. Journal of global health. 2015;5(1):010408.https://doi.org/10.7189/jogh.05.010408 Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Infectious diseases. 2018;18(11):1191-210.https://doi.org/10.1016/s1473-3099(18)30310-4 Loconsole D, Centrone F, Aprile V, Sallustio A, Casulli D, Accogli M, et al. What's Next for Flu? Out-of-Season Circulation of Influenza Viruses in Southern Italy, August 2022. Viruses. 2022;14(12).https://doi.org/10.3390/v14122689 Li Y, Reeves RM, Wang X, Bassat Q, Brooks WA, Cohen C, et al. Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis. The Lancet Global Health. 2019;7(8):e1031-e45.https://doi.org/10.1016/S2214-109X(19)30264-5 Mansuy JM, Bourcier M, Trémeaux P, Dimeglio C, Izopet J. COVID-19 pandemic period, where are the seasonal viruses? Journal of medical virology. 2021;93(7):4097-8.https://doi.org/10.1002/jmv.26959 Nickbakhsh S, Mair C, Matthews L, Reeve R, Johnson PCD, Thorburn F, et al. Virus-virus interactions impact the population dynamics of influenza and the common cold. Proceedings of the National Academy of Sciences of the United States of America. 2019;116(52):27142-50.https://doi.org/10.1073/pnas.1911083116 Fukuda Y, Togashi A, Hirakawa S, Yamamoto M, Fukumura S, Nawa T, et al. Changing Patterns of Infectious Diseases Among Hospitalized Children in Hokkaido, Japan, in the Post-COVID-19 Era, July 2019 to June 2022. The Pediatric infectious disease journal. 2023;42(9):766-73.https://doi.org/10.1097/inf.0000000000003982 Graziani A, Bozza S, Borghi M, Mencacci A, Camilloni B. Circulation and Seasonality of Respiratory Viruses in Hospitalized Patients during Five Consecutive Years (2019-2023) in Perugia, Italy. Viruses. 2024;16(9).https://doi.org/10.3390/v16091394 Piliper EA, Reed JC, Greninger AL. Clinical validation of an RSV neutralization assay and analysis of cross-sectional sera associated with 2021-2023 RSV outbreaks to investigate the immunity debt hypothesis. Microbiology spectrum. 2024;12(12):e0211524.https://doi.org/10.1128/spectrum.02115-24 Dreßen S, Schneider J, Doenhardt M, Diffloth N, Tenenbaum T, Schneider DT, et al. Persistently high burden of acute respiratory infections requiring hospitalization in German pediatric hospitals, fall/winter 2023-2024. Infection. 2025;53(2):717-25.https://doi.org/10.1007/s15010-025-02494-z Guerrero-Del-Cueto F, Lobato-Lopez S, Lozano-Duran D, Sanchez-Duran B, Ramirez-Martin L, Esteban-San-Narciso B, et al. Assessing the Impact of Nirsevimab Immunization on RSV Bronchiolitis Hospital Admissions and Their Severity: A Case-Control Study and Comparison With Pre- and Post-COVID-19 Seasons in a Tertiary Pediatric Hospital. Pediatric pulmonology. 2025;60(7):e71059.https://doi.org/10.1002/ppul.71059 Yang R, Xu H, Zhang Z, Liu Q, Zhao R, Zheng G, et al. The Epidemiology of Pathogens in Community-Acquired Pneumonia Among Children in Southwest China Before, During and After COVID-19 Non-pharmaceutical Interventions: A Cross-Sectional Study. Influenza and other respiratory viruses. 2024;18(8):e13361.https://doi.org/10.1111/irv.13361 Tamim S, Trovao NS, Paoli J, Ahad A, Badar N, Aamir UB, et al. Evolutionary trajectory and spread of respiratory syncytial virus group A in neonatal cohorts in Pakistan amidst the COVID-19 pandemic. Scientific reports. 2025;15(1):27329.https://doi.org/10.1038/s41598-025-87332-w Aziz F, Farooqui N, Abbas T, Javaid M, Rafaqat W, Zhamalbekova A, et al. Phylogenetic and phylodynamic analysis of respiratory syncytial virus strains circulating in children less than five years of age in Karachi-Pakistan. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2024;126:105694.https://doi.org/10.1016/j.meegid.2024.105694 Yang MC, Su YT, Chen PH, Tsai CC, Lin TI, Wu JR. Changing patterns of infectious diseases in children during the COVID-19 pandemic. Frontiers in cellular and infection microbiology. 2023;13:1200617.https://doi.org/10.3389/fcimb.2023.1200617 Langedijk AC, Bont LJ. Respiratory syncytial virus infection and novel interventions. Nature reviews Microbiology. 2023;21(11):734-49.https://doi.org/10.1038/s41579-023-00919-w James A, McGregor R, Lorenz N, Moreland NJ, Moyers-Gonzalez M. Modelling immunity gaps to quantify infection resurgences. Royal Society open science. 2025;12(7):250030.https://doi.org/10.1098/rsos.250030 Kalin JH, Yin Y, Tran MT, Piassek M, Fung A, Grosse S, et al. Discovery of a non-nucleoside inhibitor that binds to a novel site in the palm domain of the respiratory syncytial virus RNA-dependent RNA polymerase. Journal of virology. 2025;99(7):e0017825.https://doi.org/10.1128/jvi.00178-25 Zar HJ. New advances in RSV: Is prevention attainable? Pediatric pulmonology. 2025;60 Suppl 1(Suppl 1):S120-s2.https://doi.org/10.1002/ppul.27310 Lu CY, Lai PY, Huang JM, Chang LY, Yen TY, Tarn WY, et al. Dual targeting of the Wnt and DNAJB6/MRJ regulatory loop as an anti-RSV strategy. Virology. 2025;611:110641.https://doi.org/10.1016/j.virol.2025.110641 Garegnani L, Roson Rodriguez P, Escobar Liquitay CM, Esteban I, Franco JV. Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children. The Cochrane database of systematic reviews. 