Seasonal epidemiological and clinical characteristics of pediatric patients with respiratory syncytial virus infection by age during COVID-19: a cross-sectional study

Introduction

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection (ALRTI) in children under 5 years old. In 2019, 33 million ALRTIs caused by RSV occurred in children under 5 years old worldwide, of whom about 10% required hospitalization, resulting in about 100,000 deaths (1). Infants who are considered at the highest risk for severe disease include those born at <29 weeks’ gestational age, those with chronic lung disease, neurologic or neurodevelopmental disorders, and those with hemodynamically significant congenital heart disease (2-4). In addition, a large and consistent body of evidence documenting an increased asthma and recurrent wheezing risk in infants hospitalized for RSV-induced ALRTI suggests that infections with this pathogen during infancy may be contributing more to both short-term and long-term lower respiratory tract manifestations during early childhood than was previously appreciated (2). The multifaceted impact of RSV underlines that prevention is key, as antivirals are not yet available. Palivizumab has been a standard of care for the prevention of severe RSV illness for 25 years, which is licensed for specific high-risk infants only. We are at the advent of novel promising compounds (5,6). The landscape for RSV prevention has changed dramatically in 2023, and a protein-based maternal vaccine and monoclonal antibody are now market-approved to protect infants and children at high risk through passive immunization (7-9). In December 2023, the National Medical Products Administration of China also approved its first RSV preventive product (nirsevimab), marking this event as a key milestone in the prevention of RSV infections in China (6,9). As countries begin to roll-out the new RSV vaccines, to optimize their use, it will be important to identify which infants are at risk for severe RSV disease and have real-world efficacy data of potential changes in RSV epidemiology.

Since the coronavirus disease 2019 (COVID-19) pandemic, the introduction of non-pharmaceutical interventions (NPIs) has led to major changes in the seasonality and epidemiology of RSV. Indeed, in many countries, including China, RSV was absent during the typical spring RSV epidemic season in 2020, followed by an off-season surge after the relaxation of NPIs, thus leading to a considerable impact on global healthcare systems (10-13). It is unknown how COVID-19 will affect the seasonality of RSV in the short and medium term (next 3–5 years). Extrapolation from other pandemics may be important, for example, the 2009 influenza pandemic delayed the RSV onset on average by 0.58 months and up to 2.5 months (14). Many areas of the world experienced different degrees of off-season resurgence of cases, raising the concern that in countries emerging from pandemic restrictions, this could result in uncontrolled transmission and increased disease severity. For instance, a study in the United States indicated that more severe RSV-related diseases in infants during the COVID-19 pandemic might be associated with diminished immunity from a lack of exposure to RSV in the previous season (15). Fortunately, a study in Japan indicated that the RSV symptoms during the COVID-19 outbreak were equivalent to or milder than in the previous seasons (16), which was similar to the studies conducted in Shanghai and Beijing (17,18), characterized by fewer severe lower respiratory tract infection cases. To date, reports have been conflicting regarding changes in the age distribution and severity of RSV hospitalizations in children since the beginning of the COVID-19 pandemic, and data from different regions in China are lacking. These discrepancies may be associated with limitations of administrative data set analyses, differences in study design, patients included, or clinical management. Therefore, we aimed to describe the RSV epidemiological characteristics, the clinical characteristics, and disease severity of children with RSV infection before and during the COVID-19 pandemic. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-62/rc).

Methods

Study design and participants

This cross-sectional study enrolled children with ALRTI who were hospitalized at the Children’s Medical Center of Hunan Provincial People’s Hospital and the First Affiliated Hospital of Hunan Normal University between January 1, 2018, and December 31, 2022. The inclusion criteria were as follows: (I) <14 years of age; (II) diagnosis of ALRTI presents lower respiratory tract symptoms (e.g., tachypnea, nonproductive cough, wheezing, and increased breath sound), and signs of ALRTI (rales or wheezes) or chest imaging findings (bronchitis or pneumonia), including a diagnosis of pneumonia, bronchitis, and bronchiolitis; and (III) evidence of RSV infection. Children hospitalized with ALRTI were subjected to rapid antigen detection testing for RSV, adenovirus, influenza virus A, influenza virus B, and parainfluenza virus types 1–3. The medical records were reviewed to identify patients who were RSV-positive.

