A single tertiary hospital-based retrospective observational study on epidemiological features and clinical correlates of severe pediatric Chlamydia pneumoniae pneumonia in post-pandemic in Shanghai

Introduction

Chlamydia pneumoniae (C. pneumoniae), as a strict obligate eukaryotic intracellular parasitic pathogen, is one of the important atypical pathogens of respiratory tract infections which can be transmitted from person to person through respiratory secretions or droplets. It spreads relatively slowly, has a long course of disease, shows the characteristics of alternating sporadic and epidemic situations, and has a periodic epidemic trend (1-3). C. pneumoniae is one of the important pathogens causing interstitial lung disease in clinical practice, and it is also associated with the occurrence of many chronic lung diseases, such as asthma, atelectasis and bronchiectasis (4,5). After the withdrawal of coronavirus disease 2019 (COVID-19)-related non-pharmaceutical interventions (NPIs), long-term pathogen suppression during the pandemic induced widespread pediatric immunity debt, resulting in the rapid rebound of multiple atypical respiratory pathogens globally in recent years, and the resurgence of C. pneumoniae infection has gradually attracted clinical attention (6-8). At present, real-world epidemiological data describing CPP epidemic shift after pandemic in Chinese children remains insufficient, which constitutes the core research gap of our study. The diagnosis of CPP relies on pathogen detection. However, as C. pneumoniae is difficult to survive in vitro, the microbiological culture operation is complex and demanding, making it hard for most hospitals to carry out and unsuitable for clinical diagnosis. Serological testing method was the most commonly used in the diagnosis of CPP previously.

C. pneumoniae infection is relatively common among the population. About 60% of adults worldwide was infected at least once in their lifetime. Previous serological tests in some countries have found that the proportion of C. pneumoniae serologically positive individuals in the population is as high as over 50% (5,9,10). Therefore, distinguishing past infections from new infections solely based on positive serological antibodies has significant limitations in clinical practice. In 2012, the U.S. Food and Drug Administration approved the use of polymerase chain reaction (PCR) to identify C. pneumoniae and other microorganisms in nasopharyngeal swabs. Pathogen detection based on multiplex PCR improved the accuracy of C. pneumoniae infection diagnosis and has been widely recognized (11,12).

Most patients with C. pneumoniae infection exhibit atypical clinical symptoms. Due to factors such as compromised immunity and short duration of immunity, they are prone to cause persistent infection, recurrent infection, and subclinical infection, leading the avoidable pulmonary and extra-pulmonary complications. In severe cases, these conditions may even be life-threatening. In this study, we retrospectively analyzed the incidence of C. pneumoniae infection in hospitalized patients with respiratory diseases in our hospital after the COVID-19 pandemic, aiming to understand the clinical characteristics of SCPP after the COVID-19 pandemic in this region and investigating the clinical correlates for SCPP. The objectives were to enhance early identification and management of SCPP, slow or control disease progression in pediatric patients, and reduce the occurrence of SCPP. We present this study in accordance with the TRIPOD reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0304/rc).

Methods

Data source

All enrolled children, who were hospitalized in the Department of Respiratory, Shanghai Children’s Hospital with respiratory tract diseases, were consecutively screened during January 2022–December 2025 without selective exclusion, adopting a consecutive sampling strategy to reduce potential selection bias. As a single-center retrospective study involving all confirmed cases of CPP diagnosed across the entire hospital during the study period, a total of 121 children with CPP were included. Nucleic acid amplification testing (NAAT) was used as the basis for diagnosing C. pneumoniae infection (12). The diagnostic criteria for pneumonia and severe pneumonia were in accordance with the “Guidelines for the management of community-acquired pneumonia (CAP) in children (2024 revision)” (13): the presence of any of chest wall retractions, nasal flaring or grunting indicates hypoxemia and defines severe CAP in children; any of central cyanosis, severe respiratory distress, poor oral intake/dehydration, or altered mental status (drowsiness, coma, convulsions) is indicative of critically severe CAP. The exclusion criteria: (I) presence of preexisting conditions affecting major organ systems; (II) history of tuberculosis, autoimmune disorders, malignancy, or immunodeficiency; (III) used systemic corticosteroids or immunosuppressive agents in the past 6month; (IV) incomplete clinical documentation.

