Abstract
Background
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children, yet age-stratified clinical characteristics of hospitalized children with RSV infection remain incompletely defined. This study aimed to compare the clinical manifestations, laboratory parameters, co-infections, and disease severity between hospitalized children with RSV infection aged ≤3 years and those aged >3 years, so as to provide evidence for age-stratified diagnosis, treatment, and prevention of RSV infection.
Methods
A total of 624 hospitalized children with RSV infection admitted to Beijing Friendship Hospital, Capital Medical University, from 2023 to 2025 were retrospectively enrolled. Based on age at admission, patients were stratified into two groups: ≤3 years (n=434) and >3 years (n=190). Demographic characteristics, clinical manifestations, laboratory parameters, etiological findings, and treatment data were collected. Intergroup comparisons were performed using the χ2 test, Fisher’s exact test, Mann-Whitney U test, or independent samples t-test, as appropriate.
Results
Compared with the ≤3 years group, the >3 years group had higher rates of fever (92.6% vs. 79.5%), longer fever duration (6 vs. 5 days), severe pneumonia (13.7% vs. 6.7%), co-infection (47.4% vs. 26.0%), and longer disease course (10 vs. 8 days) (all P<0.001, except severe pneumonia P=0.005). Co-infection with Mycoplasma pneumoniae (33.7% vs. 10.1%) and other viruses (20.0% vs. 12.7%) was also more frequent in the >3 years group (all P<0.05). The ≤3 years group showed higher wheezing rates (22.6% vs. 6.3%, P<0.001). Laboratory findings revealed higher neutrophil counts (3.16×109/L vs. 2.44×109/L) and C-reactive protein (CRP) levels (3.5 vs. 1.3 mg/L) but lower white blood cell (WBC) count and lymphocyte counts in the >3 years group (all P<0.001). Glucocorticoid (11.6% vs. 7.8%) and intravenous immunoglobulin (IVIG) use (1.1% vs. 1.2%) were comparable between groups (P>0.05).
Conclusions
Compared with children aged ≤3 years, hospitalized children aged >3 years with RSV infection had higher proportions of fever, prolonged disease course, co-infection, and severe pneumonia. Early recognition and dynamic assessment should be emphasized in this age group to avoid underestimating disease severity based on age alone.
Keywords: Respiratory syncytial virus (RSV), children, age, co-infection
Highlight box.
Key findings
• Children >3 years with respiratory syncytial virus (RSV) had higher fever, co-infection, severe pneumonia, and longer illness than younger children.
What is known and what is new?
• RSV causes severe lower respiratory infections in infants and young children.
• This study reveals that hospitalized children >3 years with RSV have more severe disease and higher co-infection rates.
What is the implication, and what should change now?
• Do not assume older children have milder RSV; age-stratified assessment is essential.
Introduction
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections (ALRTIs) in children, manifesting as bronchiolitis, pneumonia, and wheezing, and accounting for a significant proportion of pediatric hospitalizations (1-3). Beyond acute respiratory symptoms, a subset of children may develop long-term pulmonary sequelae following RSV infection, including recurrent wheezing, impaired lung function, and even bronchiolitis obliterans (BO) (4,5). A previous large-scale US study reported that among children under 5 years of age hospitalized for acute respiratory illness, the RSV positivity rate was 31.4%, with 84.9% of RSV-positive cases occurring in children under 2 years of age (6). Due to their narrower airways and immature immune systems, infants and young children are more susceptible to severe disease progression and even mortality following RSV infection (7). A study reported that approximately 3.6% of deaths among children aged 28 days to 6 months were attributable to RSV infection (8). However, RSV infection is not confined to infants and young children; older children are also susceptible to RSV-associated respiratory tract infections and may require hospitalization.
Around the age of 3 years, children typically enter childcare facilities and other group living environments, marking a critical transitional period. With increased opportunities for close contact among children, childcare settings—as high-risk venues for respiratory virus transmission—may further elevate the risk of respiratory pathogen exposure and spread (9). Compared with younger children, those aged over 3 years may differ in airway development, immune status, social contact patterns, and pathogen exposure characteristics (10). Previous studies have also indicated that the clinical features and disease outcomes of RSV infection vary across pediatric age groups (11). Accordingly, the clinical manifestations, co-infection patterns, and disease severity of RSV infection in children over 3 years of age may exhibit distinct characteristics. However, most RSV-related research to date has focused on infants and young children, and clinical data on hospitalized children over 3 years with RSV infection remain limited, with age-related clinical features yet to be fully elucidated (3,12).
Therefore, this study used 3 years of age as the cutoff to perform an age-stratified analysis of hospitalized children with RSV infection, aiming to compare differences in clinical manifestations, laboratory parameters, co-infection patterns, and disease severity between children aged ≤3 years and those aged >3 years. The findings are intended to provide evidence for age-stratified assessment, clinical management, and the development of prevention and control strategies for pediatric RSV infection. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0691/rc).
