Clinical characteristics and risk factors for severe pertussis in infants aged less than 3 months

Introduction

Pertussis is a globally prevalent infectious disease caused by Bordetella pertussis, characterized by cyclical outbreaks occurring every 3–5 years (1). Although pertussis is preventable through vaccination, multiple developed countries with high vaccination coverage have experienced a resurgence since the 1980s (1). In the post-pandemic period, following the discontinuation of non-pharmaceutical interventions, large-scale outbreaks of pertussis have been reported worldwide (2,3). According to the 2024 pertussis report by World Health Organization, 941,565 cases were reported globally (4). Pertussis therefore represents a significant global public health concern. Individuals of all age groups are susceptible to pertussis; however, infants aged less than 3 months constitute a population at elevated risk for severe disease and hospitalization (4,5). Infants in this age group are more likely to develop post-tussive vomiting, paroxysmal cyanosis, hypoxemia, and concurrent severe pneumonia following infection and are at increased risk of progression to severe pertussis (6).

Although extensive research has examined pertussis in children, studies specifically focusing on infants aged less than 3 months remain limited. Clinical data were collected from infants aged less than 3 months who were diagnosed with pertussis at our Hospital between August 2021 and July 2025. The clinical characteristics and risk factors for severe disease were analyzed to enhance physician awareness of pertussis in young infants and to provide evidence to inform prevention and control strategies aimed at reducing mortality. Anhui Province is in southeastern China. Our hospital is the only provincial-level designated hospital for pediatric infectious disease management in the region and is responsible for the diagnosis and treatment of most pertussis cases in Anhui Province. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0213/rc).

Methods

Study participants

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Anhui Provincial Children’s Hospital (No. EYLL-2026-031). Due to the retrospective nature of the study, the requirement for patient consent for inclusion was waived.

Clinical data from 205 infants aged less than 3 months who were hospitalized with pertussis at our Hospital between July 2021 and August 2025 were retrospectively analyzed. The inclusion criteria were as follows: (I) age at disease onset less than 3 months, including neonates (0–28 days); and (II) fulfillment of the clinical diagnostic criteria for pertussis (7). A confirmed case of pertussis requires meeting both clinical and laboratory criteria. Clinical criteria (any of the following): (I) paroxysmal cough lasting ≥2 weeks with an inspiratory whoop, post-tussive vomiting, or cyanosis/apnea in infants aged <3 months; or (II) Cough of any duration with documented close contact with a laboratory‑confirmed pertussis case. Laboratory confirmation (any of the following): (I) positive Bordetella pertussis nucleic acid test by polymerase chain reaction (PCR) from a nasopharyngeal swab; or Bordetella pertussis identified by metagenomic next-generation sequencing from respiratory secretions.

Hospitalization criteria for infants aged <3 months with pertussis included any of the following: (I) age <2 months regardless of clinical severity; (II) presence of cyanotic episodes, apnea, or hypoxemia (oxygen saturation <92%); (III) feeding difficulty or poor oral intake; (IV) respiratory distress (tachypnea, retractions, or grunting); (V) fever ≥38.5 ℃ or suspected co‑infection; (VI) white blood cell count >30×10⁹/L; or (VII) abnormal chest imaging findings (pneumonia, pulmonary consolidation, or atelectasis). These criteria were applied consistently during the study period (2021–2025).

The exclusion criteria were as follows: (I) incomplete clinical data; and (II) severe congenital malformations, genetic disorders, or chromosomal abnormalities.

Study methods

Data collection

Clinical data of the 205 infants were extracted from the hospital’s electronic medical record system, including general characteristics, clinical manifestations, complications, laboratory findings, chest imaging, treatment, and outcomes. All data were collected, entered, and analyzed by a designated pediatric infectious disease specialist with >10 years of experience in pertussis care.

In our study, the diagnoses of pneumonia and pulmonary consolidation were based on chest imaging findings [chest X-ray or chest computed tomography (CT)] interpreted by board-certified pediatric radiologists. The definitions were shown as follows:

• Pneumonia: presence of new infiltrates on chest radiograph or chest CT, including but not limited to bronchopneumonia, interstitial pneumonia, or lobar/segmental consolidation, as interpreted by a pediatric radiologist.
• Pulmonary consolidation: a subset of pneumonia defined as a homogeneous increase in parenchymal attenuation on chest CT (or dense opacification on chest X-ray) that obscures the margins of vessels and airway walls, with air bronchograms present or absent.

