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This study aimed to describe the clinical features, complications, treatments, and mortality risk factors in children with severe pertussis over ten years in Southwest China. Methods A retrospective study was conducted on hospitalized children with severe pertussis at the Children’s Hospital of Chongqing Medical University from 2015 to 2024. Clinical data were analyzed across groups with different complications. Mortality risk factors were identified using univariate and multivariate analyses. Results A total of 1,088 cases were included. Patients were grouped into severe pneumonia, encephalitis, and combined complications. Those with both pneumonia and encephalitis had more apnea, pulmonary hypertension, extreme leukocytosis, thrombocytosis, and A. baumannii infection. They required more intensive treatments ( P < 0.05), had longer hospital stays, and the highest mortality. Seizures were more frequent in the encephalitis group, while elevated lactate and immunoglobulin use were less common ( P < 0.05). Univariate analysis linked pulmonary hypertension, high lactate, lymphocytosis, and leukocytosis to mortality. Multivariate analysis identified pulmonary hypertension, exchange transfusion, and steroid use as independent death risk factors. Conclusion Severe pertussis in children is often complicated by pneumonia and/or encephalitis, making treatment more difficult. Rising antibiotic resistance and strain differences in Bordetella pertussis may reduce treatment effectiveness. The increase in severe cases after the pandemic may be due to lower population immunity. Promoting maternal pertussis vaccination in China is urgently needed as a preventive measure. Severe pertussis Pediatric pneumonia Encephalitis Bordetella pertussis resistance Pertussis immunization Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Introduction Pertussis is a highly contagious respiratory disease that remains a significant cause of morbidity and severe complications in children. Although there is no universally accepted diagnostic standard for severe pertussis, it is commonly recognized in infants presenting with any of the following: complications, such as severe pneumonia or encephalopathy, or clinical signs, such as apnea, marked leukocytosis, or evidence of pulmonary hypertension on diagnostic imaging or echocardiography [ 1 – 3 ] . Among these, apnea is often the most prominent and alarming symptom. Severe pertussis is characterized by rapid clinical progression and poor response to treatment. Globally, the reported mortality rate ranges from 1.2-3.0% [ 4 ] . In China, although the incidence of pertussis remained relatively low for two decades, a resurgence has been observed since 2014 across several regions [5–7 ] . This trend is particularly concerning in infants who are too young to have completed the primary immunization schedule. While vaccination has significantly reduced the incidence of severe pertussis in older children and adults, infants remain the most vulnerable group, with the highest rates of hospitalization and mortality [ 8 ] . This elevated mortality is partially attributable to delayed or missed immunizations in early infancy and a limited understanding of the underlying mechanisms of disease progression. In addition, many clinicians may not be fully aware of the clinical features or risk factors associated with severe pertussis, leading to delayed diagnosis and suboptimal treatment. Given these challenges, the present study aims to characterize systematically the clinical features, complications, and treatment patterns of severe pertussis cases admitted to our hospital over the past decade. Furthermore, we seek to identify key mortality-related risk factors, in order to inform optimized diagnostic and therapeutic strategies and ultimately reduce disease burden in this high-risk pediatric population. Research Subjects and Methods Study Population This study included pediatric patients diagnosed with severe pertussis between 2015 and 2024 at the Children's Hospital of Chongqing Medical University. A total of 1,093 cases were initially identified, of which five were excluded due to treatment discontinuation, resulting in a final cohort of 1,088 patients. Diagnosis of pertussis was confirmed by either Bordetella pertussis culture or polymerase chain reaction (PCR) detection of B. pertussis DNA. Cases were classified as severe pertussis if they met any of the following criteria: (1) complications, such as severe pneumonia or encephalopathy; (2) clinical manifestations of apnea; or (3) study findings including marked leukocytosis or evidence of pulmonary hypertension. The study encompassed both intensive care unit (ICU) and non-ICU patients who met the above criteria. Given the clinical importance of severe pneumonia and encephalitis as major complications, all included patients were classified into one of the following three mutually exclusive groups for comparative analysis: (1) severe pneumonia without encephalitis; (2) encephalitis without severe pneumonia; and (3) both severe pneumonia and encephalitis. Patients with other comorbidities were still included as long as they met the diagnostic criteria for severe pertussis. Data Collection Methods Clinical and demographic data were extracted from the hospital's big-data medical record system. The collected information included sex, age, geographic origin (province or city), and pertussis vaccination history, which was verified through admission records or vaccination certificates. Clinical variables comprised presenting symptoms, duration of hospitalization, and comorbidities, such as pneumonia, encephalitis, and cardiovascular complications. Laboratory parameters included white blood cell count, lymphocyte count, platelet count, lactate concentration, and other relevant indicators. Radiological data, including chest imaging and echocardiographic findings, were reviewed to assess pulmonary and cardiac involvement. Treatment regimens were recorded, including the use of antibiotics, corticosteroids, intravenous immunoglobulin (IVIG), mechanical ventilation, exchange transfusion, and extracorporeal membrane oxygenation (ECMO). Patient outcomes, including clinical progression and discharge status, were also documented. Diagnostic criteria for pneumonia were based on clinical signs in conjunction with radiographic evidence, while encephalitis was diagnosed through a combination of neurological symptoms and supporting laboratory data. Hematological abnormalities were defined as follows: leukocytosis was considered present when the WBC count was ≥30×10⁹/L; thrombocytosis was defined as a platelet count ≥800×10⁹/L; and lymphocytosis was defined as a lymphocyte count ≥20×10⁹/L. All laboratory reference ranges followed the Chinese Health Industry Standard "Reference Intervals for Blood Cell Analysis in Children" (WS/T 779–2021). Ethical Approval The study protocol was approved by the Ethics Committee of the Children's Medical Center, Chongqing Medical University (Approval No.: [2022] 382), and conducted in accordance with the principles of the Declaration of Helsinki (10th revision). Quality Control To ensure data accuracy and consistency, a multi-step quality control process was employed throughout the study. Initially, two independent professionals with expertise in big data analytics extracted and cross-verified all clinical and laboratory information from the database. A secondary validation process was then conducted by senior clinicians, who randomly audited 10% of the included cases. During this stage, diagnostic records, laboratory test results, and treatment details were cross-checked using data from the hospital’s electronic medical record system (EMR), laboratory information system (LIS), and picture archiving and communication system (PACS). Finally, any discrepancies or inconsistencies identified during the verification process were resolved by a third-party adjudicator, following standardized procedures for data correction and imputation. This rigorous approach ensured the reliability and reproducibility of the dataset used for statistical analysis. Statistical Analysis All statistical analyses were performed using SPSS version 23.0. Categorical variables were expressed as frequencies and percentages [n (%)], and group comparisons were conducted using chi-square tests or Fisher’s exact tests where applicable (expected counts ≤5). Pairwise comparisons among the three groups were adjusted using the Bonferroni correction. Continuous variables (e.g., age, length of