Comparison of human metapneumovirus and Respiratory Syncytial Virus in children with acute lower respiratory infections in Wenzhou, China from 2021 to 2022: a retrospective study

Comparison of human metapneumovirus and Respiratory Syncytial Virus in children with acute lower respiratory infections in Wenzhou, China from 2021 to 2022: a retrospective 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 Comparison of human metapneumovirus and Respiratory Syncytial Virus in children with acute lower respiratory infections in Wenzhou, China from 2021 to 2022: a retrospective study Lili Zhu, Luyao Zeng, Manjun Zhang, Xinyu Chen, Yilin Li, Jian Yu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8501977/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 12 You are reading this latest preprint version Abstract Objective To compare the clinical characteristics of human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) infections in children hospitalized with acute lower respiratory infections (ALRI). Methods Children hospitalized with ALRI in Wenzhou, China from 2021 to 2022 were examined for HMPV and RSV in sputum or nasopharyngeal secretions by multiplex real-time quantitative polymerase chain reaction (PCR). Demographic data, clinical features, laboratory findings, and radiological characteristics were compared between HMPV group and RSV group. Results A total of 15,772 hospitalized children were screened and tested by multiplex PCR. 889 (5.6%) were HMPV-positive and 2,196 (13.9%) were RSV-positive. Compared with the RSV group, the HMPV group had a lower proportion of males (55.2% vs. 62.2%, P = 0.002), an older median age (2.5 years vs. 1.6 years, P < 0.001), and a higher proportion of underlying conditions (9.9% vs. 6.0%, P = 0.001). The HMPV group exhibited significantly longer duration of fever ( P < 0.001) and higher peak temperature ( P < 0.001) compared to the RSV group. In contrast, the RSV group were more likely to present with respiratory distress, including intercostal or subcostal retractions ( P = 0.006) and head bobbing respiration ( P = 0.032). Significantly higher levels in the HMPV group for C-reactive protein (14.18 mg/L vs. 7.80 mg/L, P < 0.001), neutrophil percentage (60.6% vs. 56.5%, P = 0.007), procalcitonin ( P = 0.001), and lactate dehydrogenase (422.0 U/L vs. 381.0 U/L, P < 0.001) than the RSV group. HMPV-infected children were more likely to exhibit patchy or linear opacities (71.5% vs. 65.1%, P = 0.016), pulmonary consolidation (4.1% vs. 2.1%, P = 0.047), and atelectasis (1.8% vs. 0%, P = 0.001) compared to the RSV-infected children. Conclusion In children hospitalized with ALRI, those infected with HMPV were more likely to be older, have underlying conditions, experience prolonged and higher-grade fever, demonstrate more pronounced systemic inflammatory responses, and prone to develop pulmonary consolidation and atelectasis compared with RSV-infected children. Human metapneumovirus Respiratory syncytial virus Acute lower respiratory tract infection Clinical characteristics Figures Figure 1 Figure 2 Introduction According to the Global Burden of Disease database, approximately 4.6 million children under five years of age died globally in 2023, with lower respiratory infections accounting for about 600,000 deaths, which is the second leading cause of mortality in this age group ( 1 ). Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are major respiratory viral pathogens responsible for acute lower respiratory infections (ALRI) in children ( 2 , 3 ). A global disease burden study encompassing 159 studies on HMPV infection estimated that, among children under five years old with ALRI, approximately 11.1 million cases annually are attributable to HMPV (8% of all ALRI cases), resulting in around 500,000 hospitalizations (3–10%) and over 10,000 deaths associated with HMPV-related ALRI ( 4 ). In comparison, RSV is estimated to cause 33.1 million ALRI episodes annually in children under five worldwide, leading to 3.2 million hospitalizations and more than 50,000 in-hospital deaths ( 5 ), imposing a substantial burden on global healthcare systems ( 6 ). HMPV is an enveloped, single-stranded, negative-sense RNA virus belonging to the subfamily Pneumovirinae, along with RSV. Children with HMPV infection typically present with upper respiratory tract symptoms such as fever, cough, nasal congestion, and rhinorrhea. In severe cases, it may progress to bronchiolitis or pneumonia, manifesting as wheezing and respiratory distress ( 7 ). These clinical features closely resemble those of RSV infection ( 8 ). However, some studies suggest that HMPV infection is associated with prolonged fever and a higher propensity to develop pneumonia compared to RSV ( 9 ). Therefore, to compare the clinical characteristics of HMPV- and RSV-associated ALRI among children. This retrospective study analyzed the epidemiological patterns and clinical features of hospitalized children with ALRI caused by either HMPV or RSV, aiming to provide a comprehensive description for these two viral infections in children in Wenzhou, China. Data from this study may benefit future recognize and prevention of HMPV and RSV infections in children. Methods 1.1 Study Design This study was a retrospective analysis. Children hospitalized with ALRI were categorized into either the HMPV group or the RSV group based on the results of respiratory pathogen nucleic acid detection by multiplex real-time quantitative polymerase chain reaction (RT-PCR). Propensity score matching (PSM) was applied to balance potential confounding variables between the two groups, including age, sex, preterm birth, and the presence of underlying conditions (e.g., asthma, congenital heart disease, airway malformations, neuromuscular disorders, and malnutrition). Clinical characteristics were subsequently compared between the matched cohorts. The study protocol was approved by the Ethics Committee of The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University (Approval No. 2021-K-224-02), with a waiver of informed consent from legal guardians. 1.2 Study Population The study population comprised children hospitalized for ALRI at The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University between January 1, 2021, and December 31, 2022. Inclusion criteria, ( 1 ) Children under the age of 18 years; ( 2 ) Diagnosis of ALRI according to established clinical criteria ( 10 ), defined as symptom duration less than 7 days; ( 3 ) Multiplex RT-PCR detection of HMPV or RSV nucleic acid in sputum or nasopharyngeal secretions. Exclusion criteria, ( 1 ) Co-infection with both RSV and HMPV; ( 2 ) Nosocomial respiratory infection; ( 3 ) Immunodeficiency or immunosuppression; ( 4 ) Severe missing data. 1.3 Respiratory Pathogen Detection Multiplex RT-PCR was used to detect nucleic acids of thirteen common respiratory pathogens in sputum or nasopharyngeal secretions, including influenza A, influenza A subtype H1N1, influenza A subtype H3N2, influenza B, parainfluenza virus, adenovirus, bocavirus, rhinovirus, HMPV, coronavirus (including OC43, 229E, NL63, and HKU1), RSV, Mycoplasma pneumoniae , and Chlamydia . Criteria for defining co-infections were based on the Handbook: Integrated Management of Childhood Illness ( 11 ) and the Clinical Guidelines for the Diagnosis and Management of Community-Acquired Pneumonia in Children (2019 edition) ( 12 ). Bacterial co-infection was defined as either a positive culture from bronchoalveolar lavage fluid, or a positive culture from sputum or nasopharyngeal secretions plus at least two of the following three criteria ( 10 , 13 ): ( 1 ) C-reactive protein (CRP) ≥ 40 mg/L; ( 2 ) Procalcitonin (PCT) ≥ 0.5 µg/L; ( 3 ) Both white blood cell count and neutrophil percentage exceeding the upper limit of normal reference values for the patient’s age. 1.4 Clinical Data Collection A standardized case report form was used to collect demographic and clinical information, including sex, age, clinical symptoms and signs, underlying conditions, laboratory findings, radiological features, and microbiological results. 1.5 Statistical Analysis Statistical analyses were performed using SPSS version 25.0. Continuous variables were assessed for normality, and normally distributed data were analyzed using analysis of variance (ANOVA), while non-normally distributed data were compared using the Mann-Whitney U test (or Wilcoxon rank-sum test). Categorical variables were analyzed using the Pearson χ² test or Fisher’s exact test, as appropriate. A two-sided P value < 0.05 was considered statistically significant. Results 2.1 Baseline Characteristics A total of 15,772 hospitalized children were examined at The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University between January 1, 2021, and December 31, 2022. Of these, 889 (5.6%) tested positive for HMPV and 2,196 (13.9%) tested positive for RSV. HMPV exhibited distinct seasonal peaks during the winter of 2021 and the spring-winter period of 2022, whereas RSV showed prominent circulation during the summer-autumn of 2021 and the autumn-winter of 2022. Notably, both viruses demonstrated a concurrent epidemic peak during the winter of 2022 (Fig. 1 ). 