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Comparison of characteristics of children hospitalized for respiratory syncytial virus infection during the pre- and post-COVID-19 eras: a multicenter retrospective study
BMC Infectious Diseases volume 24, Article number: 1009 (2024)
Abstract
Background
Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection (LRTI) among children, has resurged in the form of endemic or even pandemic in many countries and areas after the easing of COVID-19 containment measures. This study aimed to investigate the differences in epidemiological and clinical characteristics of children hospitalized for RSV infection during pre- and post-COVID-19 eras in Yunnan, China.
Methods
A total of 2553 pediatric RSV inpatients from eight hospitals in Yunnan were retrospectively enrolled in this study, including 1451 patients admitted in 2018–2019 (pre-COVID-19 group) and 1102 patients admitted in 2023 (post-COVID-19 group). According to the presence or absence of severe LRTI (SLRTI), patients in the pre- and post-COVID-19 groups were further divided into the respective severe or non-severe subgroups, thus analyzing the risk factors for RSV-associated SLRTI in the two eras. Demographic, epidemiological, clinical, and laboratory data of the patients were collected for the final analysis.
Results
A shift in the seasonal pattern of RSV activity was observed between the pre-and post-COVID-19 groups. The peak period of RSV hospitalizations in the pre-COVID-19 group was during January–April and October–December in both 2018 and 2019, whereas that in the post-COVID-19 group was from April to September in 2023. Older age, more frequent clinical manifestations (fever, acute otitis media, seizures), and elevated laboratory indicators [neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP), interleukin 6 (IL-6), co-infection rate] were identified in the post-COVID-19 group than those in the pre-COVID-19 group (all P < 0.05). Furthermore, compared to the pre-COVID-19 group, the post-COVID-19 group displayed higher rates of SLRTI and mechanical ventilation, with a longer length of hospital stay (all P < 0.05). Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6 were the shared independent risk factors for RSV-related SLRTI in both pre- and post-COVID-19 groups, whereas seizures and co-infection were independently associated with SLRTI only in the post-COVID-19 group.
Conclusions
An off-season RSV endemic was observed in Yunnan during the post-COVID-19 era, with changed clinical features and increased severity. Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6, seizures, and co-infection were the risk factors for RSV-related SLRTI in the post-COVID-19 era.
Introduction
Respiratory syncytial virus (RSV) represents a leading cause of lower respiratory tract infection (LRTI) in young children across the globe [1]. It was estimated that there were approximately 33.1Â million episodes of RSV-related LRTI per year, resulting in 3.2Â million hospital admissions and 59,600 in-hospital deaths among children aged below 5 years [2]. Of which, severe LRTI (SLRTI) has long been identified as the most dominant factor responsible for pediatric RSV-associated deaths, especially in developing countries [3, 4]. In the past, RSV activity was highly predictable due to marked seasonality in transmission, with peak seasons from October to the following April in the Northern Hemisphere and from April to September in the Southern Hemisphere [5]. However, this stable seasonal pattern of RSV spread was broken by the COVID-19 pandemic, which had posed catastrophic consequences to public health worldwide [6].
In response to the COVID-19 pandemic, most countries around the world implemented a series of rigorous non-pharmaceutical interventions (NPIs). Substantial evidence suggested that while the strict NPIs were effective in controlling COVID-19 pandemic, they also limited the seasonal circulation of RSV, with a significant decline in detection rates reaching up to 98% during the pandemic [7, 8]. However, as widely known, because of the lack of licensed RSV vaccines and the gradual decrease of maternal RSV neutralizing antibodies with increasing age, seasonal exposure to RSV has served as the primary way for children to acquire immune protection against RSV infection [9, 10]. Logically, the reduced seasonal exposure to RSV during the COVID-19 pandemic would enhance susceptibility to RSV in children, thereby increasing the severity of RSV infection. Indeed, with the gradual lifting of NPIs in the post-COVID-19 era, numerous countries, such as Australia, New Zealand, Italy, Japan, and China, have reported out-of-season RSV outbreaks, with increased proportions of RSV hospitalizations and intensive care unit (ICU) admissions [7, 11,12,13,14]. Given that COVID-19 pandemic and its related NPIs have affected the seasonal pattern, natural course, and severity of RSV infection in children, studies regarding RSV infection in post-COVID-19 era are urgently needed to further elucidate its epidemiological and clinical characteristics.