There are 66 cases in the CPP group and 55 cases in the SCPP group. Comprehensive clinical data were systematically collected from the hospital’s electronic medical records and laboratory testing systems, encompassing demographic characteristics, epidemiological history, baseline laboratory parameters, radiographic findings (chest X-ray or computed tomography), therapeutic interventions, longitudinal follow-up outcomes, etc. Given the retrospective design with concurrent measurement of exposures and endpoints, this study only explores statistical correlations rather than causal risk effects.

This retrospective study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Ethics Committee of Shanghai Children’s Hospital (ethics approval No. 2026R036-E01) and individual consent for this retrospective analysis was waived.

Methods for respiratory specimen collection and pathogen detection

Respiratory specimens, including throat swabs, sputum or bronchoalveolar lavage fluid, were collected based on the age and condition of the patients. All specimens underwent parallel detection using multiplex PCR and targeted next-generation sequencing (tNGS) to identify C. pneumoniae and co-pathogens. C. pneumoniae infection was defined as detection of C. pneumoniae DNA/RNA via NAAT with analytical validation. Additional microbiological assessments included conventional sputum culture, Gram staining, serum serology (e.g., microimmunofluorescence assay), and antigen detection, etc. All specimen handling, processing, and molecular testing were performed by certified laboratory personnel following standardized operating procedures.

Data collection

Structured electronic medical records (EMRs) from both outpatient and inpatient systems were reviewed to extract standardized variables. These included: (I) demographics (age, sex, date of symptom onset, admission date); (II) clinical course (duration of fever, length of hospital stay, disease severity classification); (III) admission laboratory parameters: white blood cell count (WBC), neutrophil percentage (N%), C-reactive protein (CRP), fibrinogen (Fib), D-dimer (D-D), lactate dehydrogenase (LDH), procalcitonin (PCT), serum ferritin, immunologic markers (cell subsets, immunoglobulin (Ig) levels, complement, and cytokine profiles [e.g., interleukin (IL), tumor necrosis factor-α (TNF-α)]; (IV) imaging findings; and (V) complications (pulmonary and extrapulmonary), mixed infection status, and treatment responses. In supplementary materials, a total of 17 cases with missing data were excluded: missing ferritin data (7 cases), immunoglobulins and complements (14 cases), cellular immune parameters (14 cases), and cytokine (9 cases). Because of the overlapping missing values existed across indicators, the sum of each individual indicator exceeds the total excluded cases.

Statistical analysis

Multiple imputation was used to replace the original single median imputation for missing continuous data. Continuous variables were assessed for normality using the Shapiro-Wilk test. Normally distributed data were presented as mean ± standard deviation (SD) and compared using independent-samples t-tests; non-normally distributed data were reported as median [interquartile range (IQR)] and analyzed using the Mann-Whitney U test. Categorical variables were summarized as frequency (percentage) [n (%)] and compared using Pearson’s Chi-squared test or Fisher’s exact test, as appropriate. Sensitivity analysis was further performed by comparing multivariate regression results of complete-case dataset and multiply-imputed dataset to verify result stability, and no substantial discrepancy in core statistical results was found between the two analytical models (Tables S1,S2). Univariable logistic regression was employed to screen potential factors associated with SCPP. Statistical analyses were conducted using SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA). A two-sided P value <0.05 was considered statistically significant.

Results

A total of 6,137 hospitalized pediatric patients were enrolled in this retrospective study; among them, 121 (1.97%) were confirmed to have CPP. The cohort comprised 73 males and 48 females. Gender-based analysis showed that male patients constituted a slightly larger proportion of the CPP cohort (60.3% vs. 39.7% for females), yet this difference did not reach statistical significance (P=0.06). Based on the 2024 Revision (13), patients were classified as having severe CPP (n=55, 45.45%) or non-severe CPP (n=66, 54.55%).

Clinical characteristics of CPP patients

The age distribution of CPP patients

The mean age of CPP patients was 9.67±3.32 years. Age distribution was as follows: <3 years (n=5, 4.13%), 3–5 years (n=6, 4.96%), 6–8 years (n=29, 23.97%), 9–11 years (n=41, 33.88%), 12–14 years (n=7, 30.58%), and 15–18 years (n=3, 2.48%). Notably, 107 patients (88.43%) fell within the 6–14 years age range (the predominant demographic group), while the peak age was 10 years (n=19, 15.70%). The age distribution pattern is illustrated in Figure 1.