hospitalization), which did not follow normal distributions, were presented as medians and interquartile ranges [M (IQR)]. Intergroup comparisons were conducted using the Kruskal–Wallis H test, followed by post hoc pairwise analyses. Univariate and multivariate logistic regression analyses were conducted to identify risk factors associated with mortality. A two-sided p -value <0.05 was considered statistically significant. Results Demographic Characteristics of Patients Severe pneumonia and encephalitis were the most common complications among children diagnosed with severe pertussis in this cohort. Specifically, 889 patients (81.71%) had severe pneumonia alone, 61 (5.61%) presented with encephalitis alone, and 138 (12.68%) experienced both complications concurrently. Age distribution revealed that the majority of cases occurred in infants under one year of age, with a concentration between 2 and 4 months. The highest median age was observed in 2023 (4.07 months), while the lowest was recorded in 2020 (2.65 months). Geographic distribution analysis showed a significantly higher incidence of severe pneumonia complicated by encephalitis among patients from Guizhou Province compared to other regions ( Table 1 ). Temporal trends demonstrated a peak in case numbers in 2024, with 349 cases (32.08%). Seasonal variation was also apparent, with the highest number of cases reported in March (158 cases, 14.52%) and April (156 cases, 14.34%), and the lowest in November (19 cases, 1.75%) ( Figure 1, Figure 2 ). The incidence of severe pneumonia remained consistently high throughout the study period, reaching a peak of 98.28% in 2024. Encephalitis showed distinct spikes in 2015 (51.52%) and 2019 (39.04%). The co-occurrence of severe pneumonia and encephalitis was notably elevated in 2019 (14.97%) and 2024 (14.32%) ( Figure 3 ). Clinical Characteristics of Patients Clinical symptoms and severity varied significantly across groups. Convulsions were markedly more common in the encephalitis-only group (Group B), whereas apnea and pulmonary hypertension were significantly more prevalent in patients with both severe pneumonia and encephalitis (Group C). Laboratory parameters revealed that elevated white blood cell counts (≥30×10 9 /L), high lactate levels (≥2.1 mmol/L), lymphocytosis, and thrombocytosis were more frequently observed in Group C, with all showing statistically significant differences across groups. Co-infection analysis showed that Acinetobacter baumannii was significantly more prevalent in Group C compared to the other groups, suggesting a possible association with disease severity. Therapeutic interventions included universal macrolide therapy, with additional antibiotics (such as cephalosporins and penicillins) used based on clinical judgment. Critically ill patients received corticosteroids and intravenous immunoglobulin. The use of third-generation cephalosporins, cotrimoxazole, methylprednisolone, and immunoglobulin differed significantly between groups, with Group C showing the highest rates of administration. Additionally, bronchoscopy and exchange transfusion were performed more frequently in Group C, reaching statistical significance. Analysis of hospitalization metrics revealed that patients in Group C had significantly longer hospital stays and higher mortality rates compared to those in Groups A and B ( Table 1 ). Imaging and Laboratory Test Results Imaging Findings Most children with severe pertussis pneumonia (n=889) underwent chest imaging, including plain radiography and computed tomography (CT). Radiological findings predominantly revealed pulmonary consolidation and atelectasis, with some cases showing pleural effusion. Among patients with pertussis complicated by encephalitis, the majority received comprehensive neuroimaging and electrophysiological assessments, including cranial CT, magnetic resonance imaging (MRI), and electroencephalography (EEG). MRI commonly revealed mild widening of the bilateral frontotemporal extracerebral spaces. EEG showed background activity consisting primarily of 2–5 Hz delta-theta rhythms in both awake and sedated states, accompanied by intermittent generalized (predominantly frontal) irregular sharp waves, sharp-slow wave complexes, or slow-wave bursts. Cerebrospinal fluid (CSF) analyses revealed mildly elevated protein levels and bacterial counts, without marked pleocytosis or hypoglycorrhachia ( Figure 4 ). Pathogen Detection All patients underwent sputum culture and multiplex respiratory pathogen screening. Secondary bacterial infections were identified in 379 out of 1,088 patients (34.83%). The most commonly isolated organisms were Haemophilus influenzae (32.72%), Streptococcus pneumoniae (16.09%), and Staphylococcus aureus (13.72%) ( Figure 5) . In addition, 511 patients (46.97%) tested positive for concurrent viral infections at admission. The most frequently detected viruses were respiratory syncytial virus (RSV) in 14.25% (55/1,088) and parainfluenza virus in 8.00% (87/1,088) of cases ( Figure 6 ). Analysis of Treatment Patterns Across the study period, all patients received azithromycin as first-line therapy. Additional antimicrobial agents included cephalosporins, penicillins, sulfonamides, glucocorticoids, and intravenous immunoglobulin (IVIG). Cephalosporins were the most frequently administered, with usage rates peaking in 2024. Among cephalosporins, third-generation agents—particularly cefoperazone-sulbactam—were predominant, being used in 368 of 679 cases (54.2%) ( Figures 7 and 8 ). Penicillins were prescribed in 246 cases, most commonly piperacillin-tazobactam (167/246, 67.89%). Glucocorticoids were administered to 349 patients, IVIG to 548 patients, and sulfonamides to 86 patients, primarily starting in 2024. Patient Outcomes A total of 20 deaths were recorded during the 10-year study period, yielding an overall mortality rate of 1.84%. No deaths were reported in 2016, 2021, or 2023, while the highest annual mortality rate occurred in 2020 (6.25%). Mortality rates in other years remained relatively stable ( Figure 9 ). Excluding patients with early mortality, the median hospital stay ranged from 9-10 days across the cohort ( Figure 10 ). Univariate analysis identified several factors significantly associated with mortality, including female sex, pulmonary hypertension, elevated lactic acid levels, lymphocytosis, leukocytosis, exchange transfusion, glucocorticoid therapy, concurrent encephalitis, combined severe pneumonia with encephalitis, and prolonged hospital stay. Detailed results and statistics are provided in Table 2 . Multivariate analysis identified pulmonary hypertension, exchange transfusion, and glucocorticoid therapy as independent risk factors significantly associated with increased mortality, whereas longer hospital stay was significantly associated with reduced risk of death ( Table 3 ). Discussion With widespread pertussis vaccination, the incidence of pertussis had remained low for many years. However, in the past decade—particularly in the post-COVID-19 era—there has been a notable resurgence of pertussis, including a gradual increase in severe cases and associated fatalities. The sharp rise in 2024 may be attributed to several factors, including potential B. pertussis mutations, antimicrobial resistance, waning vaccine-induced immunity, and greater challenges in clinical management. Alarmingly, the mortality rate of severe pertussis in some developed countries has been reported to be as high as 19.7%–31% [19-10] . Consistent with previous studies, infants under 3 months of age were disproportionately affected and represent a population at high risk for severe disease [11] .Over the ten-year study period, three small incidence peaks were observed, aligning with the known 3–5-year epidemic cycle [12] . Seasonally, pertussis incidence was highest in spring and lowest in autumn and winter. Severe pneumonia was the most common complication among critically ill patients in our cohort. This likely reflects the pathophysiology of pertussis in infants, who are unable to effectively clear respiratory secretions. B. pertussis induces diffuse bronchial inflammation, persistent immune stimulation, excessive mucus secretion, and bronchial obstruction, which together result in radiographic evidence of pulmonary consolidation and atelectasis [13] . Encephalitis was the second most frequent and severe complication, typically occurring within 2–4 weeks of symptom onset [ 14-15] . Many encephalitis cases were coinfected with opportunistic pathogens, particularly Acinetobacter baumannii , likely due to immune