Children with any of the following factors were excluded: (I) COVID-19 confirmed by laboratory test; (II) children with immunosuppression related to solid organ or hematopoietic stem cell transplantation, chemotherapy, tumors, hematological diseases, a history of human immunodeficiency virus, steroid treatment for >30 days, or immunosuppressant treatment; (III) known or suspected active tuberculosis; (IV) intra-airway foreign body; and (V) children with recurrent chronic respiratory infections.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The original study was approved by the Ethics Committee of Hunan Provincial People’s Hospital and the First Affiliated Hospital of Hunan Normal University (approval No. LL-20240124-1) and was a retrospective study. The ethical committee voted that written informed consent was not required for collecting data of RSV-positive children retrospectively.

The study flow chart is shown in Figure 1. COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2, spread rapidly at the end of 2019. Under the COVID-19 prevention measures in China, we defined January 2018 to December 2019 and January 2020 to December 2022 as the before COVID-19 and during COVID-19 periods, respectively. The patients were divided into 1–5, 6–11, 12–23, 24–59, and ≥60 months old groups.

Figure 1 Patient recruitment in the RSV infection cohort. ALRTI, acute lower respiratory tract infection; COVID-19, coronavirus disease 2019; RSV, respiratory syncytial virus.

Sample collection and laboratory tests

Nasopharyngeal swabs were obtained within 24 hours of hospitalization for virological analysis. Specimens were collected from the children by trained nurses after admission and were transported immediately to the clinical laboratory center for detection of RSV, adenovirus, influenza virus A, influenza virus B, and parainfluenza virus types 1–3. For the direct fluorescent antibody assay, cell pellets from nasopharyngeal swab samples were suspended in several drops of sterile phosphate-buffered saline, and the resulting cell suspension was spotted onto an acetone-cleaned slide. An anti-RSV monoclonal antibody labeled with fluorescein isothiocyanate from the D3 Ultra TM DFA Respiratory Virus Screening & ID Kit (Diagnostic Hybrids Inc., Athens, OH, USA) was used for RSV identification by DFA and was conducted by professional staff following standard operating procedures.

Data collection

The following data of hospitalized patients with RSV infection were collected by trained investigators by querying the hospital information system: (I) demographic characteristics; (II) underlying conditions such as congenital heart disease, prematurity, and respiratory tract abnormalities; (III) clinical information, including clinical manifestations and discharge diagnosis; and (IV) disease severity (hospitalization duration, oxygen supplementation, non-invasive ventilation (high-flow nasal cannula, continuous positive airway pressure support, and mask oxygen supply), invasive ventilation, and the rate of admission to the pediatric intensive care unit (PICU).

Statistical analysis

Statistical analysis was conducted using IBM SPSS Statistics software (version 25). We compared the demographic and clinical characteristics of patients with RSV infection before and during the COVID-19 pandemic. Categorical variables were described as numbers and proportions of cases (%). The Chi-squared test or Fisher’s exact test was used to compare categorical variables. Non-normally distributed continuous variables are expressed as medians and interquartile ranges (IQRs) and were compared using the Mann-Whitney-Wilcoxon test. Values of P<0.05 were considered indicative of significance.

Results

Epidemiological surveillance of RSV

Figure 1 shows that from January 1, 2018, to December 31, 2022, 24,072 patients with ALRTIs were enrolled in this study, including 5,689 in 2018, 7,887 in 2019, 2,994 in 2020, 4,039 in 2021, and 3,463 in 2022. The RSV detection rate was 17.68% (4,255 of 24,072). RSV-positive cases were 913 (16.05%), 1,017 (12.89%), 597 (19.94%), 1,248 (30.90%), 480 (13.86%) in 2018, 2019, 2020, 2021, 2022, respectively, with a significant statistical difference of the RSV-positive rate among the years (χ²=664.741, P<0.001). The number of hospitalizations in 2020 has significantly decreased compared to 2019 (2,994 vs. 7,887), representing a 62% decrease, the impact of the NPIs implemented against COVID-19 (which started in January 2020) was already visible in the number of hospitalizations and RSV-attributable ALRTI cases. Interestingly, the fewer number of hospitalizations was accompanied by larger RSV-test positivity rates overall (12.89% in 2019 vs. 19.94% in 2020).