Figure 1 The age distribution of children with Chlamydia pneumoniae pneumonia.

The time distribution of CPP patients

Seasonal distribution analysis revealed that during 2022–2023, no more than one case of C. pneumoniae infection was identified among hospitalized pediatric patients per season, corresponding to an incidence rate of 0% to 0.27%. However, a marked increase in C. pneumoniae infection incidence was observed beginning in 2024, peaking in spring 2025 (7.82%). Overall, seasonal variation in positive incidence was statistically significant (P<0.01), with the highest rates occurring in spring (3.10%), followed by summer (2.43%), and the lowest in autumn (1.89%).

A comparison of incidence rates across different years revealed a statistically significant difference (P<0.01). Following the COVID-19 pandemic, there had been an upward trend in the incidence of CPP among children. Specifically, only one case was confirmed in 2022, and three cases in 2023, with infection rates remaining below 0.20% in hospitalized children per year. From 2024, the incidence rate surged notably to 1.02% (23 cases), and peaking at 6.81% in 2025, with the number of confirmed cases rose to 94, representing 77.67% of the total. Detailed data on the number of CPP patients and infection rates, categorized by gender, year, and season, are provided in Table 1.

Clinical manifestations and concomitant infections of CPP patients

Among the 121 pediatric patients diagnosed with CPP enrolled in this study, paroxysmal cough was universally observed. Fever occurred in 70 patients (57.85%), wheezing in 6 patients (4.96%), and isolated cases (n=1 each) of hoarseness, pleuritic chest pain, chest tightness, and hypoxemia were documented. Two patients exhibited marked mediastinal lymphadenopathy. Pulmonary complications were identified in 32 patients (26.45%), including pleural effusion, plastic bronchitis, bronchial obstruction or ventilatory insufficiency, bronchiectasis, necrotizing pneumonia, and hypoxemia. Extrapulmonary involvement was observed in 13 patients (10.74%), most commonly presenting as hepatic dysfunction, cutaneous rash, papilledema, splenomegaly, coagulopathy, and frequent premature ventricular contractions.

In this study, 79 cases exhibited co-detection of additional respiratory pathogens: 46 patients (58.23%) had monomicrobial co-detection, while 33 patients (41.77%) demonstrated polymicrobial co-detection. Pathogen-specific detection rates were as follows: bacteria in 49 cases (62.03%), viruses in 28 cases (35.44%), and Mycoplasma pneumoniae (MP) in 25 cases (31.65%). Among the co-detected pathogens, except for MP, Haemophilus influenzae (n=23, 29.11%) was the most frequently identified, followed by Streptococcus pneumoniae (n=18, 22.78%), Staphylococcus aureus and human rhinovirus (n=17 each, 21.52%). This distribution aligns with established epidemiological patterns of respiratory pathogen co-detection in pediatric CAP.

Associated factors analysis for SCPP

Comparative analysis of clinical characteristics

A total of 121 children diagnosed with CPP were enrolled, with 55 (45.45%) were classified as severe disease and 66 (54.55%) as non-severe disease. No statistically significant differences were observed between the two groups with respect to age, sex, season of illness onset, duration of fever, or presence of respiratory pathogen co-detection (all P>0.05), supporting baseline comparability. In contrast, patients in the severe group exhibited significantly longer hospitalization duration [median (IQR): 9.0 (7.0–12.0) vs. 6.0 (5.0–8.0) days; P=0.01] and a markedly higher prevalence of pulmonary consolidation on chest imaging (96.36% vs. 75.75%; P=0.002), as summarized in Table 2.

Comparative analysis of laboratory parameters

Significant intergroup differences (P<0.05) were observed between children with SCPP and those with non-SCPP in the following laboratory parameters: N%, PCT, serum ferritin, D-D, Fib, IgE, complement 3 (C3) and complement 4 (C4), IL-6, IL-1β, CD19⁺ B lymphocyte percentage (CD19⁺%), CD4⁺/CD8⁺ T lymphocyte ratio (CD4⁺/CD8⁺). Detailed results are presented in Table 3.