2,447 children hospitalized for ALRI were included in the analysis, 675 children with HMPV-positive ALRI in the HMPV group, and 1,772 children with RSV-positive ALRI in the RSV group. The HMPV group included 373 male patients (55.2%), with a median age of 2.5 years (interquartile range [IQR], 1.1–3.7), 70 preterm births (10.3%), and 67 children with underlying conditions (9.9%). In contrast, the RSV group comprised 1,103 male patients (62.2%), with a median age of 1.6 years (IQR, 0.6–2.9), 212 preterm births (11.9%), and 108 children with underlying conditions (6.0%). Compared with the RSV group, the HMPV group had a significantly lower proportion of males ( χ² = 9.969, P = 0.002), an older median age ( Z = 100, P < 0.001), and a higher proportion of underlying conditions ( χ² = 10.805, P = 0.001). PSM was performed to balance baseline characteristics between the two groups. A total of 597 matched pairs were successfully generated (Fig. 2 ). After matching, no statistically significant differences were observed between the HMPV and RSV groups in terms of sex, age, preterm birth, or presence of underlying conditions. Baseline characteristics before and after PSM are summarized in Table 1 . Table 1 Baseline Characteristics Before and After PSM Before PSM After PSM Baseline Characteristics HMPV (n = 675) RSV (n = 1772) P HMPV (n = 597) RSV (n = 597) P Male, n(%) 373(55.2%) 1103(62.2%) 0.002 357(59.7%) 364(60.9%) 0.679 Age (years), median (IQR) 2.5(1.1,3.7) 1.6(0.6,2.9) <0.001 2.0 (1.0, 3.4) 2.3 (0.7, 3.5) 0.244 Preterm birth, n(%) 70(10.3%) 212(11.9%) 0.27 62(10.3%) 63(10.5%) 0.925 Underlying conditions, n(%) 67(9.9%) 108(6.0%) 0.001 49(8.2%) 51(8.5%) 0.834 PSM, Propensity score matching; HMPV, Human metapneumovirus; RSV, Respiratory syncytial virus; IQR, interquartile rage; A p -value < 0.05 was considered statistically significant. 2.2 Comparative analysis of clinical manifestations between HMPV and RSV infection The predominant clinical symptoms among the enrolled children were cough (99.9%), fever (87.2%), and wheezing (56.9%). Compared with the RSV group, the HMPV group exhibited a significantly longer duration of fever ( Z = 33.804, P < 0.001) and higher peak body temperature ( Z = 46.450, P < 0.001). Children in the RSV group were more likely to present with signs of respiratory distress, intercostal or subcostal retractions occurred in 30.4% of RSV cases versus 23.4% in HMPV cases ( χ² = 7.501, P = 0.006), and head bobbing respiration was observed in 4.8% versus 2.5%, respectively ( χ² = 4.625, P = 0.032). For pulmonary auscultatory, the duration of fine-to-medium crackles was significantly longer in the HMPV group than in the RSV group ( Z = 7.36, P = 0.007), whereas the duration of wheezing was slightly shorter in the HMPV group compared to the RSV group ( Z = 5.512, P = 0.019) (Table 2 ). Table 2 Comparison of Clinical Features Between HMPV and RSV infection in Children Hospitalized with ALRI Clinical Features HMPV(n = 597) RSV(n = 597) P Fever (days), median (IQR) 4.0 (3.0, 6.0) 4.0 (1.0, 5.0) <0.001 Temperature (℃), median (IQR) 39.5 (39.0, 40.0) 39.1 (38.3, 39.8) <0.001 Laryngopharyngeal phlegm, n (%) 470 (78.7%) 483 (80.9%) 0.123 Wheezing (days), median (IQR) 1.0 (0.0, 6.0) 2.0 (2.0, 5.0) 0.571 Rhinorrhoea, n(%) 326 (54.6%) 339 (56.7%) 0.449 Decreased appetite, n(%) 139 (23.2%) 141 (23.6%) 0.891 Cyanosis, n(%) 10 (1.6%) 9 (1.5%) 0.817 Polypnea, n(%) 102 (17.0%) 102 (17.0%) 1.000 Retractions, n(%) 140 (23.4%) 182 (30.4%) 0.006 Nodding breathing, n(%) 15 (2.5%) 29 (4.8%) 0.032 Duration of fine-to-medium crackles (days), median (IQR) 2.0 (0.0, 3.0) 2.0 (0.0, 3.0) 0.007 Duration of wheezes (days), median (IQR) 2.0 (0.0, 3.0) 2.0 (0.0, 4.0) 0.019 HMPV, Human metapneumovirus; RSV, Respiratory syncytial virus; ALRI, Acute lower respiratory infections; IQR, interquartile rage; A p -value < 0.05 was considered statistically significant. No statistically significant difference was observed between the two groups in the proportion of severe pneumonia cases ( χ² = 0.049, P = 0.826). 2.3 Comparison of systemic inflammatory responses between HMPV and RSV infection There was no statistically significant difference in white blood cell (WBC) count between the two groups. However, children in the HMPV group exhibited significantly higher levels of CRP (14.18 mg/L vs. 7.80 mg/L; Z = 38.076, P < 0.001), neutrophil percentage (60.6% vs. 56.5%; Z = 7.207, P = 0.007), PCT ( Z = 10.949, P = 0.001) and LDH (422.0 U/L vs. 381.0 U/L; Z = 25.274, P < 0.001) compared to those in the RSV group. 2.4 Co-infection detection in two groups Co-infections were identified in 380 children (31.8%), with no significant difference between the HMPV and RSV groups ( χ² = 0.757, P = 0.384). Bacterial co-infections occurred in 98 cases (8.2%), including Streptococcus pneumoniae (42 cases, 3.5%), Haemophilus influenzae (36 cases, 3.0%), as well as Moraxella catarrhalis. Co-infection with Mycoplasma pneumoniae or Chlamydia was detected in 110 children (9.2%). Viral co-infections were present in 215 patients (18.0%), including rhinovirus (124 cases, 10.3%), adenovirus (43 cases, 3.6%), parainfluenza virus (26 cases, 2.1%), coronavirus (19 cases, 1.5%), bocavirus (12 cases, 1.0%), influenza B (8 cases, 0.6%), and influenza A (2 cases, 0.1%). Notably, the HMPV group had a higher proportion of co-infections with parainfluenza virus (3.0% vs. 1.3%; χ² = 3.932, P = 0.047) and coronavirus (2.3% vs. 0.8%; χ² = 4.332, P = 0.037) compared to the RSV group. 2.5 Comparison of radiological findings in HMPV and RSV infection Compared with the RSV group, children in the HMPV group showed significantly higher rates of patchy or linear opacities on chest imaging (71.5% vs. 65.1%; χ² = 5.803, P = 0.016), pulmonary consolidation (4.1% vs. 2.1%; χ² = 3.935, P = 0.047), and atelectasis (1.8% vs. 0%; χ² = 11.121, P = 0.001). Conversely, the RSV group more frequently exhibited increased and thickened bronchovascular markings bilaterally (32.6% vs. 24.1%; χ² = 10.599, P = 0.001). 2.6 Treatment and disease burden in HMPV and RSV infection Intravenous immunoglobulin (IVIG) was administered in 111 children (9.2%), and antimicrobial agents were used in 882 (73.8%). No significant differences in the utilization rates of either IVIG or antibiotics were observed between the RSV group and the HMPV group. However, the duration of systemic corticosteroid therapy was significantly longer in the RSV group compared to the HMPV group ( χ² = 9.412, P = 0.002). The median length of stay was 5.0 days (IQR, 4.0–6.0), with no significant difference between groups ( Z = 0.056, P = 0.814). Median hospitalization costs showed no statistically significant difference between two groups ( Z = 0.003, P = 0.956). Discussion This retrospective study comparatively analyzed the clinical features associated with HMPV and RSV infections among children hospitalized with ALRI in Wenzhou, China. Our findings indicate that, compared with RSV-infected children, those infected with HMPV were slightly older, more frequently had underlying conditions, experienced longer fever duration and higher peak temperatures, exhibited prolonged fine-to-medium crackles on pulmonary auscultation, demonstrated more pronounced systemic inflammatory responses (elevated CRP, neutrophil percentage, PCT and LDH), and were more prone to develop pulmonary consolidation and atelectasis. In contrast, RSV-infected children presented more commonly with signs of respiratory distress and had a longer duration of wheezing. In our cohort, the detection rate of HMPV among children with acute respiratory infections from 2021 to 2022 was 5.6%, with a median age of 2.5 years, and epidemic peaks occurred during winter 2021 and spring-winter 2022, which consistent with multiple studies ( 14 , 15 ). A multicenter retrospective study across 22 hospitals in southern China (2010–2019) reported an HMPV detection rate of 3.5% among children under 14 years with acute respiratory infections, predominantly affecting those under 5 years, with consistent springtime seasonal peaks over the decade ( 16 ). Another study conducted at the Capital Institute of Pediatrics (from August 2023 to December 2024) among 8,374 hospitalized children with acute respiratory infections found an HMPV positivity rate of 3.1%, primarily in children under 6 years ( 14 ). A prospective observational study involving six hospitals in Beijing, Wenzhou, Guangzhou, Yinchuan, and Guizhou (2017–2019) reported