In the present study, we retrospectively collected the data on pediatric RSV inpatients at multiple hospitals in Yunnan, China, in 2018–2019 and 2023. A detailed analysis of epidemiology and clinical characteristics of these patients during the pre- and post-COVID-19 eras was performed to evaluate the seasonal and clinical evolution of RSV. In addition, we also compared the risk factors of RSV-associated SLRTI between the two eras, aiming to facilitate the early recognition of severe cases and reducing mortality in such patients during the post-COVID-19 era.
Methods
Study design and population
This multicenter retrospective study was conducted at eight public tertiary hospitals in Yunnan, China, enrolling children (≤ 14 years) hospitalized for RSV infection in 2019 and 2023. Patients admitted during January 2018–December 2019 and January–December 2023 were divided into the pre- and post-COVID-19 groups, retrospectively. Besides, to compare risk factors for RSV-associated SLRTI between the two eras, patients in pre- and post-COVID-19 groups were further classified into the respective severe and non-severe subgroups according to the presence or absence of SLRTI (Fig. 1).
SLRTI was defined as pneumonia or bronchiolitis accompanied by at least one of following conditions [15,16,17]: (1) a reduction in feeding amount to less than half of the normal, dehydration or refusal to feed; (2) disturbed consciousness; (3) manifestations of hypoxemia, including cyanosis, age-specific tachypnea (≥ 60 breaths/min for children under 2 months; ≥50 breaths/min for children aged 2 months to 1 year; ≥40 breaths/min for children aged > 1 to 5 years; ≥30 breaths/min for children older than 5 years), three concave signs, nasal flaring, grunting, intermittent apnea, or oxygen saturation < 88%; (4) persistent high fever for more than 5 days; (5) pulmonary imaging suggesting ≥ 2/3 unilateral lung infiltration, multilobar pulmonary infiltration, pleural effusion, pneumothorax, atelectasis, pulmonary necrosis, or pulmonary abscess; (6) extrapulmonary complications.
Ethical approval for this study was granted by the Ethics Committees of Kunming Children’s Hospital Affiliated to Kunming Medical University (approval number: 2023-05-012-K01), who also waived the written informed consent due to the retrospective design of the study.
Data extraction and definition
Data obtained from electronic medical records included demographic information (age, gender), clinical characteristics [low birthweight, preterm birth, personal and family histories of atopy, non-exclusively breastfeeding (non-EBF), underlying condition, duration of symptoms prior to admission, fever, fever peak, cough, rhinorrhea, nasal congestion, wheezing, acute otitis media, seizures, poor appetite, diarrhea, vomiting], laboratory indicators [oxygen saturation, leucocyte count, neutrophil-to-lymphocyte ratio (NLR), CD4+/CD8+ T cell ratio, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL-6), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine (Cr), urea, creatine kinase myocardial band (CK-MB), co-infection], and outcome measures [SLRTI, mechanical ventilation, ICU admission, length of hospital stay (LOS)].
In the above-mentioned data, low birthweight was defined as a birth weight of less than 2500 g; preterm birth was defined as gestational age < 37 weeks; underlying diseases included congenital heart diseases, bronchopulmonary dysplasia, pectus excavatum, malignant tumors, immunodeficiency, or severe malnutrition; non-EBF was defined as that the feeding practice within 6 months after birth was formula feeding or mixed feeding. In addition, all patients in this study had received the molecular detection of multiple respiratory pathogens, including RSV, influenza A virus (IAV), influenza B virus (IBV), human parainfluenza virus (HPIV), human adenovirus (HAdV), human rhinovirus (HRV), human metapneumovirus (HMPV), SARS-COV-2 (only in the post-COVID-19 era), mycoplasma pneumoniae (M. pneumoniae), chlamydophila pneumoniae, and legionella pneumophila. Co-infection referred to detection of another pathogen concurrent to RSV diagnosis. All data were cross-checked by two trained Ph.D. students to ensure accuracy.
Statistical analysis
Categorical variables were expressed as frequencies (n) and percentages (%) and compared using Pearson’s chi-square or Fisher’s exact test, while continuous variables with non-normal distributions tested by the Shapiro-Wilk test were summarized as medians with interquartile range (IQR) and then compared using Mann-Whitney U test. Multivariate logistic regression analysis was performed to identify the independent risk factors for SLRTI among pediatric RSV inpatients. All statistical analyses were carried out using R 3.5.1 (R Foundation, Vienna, Austria) with a significance level set at a two- tailed P value < 0.05.