Laboratory methods

BP nucleic acid detection was performed using fluorescence probe-based PCR, with reagents purchased from Shenzhen Yilifang Biotech Co., Ltd. A cycle threshold value ≤38 was defined as positive. Nasopharyngeal swabs for BP nucleic acid detection were collected using flocked swabs, immediately placed into sterile viral transport medium, and transported to the laboratory within 2 hours of collection. If immediate processing was not possible, specimens were stored at 4 ℃ for no more than 24 hours before testing. PCR testing was performed within 24 hours of collection for all samples. The typical turnaround time from specimen reception to PCR result reporting was 4–6 hours during routine working hours and 8–12 hours for samples received outside of routine hours.

In addition to BP nucleic acid detection by PCR, metagenomic sequencing was performed on sputum samples in selected cases—particularly those with severe illness, suspected co-infection, or negative PCR despite high clinical suspicion—to enable unbiased detection of multiple pathogens and to exclude alternative or additional etiologies. Sputum specimens were collected, immediately placed in sterile containers, and stored at −80 ℃ within 2 hours of collection if not sent out the same day. Specimens were shipped on dry ice to the commercial sequencing provider (Guangzhou Kingmed Diagnostics or Nanjing Dineftome Medical Laboratory) within 24 hours of collection. Unbiased sequencing of all nucleic acids in the specimens was performed and combined with a pathogenic microorganism database and specific algorithms to identify suspected pathogenic microorganisms present in the samples (8).

Patient grouping

Patients were classified into a neonatal group and a non-neonatal group according to age at disease onset. Based on whether the diagnostic criteria for severe pertussis were fulfilled, patients were further categorized into a severe group and a non-severe group. Currently, no universally accepted criteria for severe pertussis in infants are available. Based on prior studies on severe pertussis, patients who met any of the following criteria were defined as having severe pertussis: recurrent apnea, hypoxemia, respiratory failure requiring respiratory support, pertussis encephalopathy, or cardiovascular dysfunction (9). We acknowledge that variables used to define severe pertussis (apnea, hypoxemia, pertussis encephalopathy, cardiovascular dysfunction, and respiratory failure requiring ventilatory support) were not analyzed as independent outcomes in group comparisons to avoid incorporation bias. Only variables independent of the definition were compared between groups.

Operational definitions of clinical variables

Ventilatory support was defined as any form of invasive mechanical ventilation (endotracheal intubation) or non-invasive positive pressure ventilation [e.g., continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP)] administered for respiratory failure or recurrent apnea.

• Pertussis encephalopathy: presence of any of the following not attributable to other causes: generalized or focal seizures, altered mental status (lethargy, obtundation, or coma), or focal neurological deficits occurring during the acute phase of pertussis infection.
• Pulmonary hypertension: echocardiographic evidence of elevated pulmonary artery pressure (estimated systolic pulmonary artery pressure >35 mmHg or presence of right-to-left shunt across a patent foramen ovale/ductus arteriosus in the absence of congenital heart disease), or clinical signs of right heart failure combined with radiographic evidence of pulmonary oligemia.
• Respiratory failure: arterial partial pressure of oxygen (PaO₂) <60 mmHg or oxygen saturation (SpO₂) <90% despite supplemental oxygen, or partial pressure of carbon dioxide in arterial blood (PaCO₂) >50 mmHg with pH <7.35, or need for non‑invasive or invasive mechanical ventilation.
• Apnea: cessation of breathing for ≥20 seconds, or a shorter pause accompanied by bradycardia (heart rate <80 bpm in infants <3 months) or cyanosis/oxygen desaturation (SpO₂ <90%).
• Hypoxemia: SpO₂ <92% on room air or requiring supplemental oxygen to maintain SpO₂ ≥92%.
• Fever: axillary temperature ≥37.3 ℃.

Statistical analysis

Statistical analysis was performed using SPSS version 25.0 software. Normally distributed continuous variables were expressed as mean ± standard deviation, and comparisons between two groups were conducted using the t-test. Non-normally distributed continuous variables were presented as median [interquartile range (IQR)], and comparisons between two groups were conducted using the Mann-Whitney U test. Categorical variables were expressed as number, rate, or composition ratio, and comparisons between groups were conducted using the chi-squared (χ²) test (n≥40, T ≥5), continuity correction (n≥40, 1≤ T <5), or Fisher’s exact test (n<40 or T <1). Risk factor analysis was conducted using logistic regression. A P value <0.05 was considered statistically significant.

Results

General clinical data

Between July 2021 and August 2025, a total of 247 infants aged less than 3 months with pertussis were hospitalized at our hospital. After excluding 40 cases with incomplete clinical data, one case with a severe congenital malformation, and one case with a chromosomal abnormality, 205 infants were ultimately included in the study. Among the 205 patients with pertussis, 111 were male and 94 were female. The median age at disease onset was 59.0 (IQR, 40.5–73.0) days, with a range of 8 to 90 days.

