Hospitalizations trends and co-infection patterns for respiratory virus infections in children in central China 2015 to 2023: a longitudinal surveillance study

Abstract

This study presents a comprehensive epidemiological analysis of respiratory viral infections in Henan Province, China, from 2015 to 2023, encompassing 183,771 reported cases. The predominant pathogens included influenza A virus (Flu A), accounting for 58.66% of infections, followed by influenza B virus (Flu B), respiratory syncytial virus (RSV), parainfluenza virus (PIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human rhinovirus (HRV), was 19.44%, 12.00%, 9.10%, 0.44%, and 0.37%, respectively. A significantly higher detection rate was observed in males compared to females (57.22% vs. 42.78%; χ² < 0.001). Co-infections were documented in 2.16% of cases, with the most prevalent combination being Flu A + Flu B. Notably, the co-infection cases peaked in 2023, likely due to the relaxation of non-pharmaceutical interventions (NPIs) following the COVID-19 pandemic. The detailed wavelet analysis revealed distinct periodic patterns for various respiratory viruses, highlighting the necessity of adaptable vaccination strategies. These findings underscore the dynamic nature of respiratory viral epidemiology and emphasize the significance of continuous surveillance and targeted public health interventions, particularly for high-risk populations. Future research should further investigate the implications of these trends on long-term respiratory health outcomes and inform effective strategies to mitigate the burden of respiratory infections.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-025-11352-0.

Introduction

Respiratory viral infections pose a critical global public health concern, significantly contributing to morbidity and mortality rates, particularly among vulnerable populations such as infants, young children, and the elderly [1, 2]. The epidemiology of acute respiratory infections (ARI) is influenced by a complex interplay of environmental factors, demographic characteristics, and public health interventions [3]. Moreover, the susceptible population for respiratory infectious diseases is extensive, and transmission occurs readily, often propelled by diverse pathogens. Consequently, the infection situation is intricate and frequently overlapping, necessitating meticulous detection [4]. Notably, the COVID-19 pandemic has profoundly impacted the transmission dynamics of respiratory viruses in China, resulting in unprecedented shifts in infection patterns and disease severity [5].

This study was conducted at Henan Children’s Hospital, located in Zhengzhou, the capital city of Henan Province in central China. Zhengzhou has a permanent resident population of approximately 2.4 million children aged 0–14 years, making it a representative setting for pediatric respiratory infection surveillance. Between 2015 and 2023, Henan Province, a highly populous region in China, encountered a significant burden of respiratory viral infections. Gaining insights into the epidemiological patterns within this area is crucial for formulating effective public health strategies and optimizing resource allocation. Previous studies have indicated that seasonal variations, influenced by climatic conditions and social behaviors, play a pivotal role in the transmission of respiratory pathogens [6]. Moreover, viral co-infections have been linked to increased disease severity, further complicating clinical management [4, 7].

Therefore, we meticulously investigate the epidemiology and clinical features associated with six primary respiratory: parainfluenza virus (PIV), respiratory syncytial virus (RSV), influenza A virus (Flu A), influenza B virus (Flu B), human rhinovirus (HRV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children admitted to Henan Children's Hospital from 2015 to 2023, which represent the most commonly detected viral pathogens in pediatric inpatients at our hospital and are consistent with the leading causes of viral respiratory illness reported in prior regional surveillance studies. These pathogens were consistently among the most commonly identified viruses in hospitalized children. Moreover, they were associated with relatively higher disease burden, including increased severity of symptoms and hospitalization rates [8–11]. To provide a comprehensive and systematic analysis of respiratory viral infections in Henan Province, this study focuses on the prevalence of various pathogens, co-infection patterns, and the overarching impact of the COVID-19 pandemic on viral epidemiology. The findings will enhance our understanding of respiratory viral dynamics and guide targeted interventions to reduce the public health burdens.