Figure 2 shows the monthly RSV trends in Hunan from the pre-pandemic years 2018–2019 to COVID-19 pandemic year 2020–2022. We defined December to February as winter, March to May as spring, June to August as summer, and September to November as autumn. Before the COVID-19 pandemic (2018 to 2019), the prevalence of RSV showed a seasonal pattern in Hunan; the RSV-positive rate and number of cases peaked from December to February and were low in summer (Figure 2). In 2020, after the start of the COVID-19 pandemic and the national lockdown in January, the RSV detection rate and number of cases decreased sharply in February and kept at a low level until the autumn of 2020. After that, RSV infections displayed a gradual increment, peaking in the winter (February) of 2020/2021. Afterwards, RSV became prevalent throughout 2021, with monthly detection rates exceeding 10%, until the end of March 2022. These data suggested that RSV showed an abnormal transmission pattern during COVID-19 pandemic.

Figure 2 Monthly distribution of RSV among children. The number and positive rate of RSV-positive inpatients admitted to the Children’s Medical Center of Hunan Provincial People’s Hospital and the First Affiliated Hospital of Hunan Normal University from January 1, 2018 to December 31, 2022 were displayed. Before COVID-19 period, January 1, 2018 to December 31, 2019; During COVID-19 period, January 1, 2020 to December 31, 2022. The number of RSV-positive inpatients admitted to the hospital is shown in the gray column diagram, and the positive rate of RSV is shown in the black broken line graph. COVID-19, coronavirus disease 2019; RSV, respiratory syncytial virus.

Demographic characteristics

Among the 4,006 RSV-positive ALRTI children, 2,520 were males (62.91%; 2,520 of 4,006) and 1,486 were females (37.09%; 1,486 of 4,006). Children <5 years old accounted for 98.45% of them and had a median age of 10 months. There was no difference in gender distribution before and during the COVID-19 epidemic (χ²=0.950, P=0.33). In terms of age distribution, RSV-infected children with ALRTI had a median age of 8 months (IQR, 3–14 months) before the COVID-19 pandemic and 12 months (IQR, 6–24 months) during the COVID-19 pandemic (Z=−12.688, P<0.001). Compared with before the COVID-19 pandemic, the proportion of RSV-positive ALRTI children in the 1–5 months old group decreased from 37.47% to 23.61% (χ²=90.273, P<0.001), that in the 24–59 months old group increased from 12.17% to 24.29% (χ²=92.225, P<0.001), and the proportion of children in the ≥60 months old group increased from 0.84% to 2.06% (χ²=9.597, P=0.002). There were no differences in the rates of congenital heart, bronchopulmonary dysplasia, and breastfeeding between the two groups before and during the COVID-19 pandemic. Compared to before the COVID-19 pandemic, RSV-positive ALRTI hospitalized children had a higher rate of preterm births (8.37% vs. 6.50%, χ²=4.838, P=0.03) and a significantly higher rate of infants born at 29–35 weeks (χ²=4.473, P=0.03) during the COVID-19 pandemic (Table 1).

Clinical features

Among 4,006 cases of RSV infection, cough (99.75%) and wheezing (76.98%) were the main clinical manifestations. Fever and the highest body temperature of >39 ℃ were present in 67.02% and 38.24% of the children, respectively, and the median duration of fever was 4 days. Other clinical manifestations were catarrhal symptoms (34.27%), vomiting (20.07%), polypnea (14.43%), diarrhea (8.89%), cyanosis (4.59%), and convulsion (1.32%).