Results
General characteristics of patients
During the entire study period, a total of 2553 pediatric RSV inpatients were included in this study. Among which, 1451 cases (658 cases in 2018 and 793 cases in 2019) were enrolled in the pre-COVID-19 group with a median age of 5.5 (2.1, 11.2) months and a male proportion of 59.5% (864/1451), while 1102 cases were enrolled in the post-COVID-19 group with a median age of 15.1 (10.5, 21.6) months and a male proportion of 57.0% (628/1102). Patients in the post-COVID-19 group were significantly older than those in the pre-COVID-19 group (P < 0.001) (Table 1).
Epidemiological characteristics of patients
In terms of temporal distribution of admissions (Fig. 2), the post-COVID-19 group showed that the number of RSV hospitalizations began to increase rapidly in April and culminate in August, followed by a sharp decline in October, indicating a peak period of hospitalization in April–September 2023, with the monthly hospitalization counts successively being 98 (8.9%) in April, 131 (11.9%) in May, 172 (15.6%) in June, 187 (17.0%) in July, 192 (17.4%) in August, and 117 (10.6%) in September.
In contrast, the period from May to September was an relative trough for RSV hospitalizations in the pre-COVID-19 group, which showed a peak period during January–April and October–December in both 2018 and 2019.
Clinical and laboratory characteristics of patients
There were significant differences regarding clinical and laboratory characteristics between the pre- and post-COVID-19 groups (Table 2). Specifically, despite a deceased proportion of wheezing, more frequent clinical manifestations (fever, acute otitis media, seizures) and significantly elevated laboratory indicators (leukocyte count, NLR, CRP, IL-6, co-infection rate) were found in the post-COVID-19 group than the pre-COVID-19 group (all P < 0.05). More notably, the proportion of patients developing SLRTI was 21.7% (239/1102) in the post-COVID-19 group, with a mechanical ventilation rate of 7.8% (86/1102) and a median LOS of 6.0 (4.0, 8.0) days, all of which were greater than those identified in the pre-COVID-19 group [16.8% (244/1451), 4.8% (70/1451), 5.0 (4.0, 7.0) days, respectively; all P < 0.05] (Table 3).
Co-infection of patients
Co-infection was detected in 439 cases (39.8%) in the post-COVID-19 group and 518 cases (35.7%) in the pre-COVID-19 group. As summarized in Table 4, dual infection was the most common mixed infection [299 (68.1%)] in the post-COVID-19 group, followed by triple infection [98 (22.3%)] and quadruple infection [42 (9.6%)]. The three most common combinations of co-infection were RSV + IAV [60 (13.7%)], RSV + M. pneumoniae [47 (10.7%)], and RSV + HRV [38 (8.7%)].
The concurrent infection in the pre-COVID-19 group was also dominated by dual infection, with a higher proportion than that in the post-COVID-19 group [79.5% (412/518) vs. 68.1% (299/439), P < 0.001]; whereas the proportions of triple and quadruple infections were significantly lower than those in the post-COVID-19 group [15.4% (80/518) vs. 22.3% (98/439), P = 0.006; 5.0% (26/518) vs.9.6% (42/439), P = 0.006)]. The top three combinations of co-infections in the pre-COVID-19 group in order were RSV + HRV [73 (14.1%)], RSV + HMPV [69 (13.3%)], and RSV + HPIV [61 (11.8%)].
Independent risk factors for RSV-associated SLRTI
As shown in Tables 5 and 239 (21.7%) cases in the post-COVID-19 group and 244 (16.8%) cases in the pre-COVID-19 group were classified into respective severe subgroups. Patients’ characteristics of severe and non- severe subgroups in both pre- and post-COVID-19 groups were summarized in Tables 5, 6 and 7. Variables with significant differences between severe and non-severe subgroups were included into logistic regression analysis. Finally, age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, and IL-6 were identified as the shared independent risk factors of SLRTI in both pre- and post-COVID-19 groups, whereas seizures and co-infection were independently associated with SLRTI only in the post-COVID-19 group (Fig. 3).