suppression induced by the infection itself. Clinically, convulsions and cyanosis were common in these patients. Convulsions were particularly prominent in patients with isolated encephalitis, suggesting that they may serve as the initial manifestation in such cases. Additionally, respiratory arrest was more frequent in patients with combined pneumonia and encephalitis, indicating contributions from both airway compromise and central respiratory failure. Notably, cerebrospinal fluid (CSF) testing for pertussis toxin (PTx) or bacterial nucleic acid was not performed, limiting insight into the direct etiological link between B. pertussis and encephalopathy. Group C patients (combined pneumonia and encephalitis) exhibited higher leukocyte and lymphocyte counts as well as elevated lactate levels, suggesting excessive production of pertussis toxin (PTx), which promotes lymphocytosis, inhibits apoptosis, and enhances systemic inflammation. Previous studies have also associated pulmonary hypertension, leukocytosis, and lymphocytosis with increased mortality risk in infants [16] . In our study, echocardiographic findings, blood counts, and lactate levels emerged as useful markers for early risk stratification, though not all were independent predictors in multivariate analysis. For example, some immunocompromised patients did not exhibit marked leukocytosis. Elevated lactate may also persist in children with underlying metabolic disorders, thus limiting its specificity. Among the variables tested, pulmonary hypertension emerged as an independent predictor of mortality, underscoring the importance of early echocardiographic screening in suspected severe cases. Regarding treatment, macrolides remain the first-line therapy. However, resistance rates among B. pertussis isolates in China have reached 85–91.9% [ 17, 18] , which may explain the increased proportion of patients requiring alternative antibiotics in recent years. In our study, non-macrolide agents—including sulfonamides—were increasingly used, particularly in 2024, likely reflecting adjustments in clinical practice based on suspected macrolide resistance. Notably, antimicrobial susceptibility testing for B. pertussis was not routinely performed at our center, highlighting the need for future molecular resistance surveillance. The increased use of corticosteroids and immunoglobulins in patients with combined complications reflects attempts to modulate the inflammatory response and improve outcomes. However, larger-scale studies are needed to evaluate their true risk-benefit ratio. Notably, ventilatory support—whether non-invasive, invasive, or high-frequency—was used significantly more in patients with dual organ involvement, suggesting that peripheral and central mechanisms may both contribute to respiratory failure. For patients with critical leukocytosis, exchange transfusion has been proposed to rapidly reduce white cell burden and mitigate complications. Though 42 patients in our study underwent this procedure, the mortality rate remained high, and the small sample size precludes definitive conclusions. Further research is needed to identify optimal timing and patient selection criteria for this intervention. While extracorporeal membrane oxygenation (ECMO) has been reported in case studies of severe pertussis [19] , the survival rate remains low (~30%) and significantly lower than for other ECMO indications [9] . In our cohort, three patients received ECMO, but case numbers were too small to assess efficacy. Globally, despite high vaccination coverage (estimated at 86% in 2016) [20-21] , pertussis continues to cause ~24 million cases and ~160,000 deaths annually [22] . Factors contributing to its resurgence include improved surveillance, waning immunity, strain evolution, and asymptomatic transmission [23-27] . The transition to acellular pertussis vaccines (DTaP), while improving tolerability, has resulted in shorter-duration immunity and increased susceptibility in vaccinated populations [28–30]. The emergence of pertactin-deficient B. pertussis strains further undermines vaccine efficacy [28-30] . In China, pertussis vaccination begins at 3 months of age, but only 40.9% of children in our cohort had received prior vaccination. Recent data suggest that the half-life of maternal vaccine-induced antibodies is shorter than previously believed [31] , highlighting the importance of maternal immunization as a preventive strategy for infants too young for active vaccination [32-33] . Many high-burden countries have adopted maternal immunization programs [34] , but China has yet to do so [35] . Notably, ~80% of Chinese infants below vaccination age and two-thirds of reproductive-age adults lack pertussis-specific antibodies [36] , leaving them susceptible. Implementation of adult booster and maternal immunization strategies should be urgently considered. Conclusion This retrospective study analyzed clinical characteristics, complications, laboratory findings, and treatment evolution in children with severe pertussis over the past decade at a tertiary pediatric center in Southwest China. Severe pneumonia and encephalitis were the most common and critical complications. Treatment approaches have evolved to include broader use of cephalosporins, sulfonamides, corticosteroids, and immunoglobulin, alongside macrolides. Exchange transfusion and ECMO were used in selected critically ill cases, though further studies are needed to clarify their efficacy. Vaccination remains the cornerstone of pertussis prevention. However, the relatively low vaccination coverage among affected children and the vulnerability of infants under 3 months highlight the need for adjustments in the national immunization strategy. Maternal immunization, although not yet implemented in China, represents a promising approach to protect high-risk infants. Several limitations should be acknowledged. These include the retrospective design, limited sample size for certain interventions (e.g., ECMO, exchange transfusion), and absence of blood ammonia data to assess metabolic status comprehensively. Furthermore, the lack of antimicrobial resistance profiling in B. pertussis strains limited insight into treatment efficacy. Future research should focus on understanding resistance mechanisms and evaluating novel therapeutic strategies to improve outcomes in drug-resistant pertussis. Abbreviations (Listed in alphabetical order) CI: Confidence Interval CSF: Cerebrospinal Fluid DTaP: Diphtheria, Tetanus, and acellular Pertussis vaccine ECMO: Extracorporeal Membrane Oxygenation EEG: Electroencephalography ET: Exchange Transfusion IQR: Interquartile Range IVIG: Intravenous Immunoglobulin OR: Odds Ratio PCR: Polymerase Chain Reaction PTx: Pertussis Toxin WBC: White Blood Cell Declarations Acknowledgments The authors sincerely thank the Big Data Center of the Children’s Hospital of Chongqing Medical University for providing access to clinical case data. We are also grateful to the Department of Epidemiology for their valuable guidance on statistical analysis. Our heartfelt appreciation extends to all collaborators who contributed to the implementation of this study. Author Contributions YQL conceptualized and designed the study, supervised data collection and analysis, and drafted the initial manuscript. YQL and XQC jointly collected and organized the clinical data. YQL performed the statistical analyses. XQC (corresponding author) led the overall study design, coordinated research activities, and contributed to the critical revision of the manuscript. TL, WQ and LC assisted in data collection and verification. All authors read and approved the final version of the manuscript for submission. Funding This study received no specific funding. Data and Materials Availability The datasets generated and/or analyzed during the current study are not publicly available due to concerns regarding participant privacy. However, data may be made available from the corresponding author upon reasonable request and subject to institutional data use agreements. Ethics Approval and Informed Consent This study was approved by the Regional Ethics Committee of the Children’s Hospital of Chongqing Medical University (Approval No.: [2022]382). The requirement for informed consent was waived due to the retrospective design of the study and the use of anonymized clinical data. Publication Consent Statement Not Applicable. Conflict of Interest Statement The authors declare no conflicts of interest. Author Affiliation Department of Emergency, Children’s Hospital of Chongqing Medical University, Chongqing, China References Wang C, Zhang H, Zhang Y, et al. Analysis of clinical characteristics of severe pertussis in infants and children: a retrospective study. BMC Pediatr. 