Materials and methods

Study participants and case definition

The study focused on children aged 0–15 years who were admitted to Henan Children's Hospital (National Children's Regional Medical Center), the largest pediatric specialty hospital in Henan Province, presenting with symptoms resembling influenza from January 2015 to May 2023. All respiratory viral data were derived from continuous, routine hospital-based surveillance at Henan Children's Hospital. The data-set includes all pediatric inpatients who underwent nucleic acid testing for respiratory viruses during hospitalization, ensuring comprehensive and unbiased year-round data coverage. Inclusion criteria included fever (temperature ≥ 38 °C) accompanied by symptoms indicative of acute respiratory infection such as rhinorrhea, nasal congestion, cough, and pharyngitis. We extracted respiratory infection cases based on the 10th edition of the International Classification of Diseases.

Definitions

Acute respiratory infection: A comprising infection caused by infectious pathogens such as bacteria and viruses leading to acute inflammation in any part of respiratory system. It is divided into upper or lower respiratory infection based on anatomy [12].

Severe influenza illness: Illness requiring respiratory-support with non-invasive positive pressure ventilation (such as high flow nasal cannula, continuous positive airway pressure [CPAP], bi-level positive airway pressure [BIPAP]), or invasive ventilation (endotracheal intubation or ECMO), ICU admission or event of in-hospital death [13].

Sample collection and laboratory test

Respiratory specimens (throat swabs) were collected from enrolled patients with ARI within 24 h of hospitalization. The samples were stored in virus transport medium tubes (Beijing Youkang Technology Co., LTD.) at 4 °C prior to testing. Viral infections were subsequently assessed using real-time polymerase chain reaction (RT-PCR) within 48 h.

Data collection

Demographics, medical history, and clinical information (including clinical manifestations, laboratory findings, chest radiography, and treatment) were extracted from the electronic medical records of the hospital. The extracted data were recorded using a standardized data dictionary and REDCap system (Research Electronic Data Capture, Vanderbilt University, Nashville, Tennessee, USA) or EpiData v3.1.

Data analysis

The differences in patients were compared by the chi-square (χ2) test, while Fisher's Exact Test was employed to analyze small samples. All statistical analyses were conducted using SPSS version 26.0, with a significance level set at P < 0.05. Figures were generated using Excel tables (Excel 2016, Microsoft, USA), GraphPad Prism 9.0.0 (GraphPad 9.0.0 Software, San Diego, CA, USA), and Adobe Illustrator 2020 (Adobe Systems Incorporated, USA).

The MATLAB software platform was utilized to conduct Morlet wavelet transforms to identify and analyze latent periodic patterns in time series data. By visualizing the wavelet coefficients, we could investigate the temporal evolution of the dataset and uncover its underlying periodic patterns.

Results

General characteristics of study population in Henan Province, China

From 2015 to 2023, a total of 183,771 cases of respiratory viral infections were reported. The etiologies responsible for these infections included PIV (n = 16,704), RSV (n = 22,044), Flu A (n = 107,797), Flu B (n = 35,734), HRV (n = 681), and SARS-CoV-2 (n = 811). Notably, Flu A exhibited the highest detection rate at 58.66%. The distribution of cases revealed a gender discrepancy with males exhibiting a higher detection rate compared to females (57.22% vs. 42.78%; χ2 = 90.39, P < 0.001). The 3-year-old age group showed the highest detection rate (14.19%), which progressively decreased with increasing age (χ2 = 9750.467, P < 0.001) (Fig. 1, Supplementary Table 1).

Fig. 1.