Discussion
Based on multicenter data, this study assessed children hospitalized for RSV infection during the pre- (2018–2019) and post-COVID-19 eras (2023) in Yunnan, China, to clarify the differences in characteristics of pediatric RSV infection between the two periods.
Before the COVID-19 pandemic, the RSV activities generally followed a predictable seasonal pattern with epidemic peaks from October to April of the following year in the Northern Hemisphere [5]. Consistent with this knowledge, in the pre-COVID-19 group of our study, the RSV-associated hospitalizations occurred more frequently during January- April and October- December in both 2018 and 2019. Whereas the post-COVID-19 group showed a pronounced off-season RSV endemic from April to September 2023, suggesting a significant seasonal shift in RSV prevalence during the post-COVID-19 era compared to the pre-COVID-19 era. Similar phenomena were also observed in multiple countries and regions, such as Japan and Italy [18, 19]. In addition, it should be noted, as we mentioned earlier, that RSV activity was barely recorded worldwide during the COVID-19 pandemic due to the strict implementation of COVID-19-related NPIs. Therefore, it may be difficult to determine the actual epidemiological and clinical features of RSV during the pandemic period. This is also the main reason why this study did not collect RSV data from the pandemic period for comparison and analysis.
There was an increase in age of patients in the post-COVID-19 group than those in the pre-COVID-19 group. It was well known that younger children, especially those under one year of age, were the main RSV-susceptible population in the past [20]. In our study, the pre-COVID-19 group showed a median age of 5.5 months, which was quite close to that reported in the previous literature [21, 22]. However, a significantly older median age (15.1 months) was found in the post-COVID − 19 group. Similarly, Australia, one of the earliest countries suffering from the out-of-season RSV outbreak after easing of COVID-19 containment, reported that RSV patients during the post-COVID-19 period had a median age of 16.4 months, which was more than twice that observed before the emergence of COVID-19 pandemic (8.1 months) [12]. Jiang et al. [23] recently demonstrated the immunity debt due to the absent seasonal RSV circulation mainly caused by NPIs. The levels of RSV-specific antibody among children were significantly declined during the COVID-19 pandemic compared to those in the pre-pandemic period, and the changes of antibody levels presented marked variability across different age groups, with a more prominent decrease identified in older children. This might partially explain the trend towards increasing age of children with RSV infection in the post-COVID-19 era.
Besides, more frequent clinical manifestations (fever, acute otitis media, seizures), elevated inflammatory indicators (NLR, CRP, IL-6), higher proportion of SLRTI, increased requirement of mechanical ventilation, and longer LOS were observed in the post-COVID-19 group compared to those in the pre-COVID-19 group, suggesting a greater clinical severity of RSV infection in the post-COVID-19 group. The discrepancy of clinical severity between the two groups was probably linked to two factors: immunity debt caused by NPIs and immune dysregulation associated with prior SARS-CoV-2 infection [24]. First, the absence of RSV seasonal exposure due to the implementation of NPIs during COVID-19 pandemic was confirmed to generate immunity debt [8, 23], which might exacerbate the clinical course of RSV infection. Second, previous studies revealed that compared with healthy individuals, patients who had overcome acute SARS-CoV-2 infection for over two months showed significant impairment of T, NKT, and NKT-like cells [25]. Meanwhile, the absence of naive T and B cells could still be found in some recovered patients at eight months after acute SARS-CoV-2 infection [26]. Altogether, these findings implied that immune dysregulation might persist for months following the recovery from acute SARS-CoV-2 infection, potentially causing harmful effects on the immune system. Given the ultra-high prior infection rate of SARS-CoV-2 in China [27], potential immune dysregulation could be a non-negligible factor affecting RSV severity in the post-COVID-19 era. Of course, we also cannot ignore that the increased severity of symptoms observed in the post-COVID-19 group might also be attributed to an increased likelihood of encountering severe cases, given the intensified RSV circulation and its associated hospitalization burden worldwide. Consistent with this, in our study, the number of inpatients in the post-COVID-19 group (1102 cases) was indeed greater than that in any single year of the pre-COVID-19 group (658 cases in 2018 and 793 cases in 2019). Therefore, although the severity evaluation of RSV was performed based on multiple aspects (inflammatory indicators, proportion of severe case, requirement of mechanical ventilation, LOS) in this study, we must acknowledge the potential that the increase in hospitalized cases could have led to a higher likelihood of observing severe cases. In addition, it was recently proposed that conditions associated with the COVID-19 pandemic perhaps favored the emergence of more virulent or contagious RSV strains [24], but the current findings do not support this perspective [28, 29] and more reliable evidence is required.