an HMPV detection rate of 5.3% among children with ALRI, with 67.6% under 2 years of age and a predilection for spring onset ( 15 ). Similarly, a recent multicenter prospective study of over 8,600 children across seven pediatric centers (from December 2016 to March 2020) identified HMPV activity peaking between March and April ( 17 ). Collectively, these data suggest that HMPV exhibits a consistent winter-spring seasonal pattern in both northern and southern China, predominantly affecting young children, with no substantial geographic variation. In our study, the RSV detection rate among children with acute respiratory infections during 2021–2022 was 13.9%, with a median age of 1.6 years, which significantly younger than HMPV cases. While RSV typically was prevalent in winter and early spring [16], we observed an atypical seasonal pattern that a prominent surge during summer and autumn 2021, followed by a decline in winter 2021, and a resurgence in autumn-winter 2022. Similar off-season RSV peaks were reported in Morocco during summer and autumn 2021 ( 18 ). This anomaly is likely attributable to the concurrent COVID-19 pandemic. Non-pharmaceutical interventions implemented during this period markedly reduced population-level exposure to RSV, leading to declined natural immunity. With relaxation of these measures, delayed or atypical seasonal epidemics emerged ( 19 ). Similarly, a 7-year Canadian cohort study (2017–2024) by Tiffany F. et al.( 20 ) demonstrated a sharp decline in pediatric respiratory infections during 2020–2021, gradual recovery in 2021–2022, and a significant rebound in RSV and HMPV burden in 2022–2023, with seasonal patterns largely returning to pre-pandemic norms by 2023–2024. Notably, post-pandemic hospitalized children with acute respiratory infections were older and exhibited a lower male predominance, while direct impacts of COVID-19-related hospitalizations on overall ALRI admissions appeared minimal. Global surveillance data further confirm that since 2022, HMPV and RSV have re-established typical seasonal circulation in most regions following the pandemic ( 21 ), indicating that their epidemiology is influenced not only by climate and human behavior but also potentially by viral interference or interactions. Clinically, HMPV infection typically presents with fever, cough, rhinorrhea, and tachypnea, and severe cases may progress to bronchiolitis, severe pneumonia, or acute respiratory distress syndrome, symptoms overlapping considerably with RSV, leading to clinical differentiation challenging ( 14 , 15 ). In our cohort, the primary diagnosis for both HMPV and RSV ALRI was pneumonia, followed by bronchiolitis and bronchitis, consistent with prior reports ( 22 ). No significant differences were observed in the incidence of severe pneumonia or the severity of acute bronchiolitis between the two viruses. However, HMPV-infected children had a higher prevalence of underlying conditions (9.9% vs. 6.0%), aligning with recent large-scale multicenter prospective data ( 17 ), suggesting HMPV may preferentially affect children with preexisting conditions. Compared to RSV, HMPV-associated ALRI was characterized by longer fever duration, higher peak temperature, prolonged fine-to-medium crackles, and more robust systemic inflammation, evidenced by significantly elevated CRP, neutrophil percentage, PCT, and LDH. Radiologically, HMPV cases more frequently exhibited pulmonary consolidation and atelectasis, a finding corroborated by a multicenter prospective study ( 17 ), which indicating greater parenchymal involvement and systemic inflammatory response. This may reflect HMPV’s propensity for causing substantial lung injury. Ciliated respiratory epithelium serves as the primary target for HMPV following initial infection, the virus disseminates within airway cells and demonstrates enhanced replication capacity in the lower versus upper respiratory tract ( 23 ). LDH, a marker of endothelial and cellular membrane damage, is released upon injury and catalyzes pyruvate-to-lactate conversion, thereby promoting activation of macrophages and dendritic cells. Although HMPV and RSV share structural similarities, HMPV lacks two nonstructural proteins present in RSV that suppress interferon signaling. Whole-blood RNA sequencing analysis using DESeq2 by Samoriski et al.( 24 ) identified 197 differentially expressed genes between HMPV- and RSV-infected individuals. HMPV infection was associated with upregulation of genes involved in antigen binding, immunoglobulin production, and adaptive immunity, whereas RSV infection showed stronger expression of genes linked to natural killer T-cell pathways. These findings suggest distinct immunopathogenic mechanisms despite virological similarities, warranting further mechanistic investigation. Co-infections were detected in 31.8% of our patients, including 18.0% with additional viral pathogens. HMPV-infected children were more likely to co-harbor parainfluenza virus (3.0% vs. 1.3%) and coronavirus (2.3% vs. 0.8%) than RSV-infected children. Bacterial co-infection occurred in 8.2% of cases, predominantly Streptococcus pneumoniae and Haemophilus influenzae. Nevertheless, antibiotic use was remarkably high at 73.8%. This discrepancy mirrors findings by Papenburg J. et al. ( 25 ), who reported ~ 70% antibiotic administration in virally infected children despite low bacterial co-detection rates, likely due to pre-hospital antibiotic use reducing culture yield or clinical misattribution of viral symptoms to bacterial etiology. We should focus on identifying more sensitive biomarkers to guide rational antibiotic stewardship in future. The limitations of this study including it was a single-center retrospective analysis, so it may not fully represent regional epidemiology. We did not analyze viral load in relation to disease severity and explore underlying immunological mechanisms between HMPV and RSV infections. A long-term follow-up to evaluate outcomes and prognosis was not assessed in this study. Future research will address these gaps to provide stronger evidence for the pathogenesis, prevention, and management of HMPV and RSV infections. Conclusion In children hospitalized with ALRI, those infected with HMPV were more likely to be older, have underlying conditions, experience prolonged and higher-grade fever, demonstrate more pronounced systemic inflammatory responses, and prone to develop pulmonary consolidation and atelectasis compared with RSV-infected children. Abbreviations HMPV, Human metapneumovirus RSV, Respiratory syncytial virus ALRI, Acute lower respiratory infections RT-PCR, Real-time quantitative polymerase chain reaction PSM, Propensity score matching CRP, C-reactive protein PCT, Procalcitonin IQR, interquartile range LDH, dehydrogenase IVIG, Intravenous immunoglobulin Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University (Approval No. 2021-K-224-02). This study is a retrospective study with a waiver of informed consent from legal guardians. Consent for publication Not applicable. Availability for data and materials The datasets are available from the corresponding author on reasonable request. Competing Interests All authors declare that they have no relevant financial or non-financial interests to disclose. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author’s Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Manjun Zhang, Xinyu Chen, Yilin Li, Jian Yu and Shunhang Wen. The first draft of the manuscript was written by Lili Zhu and Luyao Zeng. All authors read and approved the final manuscript. Acknowledgements We thank the Laboratory Medicine of the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University for providing the data. References Infections GBDLR, Antimicrobial Resistance C. Global burden of lower respiratory infections and aetiologies, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet Infect Dis. 2025. Esposito S, Mastrolia MV. Metapneumovirus Infections and Respiratory Complications. Semin Respir Crit Care Med. 2016;37(4):512–21. 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Billard M-N, Wildenbeest JG, Braas O, Schneijdenberg R, Rodgers-Gray B, Fullarton J et al. P-2338. Global surveillance of human Metapneumovirus (hMPV) and Respiratory Syncytial Virus (RSV) epidemiology since 2022. Open Forum Infect Dis. 2025;12(Supplement_1). Howard LM, Edwards KM, Zhu Y, Griffin MR, Weinberg GA, Szilagyi PG, et al. Clinical Features of Human Metapneumovirus Infection in Ambulatory Children Aged 5–13 Years. J Pediatr Infect Dis Soc. 2018;7(2):165–8. Kuiken T, van den Hoogen BG, van Riel DA, Laman JD, van Amerongen G, Sprong L, et al. Experimental human metapneumovirus infection of cynomolgus macaques (Macaca fascicularis) results in virus replication in ciliated epithelial cells and pneumocytes with associated lesions throughout the respiratory tract. Am J Pathol. 