Number of Cases of Different Respiratory Viruses in Henan Province, China. A Cases of respiratory viral infections by serotype from 2015–2023; B Cases of respiratory viral infections by gender from 2015–2018; C. Cases of respiratory viral infections by age from 2015–2018. *To highlight variations in virus reporting between years, we presented infections from 2015–2018 separately, with adjustments made for the March 2023 peak in Flu A detection

Co-infection patterns of respiratory infections in Henan Province, China

A total of 3,976 co-infectious patients were identified in this study, accounting for 2.16% of patients. Among these individuals, 3,841 were infected with two pathogens, while 131 had three pathogens, and only 4 with four pathogens (Fig. 2A). The most prevalent double-infection pattern observed was Flu A + Flu B (n = 1221), followed by RSV + PIV (n = 641) (Fig. 2B). PIV + RSV + Flu B represented the most frequent triple-infection pattern (n = 46) (Fig. 2C), and quadruple-infection exclusively consisted of PIV + RSV + FLU A + Flu B (n = 4). Among co-infections, Flu B was the pathogen most frequently detected (20.08%). As shown in Fig. 2D, cases of co-infection peaked in 2023, with the proportion of triple-infection being highest in 2021.

Fig. 2.

Prevalence of Respiratory Viral Co-infections in Henan Province, China. A Proportion of co-infection among three patten of viruses; B Proportion of double-infection across different virus combination; C Proportion of triple-infection across different virus combination; D. Number of respiratory viral co-infection cases and co-infection rate in Henan Province from 2015 to 2023

Serotypes of respiratory tract infections in Henan Province, China

The prevalence of PIV and RSV as the dominant serotypes was observed from 2015 to 2017, as depicted in Fig. 3A. A notable peak in PIV infections was observed, constituting 56% of cases in 2016. Since 2018, an increasing trend in the prevalence of both Flu A and Flu B has been observed. Flu A predominated from 2018 to 2023, except in 2021, when Flu B accounted for 67.49% of cases. Figure 3B indicates that RSV emerged as the primary pathogen responsible for severe cases from 2016 to 2023, with exceptions in the years 2015 and 2019 when PIV and Influenza A were predominant respectively. As shown in Fig. 3C, PIV was a major pathogen causing critical illnesses from 2015 to 2020, followed by RSV in 2021, while SARS-CoV-2 became the leading pathogen from 2022 to 2023.

Fig. 3.

Pathogen Spectrum of Respiratory Patients in Henan Province, China from 2015–2023. A Distribution of pathogens in all cases; B Distribution of pathogens in severe illness cases; C Distribution of pathogens in critical illness cases

Age distribution of respiratory tract infections for respiratory pathogens

As shown in Fig. 4, children under 1 year of age displayed the highest severity and critical illness rate (29.28%, 0.20%). The severity rate gradually decreased as age increased, while the critical illness ratio displayed two minor peaks at 12 and 14 years of age (0.15%, 0.17%).

Fig. 4.

The severity and critical illness rate of respiratory infections among different ages in Henan Province, China from 2015–2023. A The severity rate among different ages in Henan province, China from 2015 to 2023; B The critical illness rate among different ages in Henan Province, China from 2015–2023

Periodicity of respiratory tract infections in Henan Province, China

According to Fig. 5, PIV, RSV, Flu A, and Flu B demonstrated winter-spring peaks (December to January). Notably, Flu A notably peaks in March, surpassing the typical winter-spring peaks. Wavelet analysis revealed distinct periodicity of respiratory virus infections during the study period (Fig. 6). Different viruses exhibited varying periodicities: PIV had a 26-month major periodicity, RSV had a 13-month major periodicity, Flu A showed a 10-month periodicity, Flu B had a 29-month major periodicity, and HRV had an 18-month periodicity. These findings suggest an annual periodicity for respiratory infections. All major prevalence periods were statistically significant at a confidence level of 95%, except for Flu A and HRV.

Fig. 5.

Seasonal Distribution of Positive Detection Rates in Patients with Respiratory Viral Infections in Henan Province, China 2015–2023

Fig. 6.