Analysis of independent associated factors

Variables exhibiting statistical significance in the univariate analysis were selected for subsequent modeling and assigned sequential numeric identifiers: length of hospital stay (X₁), consolidation (X₂), N% (X₃), PCT (X₄), serum ferritin (X₅), D-D (X₆), Fib (X₇), IgE (X₈), C3 (X₉), C4 (X₁₀), IL-6 (X₁₁), IL-1β (X₁₂), CD19⁺% (X₁₃), CD4⁺/CD8⁺ (X₁₄). Subsequent least absolute shrinkage and selection operator (LASSO) regression identified five variables as independently associated with disease severity: consolidation (X₂), N% (X₃), IgE (X₈), C4 (X₁₀), and CD19⁺% (X₁₃) (all P<0.05). Results are illustrated in Figure 2.

Figure 2 LASSO regression analysis combined with binary logistic regression for analytical screening of predictor variables for sever Chlamydia pneumoniae pneumonia. (A) Plot of binomial deviance against log-transformed lambda in LASSO regression; (B) LASSO coefficient profile plot of predictor variables versus log-transformed lambda. LASSO, least absolute shrinkage and selection operator.

Logistic multivariate regression analysis was performed on the five candidate variables identified above. Results demonstrated that N%, C4, IgE, and consolidation were independent clinical correlates of SCPP in children (all P<0.05; Table 4). Receiver operating characteristic (ROC) curve analysis was subsequently conducted to evaluate discriminative performance (Figure 3A). A clinical prediction nomogram for SCPP was then developed incorporating these four independent predictors (Figure 3B). Internal validation confirmed excellent calibration, as evidenced by a nonsignificant Hosmer-Lemeshow test (χ²=5.334, df =8, P=0.72), supporting model reliability (Figure 3C).

Figure 3 The ROC curves, nomogram model and calibration curve for sever Chlamydia pneumoniae pneumonia. (A) ROC curves of N%, IgE, C4, consolidation and joint variable: AUC represents the area under the curve; (B) calibration curves: The calibration curve is used to assess the agreement between the predicted probability of an event and the actual probability of its occurrence; (C) nomogram: the sum of the scores on each predictor, which predicts the probability that depression will occur. AUC, area under the curve; C4, complement 4; IgE, immunoglobulin E; N%, neutrophil percentage; SCPP, severe Chlamydia pneumoniae pneumonia.

Discussion

Since its initial identification and characterization in 1986, C. pneumoniae infection has garnered growing attention in clinical and epidemiological research. Recent surveillance data indicate a progressive annual increase in the incidence of C. pneumoniae infection. Clinically, it is predominantly manifested as severe paroxysmal cough, often accompanied by persistent high-grade fever, marked elevation of systemic inflammatory markers, and, in some cases, serious complications (5,10,14,15). Accumulating evidence suggests that C. pneumoniae may exhibit cyclical epidemic patterns, with peaks in transmission occurring at irregular intervals-typically every few years (3,5,9,16,17). In this study, we observed that while the overall prevalence of C. pneumoniae infection among hospitalized children in Shanghai remains relatively low, it has risen significantly over the past years. Notably, robust, nationally representative clinical epidemiological data on C. pneumoniae infection in pediatric populations across China remain scarce, limiting evidence-based surveillance and intervention strategies.

This study reveals that the overall prevalence of CPP among hospitalized children in Shanghai remains relatively low, at 1.97% during 2022–2025, consistent with prior epidemiological reports (5,9,10,16,17). However, temporal analysis uncovers a marked post-pandemic surge: C. pneumoniae incidence fell below 0.2% in 2022–2023, which may be likely reflecting residual non-pharmaceutical interventions and immune landscape shifts following the COVID-19 pandemic; but it rose sharply to 1.02% in 2024 and escalated further to 6.81% in 2025, indicating a pronounced and accelerating epidemic upsurge. Seasonally, cases continue to cluster predominantly in spring and summer months. In terms of gender, males accounted for a significantly higher proportion than females (60.33% vs. 39.67%), but there was no significant difference (χ²=3.516, P=0.06). This may be related to the underlying imbalances in gender distribution within the hospitalized pediatric cohort.

Among the 121 children diagnosed with CPP, the proportion of severe cases reached as high as 45.45%. This finding indicates that children infected with C. pneumoniae are more likely to progress to severe conditions. This phenomenon may be associated with several factors: the general population has relatively low immunity against C. pneumoniae infection; children are more prone to eliciting a strong immune response following infection; and the limited clinical understanding of C. pneumoniae along with the restricted detection methods have resulted in delays in diagnosis and treatment. Given that this study is confined to single-center research support, the higher proportion of severe cases is moderately correlated with the relatively severe condition of patients who sought medical care at tertiary hospitals. Considering that this data may exceed the actual population level, further large-sample and multi-center research data are required for validation.