2025;7(7):Cd013757.https://doi.org/10.1002/14651858.CD013757.pub3 Nygaard U, Hartling UB, Nielsen J, Vestergaard LS, Dungu KHS, Nielsen JSA, et al. Hospital admissions and need for mechanical ventilation in children with respiratory syncytial virus before and during the COVID-19 pandemic: a Danish nationwide cohort study. The Lancet Child & adolescent health. 2023;7(3):171-9.https://doi.org/10.1016/s2352-4642(22)00371-6 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 17 Oct, 2025 Reviews received at journal 15 Oct, 2025 Reviewers agreed at journal 06 Oct, 2025 Reviews received at journal 01 Oct, 2025 Reviewers agreed at journal 01 Oct, 2025 Reviewers invited by journal 11 Sep, 2025 Editor assigned by journal 11 Sep, 2025 Submission checks completed at journal 08 Sep, 2025 First submitted to journal 03 Sep, 2025 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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09:26:06","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":79121,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7525392/v1/90f356a6d1ac183e0db91be6.html"},{"id":91834395,"identity":"7ce34525-fca7-4e31-8735-e963e6f02221","added_by":"auto","created_at":"2025-09-22 09:26:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":518877,"visible":true,"origin":"","legend":"\u003cp\u003eThe trend of RSV incidence in Ganzhou, China from 2017 to 2024.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7525392/v1/756e66efaa86cb96fbec770c.png"},{"id":91834256,"identity":"0b2dff81-a9a5-4faa-9bff-428cf3ab00fa","added_by":"auto","created_at":"2025-09-22 09:25:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":138380,"visible":true,"origin":"","legend":"\u003cp\u003eSeasonal Trends in RSV Positivity Rate, 2017-2024. (Seasons: Spring, Mar-May; Summer, Jun-Aug; Autumn, Sep-Nov; Winter, Dec-Feb)\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7525392/v1/b1be1c2eb77896022b9204b5.png"},{"id":91834253,"identity":"721ec75b-86fb-4069-a7d2-93690b06b399","added_by":"auto","created_at":"2025-09-22 09:25:56","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":242227,"visible":true,"origin":"","legend":"\u003cp\u003eAge-Stratified Epidemiological Features of RSV Infections Over 8 Years.\u003c/p\u003e\n\u003cp\u003e(A) Age distribution of RSV-infected children across pandemic phases. (B) Proportion and cases of severe pneumonia among RSV-positive children by age group. (C) Hospitalization duration for severe RSV-associated pneumonia by age group. (D) Proportion and cases requiring mechanical ventilation in severe pneumonia patients by age group.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7525392/v1/95ae431bbd216daff65d2ec6.png"},{"id":91834515,"identity":"c96d9add-a835-4d57-9e2c-20b79f684771","added_by":"auto","created_at":"2025-09-22 09:26:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1178087,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7525392/v1/534219e8-e296-478b-afcf-9ba1df570b4e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Longitudinal Analysis of Respiratory Syncytial Virus in Children During and After COVID-19 Pandemic: Shifts in Seasonality and Disease Burden","fulltext":[{"header":"1 Background","content":"\u003cp\u003eRespiratory Syncytial Virus (RSV) remains a significant public health concern due to its high transmissibility, particularly as a leading cause of morbidity and mortality among infants aged 1 month to 1 year [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Globally, RSV is estimated to cause 248\u0026nbsp;million annual cases of acute lower respiratory tract infections and 76,600 deaths in children under 5 years [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], imposing substantial disease burden on both young children and older adults (\u0026ge;\u0026thinsp;65 years) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Respiratory viruses typically exhibit distinct seasonal patterns influenced by geographic regions and climatic conditions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In temperate zones, viral respiratory infections peak during winter with reduced activity in summer [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe COVID-19 pandemic and associated non-pharmaceutical interventions (NPIs) have profoundly altered the epidemiology of common respiratory infections [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Measures to control SARS-CoV-2 transmission, combined with potential viral interference, have driven significant global declines in common respiratory infections [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, as restrictions eased, respiratory viruses have demonstrated heterogeneous resurgence patterns [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These epidemiological shifts indicate that pandemic-induced behavioral modifications and interventions have fundamentally reshaped respiratory pathogen transmission dynamics. Crucially, current studies predominantly assess short-term NPI effects, lacking longitudinal observations on RSV epidemiological evolution post-policy adjustment. Accurate estimation of pediatric RSV incidence is essential for quantifying regional clinical/economic burdens and identifying populations benefiting from RSV therapeutics or prophylaxis. This study aims to quantify NPI-driven shifts in RSV seasonality and age-specific disease burden through longitudinal surveillance (2017\u0026ndash;2024), with emphasis on implications for 'immune debt'.