Among the 4,006 RSV-positive ALRTI children, 3,944 (98.45%) were <5 years old. The clinical characteristics of RSV-infected children in the hospital before and after COVID-19 pandemic were compared on the basis of age grouping. Regarding clinical symptoms, the rate of wheezing decreased in all the age groups during, as compared to before, the COVID-19 pandemic (Figure 3). The wheezing rate of children 1–5 months old decreased from 89.81% before to 72.36% during the COVID-19 pandemic (P<0.001). Except for those in the 12–23 months old group, the proportions of fever in other groups increased during the COVID-19 pandemic (P<0.05). The rates of polypnea, dyspnea, and catarrh symptoms increased in all the age groups (P<0.001). Cyanosis was more common in children 1–5 and 6–11 months during than before the COVID-19 pandemic. However, there were no differences in high fever, cough, convulsions, vomiting, and diarrhea among the age groups before and after the COVID-19 pandemic (Figure 3).

Figure 3 Comparison of clinical characteristics of RSV-positive children in different age group before and during the COVID-19 pandemic. Dark grey indicates before COVID-19 and light grey indicates during COVID-19. COVID-19, coronavirus disease 2019; RSV, respiratory syncytial virus.

Disease severity

Compared with pre-pandemic seasons [2018–2019], disease severity (oxygen administration and mechanical ventilation) increased in the pandemic seasons [2020–2022] (Table 2). Analyses stratified by age showed that disease severity was significant among the groups aged younger than 24 months. The larger proportions of children 1–5 months old (34.91% vs. 28.50%, χ²=5.577, P=0.02), 6–11 months old (29.90% vs. 22.22%, χ²=7.825, P=0.005), and 12–23 months old (25.81% vs. 14.21%, χ²=18.229, P<0.001) required oxygen support during the COVID-19 pandemic. Among aged 6–11 months old group, children during COVID-19 showed a higher rate of invasive ventilation (2.61% vs. 0.89%, χ²=4.178, P=0.04). There was no difference in hospitalization duration or the rate of admission to the PICU before, as compared to during, the COVID-19 pandemic (Table 2).

Discussion

RSV is the most important viral cause of ALRTI in children <5 years old globally (1). In 2020, the rate of RSV infection decreased markedly in the first year of the COVID-19 pandemic, and the incidence of RSV infection and bronchiolitis was very low worldwide (19-22). As public health and social measures were gradually lifted, the resurgence of RSV became a significant concern, drawing attention from experts globally. Interestingly, our study observed that RSV-positive cases were suppressed from February to August in 2020, when the most restrictive NPIs were enforced, and RSV resurged gradually from September to December 2020, when the concurrent reopening of state primary and secondary schools, indicating that the relaxed NPIs were ineffective in inhibiting RSV transmission. Therefore, from the results of the present study, the total RSV infection rate in 2020 did not decrease due to NPIs. Li and colleagues also have reported a multi-country longitudinal observational study that describes the predominant risk factor for RSV rebound is full (re)opening of schools, which explains the out-of-season RSV epidemics during the COVID-19 pandemic. The risk for RSV rebound also increases over time since the expected typical RSV onset, highlighting the role of the increased susceptible population (21). In the study, the detection rate of RSV in 2021 was abnormally high (30.90%); Northern hemisphere countries such as the United States (13), Japan (16), and Italy (22) also experienced a surge in RSV infections in 2021. The susceptible population was an important contributor to RSV infection in 2021. There was a significant RSV antibody level and function decreased in infants and women of reproductive age at 1 year after the COVID-19 pandemic, in absence of viral exposure (23,24). An inadequate rate of RSV immune protection may exacerbate subsequent seasonal RSV epidemics. This could also explain the resuscitation of infants hospitalized with RSV infection as social distancing measures were eased.