The morbidity of CPP is correlated with age. This study indicates that the age range from 9 to 14 years is the high-incidence age, which is consistent with previous research data (5,10,11,17,18). This age-distribution characteristic may be associated with a variety of factors such as more social activities for children in this age group, clustered school lifestyle, and weakened immune system which may result from the heavy study burdens, insufficient sleep and lack of outdoor exercise. However, no significant difference in age was found between the severe CPP group and the non-severe CPP group (P=0.12), suggesting that age is not the clinical correlate for SCPP.

Among the 121 cases included in this study, 79 cases (65.29%) were tested positive for other pathogens. This indicates that CPP is prone to co-infection with other pathogens, and clinicians should be vigilant about the possibility of mixed infection during clinical treatment. However, it remains to be further clarified whether the detected pathogens are the causative agents of this disease, latent carriers, colonizing bacteria, or in the recovery phase of infection.

It should be emphasized that the elevated N%, C4, IgE and dominant pulmonary consolidation are concomitant laboratory and imaging changes occurring synchronously when CPP progresses to severe disease rather than preceding causal risk factors leading to aggravation. These indicators reflect severe systemic inflammatory activation and pulmonary tissue pathological damage after SCPP onset, and can serve as auxiliary in-hospital warning markers for confirmed severe pneumonia. The percentage of neutrophils in the blood (N%), the predominant imaging manifestations of consolidation, the levels of C4 and IgE in the severe group were significantly higher compared to those in the non-severe group. This indicates that N% (OR =1.066, P=0.02), C4 (OR =1251.898, P=0.03), IgE (OR =1.001, P=0.03), and the predominant imaging manifestations of consolidation the predominant imaging manifestations of consolidation (OR =31.106, P=0.03) can serve as relatively sensitive indicators for the early prediction of SCPP. They are also important bases for the early intervention of children with CPP and the early identification of severely ill children in clinical practice, which can contribute to reducing the incidence of SCPP and alleviating the children’s condition.

The complement system assumes a central role in the immune response against pathogen invasion. Throughout the infection process, the complement system is promptly activated and initiates crucial defense mechanisms. Subsequently, pathogen is phagocytosed, activated, and eliminated by human monocytes (19). The complement system participates in regulating the intensity of both innate and specific immunity. While it can impede the infection of extracellular pathogens, its function in the infection of obligate intracellular pathogens remains ambiguous. Research has revealed that mice with complement deficiency are 100 times more prone to intracellular Chlamydia compared to wild-type mice. All complement-deficient mice succumbed to infection after the 9th day, suggesting that there might be a specific association between complement and adaptive protective immune responses against Chlamydia (20). B-cells participate in anti-chlamydial defense mechanisms, and complement activation and deposition facilitate Chlamydia binding to B-cells. Lausen et al. (21) found that when incubated in human serum, IgG antibodies and the activation products of C3 and C4 were deposited on the surface of Chlamydia. Complement activation restricted the infectivity of Chlamydia in vitro and could potentially induce Chlamydia lysis by forming a membrane attack complex. Excessive complement cascade overactivation induced by C. pneumoniae infection promotes uncontrolled local pulmonary inflammatory infiltration and tissue injury, which partly explains the elevated serum C4 concentration and dense pulmonary consolidation in SCPP patients. These studies demonstrated that C4 plays a crucial role in immune activation following Chlamydia infection, and the activation of the complement system may facilitate the recognition of Chlamydia by innate and adaptive immune cells.

Neutrophils are the earliest and most abundant innate immune cells that are recruited to the lungs subsequent to infection. They can mediate tissue damage via a potent pro-inflammatory response and participate in the early cellular defense and phagocytosis following C. pneumoniae infection (22,23). Upon infection, the pathogen initially encounters airway epithelial cells and alveolar macrophages. These cells respond to the infection by secreting inflammatory mediators, which stimulate vascular endothelial activation and the chemotaxis of immune cells (24). Neutrophils, functioning as the “vanguard”, are the first immune cells to migrate from the blood to the alveolar space. Subsequently, they send signals for the recruitment and infiltration of monocytes, thus constituting the early cellular defense against C. pneumoniae (25,26). The interaction between Chlamydia and these phagocytes may determine the course of the infection.