\u003c/p\u003e"},{"header":"2 Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Study Population and Design\u003c/h2\u003e\u003cp\u003eThis hospital-based cross-sectional study analyzed epidemiological data from children presenting with respiratory illnesses at Ganzhou Maternal and Child Health Hospital between January 2017 and December 2024. The investigation focused on patients with primary diagnosis of RSV infection, with study protocol approved by the Institutional Ethics Committee of Ganzhou Maternal and Child Health Hospital (Approval No:240127). Eligibility criteria included: 1) Hospitalized children\u0026thinsp;\u0026lt;\u0026thinsp;18 years with pneumonia diagnosis; 2) Availability of RSV real-time polymerase chain reaction (PCR) test results. Exclusion criteria comprised: 1) Children with severe congenital anomalies (e.g., congenital heart disease, immunodeficiency disorders); 2) Patients with malignancy diagnoses or those receiving immunosuppressive therapy during hospitalization. Clinico-demographic variables included admission date, visit date, length of hospitalization, age, sex, clinical manifestations, and primary diagnosis. Disease classification followed International Classification of Diseases, Tenth Revision (ICD-10) criteria. Nasopharyngeal specimens were collected within 24 hours of admission using standardized viral transport media and processed for pathogen detection within 24 hours of collection. Age was categorized as: 0\u0026ndash;3, 4\u0026ndash;6, 7\u0026ndash;12, 13\u0026ndash;36, 37\u0026ndash;72, and 73\u0026ndash;180 months. Seasonal variation was analyzed using meteorological definitions: spring (March-May), summer (June-August), autumn (September-November), and winter (December-February). To assess pandemic impacts, the study period was divided into three phases based on China's COVID-19 policy adjustments: pre-pandemic (Phase I: 2017\u0026ndash;2019), NPIs implementation (Phase II: 2020\u0026ndash;2022), and post-NPIs (Phase III: 2023\u0026ndash;2024).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Specimen Collection and Detection\u003c/h2\u003e\u003cp\u003eRSV RNA was detected using a real-time qRT-PCR assay, targeting the conserved N gene. The assay was performed with the integrated Daan Gene kit (Guangzhou, China), which combines sample preparation, nucleic acid extraction, and amplification steps. Manufacturer validation indicates a sensitivity of 95% and specificity of 99%. Samples with cycle threshold values\u0026thinsp;\u0026lt;\u0026thinsp;26 were defined as positive. The kit incorporates both a sample processing control and a probe inspection control to monitor sample processing adequacy and detect potential PCR inhibitors. Amplification and fluorescence detection were conducted on a Lepgen real-time PCR instrument (China) using specific primers and fluorescent probes. Results were determined by real-time monitoring of fluorescence signal changes during amplification.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Statistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were performed using SPSS (version 26.0; IBM Corp.). RSV positive rates were calculated for the overall cohort and for age-stratified subgroups defined by gender, season, and the three distinct COVID-19 pandemic phases. Continuous variables (e.g., age, hospital length of stay) are presented as median and interquartile range [M (P25, P75)]. Categorical variables (e.g., gender, age group, season) are expressed as frequencies and percentages. Group comparisons employed the Kruskal-Wallis rank test for continuous variables and the Chi-squared test for categorical variables; a two-tailed P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 defined statistical significance. Temporal trends were analyzed using Joinpoint Regression (version 5.0.2; National Cancer Institute), with permutation tests to determine optimal joinpoints. Trends were quantified by calculating the annual percent change (APC) and associated 95% confidence interval (CI).\u003c/p\u003e\u003c/div\u003e"},{"header":"3 Result","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Demographic characteristics of patients\u003c/h2\u003e\u003cp\u003eFrom January 2017 to December 2024, 21,744 children hospitalized with acute respiratory tract infections (ARTIs) were enrolled. RSV infection was confirmed in 4,819 cases, yielding an overall positivity rate of 22.16%. The median age of RSV-positive children was 8 months (IQR: 4\u0026ndash;12 months), with a male predominance (male-to-female ratio: 1.86:1, 3,133/1,686). Following the COVID-19 outbreak, significant phase-dependent variations were observed in both annual ARTI hospitalization rates and RSV positivity rates (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Phase III had significantly higher mean annual ARTI hospitalizations compared to both Phase I and Phase II. RSV positivity rates differed substantially across phases (χ\u0026sup2; = 86.78, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). A significant increasing trend was observed from 2017 to 2021 (annual percent change [APC]\u0026thinsp;=\u0026thinsp;+\u0026thinsp;19.46%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), peaking at 37.83% (751/1,985) in 2021. Subsequently, a significant declining trend occurred (APC = -23.26%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Furthermore, age-specific analysis revealed marked differences in RSV positivity (χ2\u0026thinsp;=\u0026thinsp;563.79, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The vast majority (94.55%; 4,556/4,819) of RSV cases occurred in children under 36 months of age, with infants under 12 months accounting for 73.03% (3,519/4,819). The highest positivity rate was observed in the 4\u0026ndash;6 months age group (27.8%, 816/2847), followed by a monotonic decrease with advancing age. Finally, no significant difference in RSV positivity rate was observed between males (22.36%, 3,133/14,012) and females (21.81%, 1.686/7.732; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic characteristics of paediatric patients with common respiratory infectious diseases.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCategory\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eARTI\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;21,744 (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRSV\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;4,819 (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePositive rate(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eH/χ2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14,012 (64.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3,133 (65.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e22.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7,732 (35.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,686 (34.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e21.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhase I (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,642(104)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e326(111)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e19.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e86.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhase II (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,853(364)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e548(179)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e29.57\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhase III (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5,629(1035)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1099(234)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e19.52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;4 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,814 (22.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,298 (26.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e26.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e\u003cp\u003e563.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"5\" rowspan=\"6\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u0026ndash;6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,847 (13.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e816 (16.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e28.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u0026ndash;12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5,914 (27.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,405 (29.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e23.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13\u0026ndash;36 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,790 (22.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,037 (21.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e21.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e37\u0026ndash;72 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,436 (11.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e232 (4.81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e73\u0026ndash;180 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e943 (4.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (0.64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Seasonal and Peak Pattern Evolution of RSV\u003c/h2\u003e\u003cp\u003eRSV seasonality exhibited significant phase-dependent variations (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Phase I was characterized by a typical winter peak (Dec-Feb). The highest positivity rate was observed in winter 2018 (43.22%, 376/870). Notably, the winter RSV positivity rate demonstrated a significant decreasing trend during this phase (Annual Percent Change [APC] = -39.38%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02), while Summer (Jun-Aug) rates remained low. Phase II displayed a disrupted seasonal pattern. A significant seasonality joinpoint occurred in 2019, triggering an autumn (Sep-Nov) 2020 shift to anomalous \"low winter/high summer\" pattern. Summer positivity surged significantly (2017\u0026ndash;2021: APC\u0026thinsp;=\u0026thinsp;+\u0026thinsp;68.91%), peaking at 57.30% (357/623) in summer 2021 the highest rate observed in the study. This inverted pattern followed a spring (Mar-May) 2020 joinpoint marking the onset of rising summer trends (2020\u0026ndash;2021: APC\u0026thinsp;=\u0026thinsp;+\u0026thinsp;60.65%).