2004;164(6):1893–900. Samoriski C, Chu CY, Falsey AR, Peterson D, Bhattacharya S, Croft DP, et al. Clinical Features and Gene Expression Patterns in Adults Hospitalized With Respiratory Syncytial Virus and Human Metapneumovirus Infection. J Infect Dis. 2025;232(Supplement1):S37–46. Papenburg J, Hamelin ME, Ouhoummane N, Carbonneau J, Ouakki M, Raymond F, et al. Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children. J Infect Dis. 2012;206(2):178–89. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 05 Mar, 2026 Reviews received at journal 22 Feb, 2026 Reviewers agreed at journal 13 Feb, 2026 Reviews received at journal 12 Feb, 2026 Reviews received at journal 10 Feb, 2026 Reviewers agreed at journal 08 Feb, 2026 Reviewers agreed at journal 29 Jan, 2026 Reviewers invited by journal 29 Jan, 2026 Editor invited by journal 05 Jan, 2026 Editor assigned by journal 04 Jan, 2026 Submission checks completed at journal 04 Jan, 2026 First submitted to journal 02 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Luyao","middleName":"","lastName":"Zeng","suffix":""},{"id":582535565,"identity":"c943efe1-f8f8-4f62-a109-f68ec541aca5","order_by":2,"name":"Manjun Zhang","email":"","orcid":"","institution":"The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Manjun","middleName":"","lastName":"Zhang","suffix":""},{"id":582535566,"identity":"754586b9-64ba-4c43-bc99-4e69babe645c","order_by":3,"name":"Xinyu Chen","email":"","orcid":"","institution":"The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xinyu","middleName":"","lastName":"Chen","suffix":""},{"id":582535567,"identity":"21007bb6-75cf-4513-ae3c-20df7a36ce78","order_by":4,"name":"Yilin Li","email":"","orcid":"","institution":"The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yilin","middleName":"","lastName":"Li","suffix":""},{"id":582535568,"identity":"2828f6c7-9a73-4c85-943d-78fede65d719","order_by":5,"name":"Jian Yu","email":"","orcid":"","institution":"The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Yu","suffix":""},{"id":582535569,"identity":"54feb863-6c0d-4af3-80e0-ae8d14d8c8cb","order_by":6,"name":"Shunhang Wen","email":"","orcid":"","institution":"The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shunhang","middleName":"","lastName":"Wen","suffix":""},{"id":582535570,"identity":"f128292d-1cb5-48d2-8855-db9402a910e7","order_by":7,"name":"Hailin Zhang","email":"","orcid":"","institution":"The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hailin","middleName":"","lastName":"Zhang","suffix":""},{"id":582535573,"identity":"807d9868-29d9-4694-9862-09c28b110a93","order_by":8,"name":"Gang Yu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYPACGwYGCSD1gOEA0VrSIFoSEojXcpgELQY30i9+Lvh1PnH+7OaDHxJ/3GHgb+9OIKAlp1h6Zt/txMY5x5IlEhKeMUicObuBkJYEad6e27nNEjkGQC2HGQwkcglqSf7N23Mut00i//MPIrWkH5Pm+XEgt0cih404WyTPvGGz5m1Irp8hkWZmkZB2mIegX/iOpz++zfPHzlh+RvLjGx9sDsvxt/fi16JwgMeAgbENIcCDVzkIyDewP2Bg+ENQ3SgYBaNgFIxkAAClnFGB5K7XowAAAABJRU5ErkJggg==","orcid":"","institution":"The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Gang","middleName":"","lastName":"Yu","suffix":""}],"badges":[],"createdAt":"2026-01-02 15:38:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8501977/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8501977/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101786771,"identity":"521147c0-963a-4ad7-a1f2-1bea0cb78819","added_by":"auto","created_at":"2026-02-03 15:42:30","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":93336,"visible":true,"origin":"","legend":"\u003cp\u003eDetection trends of human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) from 2021 to 2022\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8501977/v1/a6ce892e9ad2e9c956ba1a1d.jpg"},{"id":101786691,"identity":"b681c3fe-8566-49b8-a000-bfcdbc1d15ed","added_by":"auto","created_at":"2026-02-03 15:42:24","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":132732,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study and enrolled patients\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8501977/v1/c736c48da505ee8f081293cd.jpg"},{"id":101786779,"identity":"f3121e5c-1267-45f1-aa59-b61379e6eb8e","added_by":"auto","created_at":"2026-02-03 15:42:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1025683,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8501977/v1/9287c8f2-cd31-4c2a-8d55-54b5106cd3e6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of human metapneumovirus and Respiratory Syncytial Virus in children with acute lower respiratory infections in Wenzhou, China from 2021 to 2022: a retrospective study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to the Global Burden of Disease database, approximately 4.6\u0026nbsp;million children under five years of age died globally in 2023, with lower respiratory infections accounting for about 600,000 deaths, which is the second leading cause of mortality in this age group (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are major respiratory viral pathogens responsible for acute lower respiratory infections (ALRI) in children (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA global disease burden study encompassing 159 studies on HMPV infection estimated that, among children under five years old with ALRI, approximately 11.1\u0026nbsp;million cases annually are attributable to HMPV (8% of all ALRI cases), resulting in around 500,000 hospitalizations (3\u0026ndash;10%) and over 10,000 deaths associated with HMPV-related ALRI (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In comparison, RSV is estimated to cause 33.1\u0026nbsp;million ALRI episodes annually in children under five worldwide, leading to 3.2\u0026nbsp;million hospitalizations and more than 50,000 in-hospital deaths (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), imposing a substantial burden on global healthcare systems (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHMPV is an enveloped, single-stranded, negative-sense RNA virus belonging to the subfamily Pneumovirinae, along with RSV. Children with HMPV infection typically present with upper respiratory tract symptoms such as fever, cough, nasal congestion, and rhinorrhea. In severe cases, it may progress to bronchiolitis or pneumonia, manifesting as wheezing and respiratory distress (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). These clinical features closely resemble those of RSV infection (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). However, some studies suggest that HMPV infection is associated with prolonged fever and a higher propensity to develop pneumonia compared to RSV (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTherefore, to compare the clinical characteristics of HMPV- and RSV-associated ALRI among children. This retrospective study analyzed the epidemiological patterns and clinical features of hospitalized children with ALRI caused by either HMPV or RSV, aiming to provide a comprehensive description for these two viral infections in children in Wenzhou, China. Data from this study may benefit future recognize and prevention of HMPV and RSV infections in children.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1.1 Study Design\u003c/h2\u003e \u003cp\u003eThis study was a retrospective analysis. Children hospitalized with ALRI were categorized into either the HMPV group or the RSV group based on the results of respiratory pathogen nucleic acid detection by multiplex real-time quantitative polymerase chain reaction (RT-PCR). Propensity score matching (PSM) was applied to balance potential confounding variables between the two groups, including age, sex, preterm birth, and the presence of underlying conditions (e.g., asthma, congenital heart disease, airway malformations, neuromuscular disorders, and malnutrition). Clinical characteristics were subsequently compared between the matched cohorts. The study protocol was approved by the Ethics Committee of \u003cem\u003eThe Second Affiliated Hospital \u0026amp; Yuying Children\u0026rsquo;s Hospital of Wenzhou Medical University\u003c/em\u003e (Approval No. 2021-K-224-02), with a waiver of informed consent from legal guardians.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e1.2 Study Population\u003c/h2\u003e \u003cp\u003eThe study population comprised children hospitalized for ALRI at \u003cem\u003eThe Second Affiliated Hospital \u0026amp; Yuying Children\u0026rsquo;s Hospital of Wenzhou Medical University\u003c/em\u003e between January 1, 2021, and December 31, 2022.\u003c/p\u003e \u003cp\u003eInclusion criteria,\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Children under the age of 18 years;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Diagnosis of ALRI according to established clinical criteria (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), defined as symptom duration less than 7 days;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Multiplex RT-PCR detection of HMPV or RSV nucleic acid in sputum or nasopharyngeal secretions.