The demographic characteristics of RSV infection differed before and during the pandemic. The median age increased from 8 to 12 months of age during the pandemic, compared to before the COVID-19 pandemic (2018 to 2019). The proportion of children 1–5 months old decreased and that of children 24–59 months old significantly increased, which may be the cumulative effect of susceptible groups. Since the beginning of the COVID-19 pandemic, China has implemented a strong NPI policy, blocking the spread of RSV and increasing the susceptible population. The number of susceptible children has increased over time, resulting in a gradual increase in the median age of RSV infection (23,25). In Australia and the United Kingdom, increased susceptibility to RSV may be related to the incidence of patients 2–4 years old (10,11). In Denmark, the largest number of hospitalizations during the COVID-19 epidemic was among children 24–59 months old (26). The RSV-specific antibody concentrations among children differed according to age group during the COVID-19 pandemic. The decrease in antibody concentration was more pronounced in the 3–4 years old group, possibly explaining the more pronounced surge in RSV cases in this age group (27).

The clinical presentation of RSV infection in children varies by age and is associated with disease severity (1,4,28). Airway development and infection-induced immune responses differ according to age, affecting the clinical characteristics of RSV infection (29). In this study, we found that during the COVID-19 pandemic, wheeze was significantly reduced in every age group. While children had a significantly higher percentage of fever, except for the 12–23 months old group. Also, polypnea, dyspnea, and catarrh increased in all the age groups during the COVID-19 pandemic (P<0.001). Cyanosis was more common in children 1–5 and 6–11 months old during than before the COVID-19 pandemic. Infants and children <5 years old were less likely to be diagnosed with bronchiolitis and more likely to be diagnosed with RSV infection in 2021 and 2022, as compared to 2015 to 2019 (30). Compared to before the COVID-19 pandemic, the rate of RSV-positive children with fever was higher, and the rates of polypnea and wheezing were significantly lower (31). Liu et al. found a deceased rate of wheezing and a higher rate of fever after, compared to before, the COVID-19 pandemic, similar to our results (32). Wheezing is the most common clinical manifestation of RSV infection and an independent risk factor for its exacerbation (2), so the present study found that wheezing may not be a suitable indicator for clinical surveillance and early identification of RSV infection after the COVID-19 pandemic. In fact, RSV bronchiolitis, especially severe disease, is associated with acute and recurrent wheezing in infants. Though the mechanism is yet to be fully elucidated, the general theory proposes that the shedding of infected cells and syncytia bodies from RSV invasion might contribute to airway hyperresponsiveness, particularly when infection occurs during the airway development window in early childhood (2,33). A previous study has demonstrated that healthy preterm infants who were randomly assigned to receive palivizumab had fewer wheezing days in their first year of life, a reduced presence of any wheeze at ages 1–3 years, and reduced recent wheeze at age 6 years compared with the placebo group (34). In recent study, nirsevimab displayed similar effectiveness in mitigating the risk of wheezing during infancy for those receiving the antibody after birth. NPIs are likely to be effective in preventing RSV infection as palivizumab (35). The pandemic provided a natural experiment for longitudinal cohorts, and comparison of children born before and during the pandemic for wheezing at specific ages might be helpful despite substantial issues with confounding. Whatever the method of prevention or delay, there is evidence of potential secondary long-term benefit of RSV prevention in early life. Further studies are required to confirm the impact of the COVID-19 pandemic on recurrent wheezing, especially in those who were born during the periods when RSV lower respiratory tract infection was much reduced and to explore the long-term benefits of NPIs on RSV-related morbidity in infancy and early childhood, such as asthma.