Methods
Study population
Children hospitalized with laboratory-confirmed RSV infection at Beijing Friendship Hospital, Capital Medical University, between January 1, 2023 and December 31, 2025, were retrospectively enrolled. Demographic, clinical, laboratory, and treatment data were extracted. Inclusion criteria: (I) age 1 month to 14 years; (II) etiologically confirmed RSV infection by nucleic acid testing; (III) complete clinical records. Exclusion criteria: (I) underlying immunodeficiency, congenital heart disease, or chronic lung disease; (II) pre-admission antiviral or immunomodulatory therapy; (III) incomplete data. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Beijing Friendship Hospital (No. 2026-P2-026-01). Informed consent was waived in this retrospective study.
Data collection
Baseline characteristics included sex, age at admission, history of preterm birth, and postnatal feeding mode. Clinical features comprised the presence and duration of fever, wheezing (presence and duration), and cough (presence, character, and duration); presence of hypoxemia; co-infection with other pathogens; disease course and length of hospital stay. Laboratory parameters included white blood cell (WBC) count, neutrophil (N) count, and lymphocyte (L) count; inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6); coagulation marker D-dimer; and the cellular injury marker lactate dehydrogenase (LDH). Treatment data included the use of glucocorticoids and intravenous immunoglobulin (IVIG).
Etiological diagnostic criteria
RSV infection: RSV nucleic acid positivity on nasopharyngeal swab and/or targeted next-generation sequencing (t-NGS) positivity in bronchoalveolar lavage fluid (BALF);
Viral infection: (i) positive viral antigen or nucleic acid in respiratory specimens (nasopharyngeal aspirate or BALF); (ii) positive serum virus-specific IgM antibody; (iii) Epstein-Barr virus (EBV) infection defined as EBVCA-IgM positivity with concurrent EBNA-IgG negativity, or EBV PCR copy number >103 in BALF;
Bacterial infection: positive blood culture or sputum culture, combined with infection biomarkers including CRP and PCT to rule out colonization;
Mycoplasma pneumoniae infection: (i) single serum Mycoplasma pneumoniae antibody titer ≥1:160 [particle agglutination (PA) method], or a ≥4-fold rise in Mycoplasma pneumoniae antibody titer between acute and convalescent paired sera; (ii) positive Mycoplasma pneumoniae-DNA or Mycoplasma pneumoniae-RNA in sputum or BALF, or detection of Mycoplasma pneumoniae nucleic acid sequences by t-NGS of respiratory specimens;
Mixed infection was defined as detection of RSV together with at least one additional respiratory pathogen.
Disease severity assessment criteria
(I) Cyanosis; (II) dyspnea; (III) oxygen saturation ≤0.92; (IV) pleural effusion; (V) extrapulmonary complications; (VI) pulmonary imaging shows involvement of multiple lung lobes, or ≥2/3 of a single lung lobe. The presence of any one of the above items can confirm the diagnosis of severe illness (13).
Grouping
The study population was stratified into two groups based on age at admission: Group 1 included children aged ≤3 years, and Group 2 included children aged >3 years.
Statistical analysis
Data were analyzed using SPSS 27.0. Normality was assessed by the Shapiro-Wilk test. Normally distributed continuous variables were expressed as mean ± standard deviation (SD) and compared using the independent samples t-test; non-normally distributed variables as median [interquartile range (IQR)] using the Mann-Whitney U test. Categorical variables were presented as n (%) and compared using the χ2 test or Fisher’s exact test (expected count <5). A two-sided P<0.05 was considered significant.
Results
Comparison by year
From 2023 to 2025, a total of 624 RSV-infected hospitalized children were enrolled. The highest number was recorded in 2025 (n=389), followed by 2023 (n=126) and 2024 (n=109). The proportion of male patients was 48.4% in 2023, 58.7% in 2024, and 58.4% in 2025, with comparable male predominance in 2024 and 2025, both exceeding the 2023 proportion.
The median age was 3.0 (IQR, 0.7–6.3) years in 2023, 1.0 (IQR, 0.5–5.0) years in 2024, and 3.0 (IQR, 1.0–4.0) years in 2025. The proportion of children >6 years was relatively higher in 2023 (24.6%), whereas children ≤1 year predominated in 2024 (61.5%), and children >1 year constituted the majority in 2025 (60.2%). The preterm birth rate was 11.9% in both 2023 and 2024, decreasing to 7.7% in 2025. Exclusive breastfeeding remained the predominant feeding pattern across all years (55.6%, 49.5%, and 46.0%, respectively), while mixed feeding increased progressively (33.3%, 38.5%, and 41.9%), peaking in 2025. Exclusive formula feeding rates remained relatively stable across the 3 years (Table 1).