2021;21(1):65. https://pmc.ncbi.nlm.nih.gov/articles/PMC7863367/ Fu P, Yan G, Li Y, et al. 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Pediatrics. 2017;139:e20164091. https://publications.aap.org/pediatrics/article-abstract/139/5/e20164091/38778/Effectiveness-of-Vaccination-During-Pregnancy-to?redirectedFrom=fulltext Skoff T.H., Blain A.E., Watt J., et al. Impact of the US Maternal Tetanus, Diphtheria, and Acellular Pertussis Vaccination Program on Preventing Pertussis in Infants <2 Months of Age: A Case-Control Evaluation. Clin. Infect. Dis. 2017;65:1977–1983. https://pmc.ncbi.nlm.nih.gov/articles/PMC5754921/ Pertussis: Halting the Epidemic by Protecting Infants. Available online: http://www.bpac.org.nz/magazine/2013/march/docs/ BPJ51-pages-34-38.pdf (accessed on 13 September 2021). Li YT, Luo XQ, Zhong XB, et al. Seroprevalences of antibodies against pertussis, diphtheria, tetanus, measles, mumps and rubella: A cross-sectional study in children following vaccination procedure in Guangzhou, China. Vaccine. 2020 May 13;38(23):3960-3967.https://www.sciencedirect.com/science/article/abs/pii/S0264410X2030445X?via%3Dihub Zhiyun Chen, Jie Pang, Nan Zhang, et al. Seroprevalence Study of Pertussis in Adults at Childbearing Age and Young Infants Reveals the Necessity of Booster Immunizations in Adults in China.Vaccines (Basel) 2022 Jan; 10(1): 84.Published online 2022 Jan 6. https://pmc.ncbi.nlm.nih.gov/articles/PMC8779665/ Tables Tables 1 to 3 are available in the Supplementary Files section Supplementary Files Tables.docx Cite Share Download PDF Status: Published Journal Publication published 26 Feb, 2026 Read the published version in Italian Journal of Pediatrics → Version 1 posted Editorial decision: Major revision 13 Oct, 2025 Reviewers agreed at journal 31 Aug, 2025 Reviewers invited by journal 19 Aug, 2025 Editor assigned by journal 13 Aug, 2025 First submitted to journal 11 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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University","correspondingAuthor":false,"prefix":"","firstName":"Qifan","middleName":"","lastName":"Wu","suffix":""},{"id":502744171,"identity":"e4ef0ae5-7448-42a6-8929-afc01b45d8bb","order_by":2,"name":"Liping Tan","email":"","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Liping","middleName":"","lastName":"Tan","suffix":""},{"id":502744172,"identity":"0dc09143-91d3-4e98-ab6d-710f5077b995","order_by":3,"name":"Cong Liu","email":"","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Cong","middleName":"","lastName":"Liu","suffix":""},{"id":502744173,"identity":"680c4ebe-89b6-42d9-8866-7604009ddd65","order_by":4,"name":"Xiaoqing 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02:48:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7238222/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7238222/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13052-026-02210-z","type":"published","date":"2026-02-26T15:59:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90304202,"identity":"3f798829-3962-4b8b-aad9-5fa172c2b549","added_by":"auto","created_at":"2025-09-01 09:11:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36914,"visible":true,"origin":"","legend":"\u003cp\u003eIncidence Trends of Severe Pertussis in Children Over the Past Decade\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/6e15ff94ba0d324809477957.png"},{"id":90301886,"identity":"380668e6-400d-4652-940f-31fef797d435","added_by":"auto","created_at":"2025-09-01 09:03:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":34152,"visible":true,"origin":"","legend":"\u003cp\u003eMonthly Distribution of Pediatric Severe Pertussis Cases\u0026nbsp;\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/a217af541e0761108f309f81.png"},{"id":90304641,"identity":"85123ae0-5248-49f2-8970-b7083e2b8b08","added_by":"auto","created_at":"2025-09-01 09:19:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":90949,"visible":true,"origin":"","legend":"\u003cp\u003eAnnual Distribution of Severe Pneumonia and Encephalitis in Pediatric Pertussis Cases\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/e39244d42d2e0c0f59fa16bd.png"},{"id":90301890,"identity":"8397eb86-4b79-4f23-8d13-fc26224a5da9","added_by":"auto","created_at":"2025-09-01 09:03:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":264372,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative Chest Imaging in Children with Severe Pertussis\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/f2cdfe9d2737ae956fc65796.png"},{"id":90301889,"identity":"92213869-25b5-4e19-a444-164002bcbacb","added_by":"auto","created_at":"2025-09-01 09:03:16","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":40179,"visible":true,"origin":"","legend":"\u003cp\u003eBacterial Culture Results in Pediatric Severe Pertussis Patients\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/ab062e982dc7601f93009038.png"},{"id":90301894,"identity":"82471349-9fc3-489a-9ee4-c0d35c159767","added_by":"auto","created_at":"2025-09-01 09:03:16","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":40755,"visible":true,"origin":"","legend":"\u003cp\u003eViral Detection Results in Children with Severe Pertussis\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/641840500b911f603efe3014.png"},{"id":90304205,"identity":"7c4349f9-f086-4025-a67b-709097ded1b8","added_by":"auto","created_at":"2025-09-01 09:11:16","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":39476,"visible":true,"origin":"","legend":"\u003cp\u003eUse of Cephalosporins and Penicillins Among Pediatric Patients with Severe Pertussis\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/8442cda4b5cedb067856bbf5.png"},{"id":90304208,"identity":"662e9054-b437-493b-9580-34352a13a729","added_by":"auto","created_at":"2025-09-01 09:11:17","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":104708,"visible":true,"origin":"","legend":"\u003cp\u003eTemporal Trends in Antimicrobial and Immunomodulatory Therapy Over the Past Decade\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/985d6f017223ffdd3485e1dc.png"},{"id":90301897,"identity":"ea4bb157-560b-46bd-9901-74ddccb3d958","added_by":"auto","created_at":"2025-09-01 09:03:16","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":50534,"visible":true,"origin":"","legend":"\u003cp\u003eAnnual Mortality Distribution in Pediatric Severe Pertussis Cases\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/17b41f6e75ffa867a3ce4c4c.png"},{"id":90301895,"identity":"b7be0281-73e9-499a-8a95-baee5a609abc","added_by":"auto","created_at":"2025-09-01 09:03:16","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":43132,"visible":true,"origin":"","legend":"\u003cp\u003eAge and Length of Hospital Stay Distribution in Severe Pertussis Patients [M (IQR)]\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/34cd0fc7b9f0d1e78c3ad635.png"},{"id":103765771,"identity":"e08f32bc-ea66-4ea5-a4f9-6cc8ad95aebc","added_by":"auto","created_at":"2026-03-02 16:08:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1355863,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/140228b3-d0ef-4814-bea5-e8281dcb647f.pdf"},{"id":90304203,"identity":"485cd58f-6632-4320-beee-0fb3cc826112","added_by":"auto","created_at":"2025-09-01 09:11:16","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":34731,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7238222/v1/5d33faed03a278456231bbcc.docx"}],"financialInterests":"","formattedTitle":"Clinical Characteristics, Complications, and Mortality Risk Factors in Severe Pediatric Pertussis: A Retrospective Single-Center Study in Southwest China","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePertussis is a highly contagious respiratory disease that remains a significant cause of morbidity and severe complications in children. Although there is no universally accepted diagnostic standard for severe pertussis, it is commonly recognized in infants presenting with any of the following: complications, such as severe pneumonia or encephalopathy, or clinical signs, such as apnea, marked leukocytosis, or evidence of pulmonary hypertension on diagnostic imaging or echocardiography\u003csup\u003e[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Among these, apnea is often the most prominent and alarming symptom.