\u003c/p\u003e \u003cp\u003eExclusion criteria,\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Co-infection with both RSV and HMPV;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Nosocomial respiratory infection;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Immunodeficiency or immunosuppression;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Severe missing data.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e1.3 Respiratory Pathogen Detection\u003c/h2\u003e \u003cp\u003eMultiplex RT-PCR was used to detect nucleic acids of thirteen common respiratory pathogens in sputum or nasopharyngeal secretions, including influenza A, influenza A subtype H1N1, influenza A subtype H3N2, influenza B, parainfluenza virus, adenovirus, bocavirus, rhinovirus, HMPV, coronavirus (including OC43, 229E, NL63, and HKU1), RSV, \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e, and \u003cem\u003eChlamydia\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eCriteria for defining co-infections were based on the Handbook: Integrated Management of Childhood Illness (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) and the Clinical Guidelines for the Diagnosis and Management of Community-Acquired Pneumonia in Children (2019 edition) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Bacterial co-infection was defined as either a positive culture from bronchoalveolar lavage fluid, or a positive culture from sputum or nasopharyngeal secretions plus at least two of the following three criteria (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e):\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) C-reactive protein (CRP)\u0026thinsp;\u0026ge;\u0026thinsp;40 mg/L;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Procalcitonin (PCT)\u0026thinsp;\u0026ge;\u0026thinsp;0.5 \u0026micro;g/L;\u003c/p\u003e \u003cp\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Both white blood cell count and neutrophil percentage exceeding the upper limit of normal reference values for the patient\u0026rsquo;s age.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e1.4 Clinical Data Collection\u003c/h2\u003e \u003cp\u003eA standardized case report form was used to collect demographic and clinical information, including sex, age, clinical symptoms and signs, underlying conditions, laboratory findings, radiological features, and microbiological results.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e1.5 Statistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS version 25.0. Continuous variables were assessed for normality, and normally distributed data were analyzed using analysis of variance (ANOVA), while non-normally distributed data were compared using the \u003cem\u003eMann-Whitney U\u003c/em\u003e test (or \u003cem\u003eWilcoxon rank-sum\u003c/em\u003e test). Categorical variables were analyzed using the \u003cem\u003ePearson χ\u0026sup2;\u003c/em\u003e test or \u003cem\u003eFisher\u0026rsquo;s exact\u003c/em\u003e test, as appropriate. A two-sided \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Baseline Characteristics\u003c/h2\u003e \u003cp\u003eA total of 15,772 hospitalized children were examined at \u003cem\u003eThe Second Affiliated Hospital \u0026amp; Yuying Children\u0026rsquo;s Hospital of Wenzhou Medical University\u003c/em\u003e between January 1, 2021, and December 31, 2022. Of these, 889 (5.6%) tested positive for HMPV and 2,196 (13.9%) tested positive for RSV. HMPV exhibited distinct seasonal peaks during the winter of 2021 and the spring-winter period of 2022, whereas RSV showed prominent circulation during the summer-autumn of 2021 and the autumn-winter of 2022. Notably, both viruses demonstrated a concurrent epidemic peak during the winter of 2022 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e2,447 children hospitalized for ALRI were included in the analysis, 675 children with HMPV-positive ALRI in the HMPV group, and 1,772 children with RSV-positive ALRI in the RSV group. The HMPV group included 373 male patients (55.2%), with a median age of 2.5 years (interquartile range [IQR], 1.1\u0026ndash;3.7), 70 preterm births (10.3%), and 67 children with underlying conditions (9.9%). In contrast, the RSV group comprised 1,103 male patients (62.2%), with a median age of 1.6 years (IQR, 0.6\u0026ndash;2.9), 212 preterm births (11.9%), and 108 children with underlying conditions (6.0%). Compared with the RSV group, the HMPV group had a significantly lower proportion of males (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 9.969, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), an older median age (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;100, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and a higher proportion of underlying conditions (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 10.805, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003ePSM was performed to balance baseline characteristics between the two groups. A total of 597 matched pairs were successfully generated (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After matching, no statistically significant differences were observed between the HMPV and RSV groups in terms of sex, age, preterm birth, or presence of underlying conditions. Baseline characteristics before and after PSM are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \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\u003eBaseline Characteristics Before and After PSM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBefore PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eAfter PSM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline Characteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHMPV\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;675)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRSV\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1772)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHMPV\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;597)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRSV\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;597)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e373(55.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1103(62.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e357(59.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e364(60.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.679\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years),\u003c/p\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.5(1.1,3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6(0.6,2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003cp\u003e(1.0, 3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003cp\u003e(0.7, 3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.244\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm birth, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70(10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e212(11.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62(10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e63(10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.925\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnderlying conditions, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67(9.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108(6.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49(8.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51(8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.834\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003ePSM, Propensity score matching; HMPV, Human metapneumovirus; RSV, Respiratory syncytial virus; IQR, interquartile rage; A \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Comparative analysis of clinical manifestations between HMPV and RSV infection\u003c/h2\u003e \u003cp\u003eThe predominant clinical symptoms among the enrolled children were cough (99.9%), fever (87.2%), and wheezing (56.9%). Compared with the RSV group, the HMPV group exhibited a significantly longer duration of fever (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;33.804, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and higher peak body temperature (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;46.450, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eChildren in the RSV group were more likely to present with signs of respiratory distress, intercostal or subcostal retractions occurred in 30.4% of RSV cases versus 23.4% in HMPV cases (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 7.501, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006), and head bobbing respiration was observed in 4.8% versus 2.5%, respectively (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 4.625, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032).