Table 1. Baseline characteristics of children hospitalized for RSV infection.
| Characteristics | 2023 (n=126) | 2024 (n=109) | 2025 (n=389) |
|---|---|---|---|
| Male | 61 (48.4) | 64 (58.7) | 227 (58.4) |
| Age, years | 3.0 (0.7–6.3) | 1.0 (0.5–5.0) | 3 (1.0–4.0) |
| ≤6 months | 28 (22.2) | 28 (25.7) | 58 (14.9) |
| >6 months to ≤1 year | 21 (16.7) | 39 (35.8) | 97 (24.9) |
| >1 year to ≤3 years | 21 (16.7) | 19 (17.4) | 123 (31.6) |
| >3 years to ≤6 years | 25 (19.8) | 16 (14.7) | 85 (21.9) |
| >6 years | 31 (24.6) | 7 (6.4) | 26 (6.7) |
| Preterm birth | 15 (11.9) | 13 (11.9) | 30 (7.7) |
| Feeding mode | |||
| Exclusive breast | 70 (55.6) | 54 (49.5) | 179 (46.0) |
| Mixed | 42 (33.3) | 42 (38.5) | 163 (41.9) |
| Exclusive formula | 14 (11.1) | 13 (11.9) | 47 (12.1) |
Data are presented as n (%) or median (interquartile range). RSV, respiratory syncytial virus.
From 2023 to 2025, the predominant clinical manifestations among hospitalized RSV-infected children were fever and cough. The proportion of febrile children was 84.1% (106/126) in 2023, 78.9% (86/109) in 2024, and 84.6% (329/389) in 2025. The median fever duration was longest in 2023 at 8 (IQR, 4.25–10) days, followed by 6 (IQR, 4–9) days in 2024 and 4 (IQR, 3–6) days in 2025. Cough was the most prevalent symptom across all years, reported in 96.0% (121/126) in 2023, 92.7% (101/109) in 2024, and 95.4% (371/389) in 2025. The proportion of wheezing was recorded as 13.5% (17/126) in 2023, 24.8% (27/109) in 2024, and 17.0% (66/389) in 2025. Hypoxemia cases were relatively more frequent in 2025, accounting for 2.6% (10/389).
The median hospitalization duration was consistently 5 days across all three years. The median disease course was 11 (IQR, 9–14) days in 2023, 10 (IQR, 7–13) days in 2024, and 8 (IQR, 6–10) days in 2025, showing a progressively shorter trend from 2023 to 2025. Regarding co-infections, 2023 had the highest proportions across all categories: co-infection (65.9%), bacterial co-infection (11.1%), other viral co-infection (31.0%), and Mycoplasma pneumoniae co-infection (46.8%). The proportion of severe pneumonia was highest in 2023 (19.0%), followed by 2024 (8.3%) and 2025 (5.7%), with a clear declining trend (Table 2).
Table 2. Clinical characteristics of hospitalized children with RSV infection.
| Characteristics | 2023 (n=126) | 2024 (n=109) | 2025 (n=389) | P |
|---|---|---|---|---|
| Fever | 106 (84.1) | 86 (78.9) | 329 (84.6) | 0.37 |
| Fever duration, days† | 8 [4.25–10] | 6 [4–9] | 4 [3–6] | <0.001 |
| Wheezing | 17 (13.5) | 27 (24.8) | 66 (17.0) | 0.07 |
| Cough | 121 (96.0) | 101 (92.7) | 371 (95.4) | 0.44 |
| Hospitalization, days | 5 [4–7] | 5 [4–7] | 5 [4–6] | 0.004 |
| Disease course, days | 11 [9–14] | 10 [7–13] | 8 [6–10] | <0.001 |
| Hypoxemia | 2 (1.6) | 0 (0.0) | 10 (2.6) | 0.21 |
| Mixed infection | 83 (65.9) | 32 (29.4) | 88 (22.6) | <0.001 |
| Bacterial | 14 (11.1) | 7 (6.4) | 25 (6.4) | |
| Other virus | 39 (31.0) | 13 (11.9) | 41 (10.5) | |
| Mycoplasma pneumoniae | 59 (46.8) | 19 (17.4) | 30 (7.7) | |
| Severe pneumonia | 24 (19.0) | 9 (8.3) | 22 (5.7) | <0.001 |
Data are presented as n (%) or median [interquartile range]. †, days of fever were calculated only among children with fever. RSV, respiratory syncytial virus.
Comparison by age
Children were stratified into two age groups: Group 1 (n=434) and Group 2 (n=190). A significant difference in sex distribution was observed between the two groups, with a higher proportion of males in Group 1 than in Group 2 [60.1% (261/434) vs. 47.9% (91/190), P=0.005]. Feeding patterns also differed significantly between groups (P=0.03, Table 3).
Table 3. Comparison of basic characteristics of hospitalized children with RSV infection across different age groups.
| Basic characteristics | Group 1 (n=434) | Group 2 (n=190) | P |
|---|---|---|---|
| Male | 261 (60.1) | 91 (47.9) | 0.005 |
| Preterm birth | 40 (9.2) | 18 (9.5) | 0.92 |
| Feeding mode | 0.03 | ||
| Exclusive breast | 197 (45.4) | 106 (55.8) | |
| Mixed | 178 (41.0) | 69 (36.3) | |
| Exclusive formula | 59 (13.6) | 15 (7.9) |
Data are presented as n (%). Group 1: children aged ≤3 years; Group 2: children aged >3 years. RSV, respiratory syncytial virus.