Wavelet Analysis of Serotype-specific Time Series Notifications of Respiratory Virus Infections in Henan Province, China A-E: Local wavelet power spectrum for RSV (A), PIV (B), Flu A (C), Flu B (D), and HRV (E)

Clinical symptoms and disease severity before and after the COVID-19 epidemic

To evaluate the distribution of viral detection before and after the COVID-19 pandemic, the study was divided into three periods: pre-COVID-19 (2015–2019), the COVID-19 prevalence period (2020–2022), and the post-lifting of NPIs in 2023. During the pre-COVID-19 era, notable detection rates were observed for symptoms such as cough (0.205%), fever (2.713%), vomiting (0.398%), encephalitis (0.278%), and bronchiolitis (8.092%). During the COVID-19 period, the highest detection rates were noted for severe and critical illness (16.30%), pneumonia (14.820%), and respiratory failure (0.061%). In 2023, shock (0.018%), laryngitis (0.863%), and myocardial damage (0.104%) showed significant increases in their detection rates. The differences between these periods were highly significant (P < 0.001) (Table 1).

Table 1.

Clinical symptoms and complications of infection during hospitalization

Category	2015–2019	2020–2022	2023	χ2	P
Severity of illness
Severity	9501 (10.86%)	7458 (16.30%)	3103 (6.12%)	2570.167	< 0.001
Critical illness	18 (0.021%)	36 (0.079%)	26 (0.051%)	24.317	< 0.001
Symptoms
Cough	179 (0.205%)	91 (0.199%)	31 (0.061%)	45.134	< 0.001
Fever	2373 (2.712%)	991 (2.166%)	344 (0.678%)	680.006	< 0.001
Vomit	348 (0.398%)	169 (0.369%)	29 (0.057%)	136.772	< 0.001
Shock	2 (0.002%)	6 (0.013%)	9 (0.018%)	141.03	< 0.001
Complications
Laryngitis	350 (0.400%)	369 (0.807%)	438 (0.863%)	141.03	< 0.001
Pneumonia	8117 (0.734%)	6774 (1.047%)	2932 (0.154%)	2100.651	< 0.001
Encephalitis	243 (0.278%)	60 (0.131%)	12 (0.024%)	127.025	< 0.001
Bronchitis	7078 (8.090%)	3574 (7.813%)	3298 (6.500%)	120.48	< 0.001
Myocardial damage	41 (0.047%)	45 (0.098%)	53 (0.104%)	18.308	< 0.001
Respiratory failure	11 (0.013%)	30 (0.061%)	19 (0.038%)	26.39	< 0.001

Etiological characteristics of severe and critically ill patients

From 2015 to 2023, RSV caused 45.39% of severe child illnesses, while SARS-CoV-2 led to 57.50% of critical cases, and PIV accounted for 20.00%, as shown in Table 2.

Table 2.

Etiological characteristics of severe and critically ill patients from 2015 to 2023

Severity of illness	PIV	RSV	Flu A	Flu B	HRV	SARS-CoV-2	χ2	P
Severe case	4560 (22.78%)	9085 (45.39%)	2610 (13.04%)	2716 (13.57%)	610 (3.05%)	436 (2.18%)	39,773.704	< 0.001
Critical illness	16 (13.33%)	5 (4.17%)	6 (5.00%)	46 (38.33%)	1 (0.83%)	46 (38.33%)	438.864*	< 0.001

Discussion

This study presents a comprehensive epidemiological overview of respiratory viral infections in Henan Province, China, from 2015 to 2023. It emphasizes the burden, co-infection patterns, and shifting trends in viral predominance within the context of the COVID-19 pandemic. The findings highlight crucial aspects of viral transmission dynamics, age-related susceptibility factors, and clinical outcomes that are pivotal for informing future public health strategies, particularly targeting vulnerable populations such as young children.