In addition, disease severity parameters were increased in infants younger than 24 months during pandemic and post-pandemic seasons vs. pre-pandemic years. In this study, the severity of RSV infection in children <2 years old increased during the COVID-19 epidemic, as reflected by the oxygen support rate. In the 6–11 months old group, the rate of invasive ventilation increased, whereas disease severity in the >2 years old group did not change. The severity of RSV described in our study follows trends that are similar to those presented in other studies (15,26), but age-specific variation in severity was observed. For example, a national, population-based study in Denmark in 2021-2022 found an increase in the incidence rate of RSV-associated admissions and mechanical ventilation, especially among children aged 2 to 5 years, underscoring the importance of ongoing monitoring of age-specific disease incidence of RSV (26). For instance, a study in the United States indicated more severe RSV-related diseases in infants younger than 12 months during the COVID-19 pandemic according to oxygen administration, length of stay and PICU admission. Severity indicators such as supplemental oxygen and invasive mechanical ventilation varied by age, which could indicate different criteria for admission or different underlying characteristics of the populations at each study site. Furthermore, controversy on this severity topic can be partially explained by the discrepant NPIs between different regions and clinical Management. In Beijing and Shanghai, children would be more active in medical treatment and drug intervention, referring to epidemic prevention and control strategies, thus showing more mild clinical symptoms (17,18). Nygaard et al. found that children with co-infections can complicate RSV respiratory episodes, leading to increased severity (26). However, hospitalized children with a single RSV infection as the study population also has a certain impact on the judgment of disease severity (18). Primary RSV infections cause severe illness in the early stages of infancy (4), and the majority of children are considered to have been infected before the age of 2 years (36). Children <2 years old have small airway diameters and low respiratory-function reserves and are more likely to suffer a severe primary RSV infection. This highlights the importance of preventing primary RSV infection in infancy. Reinfections occur throughout life, and disease severity diminishes with subsequent exposures (36). The implementation of NPIs during the COVID-19 pandemic resulted in an increase in primary infection in older children because they lack memory T- and B-cell immunity in the absence of the virus (37,38). The incidence, but not the severity, of primary RSV infection in the 24–59 months old group was higher than previously. Therefore, most primary RSV infections in children ≥2 years of age may not result in severe disease and age is the most important risk factor for severe RSV infection, despite the presence of immune-debilitating factors. Disease severity was increased in children <2 years old, suggesting that in addition to immune-debilitating, disease severity is influenced by, for example, age and preterm birth, which may be related to the maternal antibody titer. Changes in the epidemiology and/or severity of RSV infection during the COVID-19 pandemic may be ascribed to the interactions between multiple known and/or unknown factors. Further research is needed to confirm and extend these findings.

There are some limitations in this study. First, the study was observational, and the associations that we identified may or may not be causal. Second, it is a single-center study, children in our study may not be representative of all areas, which may limit generalizability. Third, RSV typing was absent and we failed to explore the mechanism of changes in clinical characteristics and epidemic trend of RSV infection after the epidemic, which was limited by our laboratory testing methods and the fact that the study was retrospective. Fourth, the study focused exclusively on hospitalized patients with ALRTI who had undergone a nasopharyngeal examination. RSV infection children were subject to possible changes in the healthcare-seeking behaviors associated with the COVID-19 pandemic. During the severe period of COVID-19, people’s visits to hospitals for emergencies and face-to-face outpatient clinic visits were delayed, and most patients did not visit hospitals due to mild clinical issues. One strength of our study is that data were drawn from a well-established system that captures hospitalizations for acute lower respiratory infection for which all patients have been routinely respiratory viral tested since 2012, so there was stability in terms of applications of consistent case definitions, specimen collection, and testing, as well as quality control, ensuring the comparability between the pandemic and the pre-pandemic periods. There was also no data capture bias because data for all children hospitalized with an acute respiratory illness were captured throughout the years.

Conclusions

Since 2020, COVID-19 has affected the spread of RSV. There is an atypical upsurge of RSV infection in the autumn of 2020 and throughout 2021 after a major suppression in February 2020. In the context of COVID-19, the median age increased in children with ALRTI infected by RSV, the proportion of wheezing decreased, and the disease severity was greater in children ≤2 years of age. The severity of RSV during the COVID-19 pandemic needs to be investigated to prevent rebounds and unexpected effects, and the epidemiology of RSV needs to be monitored.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-62/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-62/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-62/prf

Funding: This study was supported by grants from the Hunan Provincial Medicine and Health Research Program (No. C202306016954), the 2023 Major Scientific Research Project for High-Level Health Talents in Hunan Province (No. R2023119), the Hunan Provincial Key Laboratory of Children’s Respiratory Diseases (No. 2019TP1043), and the Hunan Provincial People’s Hospital Benevolence Foundation (No. RS2022B03).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-62/coif). The authors have no conflicts of interest to declare.