Comparison of clinical features between the two groups revealed that the proportion of febrile children was significantly higher in the >3 years group: 79.5% (345/434) in Group 1 vs. 92.6% (176/190) in Group 2 (P<0.001). The fever duration was also significantly longer in Group 2 [6 (IQR, 4–9) days] than in Group 1 [5 (IQR, 3–6) days] (P<0.001).
The proportion of wheezing was significantly higher in the ≤3 years group: 22.6% (98/434) in Group 1 vs. 6.3% (12/190) in Group 2 (P<0.001). Cough duration was significantly longer in Group 2 [10 (IQR, 7–13) days] than in Group 1 [8 (IQR, 6–11) days] (P<0.001). The proportion of severe pneumonia was higher in the >3 years group: 6.7% (29/434) in Group 1 vs. 13.7% (26/190) in Group 2 (P=0.005). Disease course was also significantly longer in Group 2 [10 (IQR, 8–13) days] than in Group 1 [8 (IQR, 7–11) days] (P<0.001, Table 4).
Table 4. Comparison of clinical features of hospitalized children with RSV infection across different age groups.
| Clinical features | Group 1 (n=434) | Group 2 (n=190) | P |
|---|---|---|---|
| Fever | 345 (79.5) | 176 (92.6) | <0.001 |
| Fever duration, days† | 5 [3–6] | 6 [4–9] | <0.001 |
| Wheezing | 98 (22.6) | 12 (6.3) | <0.001 |
| Wheezing duration, days | 5 [4–8] | 6 [4–8] | 0.58 |
| Cough | 412 (94.9) | 181 (95.3) | 0.86 |
| Cough duration, days | 8 [6–11] | 10 [7–13] | <0.001 |
| Hypoxemia | 10 (2.3) | 2 (1.1) | 0.38‡ |
| Severe pneumonia | 29 (6.7) | 26 (13.7) | 0.005 |
| Disease course, days | 8 [7–11] | 10 [8–13] | <0.001 |
| Hospitalization, days | 5 [4–6] | 5 [4–6] | 0.44 |
Data are presented as n (%) or median [interquartile range]. Group 1: children aged ≤3 years; Group 2: children aged >3 years. †, days of fever were calculated only among children with fever. ‡, Fisher’s exact test was used. RSV, respiratory syncytial virus.
Comparison of laboratory indicators between age groups showed that the ≤3 years group had significantly higher WBC, lymphocyte count, and LDH levels than the >3 years group, while neutrophil count and CRP levels were significantly lower in the ≤3 years group (all P<0.05) (Table 5).
Table 5. Comparison of laboratory indicators among hospitalized children with RSV infection across different age groups .
| Laboratory indicators | Group 1 (n=434) | Group 2 (n=190) | P |
|---|---|---|---|
| WBC, ×109/L | 8.41 [6.67–10.53] | 6.92 [5.69–8.99] | <0.001 |
| Neutrophil, ×109/L | 2.44 [1.70–3.75] | 3.16 [2.14–4.35] | <0.001 |
| Lymphocyte, ×109/L | 4.59 [3.42–6.14] | 3.03 [2.25–3.70] | <0.001 |
| CRP, mg/L | 1.3 [0.5–5.8] | 3.5 [1.0–7.7] | <0.001 |
| LDH, U/L | 316 [279–363] | 278 [230–309] | <0.001 |
| D-dimer, mg/L | 0.29 [0.19–0.44] | 0.35 [0.19–0.58] | 0.12 |
| PCT, ng/mL | 0.11 [0.07–0.23] | 0.13 [0.07–0.22] | 0.85 |
| IL-6, ng/mL | 7.3 [1.5–19.9] | 5.5 [1.5–18.9] | 0.06 |
Data are presented as median [interquartile range]. Group 1: children aged ≤3 years; Group 2: children aged >3 years. CRP, C-reactive protein; IL-6, interleukin-6; LDH, lactate dehydrogenase; PCT, procalcitonin; RSV, respiratory syncytial virus; WBC, white blood cell count.
Comparison of treatment between age groups showed no significant differences in the use of glucocorticoids or IVIG between Group 1 and Group 2 (both P>0.05, Table 6).
Table 6. Comparison of medication use of hospitalized children with RSV infection across different age groups .
| Medication | Group 1 (n=434) | Group 2 (n=190) | P |
|---|---|---|---|
| IVIG, n (%) | 5 (1.2) | 2 (1.1) | >0.99† |
| Glucocorticoids, n (%) | 34 (7.8) | 22 (11.6) | 0.13 |
Group 1: children aged ≤3 years; Group 2: children aged >3 years. †, Fisher’s exact test was used. IVIG, intravenous immunoglobulin; RSV, respiratory syncytial virus.