The predominance of Flu A, accounting for 58.66% of reported cases, is consistent with existing epidemiological evidence indicating its dominance in respiratory infections conducted in China [14]. Despite the overall reduction in viral transmission during the pandemic, Flu A remained the dominant strain. A substantial number of individuals in the low-risk period reverted to their normal routines, contributing to the surge in respiratory viral infections witnessed in late 2021 and from July to September 2022. Similar findings by Austrian researchers suggest that lifting NPIs can lead to a resurgence of respiratory infections [15], highlighting the crucial role of individual behavior in disease transmission dynamics and reinforcing the importance of continued adherence to preventive measures even after NPIs are lifted. RSV, responsible for 45.27% of severe cases, also imposes a substantial infection burden in Henan Province. PIV, as a significant contributor to pneumonia, poses a grave threat to children [16]. Findings from a study conducted in Russia [17] underscore that 51.7% of children infected with PIV experienced severe symptoms. Similarly, PIV emerges as the primary cause of critical illnesses in Henan Province. These findings underscore the significance of early recognition and treatment for respiratory viral infections to mitigate virus transmission and disease progression.

The gender disparity observed in this study, with males exhibiting a significantly higher detection rate (57.22%) compared to females (42.78%), raises important questions regarding gender-related susceptibility to viral infections. Possible explanations could include behavioral factors, such as increased exposure to environmental risks among males, or immunological differences that have been suggested by prior studies to influence viral susceptibility and disease severity [18]. Further investigations are warranted to elucidate these factors.

The age distribution of respiratory viral infections demonstrated a peak detection rate in children under the age of 3, with younger children, particularly those under 1 year old, exhibiting the highest rates of severity and critical illness. This observation is consistent with previous studies identifying young children as disproportionately affected by respiratory viral infections due to their immature immune systems [18]. While peak detection rates for viruses may vary slightly by age, preschool-aged children account for a significant majority of cases. Studies have shown that the risk of infection with respiratory viruses such as PIV, HCoV, and HRV is generally higher among young children [19] and tends to decrease with age, likely due to the gradual maturation of the immune system. However, this decline in risk tends to plateau beyond a certain age and may even reverse, possibly due to increased social interactions and broader exposure in older children [20–22]. The elevated transmission risk in this group may also be attributed to greater contact opportunities in densely populated school environments compared to other community settings [23, 24]. Therefore, reducing the incidence of critical illnesses necessitates intensified immunization campaigns and comprehensive monitoring of disease progression among younger children. To enhance public awareness regarding strategies for preventing viral infections across various age groups, it is imperative to prioritize health education initiatives in childcare institutions and schools. Co-infections can present challenges in the diagnosis, treatment, epidemic prevention, and control of respiratory infections, resulting in varying degrees of disease severity changes in patients. Previous studies have demonstrated that co-infections may lead to an increased hospitalization rate among individuals with respiratory viral infections, indicating a worsening of disease severity and the potential for causing a significant public health threat due to co-infections [7, 25]. In our study, the most prevalent double-infection pattern was Flu A + Flu B, accounting for 30.71% of co-infections. This could be attributed to the resurgence of seasonal influenza viruses to pre-pandemic levels after 2021 combined with low flu vaccination coverage, particularly among children. This finding emphasizes the possibility of concurrent circulation of multiple strains virus which can exacerbate disease severity and complicate clinical management. The clinical implications of co-infections include increased morbidity and mortality rates, especially among high-risk groups such as young children and the elderly [7, 25]. The PIV + RSV + Flu B combination observed as the most common triple-infection pattern further highlights the potential for viral synergy where co-infected viruses may modulate each other's pathogenicity leading to more severe clinical outcomes. The variation in co-infection rates may reflect disparities in transmission dynamics, viral interference, or reporting practices during the pandemic period. However, it is important to note that SARS-CoV-2 emerged as a major pathogen post-2020 particularly associated with severe and critical illness cases underscoring its significant impact on respiratory viral epidemiology. The long-term consequences of SARS-CoV-2, particularly its role in exacerbating or co-infecting with other respiratory viruses, remain an area of critical importance for ongoing research [26].