Furthermore, the activation of complement notably enhances the intracellular neutralization of C. pneumoniae by monocytes and neutrophils in peripheral blood, thereby augmenting the body’s capacity to eliminate C. pneumoniae infection. Research has revealed that complements interfere with the entry of Chlamydia into permissive cells via complement-mediated bacterial lysis and restrict C. pneumoniae infection in vitro by marking bacteria for efficient phagocytosis by monocytes and neutrophils (27). This indicates that the combined utilization of complement and neutrophils may be more effective in reducing the infectivity of Chlamydia compared to complement alone. Through quantitative detection of the phagocytic of Chlamydia during primary infection, it was discovered that the phagocytosis of Chlamydia by monocytes and neutrophils was more efficient in the culture medium containing normal human serum compared to that containing heat-inactivated normal human serum (21), which implies that complement activation plays a significant role in the phagocytosis of Chlamydia. Those evidence indicated that complement activation enhances the phagocytic uptake and intracellular killing of Chlamydia by monocytes and neutrophils. These findings are consistent with those reported in prior studies (28).

C. pneumoniae intracellular infection can induce Th2-skewed immune response in host immune cells, which promotes excessive IgE synthesis and secretion; elevated IgE further stimulates the release of multiple inflammatory mediators, exacerbates airway inflammation, which is the core immunological mechanism linking high serum IgE to SCPP occurrence. Following the infection of the respiratory system by C. pneumoniae, it can result in pronounced coughing symptoms, and some individuals may be accompanied by wheezing. This phenomenon may be attributable to the induction of IgE production in the host. C. pneumoniae infection mediates the elevation of IgE via the activation of Th2 lymphocytes, and this reaction leads to the release of chemical mediators that trigger airway inflammation. This may represent a potential mechanism for the onset of asthma in children infected with C. pneumoniae and is closely linked to the persistence or exacerbation of asthma symptoms (29,30). Research has indicated that C. pneumoniae infection can induce a specific IgE response in patients with asthma. Among 95% of asthma patients with detectable C. pneumoniae-IgG antibodies, specific IgE antibodies were also identified, and the levels were relatively elevated (31). Hahn et al. found that (32) about 50% of adult asthma patients had C. pneumoniae-specific IgE, and it was also associated with the severity of disease. In comparison with children presenting solely respiratory symptoms, those with extrapulmonary manifestations exhibited higher total IgE levels in serum, and this change is regarded as being associated with the immune imprinting that produces IgE (i.e., cellular processes and cytokine environment) (33). It can be inferred that the IgE level in serum may be correlated with C. pneumoniae infection, particularly the onset of SCPP, which is in line with the findings of our study. Nevertheless, Smith-Norowitz et al. proposed that the elevation in IgE induced by C. pneumoniae infection primarily consists of specific IgE and exhibits no significant correlation with the total IgE level (31). This phenomenon might be associated with individual disparities among samples and regional variations, and it may require further data from large-scale samples and multi-center studies to substantiate.

Conclusions

C. pneumoniae is one of the significant atypical pathogens in clinical pediatrics. The proportion of CPP among the total hospitalized showed a significant annual increasing trend after the COVID-19 pandemic. Its clinical manifestations predominantly present as atypical symptoms, including cough, fever, and wheezing. Owing to the atypical clinical symptoms and the imperfect detection methods, it is highly likely to result in early missed diagnosis and misdiagnosis, thereby delaying the diagnosis and treatment and influencing the condition and prognosis of the children. N%, C4, IgE, and the predominant imaging manifestations of consolidation were independent in-hospital concomitant clinical correlates of SCPP, which can be used as auxiliary warning markers after children develop severe pneumonia. Early intervention for these individuals is critically important for alleviating condition, decelerating the progression of disease, and reducing the incidence of severe cases. As the limited sample size of this study may constrain the generalizability of the findings, further validation through larger-scale, multicenter studies is warranted.

Acknowledgments

The authors would like to thank the clinical staff, specifically the medical doctors and nurses, for their help with collecting clinical specimens, and all of the children and their parents for their participation and cooperation.

Footnote

Reporting Checklist: The authors have completed the TRIPOD reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0304/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0304/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0304/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0304/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 study was approved by the Ethics Committee of Shanghai Children’s Hospital (No. 2026R036- E01) and individual consent for this retrospective analysis was waived

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/.

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