Comparison of co-infections between age groups showed that the >3 years group (Group 2) had a significantly higher proportion of mixed infections than the ≤3 years group (Group 1): 47.4% (90/190) vs. 26.0% (113/434) (P<0.001). The proportion of other viral co-infection was also higher in Group 2: 20.0% (38/190) vs. 12.7% (55/434) (P=0.02). Similarly, Mycoplasma pneumoniae co-infection was more frequent in Group 2: 33.7% (64/190) vs. 10.1% (44/434) (P<0.001, Table 7).
Table 7. Comparison of co-infection status among hospitalized children with RSV infection across different age groups.
| Co-infection type | Group 1 (n=434) | Group 2 (n=190) | P |
|---|---|---|---|
| Mixed infection, n (%) | 113 (26.0) | 90 (47.4) | <0.001 |
| Bacterial, n (%) | 34 (7.8) | 9 (4.7) | 0.16 |
| Other virus, n (%) | 55 (12.7) | 38 (20.0) | 0.02 |
| Mycoplasma pneumoniae, n (%) | 44 (10.1) | 64 (33.7) | <0.001 |
Group 1: children aged ≤3 years; Group 2: children aged >3 years. RSV, respiratory syncytial virus.
Discussion
This study analyzed clinical features, laboratory parameters, co-infection patterns, and age-group differences among hospitalized children with RSV infection from 2023 to 2025. RSV-related hospitalizations in 2025 were markedly higher than in 2023 and 2024, indicating annual fluctuations in epidemic intensity. RSV seasonality, transmission intensity, and affected population structure are known to vary by time, region, and public health context. Year-round RSV circulation during 2020–2021 was attributed to non-pharmaceutical interventions and subsequent policy changes, with age-specific incidence patterns not always synchronized within the same season (14,15). In 2024, the median age was lowest, with 78.9% of patients aged ≤3 years, suggesting a younger age distribution among hospitalized children that year. This finding may be related to temporal variation in the population affected by RSV; however, the present study was not designed to determine whether this pattern reflected a concentrated infant outbreak in the region (1,16). This aligns with a Henan Province study reporting that 71.9% of hospitalized RSV cases in 2024 were aged <3 years (17).
Notably, wheezing was most prevalent in 2024, which may be related to the younger age distribution that year, as immature airways with narrow lumens predispose younger children to mucosal edema, excessive secretions, and small airway obstruction after infection (18). From 2023 to 2025, fever duration, disease course, severe pneumonia rate, and co-infection rate all declined. This trend may reflect the post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RSV resurgence gradually reverting to seasonal patterns, alongside increased natural exposure and partial immune recovery (19). Evidence confirms that SARS-CoV-2 circulation and associated non-pharmaceutical interventions substantially disrupted RSV seasonality and age distribution in children, with a gradual return toward pre-pandemic patterns (20). Thus, the observed annual changes may represent a transition from post-pandemic epidemiological disruption toward stabilization, though this requires validation through multicenter longitudinal surveillance.
Age-stratified analysis revealed a higher proportion of males in the ≤3 years group. Previous studies suggest male infants are at relatively higher risk of RSV infection and respiratory disease, possibly due to slower airway and lung maturation, weaker early antiviral responses, and a more pronounced Th2/Th17 immune bias (21,22). The >3 years group had a higher exclusive breastfeeding rate, which prior evidence associates with reduced risk and severity of RSV-related acute lower respiratory infections through passive immune protection, antibody transfer, and modulation of microbiome and immune-metabolic development (23). However, this age-group difference in exclusive breastfeeding was not consistent with the expected protective association reported in previous studies. As a retrospective study relying on medical records, feeding data may be subject to incomplete documentation and recall bias. Thus, these results should be interpreted cautiously, and no causal inference regarding the association between feeding mode and RSV disease risk or severity can be drawn.
Regarding clinical manifestations, the >3 years group had higher fever rates and longer fever duration, whereas the ≤3 years group showed higher wheezing rates, indicating distinct age-related clinical profiles. Younger children have narrower airways and are more prone to mucosal edema and secretion accumulation, causing small airway obstruction, along with a Th2-biased immune response favoring wheezing. In contrast, older children with more mature immune systems may mount stronger inflammatory responses, which may contribute to the higher fever incidence and prolonged fever duration (24). These proposed mechanisms should be interpreted cautiously, as the observed age-group differences were based on unadjusted comparisons.