\u003c/p\u003e \u003cp\u003eFor pulmonary auscultatory, the duration of fine-to-medium crackles was significantly longer in the HMPV group than in the RSV group (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.36, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007), whereas the duration of wheezing was slightly shorter in the HMPV group compared to the RSV group (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5.512, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.019) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Clinical Features Between HMPV and RSV infection in Children Hospitalized with ALRI\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Features\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHMPV(n\u0026thinsp;=\u0026thinsp;597)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRSV(n\u0026thinsp;=\u0026thinsp;597)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\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\u003eFever (days), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.0 (3.0, 6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.0 (1.0, 5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemperature (℃), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e39.5 (39.0, 40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39.1 (38.3, 39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaryngopharyngeal phlegm, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e470 (78.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e483 (80.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.123\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWheezing (days), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0 (0.0, 6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.0 (2.0, 5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.571\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRhinorrhoea, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e326 (54.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e339 (56.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.449\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecreased appetite, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e139 (23.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e141 (23.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.891\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyanosis, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.817\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolypnea, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e102 (17.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e102 (17.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetractions, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e140 (23.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e182 (30.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNodding breathing, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of fine-to-medium crackles (days), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.0 (0.0, 3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.0 (0.0, 3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of wheezes (days), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.0 (0.0, 3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.0 (0.0, 4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eHMPV, Human metapneumovirus; RSV, Respiratory syncytial virus; ALRI, Acute lower respiratory infections; IQR, interquartile rage; A \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNo statistically significant difference was observed between the two groups in the proportion of severe pneumonia cases (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 0.049, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.826).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Comparison of systemic inflammatory responses between HMPV and RSV infection\u003c/h2\u003e \u003cp\u003eThere was no statistically significant difference in white blood cell (WBC) count between the two groups. However, children in the HMPV group exhibited significantly higher levels of CRP (14.18 mg/L \u003cem\u003evs.\u003c/em\u003e 7.80 mg/L; \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;38.076, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), neutrophil percentage (60.6% \u003cem\u003evs.\u003c/em\u003e 56.5%; \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7.207, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007), PCT (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;10.949, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and LDH (422.0 U/L \u003cem\u003evs.\u003c/em\u003e 381.0 U/L; \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;25.274, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to those in the RSV group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Co-infection detection in two groups\u003c/h2\u003e \u003cp\u003eCo-infections were identified in 380 children (31.8%), with no significant difference between the HMPV and RSV groups (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 0.757, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.384). Bacterial co-infections occurred in 98 cases (8.2%), including Streptococcus pneumoniae (42 cases, 3.5%), Haemophilus influenzae (36 cases, 3.0%), as well as Moraxella catarrhalis. Co-infection with \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e or \u003cem\u003eChlamydia\u003c/em\u003e was detected in 110 children (9.2%). Viral co-infections were present in 215 patients (18.0%), including rhinovirus (124 cases, 10.3%), adenovirus (43 cases, 3.6%), parainfluenza virus (26 cases, 2.1%), coronavirus (19 cases, 1.5%), bocavirus (12 cases, 1.0%), influenza B (8 cases, 0.6%), and influenza A (2 cases, 0.1%).\u003c/p\u003e \u003cp\u003eNotably, the HMPV group had a higher proportion of co-infections with parainfluenza virus (3.0% \u003cem\u003evs.\u003c/em\u003e 1.3%; χ\u0026sup2; = 3.932, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047) and coronavirus (2.3% \u003cem\u003evs.\u003c/em\u003e 0.8%; \u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 4.332, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037) compared to the RSV group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Comparison of radiological findings in HMPV and RSV infection\u003c/h2\u003e \u003cp\u003eCompared with the RSV group, children in the HMPV group showed significantly higher rates of patchy or linear opacities on chest imaging (71.5% \u003cem\u003evs.\u003c/em\u003e 65.1%; \u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 5.803, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), pulmonary consolidation (4.1% \u003cem\u003evs.\u003c/em\u003e 2.1%; \u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 3.935, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047), and atelectasis (1.8% \u003cem\u003evs.\u003c/em\u003e 0%; \u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 11.121, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). Conversely, the RSV group more frequently exhibited increased and thickened bronchovascular markings bilaterally (32.6% \u003cem\u003evs.\u003c/em\u003e 24.1%; \u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 10.599, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Treatment and disease burden in HMPV and RSV infection\u003c/h2\u003e \u003cp\u003eIntravenous immunoglobulin (IVIG) was administered in 111 children (9.2%), and antimicrobial agents were used in 882 (73.8%). No significant differences in the utilization rates of either IVIG or antibiotics were observed between the RSV group and the HMPV group. However, the duration of systemic corticosteroid therapy was significantly longer in the RSV group compared to the HMPV group (\u003cem\u003eχ\u0026sup2;\u003c/em\u003e = 9.412, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e \u003cp\u003eThe median length of stay was 5.0 days (IQR, 4.0\u0026ndash;6.0), with no significant difference between groups (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.056, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.814). Median hospitalization costs showed no statistically significant difference between two groups (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.956).