In addition, one noteworthy phenomenon was that compared to the pre-COVID-19 group, the post-COVID-19 group showed a significantly increased incidence of seizures (11.9% vs. 4.9%), which might serve as the vital evidence suggesting the association between COVID-19 pandemic and the heightened clinical severity of RSV infection during the post-pandemic period. Combined with previous studies [27, 30,31,32,33], the reactivation of residual SARS-CoV-2 virus among the recovered individuals and/or the current co-infection with Omicron variant might partially account for the raised incidence of seizures in pediatric RSV infection. Furthermore, even before the COVID-19 pandemic, RSV infection itself could lead to fatal neurological damage in children [34], so attention to neurological complications is particularly needed in the clinical management of pediatric RSV infection during the post-COVID-19 period. Another significant clinical alteration of RSV infection in the post-COVID-19 era was the decreased proportion of wheezing (44.9% and 40.7% in pre- and post-COVID-19 groups, respectively), which was one of the most common symptoms of children with RSV infection in the past. This change implied that clinicians also should pay sufficient attention to RSV patients without wheezing during the post-COVID-19 era, in order to avoid missed diagnosis and misdiagnosis.
Moreover, in this study, the post-COVID-19 group showed a higher proportion of co-infections (39.8% vs. 35.7%), with more frequent multiple infections (triple infection: 22.3% vs. 15.4%; quadruple infection: 9.6% vs. 5.0%), compared to the pre-COVID-19 group. This phenomenon might also be relevant to the NPIs-induced immunity debt, which affected not only RSV but also other pathogens. Variable degrees of resurgences in multiple pathogens, such as influenza viruses and M. pneumoniae, have been reported after the easing of NPIs [8, 35]. This perhaps represented a potential cause underlying the increased co-infections, especially multiple infections, during the post-COVID-19 era. Simultaneously, increased co-infection might be one of reasons why the RSV infection in the post-COVID-19 group displayed a greater clinical severity than the traditional seasonal RSV infection, because numerous studies have shown that mixed infections tended to be closely linked to more severe clinical outcomes [36]. Furthermore, significant differences in the pathogen spectrum of co-infections were observed between the two groups. In the post-COVID-19 group, the top three combinations of co-infections were RSV + IAV, RSV + M. pneumoniae, and RSV + HRV, while they were RSV + HRV, RSV + HMPV, and RSV + HPIV in the pre-COVID-19 group. Particularly, it is important to mention that incidences of RSV + IAV and RSV + M. pneumoniae in the post-COVID-19 group were significantly higher than those in the pre-COVID-19 group. Haney et al. [37]. have confirmed that the co-infection of RSV and IAV forms hybrid virus particles (HVPs), which can utilize RSV fusion glycoprotein to escape antiviral neutralizing antibodies, thus enhancing viral infection and transmission among cells. This interaction between RSV and IVA might affect virus pathogenesis by expanding virus tropism and enabling immune escape. This experimental finding may well explain the clinical observation that co-infection of RSV/IVA is associated with more severe outcomes [38, 39]. A similar trend was reported in individuals concurrently infected with RSV and M. pneumoniae, where the clinical severity was significantly higher in those with co-infection compared to those with single RSV infection [40]. Therefore, the changes in pathogen spectrum of mixed infections might also be one of the potential factors causing the variation in clinical characteristics and severity of RSV infection between pre- and post-COVID-19 groups.
To better facilitate the understanding and early recognition of RSV-associated SLRTI, we identified and further compared the independent risk factors of SLRTI between the pre- and post-COVID-19 groups. The result showed that age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, and IL-6 were independently associated with occurrence of RSV-associated SLRTI in both pre- and post-COVID-19 groups. This was not unexpected, because these factors have been widely reported and recognized as the effective predictors for severe RSV infection in previous research [21, 41, 42]. However, an interesting finding in our study was that in addition to the seven shared risk factors, seizures and co-infection were identified as the risk factors of SLRTI only in the post-COVID-19 group. This again suggested that more frequent seizures and co-infection were likely to be significant characteristics of RSV infection in the post-COVID-19 era and played important roles in the progression of RSV infection, reflecting the potential impact of COVID-19 pandemic on RSV infection. Therefore, strengthening the evaluation of these above indicators, especially seizures and co-infections, are essential for the early recognition of RSV-associated SLRTI in the post-COVID-19 era.