Notably, the >3 years group had a higher proportion of severe pneumonia and longer disease course than the ≤3 years group. Although young infants are generally considered at high risk for severe RSV infection, our results suggest that older children may also develop substantial disease severity. Neutrophil counts and CRP levels were higher in the >3 years group, indicating a more pronounced inflammatory response characterized by neutrophilia and enhanced acute-phase inflammation. RSV disease severity depends not only on viral replication but also on host immune-inflammatory responses. Elevated chemokines such as IL-8 and CCL-5 promote inflammatory cell recruitment and correlate with RSV severity, while CD4+ T cell-mediated Th2, Th9, and Th17 responses contribute to mucus secretion, inflammatory cell infiltration, and lung function impairment (25-27). Thus, the higher CRP and neutrophil counts in the >3 years group may reflect a more robust inflammatory response and may be associated with the prolonged fever, extended disease course, and increased severe pneumonia rate observed in this group.
Conversely, the >3 years group had a higher co-infection rate, particularly with Mycoplasma pneumoniae and other viruses. Co-detection may amplify airway inflammation and increase disease severity (28). Thus, the elevated severe pneumonia rate in the >3 years group may reflect the combined effects of age-related inflammatory characteristics and co-infections. Clinically, older RSV-infected children with persistent fever, prolonged disease course, or elevated inflammatory markers may warrant intensified monitoring and dynamic reassessment.
The >3 years group also had a significantly higher co-infection rate, particularly with other respiratory viruses and Mycoplasma pneumoniae. After entering childcare or school settings, increased group living and close contact raise respiratory pathogen exposure, elevating infection and reinfection risks (29,30). Prospective cohort studies confirm that collective childcare significantly increases infectious disease burden, especially respiratory infections, with higher contact intensity correlating with elevated viral infection risk (31,32). Additionally, Mycoplasma pneumoniae infection predominantly affects preschool- and school-age children, consistent with our finding of a higher co-infection rate in the >3 years group (33).
The higher co-infection rate in the >3 years group was accompanied by a longer disease course and a higher incidence of severe pneumonia, suggesting that co-infection may contribute to RSV disease progression. Prior evidence demonstrates complex, multi-level inter-pathogen interactions: intracellular (e.g., viral complementation), tissue-level (e.g., target cell competition, impaired mucociliary clearance), and systemic (e.g., immune deviation, amplified cytokine responses), collectively modulating disease trajectory and severity (34,35). However, given the absence of multivariate adjustment in this study, whether co-infection independently predicts severe pneumonia requires further confirmation.
Regarding treatment, no significant intergroup differences were observed in corticosteroid or IVIG use, consistent with current guidelines that prioritize supportive care for RSV infection. Neither agent is routinely recommended for RSV management and may be considered only in severe, critical, or special clinical scenarios based on individual patient assessment (36).
Given the significant disease burden posed by RSV, recent progress in RSV prevention deserves close attention. Nirsevimab, a long-acting monoclonal antibody, offers season-long protection with a single dose, and both clinical trials and real-world data confirm its effectiveness in lowering the risk of RSV-associated lower respiratory tract infection and hospitalization in infants (37). Furthermore, a Korean study found that for infants born between April and November, the direct out-of-pocket cost of nirsevimab may be lower or comparable to that of the palivizumab regimen, indicating potential economic benefits (38). Future research should continue to track developments in RSV prevention, including nirsevimab, and assess their practical value.
Limitations
This study has several limitations. First, as a single-center retrospective study restricted to hospitalized children, selection bias is possible, and generalization to outpatient or community settings should be made cautiously. Second, reliance on medical records may compromise data completeness and accuracy. Third, inter-annual variations in pathogen testing scope and frequency may have affected co-infection detection rates. Fourth, the 3-year age cutoff, while clinically practical, may mask finer age-stratified differences. Finally, the absence of multivariable adjustment precluded adequate control for potential confounders, such as underlying comorbidities, prematurity, immune status, baseline disease severity, and treatment timing. Therefore, the observed associations, particularly that between co-infection and severe pneumonia, should not be interpreted as independent or causal effects. These findings necessitate validation through multicenter, large-sample, prospective studies with appropriate adjustment for potential confounding factors.
Conclusions
In summary, hospitalized RSV-infected children >3 years differed from those ≤3 years in clinical presentation, co-infection patterns, and disease severity. Compared with younger children, the >3 years group was more prone to fever, prolonged disease course, co-infection, and severe pneumonia. Age-stratified assessment should be emphasized in clinical practice, with particular attention to the risk of multi-pathogen co-infection and disease progression in older children.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Beijing Friendship Hospital (No. 2026-P2-026-01). Informed consent was waived in this retrospective study.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0691/rc
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0691/coif). The authors have no conflicts of interest to declare.