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study comparatively analyzed the clinical features associated with HMPV and RSV infections among children hospitalized with ALRI in Wenzhou, China. Our findings indicate that, compared with RSV-infected children, those infected with HMPV were slightly older, more frequently had underlying conditions, experienced longer fever duration and higher peak temperatures, exhibited prolonged fine-to-medium crackles on pulmonary auscultation, demonstrated more pronounced systemic inflammatory responses (elevated CRP, neutrophil percentage, PCT and LDH), and were more prone to develop pulmonary consolidation and atelectasis. In contrast, RSV-infected children presented more commonly with signs of respiratory distress and had a longer duration of wheezing.\u003c/p\u003e \u003cp\u003eIn our cohort, the detection rate of HMPV among children with acute respiratory infections from 2021 to 2022 was 5.6%, with a median age of 2.5 years, and epidemic peaks occurred during winter 2021 and spring-winter 2022, which consistent with multiple studies (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). A multicenter retrospective study across 22 hospitals in southern China (2010\u0026ndash;2019) reported an HMPV detection rate of 3.5% among children under 14 years with acute respiratory infections, predominantly affecting those under 5 years, with consistent springtime seasonal peaks over the decade (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Another study conducted at the Capital Institute of Pediatrics (from August 2023 to December 2024) among 8,374 hospitalized children with acute respiratory infections found an HMPV positivity rate of 3.1%, primarily in children under 6 years (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). A prospective observational study involving six hospitals in Beijing, Wenzhou, Guangzhou, Yinchuan, and Guizhou (2017\u0026ndash;2019) reported an HMPV detection rate of 5.3% among children with ALRI, with 67.6% under 2 years of age and a predilection for spring onset (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Similarly, a recent multicenter prospective study of over 8,600 children across seven pediatric centers (from December 2016 to March 2020) identified HMPV activity peaking between March and April (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Collectively, these data suggest that HMPV exhibits a consistent winter-spring seasonal pattern in both northern and southern China, predominantly affecting young children, with no substantial geographic variation.\u003c/p\u003e \u003cp\u003eIn our study, the RSV detection rate among children with acute respiratory infections during 2021\u0026ndash;2022 was 13.9%, with a median age of 1.6 years, which significantly younger than HMPV cases. While RSV typically was prevalent in winter and early spring [16], we observed an atypical seasonal pattern that a prominent surge during summer and autumn 2021, followed by a decline in winter 2021, and a resurgence in autumn-winter 2022. Similar off-season RSV peaks were reported in Morocco during summer and autumn 2021 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). This anomaly is likely attributable to the concurrent COVID-19 pandemic. Non-pharmaceutical interventions implemented during this period markedly reduced population-level exposure to RSV, leading to declined natural immunity. With relaxation of these measures, delayed or atypical seasonal epidemics emerged (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Similarly, a 7-year Canadian cohort study (2017\u0026ndash;2024) by Tiffany F. et al.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) demonstrated a sharp decline in pediatric respiratory infections during 2020\u0026ndash;2021, gradual recovery in 2021\u0026ndash;2022, and a significant rebound in RSV and HMPV burden in 2022\u0026ndash;2023, with seasonal patterns largely returning to pre-pandemic norms by 2023\u0026ndash;2024. Notably, post-pandemic hospitalized children with acute respiratory infections were older and exhibited a lower male predominance, while direct impacts of COVID-19-related hospitalizations on overall ALRI admissions appeared minimal. Global surveillance data further confirm that since 2022, HMPV and RSV have re-established typical seasonal circulation in most regions following the pandemic (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), indicating that their epidemiology is influenced not only by climate and human behavior but also potentially by viral interference or interactions.\u003c/p\u003e \u003cp\u003eClinically, HMPV infection typically presents with fever, cough, rhinorrhea, and tachypnea, and severe cases may progress to bronchiolitis, severe pneumonia, or acute respiratory distress syndrome, symptoms overlapping considerably with RSV, leading to clinical differentiation challenging (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In our cohort, the primary diagnosis for both HMPV and RSV ALRI was pneumonia, followed by bronchiolitis and bronchitis, consistent with prior reports (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). No significant differences were observed in the incidence of severe pneumonia or the severity of acute bronchiolitis between the two viruses. However, HMPV-infected children had a higher prevalence of underlying conditions (9.9% \u003cem\u003evs.\u003c/em\u003e 6.0%), aligning with recent large-scale multicenter prospective data (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), suggesting HMPV may preferentially affect children with preexisting conditions.\u003c/p\u003e \u003cp\u003eCompared to RSV, HMPV-associated ALRI was characterized by longer fever duration, higher peak temperature, prolonged fine-to-medium crackles, and more robust systemic inflammation, evidenced by significantly elevated CRP, neutrophil percentage, PCT, and LDH. Radiologically, HMPV cases more frequently exhibited pulmonary consolidation and atelectasis, a finding corroborated by a multicenter prospective study (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), which indicating greater parenchymal involvement and systemic inflammatory response. This may reflect HMPV\u0026rsquo;s propensity for causing substantial lung injury. Ciliated respiratory epithelium serves as the primary target for HMPV following initial infection, the virus disseminates within airway cells and demonstrates enhanced replication capacity in the lower versus upper respiratory tract (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). LDH, a marker of endothelial and cellular membrane damage, is released upon injury and catalyzes pyruvate-to-lactate conversion, thereby promoting activation of macrophages and dendritic cells.\u003c/p\u003e \u003cp\u003eAlthough HMPV and RSV share structural similarities, HMPV lacks two nonstructural proteins present in RSV that suppress interferon signaling. Whole-blood RNA sequencing analysis using DESeq2 by Samoriski et al.(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) identified 197 differentially expressed genes between HMPV- and RSV-infected individuals. HMPV infection was associated with upregulation of genes involved in antigen binding, immunoglobulin production, and adaptive immunity, whereas RSV infection showed stronger expression of genes linked to natural killer T-cell pathways. These findings suggest distinct immunopathogenic mechanisms despite virological similarities, warranting further mechanistic investigation.\u003c/p\u003e \u003cp\u003eCo-infections were detected in 31.8% of our patients, including 18.0% with additional viral pathogens. HMPV-infected children were more likely to co-harbor parainfluenza virus (3.0% \u003cem\u003evs.\u003c/em\u003e 1.3%) and coronavirus (2.3% \u003cem\u003evs.\u003c/em\u003e 0.8%) than RSV-infected children. Bacterial co-infection occurred in 8.2% of cases, predominantly Streptococcus pneumoniae and Haemophilus influenzae. Nevertheless, antibiotic use was remarkably high at 73.8%. This discrepancy mirrors findings by Papenburg J. et al. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), who reported\u0026thinsp;~\u0026thinsp;70% antibiotic administration in virally infected children despite low bacterial co-detection rates, likely due to pre-hospital antibiotic use reducing culture yield or clinical misattribution of viral symptoms to bacterial etiology. We should focus on identifying more sensitive biomarkers to guide rational antibiotic stewardship in future.\u003c/p\u003e \u003cp\u003eThe limitations of this study including it was a single-center retrospective analysis, so it may not fully represent regional epidemiology. We did not analyze viral load in relation to disease severity and explore underlying immunological mechanisms between HMPV and RSV infections. A long-term follow-up to evaluate outcomes and prognosis was not assessed in this study. Future research will address these gaps to provide stronger evidence for the pathogenesis, prevention, and management of HMPV and RSV infections.