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. The original study was approved by the Ethics Committee of Hunan Provincial People’s Hospital and the First Affiliated Hospital of Hunan Normal University (approval No. LL-20240124-1) and was a retrospective study. The ethical committee voted that written informed consent was not required for collecting data of respiratory syncytial virus positive children retrospectively.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. 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. [Crossref] [PubMed]
2. Zar HJ, Cacho F, Kootbodien T, et al. Early-life respiratory syncytial virus disease and long-term respiratory health. Lancet Respir Med 2024;12:810-21. [Crossref] [PubMed]
3. Thorburn K. Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection. Arch Dis Child 2009;94:99-103. [Crossref] [PubMed]
4. Mazur NI, Caballero MT, Nunes MC. Severe respiratory syncytial virus infection in children: burden, management, and emerging therapies. Lancet 2024;404:1143-56. [Crossref] [PubMed]
5. Palivizumab, a Humanized Respiratory Syncytial Virus Monoclonal Antibody, Reduces Hospitalization From Respiratory Syncytial Virus Infection in High-risk Infants. Pediatrics 1998;102:531-7. [Crossref]
6. Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med 2023;388:1451-64. [Crossref] [PubMed]
7. Two vaccines (Arexvy and Abrysvo) for prevention of RSV disease. Med Lett Drugs Ther 2023;65:155-6. [Crossref] [PubMed]
8. Keam SJ. Nirsevimab: First Approval. Drugs 2023;83:181-7. [Crossref] [PubMed]
9. Hammitt LL, Dagan R, Yuan Y, et al. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. N Engl J Med 2022;386:837-46. [Crossref] [PubMed]
10. Bardsley M, Morbey RA, Hughes HE, et al. Epidemiology of respiratory syncytial virus in children younger than 5 years in England during the COVID-19 pandemic, measured by laboratory, clinical, and syndromic surveillance: a retrospective observational study. Lancet Infect Dis 2023;23:56-66. [Crossref] [PubMed]
11. Foley DA, Phuong LK, Peplinski J, et al. Examining the interseasonal resurgence of respiratory syncytial virus in Western Australia. Arch Dis Child 2022;107:e7. [Crossref] [PubMed]
12. Xie LY, Wang T, Yu T, et al. Seasonality of respiratory syncytial virus infection in children hospitalized with acute lower respiratory tract infections in Hunan, China, 2013-2022. Virol J 2024;21:62. [Crossref] [PubMed]
13. Hamid S, Winn A, Parikh R, et al. Seasonality of Respiratory Syncytial Virus - United States, 2017-2023. MMWR Morb Mortal Wkly Rep 2023;72:355-61. [Crossref] [PubMed]
14. Li Y, Wang X, Msosa T, et al. The impact of the 2009 influenza pandemic on the seasonality of human respiratory syncytial virus: A systematic analysis. Influenza Other Respir Viruses 2021;15:804-12. [Crossref] [PubMed]
15. Garcia-Maurino C, Brenes-Chacón H, Halabi KC, et al. Trends in Age and Disease Severity in Children Hospitalized With RSV Infection Before and During the COVID-19 Pandemic. JAMA Pediatr 2024;178:195-7. [Crossref] [PubMed]
16. Ozeki S, Kawada JI, Yamashita D, et al. Impact of the Coronavirus Disease 2019 Pandemic on the Clinical Features of Pediatric Respiratory Syncytial Virus Infection in Japan. Open Forum Infect Dis 2022;9:ofac562. [Crossref] [PubMed]
17. Jia R, Lu L, Su L, et al. Resurgence of Respiratory Syncytial Virus Infection During COVID-19 Pandemic Among Children in Shanghai, China. Front Microbiol 2022;13:938372. [Crossref] [PubMed]
18. Jiang ML, Xu YP, Wu H, et al. Changes in endemic patterns of respiratory syncytial virus infection in pediatric patients under the pressure of nonpharmaceutical interventions for COVID-19 in Beijing, China. J Med Virol 2023;95:e28411. [Crossref] [PubMed]