\u003c/p\u003e\u003cp\u003ePhase III exhibited spring-peak dominance. Spring 2023 reached 38.25% (757/1,979), significantly exceeding Phase I spring rates ( \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Winter rates rebounded after a 2022 joinpoint (2022\u0026ndash;2024: APC\u0026thinsp;=\u0026thinsp;+\u0026thinsp;53.14%), while summer rates declined sharply (2021\u0026ndash;2024: APC = -43.36%). Autumn showed relative stability (2019\u0026ndash;2024: APC = -0.14%). Overall, the seasonal peak of RSV incidence sequentially shifted across phases. Initiating in winter (Phase I), transitioning to summer (Phase II), and ultimately establishing in spring (Phase III). Correspondingly, winter positivity declined significantly (AAPC = -21.01%, 95% CI: -39.82 to -10.80, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) while spring positivity increased (AAPC\u0026thinsp;=\u0026thinsp;+\u0026thinsp;13.27%, 95% CI: -13.81 to 47.92) across the study period.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Age Stratification and Disease Severity in RSV Infections Across Pandemic Phases\u003c/h2\u003e\u003cp\u003eSignificant phase-dependent restructuring of the age distribution among RSV-positive children was observed (χ\u0026sup2;=304.09, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA), characterized by three distinct patterns: 1. A progressive decrease in infants aged\u0026thinsp;\u0026lt;\u0026thinsp;4 months (phase I: 39.16%, 383/978; phase II: 28.16%, 463/1644; phase III: 20.57%, 452/2197; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). 2. A significant increase in the proportion of infants aged 7\u0026ndash;12 months, which became predominant in phase III (38.46%, 845/2197) compared to phase I (20.45%, 200/978) and phase II (21.90%,360/1644; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). 3. A transient peak in children aged 13\u0026ndash;36 months during phase II (27.98%, 460/1644 vs. 15.13%, 148/978 in phase I and 19.53% (429/2197) in phase III; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Concurrently, progression to severe pneumonia showed no phase-dependent variation for 4-6-month (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.25) or 37\u0026ndash;72 months groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.69), though 4\u0026ndash;6 months severe cases exhibited significantly prolonged hospitalization in Phase III (median 19 days vs. 14 days in both Phase I [\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007] and Phase II [\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023]; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). Further analysis revealed divergent mechanical ventilation trajectories: Infants\u0026thinsp;\u0026lt;\u0026thinsp;4 months showed a numerical decrease from 39.29%(11/28)in phase I to 20.59%(7/34) in phase III (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.26). Infants aged 4\u0026ndash;6 months consistently had the highest numerical rates across phases (phase I: 43.33%, 13/30; phase III: 31.37%, 16/51;\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.56). Children aged 13\u0026ndash;36 months had no need for ventilation in phase I, but exhibited low rates (8%, 4/50) in phases II and III (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.85).\u003c/p\u003e\u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThis study demonstrates the impact of COVID-19 NPIs on the epidemic characteristics and seasonality of Respiratory Syncytial Virus (RSV) among hospitalized children at the Maternal and Child Health Hospital of Ganzhou from 2017 to 2024.\u003c/p\u003e\u003cp\u003eNPIs significantly altered the seasonal epidemic pattern of RSV, resulting in enhanced transmission during non-epidemic seasons. Prior to NPI implementation, RSV in the Ganzhou region exhibited a typical winter epidemic peak. NPIs markedly disrupted this pattern, consistent with observations in countries like Japan [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and Italy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] where summer-autumn peaks replaced winter peaks. The characteristic reversal in 2020 (winter trough-summer peak), culminating in the peak positivity rate (57.3%) in summer 2021, indicates that stringent NPIs effectively suppressed winter RSV transmission. This suppression resulted in an accumulation of population susceptibility, termed \"immunity debt\" [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], triggering an explosive off-season epidemic peak upon NPI relaxation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, a study in Southwest China [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] suggested a potential competitive suppression dynamic between RSV and influenza viruses. The synchronous suppression of influenza by NPIs may have conferred a seasonal transmission advantage to RSV. Viral evolution also likely contributed to atypical transmission. A P376S mutation in the F protein emerged within the RSV-A subtype circulating during NPIs, potentially enhancing viral membrane fusion efficiency and immune evasion capabilities [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This mutation could underlie the anomalous off-season transmission observed in Phase II (summer 2021 peak), although validation through more comprehensive regional genomic surveillance is required [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the post-NPI period, the RSV positivity rate in 2023 (25.81%), while lower than the Phase II peak, remained significantly elevated above the pre-pandemic baseline, indicating persistently elevated transmission. Rebuilding population immunity may have partially mitigated this resurgence [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Throughout the study period, the RSV seasonal peak progressively shifted earlier: from winter in Phase I, to autumn (2020) and summer (2021) in Phase II, and stabilizing in spring (2023\u0026ndash;2024) during Phase III. These findings suggest that a multi-year \"recalibration period\" is required for the restoration of baseline seasonal patterns, highlighting the necessity for prolonged RSV surveillance. Consequently, extending immunoprophylaxis strategies to cover the spring season is a critical priority for high-risk infant populations [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSignificant shifts in the age distribution of RSV-infected patients across phases reflect transformations in the immunological landscape. The proportion of infants aged\u0026thinsp;\u0026lt;\u0026thinsp;4 months decreased substantially from 39.16% in Phase I to 28.16% in Phase II and 20.57% in Phase III. Concurrently, older infants (particularly 7\u0026ndash;12 months) experienced an \"immune debt\" due to the lack of natural infection during NPIs. This resulted in this group becoming the primary drivers of infection in Phase III (constituting 38.46%), strongly supporting the \"immune debt\" hypothesis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFurthermore, differences in disease severity across age groups reveal complex interactions between immune maturity and prior viral exposure history. For infants\u0026thinsp;\u0026lt;\u0026thinsp;4 months, the mechanical ventilation rate decreased from 39.29% in Phase I to 20.59% in Phase III, potentially attributable to improved prevention and treatment strategies for high-risk groups [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Conversely, infants aged 4\u0026ndash;6 months in Phase III exhibited prolonged hospital stays, suggesting underlying pathophysiological alterations; for instance, activation of the Wnt-CstF64-MRJ signaling axis might extend tissue repair cycles [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Of particular note, the mechanical ventilation rate for severe pneumonia among toddlers aged 13\u0026ndash;36 months increased to 8% in Phase II. As \"immunologically na\u0026iuml;ve\" individuals whose first RSV exposure was delayed by NPIs, their primary infection may result in higher viral loads and more severe lower respiratory tract disease [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], warranting consideration for expanded monoclonal antibody coverage in this age group to prevent severe outcomes [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. This heightened severity aligns with reports that among otherwise healthy young children (\u0026lt;\u0026thinsp;5 years) with RSV requiring mechanical ventilation, a substantial proportion (up to 87%) present with non-bronchiolitis complications [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], a phenotype potentially amplified in populations experiencing delayed first exposure due to an immune debt.\u003c/p\u003e\u003cp\u003eThe single-hospital design of this study may underestimate the true community-level transmission intensity. Furthermore, the lack of systematic viral genotyping data limits our ability to perform in-depth analysis of the transmission dynamics and pathogenicity of specific strains.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eNPIs shifted RSV epidemics in Ganzhou from winter to spring and redirected disease burden toward infants aged 7\u0026ndash;12 months. We recommend extending immunoprophylaxis to cover spring seasons and enhancing surveillance for older infants with delayed primary infections.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQYG drafted this manuscript. \u0026nbsp;GHL performed the analysis. \u0026nbsp;ZYL collected the raw data. \u0026nbsp;GZL conducted Conception. \u0026nbsp;The authors have accepted responsibility for the entire content of this manuscript and approved its submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Ganzhou Guiding Science and Technology Program under grant number GZ2024YLJ208.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the participating patients and their families, as well as the clinical staff involved in patient care and sample collection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study protocol was reviewed and approved by the Institutional Ethics Committee of Ganzhou Maternal and Child Health Hospital (Approval No: 240127).