Data Sharing Statement
Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0691/dss
References
- 1. Zhang XL, Zhang X, Hua W, et al. Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children. World J Pediatr 2024;20:11-25.. 10.1007/s12519-023-00777-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. McLaughlin JM, Khan F, Schmitt HJ, et al. Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis. J Infect Dis 2022;225:1100-11.. 10.1093/infdis/jiaa752 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Ponce LJ, Wu T, Sim DJ, et al. Respiratory syncytial virus hospitalization costs, rates, and seasonality in Asia: a systematic review and meta-analysis. EClinicalMedicine 2025;86:103350.. 10.1016/j.eclinm.2025.103350 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Ma R, Zhang C, Zhang Y, et al. The impact of respiratory syncytial virus on asthma development and exacerbation. Ann Allergy Asthma Immunol 2025;135:268-75.. 10.1016/j.anai.2025.05.011 [DOI] [PubMed] [Google Scholar]
- 5. Jiang MY, Duan YP, Tong XL, et al. Clinical manifestations of respiratory syncytial virus infection and the risk of wheezing and recurrent wheezing illness: a systematic review and meta-analysis. World J Pediatr 2023;19:1030-40.. 10.1007/s12519-023-00743-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Curns AT, Rha B, Lively JY, et al. Respiratory Syncytial Virus-Associated Hospitalizations Among Children <5 Years Old: 2016 to 2020. Pediatrics 2024;153:e2023062574.. 10.1542/peds.2023-062574 [DOI] [PubMed] [Google Scholar]
- 7. Bont L, Kimpen JL. Immunological mechanisms of severe respiratory syncytial virus bronchiolitis. Intensive Care Med 2002;28:616-21.. 10.1007/s00134-002-1256-z [DOI] [PubMed] [Google Scholar]
- 8. Li Y, Wang X, Blau DM, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet 2022;399:2047-64.. 10.1016/S0140-6736(22)00478-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Shi C, Wang X, Ye S, et al. Understanding the risk of transmission of respiratory viral infections in childcare centres: protocol for the DISeases TrANsmission in ChildcarE (DISTANCE) multicentre cohort study. BMJ Open Respir Res 2023;10:e001617.. 10.1136/bmjresp-2023-001617 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Xu-Chen X, Weinstock J, Rastogi D, et al. The airway epithelium during infancy and childhood: A complex multicellular immune barrier. Basic review for clinicians. Paediatr Respir Rev 2021;38:9-15.. 10.1016/j.prrv.2021.04.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Toepfer AP, Amarin JZ, Spieker AJ, et al. Seasonality, Clinical Characteristics, and Outcomes of Respiratory Syncytial Virus Disease by Subtype Among Children Aged <5 Years: New Vaccine Surveillance Network, United States, 2016-2020. Clin Infect Dis 2024;78:1352-9.. 10.1093/cid/ciae085 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Abu-Raya B, Reicherz F, Lavoie PM. Correlates of Protection Against Respiratory Syncytial Virus Infection in Infancy. Clin Rev Allergy Immunol 2022;63:371-80.. 10.1007/s12016-022-08948-8 [DOI] [PubMed] [Google Scholar]
- 13. Subspecialty Group of Respiratory, the Society of Pediatrics, Chinese Medical Association. Editorial Board, Chinese Journal of Pediatrics. China Medicine Education Association Committee on Pediatrics . [Guidelines for the management of community-acquired pneumonia in children (2024 revision)]. Zhonghua Er Ke Za Zhi 2024;62:920-30.. 10.3760/cma.j.cn112140-20240728-00523 [DOI] [PubMed] [Google Scholar]
- 14. Li M, Cong B, Wei X, et al. Characterising the changes in RSV epidemiology in Beijing, China during 2015-2023: results from a prospective, multi-centre, hospital-based surveillance and serology study. Lancet Reg Health West Pac 2024;45:101050.. 10.1016/j.lanwpc.2024.101050 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Guo L, Deng S, Sun S, et al. Respiratory syncytial virus seasonality, transmission zones, and implications for seasonal prevention strategy in China: a systematic analysis. Lancet Glob Health 2024;12:e1005-16.. 10.1016/S2214-109X(24)00090-1 [DOI] [PubMed] [Google Scholar]
- 16. Wang L, Yu JX, Liu YL, et al. [Epidemiological characteristics of human respiratory syncytial virus in Guangdong Province from 2023 to 2024]. Zhonghua Yu Fang Yi Xue Za Zhi 2026;60:161-7.. 10.3760/cma.j.cn112150-20250226-00144 [DOI] [PubMed] [Google Scholar]