The present study has several limitations that should be considered. First, there were inherent biases due to the retrospective nature of study. Second, only inpatients were included in this study. To better explore epidemic dynamics of RSV, outpatients should be enrolled in future research. Another limitation is that only one year of post-pandemic RSV data was collected and analyzed, so it might not be able to fully reflect the dynamic changes of RSV during this period. In addition, the present study did not classify underlying condition in detail, which resulted in the failure to fully explain the influence of different comorbidities on the occurrence of RSV-associated SLRTI, despite identifying underlying condition as an independent risk factor. Finally, we did not analyze the circulating RSV strains at the genomic level to assess possible discrepancy between the pre- and post-COVID-19 periods.
Conclusions
This multicenter retrospective study indicated an out-of-season RSV endemic in Yunnan, China, during the post-COVID-19 era, with a peak period of pediatric RSV hospitalization from April to September 2023. Children hospitalized for RSV infection in the post-pandemic era showed a trend towards older age, different clinical features, and increased severity. Meanwhile, in addition to seven shared risk factors (age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6) for RSV-associated SLRTI in both pre- and post-COVID-19 groups, seizures and co-infection were independently associated with SLRTI among patients only in the post-COVID-19 group. It is essential for clinicians to be aware of these changes and differences between the two periods, in order to optimize the clinical management of such patients and reduce the occurrence of RSV-related SLRTI and deaths.
Data availability
No datasets were generated or analysed during the current study.
Abbreviations
- ALT:
-
Alanine transaminase
- AST:
-
Aspartate transaminase
- CK:
-
MB-Creatine kinase-MB
- Cr:
-
Creatinine
- CRP:
-
C-reactive protein
- EBF:
-
Exclusively breastfeeding
- ESR:
-
Erythrocyte sedimentation rate
- HAdV:
-
Human adenovirus
- HMPV:
-
Human metapneumovirus
- HPIV:
-
Human parainfluenza virus
- HRV:
-
Human rhinovirus
- HVPs:
-
Hybrid virus particles
- IAV:
-
Influenza A virus
- IBV:
-
Influenza B virus
- ICU:
-
Intensive care unit
- IL:
-
6-Interleukin 6
- IQR:
-
Interquartile range
- LDH:
-
Lactate dehydrogenase
- LOS:
-
Length of hospital stay
- M. pneumoniae:
-
Mycoplasma pneumoniae
- NLR:
-
Neutrophil-to-lymphocyte ratio
- NPIs:
-
Non-pharmaceutical interventions
- PCT:
-
Procalcitonin
- RSV:
-
Respiratory syncytial virus
- SLRTI:
-
Severe lower respiratory tract infection
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This work was supported by the National Natural Science Foundation of China (grant numbers: 81960021 and 82360025) and the Yunnan Provincial Department of Education Science Research Fund Project (grant number: 2023Y0790).
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L.H.F. contributed to conceptualization, formal analysis, funding acquisition, and writing–original draft. W.Y.Y., Z.X.Z., and L.H.Y. were involved in methodology, formal analysis, and supervision. X.M., L.R., L.C.Y., L.W., F.Q.L., G.Y.J., and H.R.W. performed data extraction and visualization. F.H.M. contributed to conceptualization, methodology, project administration, funding acquisition, supervision, writing–review and editing. All authors read and approved the final manuscript.
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This study was approved by the Ethics Committees of Kunming Children’s Hospital Affiliated to Kunming Medical University (the lead institution of this study) (2023-05-012-K01), who also waived the informed consent due to the retrospective design of the study.
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Liu, HF., Wang, YY., Zhang, XZ. et al. Comparison of characteristics of children hospitalized for respiratory syncytial virus infection during the pre- and post-COVID-19 eras: a multicenter retrospective study. BMC Infect Dis 24, 1009 (2024). https://doi.org/10.1186/s12879-024-09783-2
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DOI: https://doi.org/10.1186/s12879-024-09783-2