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors (Qiying Gu, Guihua Lai, Zhiyong Lai, Guanzhen Lai) have read and approved the final version of this manuscript and consent to its publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the participating patients and their families, as well as the clinical staff involved in patient care and sample collection.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShi T, McLean K, Campbell H, Nair H. Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta-analysis. Journal of global health. 2015;5(1):010408.https://doi.org/10.7189/jogh.05.010408\u003c/li\u003e\n\u003cli\u003eEstimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Infectious diseases. 2018;18(11):1191-210.https://doi.org/10.1016/s1473-3099(18)30310-4\u003c/li\u003e\n\u003cli\u003eLoconsole D, Centrone F, Aprile V, Sallustio A, Casulli D, Accogli M, et al. What\u0026apos;s Next for Flu? Out-of-Season Circulation of Influenza Viruses in Southern Italy, August 2022. Viruses. 2022;14(12).https://doi.org/10.3390/v14122689\u003c/li\u003e\n\u003cli\u003eLi Y, Reeves RM, Wang X, Bassat Q, Brooks WA, Cohen C, et al. Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis. The Lancet Global Health. 2019;7(8):e1031-e45.https://doi.org/10.1016/S2214-109X(19)30264-5\u003c/li\u003e\n\u003cli\u003eMansuy JM, Bourcier M, Tr\u0026eacute;meaux P, Dimeglio C, Izopet J. COVID-19 pandemic period, where are the seasonal viruses? Journal of medical virology. 2021;93(7):4097-8.https://doi.org/10.1002/jmv.26959\u003c/li\u003e\n\u003cli\u003eNickbakhsh S, Mair C, Matthews L, Reeve R, Johnson PCD, Thorburn F, et al. Virus-virus interactions impact the population dynamics of influenza and the common cold. Proceedings of the National Academy of Sciences of the United States of America. 2019;116(52):27142-50.https://doi.org/10.1073/pnas.1911083116\u003c/li\u003e\n\u003cli\u003eFukuda Y, Togashi A, Hirakawa S, Yamamoto M, Fukumura S, Nawa T, et al. Changing Patterns of Infectious Diseases Among Hospitalized Children in Hokkaido, Japan, in the Post-COVID-19 Era, July 2019 to June 2022. The Pediatric infectious disease journal. 2023;42(9):766-73.https://doi.org/10.1097/inf.0000000000003982\u003c/li\u003e\n\u003cli\u003eGraziani A, Bozza S, Borghi M, Mencacci A, Camilloni B. Circulation and Seasonality of Respiratory Viruses in Hospitalized Patients during Five Consecutive Years (2019-2023) in Perugia, Italy. Viruses. 2024;16(9).https://doi.org/10.3390/v16091394\u003c/li\u003e\n\u003cli\u003ePiliper EA, Reed JC, Greninger AL. Clinical validation of an RSV neutralization assay and analysis of cross-sectional sera associated with 2021-2023 RSV outbreaks to investigate the immunity debt hypothesis. Microbiology spectrum. 2024;12(12):e0211524.https://doi.org/10.1128/spectrum.02115-24\u003c/li\u003e\n\u003cli\u003eDre\u0026szlig;en S, Schneider J, Doenhardt M, Diffloth N, Tenenbaum T, Schneider DT, et al. Persistently high burden of acute respiratory infections requiring hospitalization in German pediatric hospitals, fall/winter 2023-2024. Infection. 2025;53(2):717-25.https://doi.org/10.1007/s15010-025-02494-z\u003c/li\u003e\n\u003cli\u003eGuerrero-Del-Cueto F, Lobato-Lopez S, Lozano-Duran D, Sanchez-Duran B, Ramirez-Martin L, Esteban-San-Narciso B, et al. Assessing the Impact of Nirsevimab Immunization on RSV Bronchiolitis Hospital Admissions and Their Severity: A Case-Control Study and Comparison With Pre- and Post-COVID-19 Seasons in a Tertiary Pediatric Hospital. Pediatric pulmonology. 2025;60(7):e71059.https://doi.org/10.1002/ppul.71059\u003c/li\u003e\n\u003cli\u003eYang R, Xu H, Zhang Z, Liu Q, Zhao R, Zheng G, et al. The Epidemiology of Pathogens in Community-Acquired Pneumonia Among Children in Southwest China Before, During and After COVID-19 Non-pharmaceutical Interventions: A Cross-Sectional Study. Influenza and other respiratory viruses. 2024;18(8):e13361.https://doi.org/10.1111/irv.13361\u003c/li\u003e\n\u003cli\u003eTamim S, Trovao NS, Paoli J, Ahad A, Badar N, Aamir UB, et al. Evolutionary trajectory and spread of respiratory syncytial virus group A in neonatal cohorts in Pakistan amidst the COVID-19 pandemic. Scientific reports. 2025;15(1):27329.https://doi.org/10.1038/s41598-025-87332-w \u003c/li\u003e\n\u003cli\u003eAziz F, Farooqui N, Abbas T, Javaid M, Rafaqat W, Zhamalbekova A, et al. Phylogenetic and phylodynamic analysis of respiratory syncytial virus strains circulating in children less than five years of age in Karachi-Pakistan. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2024;126:105694.https://doi.org/10.1016/j.meegid.2024.105694\u003c/li\u003e\n\u003cli\u003eYang MC, Su YT, Chen PH, Tsai CC, Lin TI, Wu JR. Changing patterns of infectious diseases in children during the COVID-19 pandemic. Frontiers in cellular and infection microbiology. 2023;13:1200617.https://doi.org/10.3389/fcimb.2023.1200617\u003c/li\u003e\n\u003cli\u003eLangedijk AC, Bont LJ. Respiratory syncytial virus infection and novel interventions. Nature reviews Microbiology. 2023;21(11):734-49.https://doi.org/10.1038/s41579-023-00919-w\u003c/li\u003e\n\u003cli\u003eJames A, McGregor R, Lorenz N, Moreland NJ, Moyers-Gonzalez M. Modelling immunity gaps to quantify infection resurgences. Royal Society open science. 