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn children hospitalized with ALRI, those infected with HMPV were more likely to be older, have underlying conditions, experience prolonged and higher-grade fever, demonstrate more pronounced systemic inflammatory responses, and prone to develop pulmonary consolidation and atelectasis compared with RSV-infected children.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHMPV, Human metapneumovirus\u003c/p\u003e\n\u003cp\u003eRSV, Respiratory syncytial virus\u003c/p\u003e\n\u003cp\u003eALRI, Acute lower respiratory infections\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRT-PCR, Real-time quantitative polymerase chain reaction\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePSM, Propensity score matching\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCRP, C-reactive protein\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePCT, Procalcitonin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIQR, interquartile range\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLDH, dehydrogenase\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIVIG, Intravenous immunoglobulin\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and approved by\u0026nbsp;the Ethics Committee of the Second Affiliated Hospital \u0026amp; Yuying Children\u0026rsquo;s Hospital of Wenzhou Medical University (Approval No. 2021-K-224-02). This study is a retrospective study with a waiver of informed consent from legal guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability for data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the\u0026nbsp;\u003c/p\u003e\n\u003cp\u003epreparation of this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ecollection and analysis were performed by\u0026nbsp;Manjun Zhang, Xinyu Chen, Yilin Li, Jian Yu and Shunhang Wen.\u0026nbsp;The first draft of the manuscript was written by\u0026nbsp;Lili\u0026nbsp;Zhu\u003csup\u003e\u0026nbsp;\u003c/sup\u003eand Luyao\u0026nbsp;Zeng. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the Laboratory Medicine of the Second Affiliated Hospital \u0026amp; Yuying Children\u0026rsquo;s Hospital of Wenzhou Medical University for providing the data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eInfections GBDLR, Antimicrobial Resistance C. Global burden of lower respiratory infections and aetiologies, 1990\u0026ndash;2023: a systematic analysis for the Global Burden of Disease Study 2023. 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Global surveillance of human Metapneumovirus (hMPV) and Respiratory Syncytial Virus (RSV) epidemiology since 2022. Open Forum Infect Dis. 2025;12(Supplement_1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoward LM, Edwards KM, Zhu Y, Griffin MR, Weinberg GA, Szilagyi PG, et al. Clinical Features of Human Metapneumovirus Infection in Ambulatory Children Aged 5\u0026ndash;13 Years. J Pediatr Infect Dis Soc. 2018;7(2):165\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuiken T, van den Hoogen BG, van Riel DA, Laman JD, van Amerongen G, Sprong L, et al. Experimental human metapneumovirus infection of cynomolgus macaques (Macaca fascicularis) results in virus replication in ciliated epithelial cells and pneumocytes with associated lesions throughout the respiratory tract. Am J Pathol. 2004;164(6):1893\u0026ndash;900.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSamoriski C, Chu CY, Falsey AR, Peterson D, Bhattacharya S, Croft DP, et al. Clinical Features and Gene Expression Patterns in Adults Hospitalized With Respiratory Syncytial Virus and Human Metapneumovirus Infection. J Infect Dis. 2025;232(Supplement1):S37\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapenburg J, Hamelin ME, Ouhoummane N, Carbonneau J, Ouakki M, Raymond F, et al. Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children. J Infect Dis. 2012;206(2):178\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Human metapneumovirus, Respiratory syncytial virus, Acute lower respiratory tract infection, Clinical characteristics","lastPublishedDoi":"10.21203/rs.3.rs-8501977/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8501977/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo compare the clinical characteristics of human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) infections in children hospitalized with acute lower respiratory infections (ALRI).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eChildren hospitalized with ALRI in Wenzhou, China from 2021 to 2022 were examined for HMPV and RSV in sputum or nasopharyngeal secretions by multiplex real-time quantitative polymerase chain reaction (PCR). Demographic data, clinical features, laboratory findings, and radiological characteristics were compared between HMPV group and RSV group.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 15,772 hospitalized children were screened and tested by multiplex PCR. 889 (5.6%) were HMPV-positive and 2,196 (13.9%) were RSV-positive. Compared with the RSV group, the HMPV group had a lower proportion of males (55.2% \u003cem\u003evs.\u003c/em\u003e 62.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), an older median age (2.5 years \u003cem\u003evs.\u003c/em\u003e 1.6 years, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and a higher proportion of underlying conditions (9.9% \u003cem\u003evs.\u003c/em\u003e 6.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). The HMPV group exhibited significantly longer duration of fever (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and higher peak temperature (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to the RSV group. In contrast, the RSV group were more likely to present with respiratory distress, including intercostal or subcostal retractions (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006) and head bobbing respiration (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032). Significantly higher levels in the HMPV group for C-reactive protein (14.18 mg/L \u003cem\u003evs.\u003c/em\u003e 7.80 mg/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), neutrophil percentage (60.6% \u003cem\u003evs.\u003c/em\u003e 56.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007), procalcitonin (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), and lactate dehydrogenase (422.0 U/L \u003cem\u003evs.\u003c/em\u003e 381.0 U/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) than the RSV group. HMPV-infected children were more likely to exhibit patchy or linear opacities (71.5% \u003cem\u003evs.\u003c/em\u003e 65.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), pulmonary consolidation (4.1% \u003cem\u003evs.\u003c/em\u003e 2.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047), and atelectasis (1.8% \u003cem\u003evs.\u003c/em\u003e 0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) compared to the RSV-infected children.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn children hospitalized with ALRI, those infected with HMPV were more likely to be older, have underlying conditions, experience prolonged and higher-grade fever, demonstrate more pronounced systemic inflammatory responses, and prone to develop pulmonary consolidation and atelectasis compared with RSV-infected children.\u003c/p\u003e","manuscriptTitle":"Comparison of human metapneumovirus and Respiratory Syncytial Virus in children with acute lower respiratory infections in Wenzhou, China from 2021 to 2022: a retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-03 15:42:14","doi":"10.21203/rs.3.rs-8501977/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-05T05:42:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-22T09:26:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319147785939566307895211071303607554580","date":"2026-02-13T11:35:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-12T07:49:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-10T21:43:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"188446390583308065570262432132981765491","date":"2026-02-09T00:22:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"28611067315778928606801249055685040803","date":"2026-01-29T13:09:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-29T10:00:11+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-05T12:06:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-05T01:41:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-05T01:41:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-01-02T15:32:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6c81bb72-62c3-449b-b04a-8ca7ba2b75d6","owner":[],"postedDate":"February 3rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T06:28:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-03 15:42:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8501977","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8501977","identity":"rs-8501977","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}