\u003c/p\u003e\u003cp\u003eSevere pertussis is characterized by rapid clinical progression and poor response to treatment. Globally, the reported mortality rate ranges from 1.2-3.0%\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. In China, although the incidence of pertussis remained relatively low for two decades, a resurgence has been observed since 2014 across several regions\u003csup\u003e[5\u0026ndash;7 ]\u003c/sup\u003e. This trend is particularly concerning in infants who are too young to have completed the primary immunization schedule. While vaccination has significantly reduced the incidence of severe pertussis in older children and adults, infants remain the most vulnerable group, with the highest rates of hospitalization and mortality\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThis elevated mortality is partially attributable to delayed or missed immunizations in early infancy and a limited understanding of the underlying mechanisms of disease progression. In addition, many clinicians may not be fully aware of the clinical features or risk factors associated with severe pertussis, leading to delayed diagnosis and suboptimal treatment.\u003c/p\u003e\u003cp\u003eGiven these challenges, the present study aims to characterize systematically the clinical features, complications, and treatment patterns of severe pertussis cases admitted to our hospital over the past decade. Furthermore, we seek to identify key mortality-related risk factors, in order to inform optimized diagnostic and therapeutic strategies and ultimately reduce disease burden in this high-risk pediatric population.\u003c/p\u003e"},{"header":"Research Subjects and Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy Population\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study included pediatric patients diagnosed with severe pertussis between 2015 and 2024 at the Children's Hospital of Chongqing Medical University. A total of 1,093 cases were initially identified, of which five were excluded due to treatment discontinuation, resulting in a final cohort of 1,088 patients. Diagnosis of pertussis was confirmed by either \u003cem\u003eBordetella pertussis\u003c/em\u003e culture or polymerase chain reaction (PCR) detection of \u003cem\u003eB. pertussis\u003c/em\u003e DNA.\u003c/p\u003e\n\u003cp\u003eCases were classified as severe pertussis if they met any of the following criteria: (1) complications, such as severe pneumonia or encephalopathy; (2) clinical manifestations of apnea; or (3) study findings including marked leukocytosis or evidence of pulmonary hypertension. The study encompassed both intensive care unit (ICU) and non-ICU patients who met the above criteria.\u003c/p\u003e\n\u003cp\u003eGiven the clinical importance of severe pneumonia and encephalitis as major complications, all included patients were classified into one of the following three mutually exclusive groups for comparative analysis: (1) severe pneumonia without encephalitis; (2) encephalitis without severe pneumonia; and (3) both severe pneumonia and encephalitis. Patients with other comorbidities were still included as long as they met the diagnostic criteria for severe pertussis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData Collection Methods\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical and demographic data were extracted from the hospital's big-data medical record system. The collected information included sex, age, geographic origin (province or city), and pertussis vaccination history, which was verified through admission records or vaccination certificates. Clinical variables comprised presenting symptoms, duration of hospitalization, and comorbidities, such as pneumonia, encephalitis, and cardiovascular complications. Laboratory parameters included white blood cell count, lymphocyte count, platelet count, lactate concentration, and other relevant indicators. Radiological data, including chest imaging and echocardiographic findings, were reviewed to assess pulmonary and cardiac involvement. Treatment regimens were recorded, including the use of antibiotics, corticosteroids, intravenous immunoglobulin (IVIG), mechanical ventilation, exchange transfusion, and extracorporeal membrane oxygenation (ECMO). Patient outcomes, including clinical progression and discharge status, were also documented.\u003c/p\u003e\n\u003cp\u003eDiagnostic criteria for pneumonia were based on clinical signs in conjunction with radiographic evidence, while encephalitis was diagnosed through a combination of neurological symptoms and supporting laboratory data. Hematological abnormalities were defined as follows: leukocytosis was considered present when the WBC count was ≥30×10⁹/L; thrombocytosis was defined as a platelet count ≥800×10⁹/L; and lymphocytosis was defined as a lymphocyte count ≥20×10⁹/L. All laboratory reference ranges followed the Chinese Health Industry Standard \"Reference Intervals for Blood Cell Analysis in Children\" (WS/T 779–2021).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthical Approval\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Ethics Committee of the Children's Medical Center, Chongqing Medical University (Approval No.: [2022] 382), and conducted in accordance with the principles of the Declaration of Helsinki (10th revision).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eQuality Control\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo ensure data accuracy and consistency, a multi-step quality control process was employed throughout the study. Initially, two independent professionals with expertise in big data analytics extracted and cross-verified all clinical and laboratory information from the database. A secondary validation process was then conducted by senior clinicians, who randomly audited 10% of the included cases. During this stage, diagnostic records, laboratory test results, and treatment details were cross-checked using data from the hospital’s electronic medical record system (EMR), laboratory information system (LIS), and picture archiving and communication system (PACS). Finally, any discrepancies or inconsistencies identified during the verification process were resolved by a third-party adjudicator, following standardized procedures for data correction and imputation. This rigorous approach ensured the reliability and reproducibility of the dataset used for statistical analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical Analysis \u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using SPSS version 23.0. Categorical variables were expressed as frequencies and percentages [n (%)], and group comparisons were conducted using chi-square tests or Fisher’s exact tests where applicable (expected counts ≤5). Pairwise comparisons among the three groups were adjusted using the Bonferroni correction.\u003c/p\u003e\n\u003cp\u003eContinuous variables (e.g., age, length of hospitalization), which did not follow normal distributions, were presented as medians and interquartile ranges [M (IQR)]. Intergroup comparisons were conducted using the Kruskal–Wallis H test, followed by post hoc pairwise analyses.\u003c/p\u003e\n\u003cp\u003eUnivariate and multivariate logistic regression analyses were conducted to identify risk factors associated with mortality. A two-sided \u003cem\u003ep\u003c/em\u003e-value \u0026lt;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDemographic Characteristics of Patients\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSevere pneumonia and encephalitis were the most common complications among children diagnosed with severe pertussis in this cohort. Specifically, 889 patients (81.71%) had severe pneumonia alone, 61 (5.61%) presented with encephalitis alone, and 138 (12.68%) experienced both complications concurrently.\u003c/p\u003e\n\u003cp\u003eAge distribution revealed that the majority of cases occurred in infants under one year of age, with a concentration between 2 and 4 months. The highest median age was observed in 2023 (4.07 months), while the lowest was recorded in 2020 (2.65 months).