2025;12(7):250030.https://doi.org/10.1098/rsos.250030\u003c/li\u003e\n\u003cli\u003eKalin JH, Yin Y, Tran MT, Piassek M, Fung A, Grosse S, et al. Discovery of a non-nucleoside inhibitor that binds to a novel site in the palm domain of the respiratory syncytial virus RNA-dependent RNA polymerase. Journal of virology. 2025;99(7):e0017825.https://doi.org/10.1128/jvi.00178-25\u003c/li\u003e\n\u003cli\u003eZar HJ. New advances in RSV: Is prevention attainable? Pediatric pulmonology. 2025;60 Suppl 1(Suppl 1):S120-s2.https://doi.org/10.1002/ppul.27310\u003c/li\u003e\n\u003cli\u003eLu CY, Lai PY, Huang JM, Chang LY, Yen TY, Tarn WY, et al. Dual targeting of the Wnt and DNAJB6/MRJ regulatory loop as an anti-RSV strategy. Virology. 2025;611:110641.https://doi.org/10.1016/j.virol.2025.110641\u003c/li\u003e\n\u003cli\u003eGaregnani L, Roson Rodriguez P, Escobar Liquitay CM, Esteban I, Franco JV. Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children. The Cochrane database of systematic reviews. 2025;7(7):Cd013757.https://doi.org/10.1002/14651858.CD013757.pub3\u003c/li\u003e\n\u003cli\u003eNygaard U, Hartling UB, Nielsen J, Vestergaard LS, Dungu KHS, Nielsen JSA, et al. Hospital admissions and need for mechanical ventilation in children with respiratory syncytial virus before and during the COVID-19 pandemic: a Danish nationwide cohort study. The Lancet Child \u0026amp; adolescent health. 2023;7(3):171-9.https://doi.org/10.1016/s2352-4642(22)00371-6\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-epidemiology-and-global-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Epidemiology and Global Health](https://www.springer.com/journal/44197)","snPcode":"44197","submissionUrl":"https://submission.nature.com/new-submission/44197/3","title":"Journal of Epidemiology and Global Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"RSV, COVID-19, epidemiology, seasonality, surveillance, children, immune debt","lastPublishedDoi":"10.21203/rs.3.rs-7525392/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7525392/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eNon-pharmaceutical interventions (NPIs) against COVID-19 globally altered RSV seasonality, yet longitudinal evidence on age-specific severity changes remains scarce in China.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eIn this hospital-based surveillance study, 21,744 children hospitalized with acute respiratory infections (ARI) were enrolled. RSV was detected via RT-PCR across three phases: pre-pandemic (2017\u0026ndash;2019), NPIs implementation (2020\u0026ndash;2022), and post-NPIs (2023\u0026ndash;2024).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eRSV positivity varied significantly between phases (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), peaking at 37.83% (751/1,985) in 2021. Seasonal peaks shifted from winter (pre-pandemic) to spring (post-NPIs). The disease burden shifted toward infants aged 7\u0026ndash;12 months (38.46%, 845/2,197 vs. 20.45%, 200/978 pre-pandemic; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Notably, mechanical ventilation was required in 8.00% (4/50) and 5.71% (2/35) of severe pneumonia cases aged 13\u0026ndash;36 months during Phases II and III, respectively, whereas no cases were recorded pre-pandemic (0/14; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.85).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eNPIs fundamentally reshaped RSV epidemiology, inducing seasonal shifts and redirecting disease burden toward older infants experiencing delayed primary infection due to \"immune debt.\"\u003c/p\u003e","manuscriptTitle":"Longitudinal Analysis of Respiratory Syncytial Virus in Children During and After COVID-19 Pandemic: Shifts in Seasonality and Disease Burden","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 09:24:42","doi":"10.21203/rs.3.rs-7525392/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-17T11:15:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-15T20:36:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"5056941719027885273466693380466519036","date":"2025-10-06T07:38:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-01T13:00:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15203684156867213276947524184714325626","date":"2025-10-01T12:09:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-11T05:17:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-11T05:15:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-08T08:01:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Epidemiology and Global Health","date":"2025-09-03T09:27:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-epidemiology-and-global-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Epidemiology and Global Health](https://www.springer.com/journal/44197)","snPcode":"44197","submissionUrl":"https://submission.nature.com/new-submission/44197/3","title":"Journal of Epidemiology and Global Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1e766891-13cd-4e82-b38d-8f670750f244","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-05T10:54:01+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-22 09:24:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7525392","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7525392","identity":"rs-7525392","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}