- 17. Xia Z, Li X, Shen A, et al. Six-year epidemiological dynamics of human respiratory syncytial virus infections in children in central China (2019-2024): pandemic suppression, 2023 resurgence, and immune debt effect. Front Cell Infect Microbiol 2025;15:1691957.. 10.3389/fcimb.2025.1691957 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Le Souëf P. Viral infections in wheezing disorders. Eur Respir Rev 2018;27:170133.. 10.1183/16000617.0133-2017 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Abu-Raya B, Viñeta Paramo M, Reicherz F, et al. Why has the epidemiology of RSV changed during the COVID-19 pandemic?. EClinicalMedicine 2023;61:102089.. 10.1016/j.eclinm.2023.102089 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Rave N, de Bruijne MEM, Stellato RK, et al. Normalization of Seasonality and Age Distribution of Pediatric RSV Infection Following the Pandemic Disruption in the Netherlands. Open Forum Infect Dis 2026;13:ofaf759.. 10.1093/ofid/ofaf759 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Malinczak CA, Fonseca W, Rasky AJ, et al. Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease. Mucosal Immunol 2019;12:969-79.. 10.1038/s41385-019-0171-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Harvey BJ, McElvaney NG. Sex differences in airway disease: estrogen and airway surface liquid dynamics. Biol Sex Differ 2024;15:56.. 10.1186/s13293-024-00633-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Mineva GM, Purtill H, Dunne CP, et al. Impact of breastfeeding on the incidence and severity of respiratory syncytial virus (RSV)-associated acute lower respiratory infections in infants: a systematic review highlighting the global relevance of primary prevention. BMJ Glob Health 2023;8:e009693.. 10.1136/bmjgh-2022-009693 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Li L, Wang H, Liu A, et al. Age-Dependent Clinical Characteristics of Acute Lower Respiratory Infections in Young Hospitalized Children with Respiratory Syncytial Virus Infection. Infect Drug Resist 2022;15:5971-9.. 10.2147/IDR.S380681 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Brand HK, Ferwerda G, Preijers F, et al. CD4+ T-cell counts and interleukin-8 and CCL-5 plasma concentrations discriminate disease severity in children with RSV infection. Pediatr Res 2013;73:187-93.. 10.1038/pr.2012.163 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Christiaansen AF, Knudson CJ, Weiss KA, et al. The CD4 T cell response to respiratory syncytial virus infection. Immunol Res 2014;59:109-17.. 10.1007/s12026-014-8540-1 [DOI] [PubMed] [Google Scholar]
- 27. Russell CD, Unger SA, Walton M, et al. The Human Immune Response to Respiratory Syncytial Virus Infection. Clin Microbiol Rev 2017;30:481-502.. 10.1128/CMR.00090-16 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Lin GL, Drysdale SB, Snape MD, et al. Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus. Nat Commun 2024;15:2379.. 10.1038/s41467-024-46648-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. McGrath-Morrow SA, Agarwal A, Alexiou S, et al. Daycare Attendance is Linked to Increased Risk of Respiratory Morbidities in Children Born Preterm with Bronchopulmonary Dysplasia. J Pediatr 2022;249:22-28.e1.. 10.1016/j.jpeds.2022.06.037 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. He L, Weng J, Zhu F, et al. The morbidity spectrum of influenza, respiratory syncytial virus, human metapneumovirus and human parainfluenza virus in young children by age and country income level: A systematic review and meta-analysis. Int J Infect Dis 2025;157:107938.. 10.1016/j.ijid.2025.107938 [DOI] [PubMed] [Google Scholar]
- 31. Côté SM, Petitclerc A, Raynault MF, et al. Short- and long-term risk of infections as a function of group child care attendance: an 8-year population-based study. Arch Pediatr Adolesc Med 2010;164:1132-7.. 10.1001/archpediatrics.2010.216 [DOI] [PubMed] [Google Scholar]
- 32. Søegaard SH, Spanggaard M, Rostgaard K, et al. Childcare attendance and risk of infections in childhood and adolescence. Int J Epidemiol 2023;52:466-75.. 10.1093/ije/dyac219 [DOI] [PubMed] [Google Scholar]
- 33. Shah SS. Mycoplasma pneumoniae as a Cause of Community-Acquired Pneumonia in Children. Clin Infect Dis 2019;68:13-4.. 10.1093/cid/ciy421 [DOI] [PubMed] [Google Scholar]
- 34. Mochan E, Sego TJ. Mathematical Modeling of the Lethal Synergism of Coinfecting Pathogens in Respiratory Viral Infections: A Review. Microorganisms 2023;11:2974.. 10.3390/microorganisms11122974 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Delima GK, Ganti K, Holmes KE, et al. Influenza A virus coinfection dynamics are shaped by distinct virus-virus interactions within and between cells. PLoS Pathog 2023;19:e1010978.. 10.1371/journal.ppat.1010978 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Committee of Pediatrics, China Medical Education Association. Subspecialty Group of Respiratory Diseases, Society of Pediatrics, Chinese Medical Association. Pediatric Respiratory Work Committee, Society of Pulmonologists, Chinese Medical Doctor Association et al. Guideline for the diagnosis, treatment, and prevention of respiratory syncytial virus infection in children in China. Pediatr Investig 2025;9:205-20.. 10.1002/ped4.70010 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Kim HJ, Choi S, Choe YJ. RSV Prevention Strategies in Korean Children: A Review of Current Approaches and Emerging Options. Infect Chemother 2025;57:31-7.. 10.3947/ic.2024.0122 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Yun KW, Kang D. Direct Out-of-Pocket Costs of Nirsevimab vs. Palivizumab during the First Respiratory Syncytial Virus Season: A Comparative Analysis. Infect Chemother 2025;57:305-9.. 10.3947/ic.2025.0017 [DOI] [PMC free article] [PubMed] [Google Scholar]