\u003c/p\u003e\n\u003cp\u003eGeographic distribution analysis showed a significantly higher incidence of severe pneumonia complicated by encephalitis among patients from Guizhou Province compared to other regions (\u003cstrong\u003eTable 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eTemporal trends demonstrated a peak in case numbers in 2024, with 349 cases (32.08%). Seasonal variation was also apparent, with the highest number of cases reported in March (158 cases, 14.52%) and April (156 cases, 14.34%), and the lowest in November (19 cases, 1.75%) (\u003cstrong\u003eFigure 1, Figure 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eThe incidence of severe pneumonia remained consistently high throughout the study period, reaching a peak of 98.28% in 2024. Encephalitis showed distinct spikes in 2015 (51.52%) and 2019 (39.04%). The co-occurrence of severe pneumonia and encephalitis was notably elevated in 2019 (14.97%) and 2024 (14.32%) (\u003cstrong\u003eFigure 3\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical Characteristics of Patients\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical symptoms and severity varied significantly across groups. Convulsions were markedly more common in the encephalitis-only group (Group B), whereas apnea and pulmonary hypertension were significantly more prevalent in patients with both severe pneumonia and encephalitis (Group C).\u003c/p\u003e\n\u003cp\u003eLaboratory parameters revealed that elevated white blood cell counts (\u0026ge;30\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L), high lactate levels (\u0026ge;2.1 mmol/L), lymphocytosis, and thrombocytosis were more frequently observed in Group C, with all showing statistically significant differences across groups.\u003c/p\u003e\n\u003cp\u003eCo-infection analysis showed that \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e was significantly more prevalent in Group C compared to the other groups, suggesting a possible association with disease severity.\u003c/p\u003e\n\u003cp\u003eTherapeutic interventions included universal macrolide therapy, with additional antibiotics (such as cephalosporins and penicillins) used based on clinical judgment. Critically ill patients received corticosteroids and intravenous immunoglobulin. The use of third-generation cephalosporins, cotrimoxazole, methylprednisolone, and immunoglobulin differed significantly between groups, with Group C showing the highest rates of administration. Additionally, bronchoscopy and exchange transfusion were performed more frequently in Group C, reaching statistical significance.\u003c/p\u003e\n\u003cp\u003eAnalysis of hospitalization metrics revealed that patients in Group C had significantly longer hospital stays and higher mortality rates compared to those in Groups A and B (\u003cstrong\u003eTable 1\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eImaging and Laboratory Test Results\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eImaging Findings\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMost children with severe pertussis pneumonia (n=889) underwent chest imaging, including plain radiography and computed tomography (CT). Radiological findings predominantly revealed pulmonary consolidation and atelectasis, with some cases showing pleural effusion.\u003c/p\u003e\n\u003cp\u003eAmong patients with pertussis complicated by encephalitis, the majority received comprehensive neuroimaging and electrophysiological assessments, including cranial CT, magnetic resonance imaging (MRI), and electroencephalography (EEG). MRI commonly revealed mild widening of the bilateral frontotemporal extracerebral spaces. EEG showed background activity consisting primarily of 2\u0026ndash;5 Hz delta-theta rhythms in both awake and sedated states, accompanied by intermittent generalized (predominantly frontal) irregular sharp waves, sharp-slow wave complexes, or slow-wave bursts. Cerebrospinal fluid (CSF) analyses revealed mildly elevated protein levels and bacterial counts, without marked pleocytosis or hypoglycorrhachia (\u003cstrong\u003eFigure 4\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePathogen Detection\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients underwent sputum culture and multiplex respiratory pathogen screening. Secondary bacterial infections were identified in 379 out of 1,088 patients (34.83%). The most commonly isolated organisms were \u003cem\u003eHaemophilus influenzae\u003c/em\u003e (32.72%), \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e (16.09%), and \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (13.72%) (\u003cstrong\u003eFigure 5)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eIn addition, 511 patients (46.97%) tested positive for concurrent viral infections at admission. The most frequently detected viruses were respiratory syncytial virus (RSV) in 14.25% (55/1,088) and parainfluenza virus in 8.00% (87/1,088) of cases (\u003cstrong\u003eFigure 6\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAnalysis of Treatment Patterns\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcross the study period, all patients received azithromycin as first-line therapy. Additional antimicrobial agents included cephalosporins, penicillins, sulfonamides, glucocorticoids, and intravenous immunoglobulin (IVIG). Cephalosporins were the most frequently administered, with usage rates peaking in 2024. Among cephalosporins, third-generation agents\u0026mdash;particularly cefoperazone-sulbactam\u0026mdash;were predominant, being used in 368 of 679 cases (54.2%) (\u003cstrong\u003eFigures 7 and 8\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003ePenicillins were prescribed in 246 cases, most commonly piperacillin-tazobactam (167/246, 67.89%). Glucocorticoids were administered to 349 patients, IVIG to 548 patients, and sulfonamides to 86 patients, primarily starting in 2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatient Outcomes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 20 deaths were recorded during the 10-year study period, yielding an overall mortality rate of 1.84%. No deaths were reported in 2016, 2021, or 2023, while the highest annual mortality rate occurred in 2020 (6.25%). Mortality rates in other years remained relatively stable (\u003cstrong\u003eFigure 9\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eExcluding patients with early mortality, the median hospital stay ranged from 9-10 days across the cohort (\u003cstrong\u003eFigure 10\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eUnivariate analysis identified several factors significantly associated with mortality, including female sex, pulmonary hypertension, elevated lactic acid levels, lymphocytosis, leukocytosis, exchange transfusion, glucocorticoid therapy, concurrent encephalitis, combined severe pneumonia with encephalitis, and prolonged hospital stay. Detailed results and statistics are provided in \u003cstrong\u003eTable 2\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Multivariate analysis identified pulmonary hypertension, exchange transfusion, and glucocorticoid therapy as independent risk factors significantly associated with increased mortality, whereas longer hospital stay was significantly associated with reduced risk of death (\u003cstrong\u003eTable 3\u003c/strong\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWith widespread pertussis vaccination, the incidence of pertussis had remained low for many years. However, in the past decade—particularly in the post-COVID-19 era—there has been a notable resurgence of pertussis, including a gradual increase in severe cases and associated fatalities. The sharp rise in 2024 may be attributed to several factors, including potential \u003cem\u003eB. pertussis\u003c/em\u003e mutations, antimicrobial resistance, waning vaccine-induced immunity, and greater challenges in clinical management. Alarmingly, the mortality rate of severe pertussis in some developed countries has been reported to be as high as 19.7%–31%\u003csup\u003e[19-10]\u003c/sup\u003e. Consistent with previous studies, infants under 3 months of age were disproportionately affected and represent a population at high risk for severe disease\u003csup\u003e[11]\u003c/sup\u003e.Over the ten-year study period, three small incidence peaks were observed, aligning with the known 3–5-year epidemic cycle\u003csup\u003e[12]\u003c/sup\u003e. Seasonally, pertussis incidence was highest in spring and lowest in autumn and winter.