The observed peak in co-infections in 2023 can likely be attributed to the widespread relaxation of NPIs post-COVID-19, which may lead to increased viral transmission [27]. During the pandemic, NPIs such as social distancing, mask-wearing, and lockdowns significantly reduced the circulation of many respiratory viruses. With the lifting of these restrictions, individuals who had been less exposed to common pathogens over several years, potentially leading to a state of “immune debt”, rendering them more susceptible to infections and contributing to the resurgence of respiratory viral activity [28, 29]. Additionally, the high proportion of triple infections in 2021 might reflect unique viral dynamics during that period. While NPIs effectively suppressed some viral spread, certain respiratory viruses, such as RSV and Influenza, experienced altered transmission patterns [30, 31]. The COVID-19 pandemic has significantly reshaped the global epidemiology of respiratory viruses. Several recent studies have reported changes in circulation patterns, seasonality, and age distribution of various respiratory pathogens, consistent with our findings. A study from Iran documented a delayed resurgence of RSV in April 2022 following the relaxation of COVID-19 control measures, which led to an unexpected outbreak among a small group of children in Southwest Iran [32]. Similarly, another study observed a temporary suppression of respiratory viruses during periods of high COVID-19 transmission, followed by a gradual resurgence [33]. These observations align with the post-pandemic increase in RSV detection in our study and suggest a shared pattern of RSV re-emergence due to reduced population immunity after extended implementation of NPIs. Additionally, hygiene habits and social distancing measures might have important role in decreasing of virus transmission. Furthermore, a retrospective cohort study on Flu A among hospitalized children before, during, and after the pandemic revealed a marked decline in Flu A cases during the pandemic, with more severe clinical presentations observed post-pandemic [34]. Additionally, a systematic review by Maglione et al. [34] further summarized global changes in respiratory virus activity among children during the COVID-19 era, concluding that NPIs, while effective in curbing the spread of COVID-19, also led to substantial epidemiological shifts in common respiratory viruses. These findings underscore the importance of ongoing surveillance and consideration regarding how changes in public health measures and viral behavior may influence the epidemiology of respiratory infections. They highlight the significance of targeted prevention strategies such as vaccination campaigns, particularly during periods following widespread implementation or relaxation of NPIs. Detailed wavelet analysis revealed distinct periodicities in the circulation of respiratory viruses, which carry important implications for public health planning and resource allocation. The identification of a 26-month periodicity for PIV, a 13-month periodicity for RSV, a 10-month periodicity for Flu A, a 29-month periodicity for Flu B, and an 18-month periodicity for HRV suggests that respiratory viruses follow predictable seasonal patterns, influenced by environmental factors, such as temperature and humidity, as well as population immunity. These findings support previous studies indicating the presence of distinct seasonal patterns in viral respiratory infections, particularly in temperate climates [35, 36]. Interestingly, the peak occurrence of Flu A infections in March, deviating from the typical winter-spring peak observed in other respiratory viruses, suggests the necessity for flexible timing of vaccination campaigns. This observation may reflect specific environmental conditions or population behaviors during this period that could facilitate influenza virus transmission. Understanding these intricacies is crucial for optimizing vaccination strategies and mitigating the seasonal burden imposed by respiratory infections.