19. Teirlinck AC, Johannesen CK, Broberg EK, et al. New perspectives on respiratory syncytial virus surveillance at the national level: lessons from the COVID-19 pandemic. Eur Respir J 2023;61:2201569. [Crossref] [PubMed]
20. Van Brusselen D, De Troeyer K, Ter Haar E, et al. Bronchiolitis in COVID-19 times: a nearly absent disease? Eur J Pediatr 2021;180:1969-73. [Crossref] [PubMed]
21. Li Y, Wang X, Cong B, et al. Understanding the Potential Drivers for Respiratory Syncytial Virus Rebound During the Coronavirus Disease 2019 Pandemic. J Infect Dis 2022;225:957-64. [Crossref] [PubMed]
22. Loconsole D, Centrone F, Rizzo C, et al. Out-of-Season Epidemic of Respiratory Syncytial Virus during the COVID-19 Pandemic: The High Burden of Child Hospitalization in an Academic Hospital in Southern Italy in 2021. Children (Basel) 2022;9:848. [Crossref] [PubMed]
23. Reicherz F, Xu RY, Abu-Raya B, et al. Waning Immunity Against Respiratory Syncytial Virus During the Coronavirus Disease 2019 Pandemic. J Infect Dis 2022;226:2064-8. [Crossref] [PubMed]
24. Grobben M, Juncker HG, van der Straten K, et al. Decreased Passive Immunity to Respiratory Viruses through Human Milk during the COVID-19 Pandemic. Microbiol Spectr 2022;10:e0040522. [Crossref] [PubMed]
25. den Hartog G, van Kasteren PB, Schepp RM, et al. Decline of RSV-specific antibodies during the COVID-19 pandemic. Lancet Infect Dis 2023;23:23-5. [Crossref] [PubMed]
26. Nygaard U, Hartling UB, Nielsen J, et al. Hospital admissions and need for mechanical ventilation in children with respiratory syncytial virus before and during the COVID-19 pandemic: a Danish nationwide cohort study. Lancet Child Adolesc Health 2023;7:171-9. [Crossref] [PubMed]
27. Jiang W, Xu L, Wang Y, et al. Exploring immunity debt: Dynamic alterations in RSV antibody levels in children under 5 years during the COVID-19 pandemic. J Infect 2024;88:53-6. [Crossref] [PubMed]
28. Colosia A, Costello J, McQuarrie K, et al. Systematic literature review of the signs and symptoms of respiratory syncytial virus. Influenza Other Respir Viruses 2023;17:e13100. [Crossref] [PubMed]
29. Openshaw P, Edwards S, Helms P. Changes in rib cage geometry during childhood. Thorax 1984;39:624-7. [Crossref] [PubMed]
30. Suss RJ, Simões EAF. Respiratory Syncytial Virus Hospital-Based Burden of Disease in Children Younger Than 5 Years, 2015-2022. JAMA Netw Open 2024;7:e247125. [Crossref] [PubMed]
31. Lu Y, Chen Q, Ren S, et al. Impact of COVID-19 Nonpharmaceutical Interventions on Respiratory Syncytial Virus Infections in Hospitalized Children. Influenza Other Respir Viruses 2024;18:e13291. [Crossref] [PubMed]
32. 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 2024;24:1009. [Crossref] [PubMed]
33. 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. [Crossref] [PubMed]
34. Blanken MO, Rovers MM, Molenaar JM, et al. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med 2013;368:1791-9. [Crossref] [PubMed]
35. Ma KS, Tsai SY, El Saleeby CM, et al. Nirsevimab decreased the subsequent risk of respiratory syncytial virus infection and wheezing in the 2023-2024 RSV season. Pediatr Res 2025; Epub ahead of print. [Crossref] [PubMed]
36. Glezen WP, Taber LH, Frank AL, et al. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 1986;140:543-6. [PubMed]
37. Agac A, Kolbe SM, Ludlow M, et al. Host Responses to Respiratory Syncytial Virus Infection. Viruses 2023;15:1999. [Crossref] [PubMed]
38. Ang HJ, Menegale F, Preziosi G, et al. Reconstructing the impact of COVID-19 on the immunity gap and transmission of respiratory syncytial virus in Lombardy, Italy. EBioMedicine 2023;95:104745. [Crossref] [PubMed]