\u003c/p\u003e\n\u003cp\u003eSevere pneumonia was the most common complication among critically ill patients in our cohort. This likely reflects the pathophysiology of pertussis in infants, who are unable to effectively clear respiratory secretions. \u003cem\u003eB. pertussis\u003c/em\u003e induces diffuse bronchial inflammation, persistent immune stimulation, excessive mucus secretion, and bronchial obstruction, which together result in radiographic evidence of pulmonary consolidation and atelectasis\u003csup\u003e[13]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eEncephalitis was the second most frequent and severe complication, typically occurring within 2–4 weeks of symptom onset\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e14-15]\u003c/sup\u003e. Many encephalitis cases were coinfected with opportunistic pathogens, particularly \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e, likely due to immune suppression induced by the infection itself. Clinically, convulsions and cyanosis were common in these patients. Convulsions were particularly prominent in patients with isolated encephalitis, suggesting that they may serve as the initial manifestation in such cases. Additionally, respiratory arrest was more frequent in patients with combined pneumonia and encephalitis, indicating contributions from both airway compromise and central respiratory failure. Notably, cerebrospinal fluid (CSF) testing for pertussis toxin (PTx) or bacterial nucleic acid was not performed, limiting insight into the direct etiological link between \u003cem\u003eB. pertussis\u003c/em\u003e and encephalopathy.\u003c/p\u003e\n\u003cp\u003eGroup C patients (combined pneumonia and encephalitis) exhibited higher leukocyte and lymphocyte counts as well as elevated lactate levels, suggesting excessive production of pertussis toxin (PTx), which promotes lymphocytosis, inhibits apoptosis, and enhances systemic inflammation. Previous studies have also associated pulmonary hypertension, leukocytosis, and lymphocytosis with increased mortality risk in infants\u003csup\u003e[16]\u003c/sup\u003e. In our study, echocardiographic findings, blood counts, and lactate levels emerged as useful markers for early risk stratification, though not all were independent predictors in multivariate analysis. For example, some immunocompromised patients did not exhibit marked leukocytosis. Elevated lactate may also persist in children with underlying metabolic disorders, thus limiting its specificity.\u003c/p\u003e\n\u003cp\u003eAmong the variables tested, pulmonary hypertension emerged as an independent predictor of mortality, underscoring the importance of early echocardiographic screening in suspected severe cases.\u003c/p\u003e\n\u003cp\u003eRegarding treatment, macrolides remain the first-line therapy. However, resistance rates among \u003cem\u003eB. pertussis\u003c/em\u003e isolates in China have reached 85–91.9%\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e17, 18]\u003c/sup\u003e, which may explain the increased proportion of patients requiring alternative antibiotics in recent years. In our study, non-macrolide agents—including sulfonamides—were increasingly used, particularly in 2024, likely reflecting adjustments in clinical practice based on suspected macrolide resistance. Notably, antimicrobial susceptibility testing for \u003cem\u003eB. pertussis\u003c/em\u003e was not routinely performed at our center, highlighting the need for future molecular resistance surveillance.\u003c/p\u003e\n\u003cp\u003eThe increased use of corticosteroids and immunoglobulins in patients with combined complications reflects attempts to modulate the inflammatory response and improve outcomes. However, larger-scale studies are needed to evaluate their true risk-benefit ratio. Notably, ventilatory support—whether non-invasive, invasive, or high-frequency—was used significantly more in patients with dual organ involvement, suggesting that peripheral and central mechanisms may both contribute to respiratory failure.\u003c/p\u003e\n\u003cp\u003eFor patients with critical leukocytosis, exchange transfusion has been proposed to rapidly reduce white cell burden and mitigate complications. Though 42 patients in our study underwent this procedure, the mortality rate remained high, and the small sample size precludes definitive conclusions. Further research is needed to identify optimal timing and patient selection criteria for this intervention.\u003c/p\u003e\n\u003cp\u003eWhile extracorporeal membrane oxygenation (ECMO) has been reported in case studies of severe pertussis \u003csup\u003e[19]\u003c/sup\u003e, the survival rate remains low (~30%) and significantly lower than for other ECMO indications\u003csup\u003e[9]\u003c/sup\u003e. In our cohort, three patients received ECMO, but case numbers were too small to assess efficacy.\u003c/p\u003e\n\u003cp\u003eGlobally, despite high vaccination coverage (estimated at 86% in 2016)\u003csup\u003e[20-21]\u003c/sup\u003e, pertussis continues to cause ~24 million cases and ~160,000 deaths annually\u003csup\u003e[22]\u003c/sup\u003e. Factors contributing to its resurgence include improved surveillance, waning immunity, strain evolution, and asymptomatic transmission\u003csup\u003e[23-27]\u003c/sup\u003e. The transition to acellular pertussis vaccines (DTaP), while improving tolerability, has resulted in shorter-duration immunity and increased susceptibility in vaccinated populations [28–30]. The emergence of pertactin-deficient B. pertussis strains further undermines vaccine efficacy\u003csup\u003e[28-30]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn China, pertussis vaccination begins at 3 months of age, but only 40.9% of children in our cohort had received prior vaccination. Recent data suggest that the half-life of maternal vaccine-induced antibodies is shorter than previously believed\u003csup\u003e[31]\u003c/sup\u003e, highlighting the importance of maternal immunization as a preventive strategy for infants too young for active vaccination\u003csup\u003e[32-33]\u003c/sup\u003e. Many high-burden countries have adopted maternal immunization programs\u003csup\u003e[34]\u003c/sup\u003e, but China has yet to do so\u003csup\u003e[35]\u003c/sup\u003e. Notably, ~80% of Chinese infants below vaccination age and two-thirds of reproductive-age adults lack pertussis-specific antibodies\u003csup\u003e[36]\u003c/sup\u003e, leaving them susceptible. Implementation of adult booster and maternal immunization strategies should be urgently considered.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis retrospective study analyzed clinical characteristics, complications, laboratory findings, and treatment evolution in children with severe pertussis over the past decade at a tertiary pediatric center in Southwest China. Severe pneumonia and encephalitis were the most common and critical complications. Treatment approaches have evolved to include broader use of cephalosporins, sulfonamides, corticosteroids, and immunoglobulin, alongside macrolides. Exchange transfusion and ECMO were used in selected critically ill cases, though further studies are needed to clarify their efficacy.\u003c/p\u003e\n\u003cp\u003eVaccination remains the cornerstone of pertussis prevention. However, the relatively low vaccination coverage among affected children and the vulnerability of infants under 3 months highlight the need for adjustments in the national immunization strategy. Maternal immunization, although not yet implemented in China, represents a promising approach to protect high-risk infants.\u003c/p\u003e\n\u003cp\u003eSeveral limitations should be acknowledged. These include the retrospective design, limited sample size for certain interventions (e.g., ECMO, exchange transfusion), and absence of blood ammonia data to assess metabolic status comprehensively. Furthermore, the lack of antimicrobial resistance profiling in \u003cem\u003eB. pertussis\u003c/em\u003e strains limited insight into treatment efficacy. Future research should focus on understanding resistance mechanisms and evaluating novel therapeutic strategies to improve outcomes in drug-resistant pertussis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e(Listed in alphabetical order)\u003c/p\u003e\n\u003cp\u003eCI: Confidence Interval\u003c/p\u003e\n\u003cp\u003eCSF: Cerebrospinal Fluid\u003c/p\u003e\n\u003cp\u003eDTaP: Diphtheria, Tetanus, and acellular Pertussis vaccine\u003c/p\u003e\n\u003cp\u003eECMO: Extracorporeal Membrane Oxygenation\u003c/p\u003e\n\u003cp\u003eEEG: Electroencephalography\u003c/p\u003e\n\u003cp\u003eET: Exchange Transfusion\u003c/p\u003e\n\u003cp\u003eIQR: Interquartile Range\u003c/p\u003e\n\u003cp\u003eIVIG: Intravenous Immunoglobulin\u003c/p\u003e\n\u003cp\u003eOR: Odds Ratio\u003c/p\u003e\n\u003cp\u003ePCR: Polymerase Chain Reaction\u003c/p\u003e\n\u003cp\u003ePTx: Pertussis Toxin\u003c/p\u003e\n\u003cp\u003eWBC: White Blood Cell\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors sincerely thank the Big Data Center of the Children’s Hospital of Chongqing Medical University for providing access to clinical case data. We are also grateful to the Department of Epidemiology for their valuable guidance on statistical analysis. Our heartfelt appreciation extends to all collaborators who contributed to the implementation of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYQL conceptualized and designed the study, supervised data collection and analysis, and drafted the initial manuscript. YQL and XQC jointly collected and organized the clinical data. YQL performed the statistical analyses. XQC (corresponding author) led the overall study design, coordinated research activities, and contributed to the critical revision of the manuscript. TL, WQ and LC assisted in data collection and verification. All authors read and approved the final version of the manuscript for submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received no specific funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData and Materials Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to concerns regarding participant privacy. However, data may be made available from the corresponding author upon reasonable request and subject to institutional data use agreements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval and Informed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Regional Ethics Committee of the Children’s Hospital of Chongqing Medical University (Approval No.: [2022]382). The requirement for informed consent was waived due to the retrospective design of the study and the use of anonymized clinical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublication Consent Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Affiliation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Emergency, Children’s Hospital of Chongqing Medical University, Chongqing, China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWang C, Zhang H, Zhang Y, et al. Analysis of clinical characteristics of severe pertussis in infants and children: a retrospective study. 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Acellular pertussis vaccines protect against disease but fail toprevent infection and transmission in a nonhuman primate model. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111(2):787\u0026ndash;92. https://doi.org/10.1073/pnas.1314688110 PMID: 24277828; PubMed Central PMCID: PMC3896208\u003c/li\u003e\n \u003cli\u003e\u003cu\u003eAlthouse BM, Scarpino SV. Asymptomatic transmission and the resurgence of Bordetella pertussis.BMC medicine. 2015; 13:146. https://doi.org/10.1186/s12916-015-0382-8 PMID: 26103968; PubMedCentral PMCID: PMC4482312.\u0026nbsp;\u003c/u\u003e\u003c/li\u003e\n \u003cli\u003ePawloski LC, Queenan AM, Cassiday PK, et al. Prevalence and molecular characterization of pertactin-deficient Bordetella pertussis in the United States. Clin Vaccine Immunol. 2014; 21(2): 119\u0026ndash;125. https://pmc.ncbi.nlm.nih.gov/articles/PMC3910938/[PubMed: 24256623]\u003c/li\u003e\n \u003cli\u003eQueenan AM, Cassiday PK, Evangelista A. Pertactin-negative variants of Bordetella pertussis in the United States. N Engl J Med. 2013; 368(6):583\u0026ndash;584. https://pubmed.ncbi.nlm.nih.gov/23388024/[PubMed: 23388024]\u003c/li\u003e\n \u003cli\u003e\u003ccite\u003eHealy C.M., Rench M.A., Swaim L.S., et al. Kinetics of maternal pertussis-specific antibodies in infants of mothers vaccinated with tetanus, diphtheria and acellular pertussis (Tdap) during pregnancy. Vaccine. 2020;38:5955\u0026ndash;5961.\u0026nbsp;\u003c/cite\u003ehttps://pmc.ncbi.nlm.nih.gov/articles/PMC8779665/#sec4-vaccines-10-00084\u003c/li\u003e\n \u003cli\u003e\u003ccite\u003eHalperin S.A., Langley J.M., Ye L., et al. A Randomized Controlled Trial of the Safety and Immunogenicity of Tetanus, Diphtheria, and Acellular Pertussis Vaccine Immunization during Pregnancy and Subsequent Infant Immune Response. Clin. Infect. Dis. 2018;67:1063\u0026ndash;1071.https://academic.oup.com/cid/article/67/7/1063/5053576?login=false\u003c/cite\u003e\u003c/li\u003e\n \u003cli\u003e\u003ccite\u003eBaxter R., Bartlett J., Fireman B., et al. Effectiveness of Vaccination during Pregnancy to Prevent Infant Pertussis.\u0026nbsp;\u003c/cite\u003e\u003ccite\u003ePediatrics. 2017;139:e20164091.\u0026nbsp;\u003c/cite\u003ehttps://publications.aap.org/pediatrics/article-abstract/139/5/e20164091/38778/Effectiveness-of-Vaccination-During-Pregnancy-to?redirectedFrom=fulltext\u003c/li\u003e\n \u003cli\u003e\u003ccite\u003eSkoff T.H., Blain A.E., Watt J., et al. Impact of the US Maternal Tetanus, Diphtheria, and Acellular Pertussis Vaccination Program on Preventing Pertussis in Infants \u0026lt;2 Months of Age: A Case-Control Evaluation. Clin. Infect. Dis. 2017;65:1977\u0026ndash;1983.\u0026nbsp;\u003c/cite\u003ehttps://pmc.ncbi.nlm.nih.gov/articles/PMC5754921/\u003c/li\u003e\n \u003cli\u003ePertussis: Halting the Epidemic by Protecting Infants. Available online: http://www.bpac.org.nz/magazine/2013/march/docs/ BPJ51-pages-34-38.pdf (accessed on 13 September 2021).\u003c/li\u003e\n \u003cli\u003eLi YT, Luo XQ, Zhong XB, et al. Seroprevalences of antibodies against pertussis, diphtheria, tetanus, measles, mumps and rubella: A cross-sectional study in children following vaccination procedure in Guangzhou, China. Vaccine. 2020 May 13;38(23):3960-3967.https://www.sciencedirect.com/science/article/abs/pii/S0264410X2030445X?via%3Dihub\u003c/li\u003e\n \u003cli\u003eZhiyun Chen, Jie Pang, Nan Zhang, et al. Seroprevalence Study of Pertussis in Adults at Childbearing Age and Young Infants Reveals the Necessity of Booster Immunizations in Adults in China.Vaccines (Basel) 2022 Jan; 10(1): 84.Published online 2022 Jan 6. https://pmc.ncbi.nlm.nih.gov/articles/PMC8779665/\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Severe pertussis, Pediatric pneumonia, Encephalitis, Bordetella pertussis resistance, Pertussis immunization","lastPublishedDoi":"10.21203/rs.3.rs-7238222/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7238222/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and Objective\u003c/h2\u003e\u003cp\u003ePertussis remains a serious threat to infants and young children, especially when complicated by pneumonia or encephalitis. This study aimed to describe the clinical features, complications, treatments, and mortality risk factors in children with severe pertussis over ten years in Southwest China.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective study was conducted on hospitalized children with severe pertussis at the Children\u0026rsquo;s Hospital of Chongqing Medical University from 2015 to 2024. Clinical data were analyzed across groups with different complications. Mortality risk factors were identified using univariate and multivariate analyses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 1,088 cases were included. Patients were grouped into severe pneumonia, encephalitis, and combined complications. Those with both pneumonia and encephalitis had more apnea, pulmonary hypertension, extreme leukocytosis, thrombocytosis, and \u003cem\u003eA. baumannii\u003c/em\u003e infection. They required more intensive treatments (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), had longer hospital stays, and the highest mortality. Seizures were more frequent in the encephalitis group, while elevated lactate and immunoglobulin use were less common (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Univariate analysis linked pulmonary hypertension, high lactate, lymphocytosis, and leukocytosis to mortality. Multivariate analysis identified pulmonary hypertension, exchange transfusion, and steroid use as independent death risk factors.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eSevere pertussis in children is often complicated by pneumonia and/or encephalitis, making treatment more difficult. Rising antibiotic resistance and strain differences in \u003cem\u003eBordetella pertussis\u003c/em\u003e may reduce treatment effectiveness. The increase in severe cases after the pandemic may be due to lower population immunity. Promoting maternal pertussis vaccination in China is urgently needed as a preventive measure.\u003c/p\u003e","manuscriptTitle":"Clinical Characteristics, Complications, and Mortality Risk Factors in Severe Pediatric Pertussis: A Retrospective Single-Center Study in Southwest China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 09:03:11","doi":"10.21203/rs.3.rs-7238222/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-10-13T08:24:42+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-08-31T18:03:12+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-19T19:50:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-13T13:20:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Italian Journal of Pediatrics","date":"2025-08-11T21:10:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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