Our findings underscore the dynamic changes in respiratory virus circulation during and after the COVID-19 pandemic. In accordance with the findings of Hoy et al. [37], there was a notable increase in severity of children's admissions to emergency and critical care compared to the pre-COVID-19 period. The compromised immune response triggered by SARS-CoV-2 may render children more susceptible to severe illness. Following the relaxation of NPI in 2023, we observed an elevated incidence rate of acute laryngitis, myocardial damage, and respiratory failure among children as compared to previous records. This could be attributed to increased outdoor activities for children and stringent preventive measures implemented during the pandemic that reduced their exposure while increasing vulnerability to viral infections [38]. As we transition into a post-pandemic era, it is imperative to strike a balance between public health priorities and normalizing exposure to respiratory pathogens. These observations also highlight the broader global need to strengthen preparedness for future viral threats. Preventing the next pandemic requires an integrated and forward-looking strategy. Strengthened surveillance and early warning systems are crucial for the timely detection of emerging pathogens. Rapid, accurate diagnostic tools should be developed and made widely accessible to support early identification and control. Moreover, building robust and well-resourced healthcare systems is essential to manage future health crises effectively. Continued investment in medical countermeasures, including vaccines and antiviral therapies, will also be key. Finally, long-term global collaboration and sustainable financial support are critical to ensuring a coordinated and equitable response to future outbreaks [39, 40]. Policymakers should consider these dynamics when formulating future public health strategies, ensuring that interventions not only address immediate health threats but also foster long-term resilience against respiratory infections within the population.

Conclusion

In conclusion, this study provides valuable insights into the epidemiology and clinical impact of respiratory viral infections in Henan Province over an eight-year period from 2015 to 2023, with a specific focus on the profound effects of the COVID-19 pandemic and patterns of co-infection. These findings emphasize the necessity for ongoing surveillance and targeted interventions to effectively manage co-infections and severe cases. Future research should concentrate on elucidating molecular mechanisms underlying viral co-infections, exploring potential long-term sequelae of COVID-19 on respiratory and systemic health, optimizing vaccination strategies to address the evolving landscape of respiratory viruses, as well as mitigating the burden posed by respiratory infections and improving outcomes for affected populations worldwide.

Study limitations

Several limitations of this study should be acknowledged. First, the data were obtained from a single region, which may limit the generalizability of the findings to other geographical areas. Second, the study was based on retrospective surveillance data, and thus may be affected by reporting bias or incomplete case documentation. Third, potential confounding factors, such as vaccination status, underlying health conditions, and socio-economic factors, were not available in the data and could not be adjusted for in the analysis. Future multi-center prospective studies with more comprehensive data collection are warranted to validate and extend these findings.

Authors’ contributions

Conceptualization, B.D., F.W., and Y.J.; methodology, data curation, writing—original draft preparation, B.D.; software, supervision, writing—review and editing, Y.J.; resources, project administration, Y.J.; funding acquisition, Y.J., and F.W.; validation, Y.S., and H.C., R.Z., C.W., J.Z., Q.L., and Q.W.; formal analysis, F. W.; investigation, F.S.; visualization, C.S. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by China Postdoctoral Science Foundation (No. 2024T170246, No. 2024M750815), supported by the Open Grant from the Pingyuan Laboratory (No. 2023PY-OP-0202), and supported by Open Project of Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care (No. ERC202302), supported by the 2024 Science and Technology Research Project of Henan Provincial Science and Technology Department (242102310022), supported by the Zhengzhou Science and Technology Beneficiary Program Project (No. 2022KJHM0004), supported by the Open Project of Key Laboratory of Infection and Immunity of Anhui Higher Education Institutes (No. I&I-2024-R01), supported by the Open Project of Key Laboratory of Children's Disease Research in Guangxi's Colleges and Universities (No. GXCDR202401), supported by Program for Innovative Talents in Higher Education Institutions of Henan Province (No. 25HASTIT055), and supported by Outstanding Youth Science Foundation of Henan Province (No. 252300421122).

Data availability

All relevant data are within the manuscript and its Supporting Information files. The study received approval from the Life Sciences Institutional Review Board of Zhengzhou University (ZZUIRB2023-180). Written informed consent was obtained from the parents or guardians of the study participants.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Life Sciences Institutional Review Board of Zhengzhou University (ZZUIRB2023-180). Written informed consent was obtained from the parents or legal guardians of all participants.

Consent for publication

Written informed consent for publication of their clinical details was obtained from the parent of the patient.

Competing interests

The authors declare no competing interests.