The number of cases by year was as follows: 9 cases in 2021 (4.4%, 9/205), 38 cases in 2022 (18.5%, 38/205), 8 cases in 2023 (3.9%, 8/205), 144 cases in 2024 (70.2%, 144/205), and 6 cases in 2025 (2.9%, 6/205). A history of contact with individuals with cough was reported in 95 patients (46.3%, 95/205), including 34 cases involving parents (35.8%, 34/95), 20 cases involving siblings (21.1%, 20/95), and 47 cases involving other relatives (49.5%, 47/95).

Clinical characteristics

Clinical manifestations

Paroxysmal cough was the most common manifestation, observed in 204 of 205 patients (99.5%). The single patient without cough was an 8-day-old neonate who presented with excessive oral frothing and transient cyanotic episodes, without any coughing. The diagnosis of pertussis in this infant was prompted by a confirmed pertussis diagnosis in the mother and was subsequently confirmed by positive BP nucleic acid testing. Cyanotic episodes occurred in 48.3% (99/205), post‑tussive vomiting in 30.2% (62/205), whooping cough in 25.9% (53/205), and fever in 13.7% (28/205). Other manifestations (apnea, wheezing, bradycardia) were less frequent (<30%).

Auxiliary examinations

The median maximum peripheral blood white blood cell (WBC) count was 16.89 (IQR, 12.93–23.01) ×10⁹/L, with a range of 6.77×10⁹/L to 99.12×10⁹/L. Elevated maximum WBC counts (>15×10⁹/L; >20×10⁹/L in neonates) were identified in 122 patients (59.5%, 122/205), including 19 (9.3%, 19/205) with counts >30×10⁹/L and 4 (2.0%, 4/205) with counts >50×10⁹/L. A lymphocyte percentage >60% was observed in 162 patients (79.0%, 162/205).

Co-infection and complications

Concurrent detection of other respiratory pathogens was reported in 97 patients (47.32%, 97/205). Among these, 74 (36.1%, 74/205) had mixed viral infections, and 48 (23.4%) had mixed bacterial infections, including 43 with typical bacteria and 5 with Mycoplasma pneumoniae.

Pneumonia developed in 180 patients (87.8%, 180/205). Pulmonary consolidation was observed in 14 (6.8%, 14/205). Pertussis encephalopathy occurred in 6 (2.9%, 6/205). Pulmonary hypertension was identified in 2 (1.0%, 2/205). Respiratory failure developed in 15 (7.3%, 15/205), and hypoxemia was reported in 13 (6.3%, 13/205).

Age-group comparison

The neonatal group comprised 20 patients (9.8%, 20/205), with a median age at disease onset of 24.50 (IQR, 18.75–27.75) days, ranging from 8 to 28 days. Among the 20 neonates, 5 (25.0%) developed severe pertussis, compared with 22 of 185 (11.9%) in the non-neonatal group; the difference was not statistically significant (P=0.19).

Regarding cough duration prior to diagnosis, 18 patients (90%, 18/20) in the neonatal group had a duration of less than 1 week, compared with 59 (31.9%, 59/185) in the non-neonatal group. One patient (5.0%, 1/20) in the neonatal group had a duration of 1–2 weeks, compared with 77 (41.6%, 77/185) in the non-neonatal group. One patient (5.0%, 1/20) in the neonatal group had a duration greater than 2 weeks, compared with 49 (26.5%, 49/185) in the non-neonatal group. The distribution of cough duration prior to diagnosis differed significantly between the neonatal and non‑neonatal groups (P<0.001).

A higher proportion of patients in the neonatal group had a history of contact with coughing individuals than those in the non-neonatal group. Lower proportions of whooping cough, post-tussive vomiting, wheezing, and lymphocyte percentage >60% were observed in the neonatal group, with statistically significant differences (P<0.05). Co-infection was more frequent in the non-neonatal group than in the neonatal group (69.7% vs. 25.0%, P=0.03).

No statistically significant differences were identified between the two groups with respect to sex, paroxysmal cough, cyanotic episodes, apnea, fever, maximum WBC count, concurrent pneumonia, concurrent pulmonary consolidation, concurrent pertussis encephalopathy, or concurrent pulmonary hypertension (P>0.05), as presented in Table 1.

Clinical characteristics and risk factor analysis of the severe group

The severe group comprised 27 patients (13.2%, 27/205). Compared with the non-severe group, the severe group had higher proportions of cyanotic episodes, fever, elevated maximum WBC count, maximum WBC count >30×10⁹/L, maximum WBC count >50×10⁹/L, and concurrent pulmonary consolidation. Lower proportions of whooping cough and lymphocyte percentage >60% were identified in the severe group. These differences were statistically significant (P<0.05). The overall co-infection rate did not differ significantly between the severe and non-severe groups [63.0% (17/27) vs. 44.9% (80/178), P=0.08]. However, the severe group had a significantly higher proportion of bacterial co-infection compared with the non-severe group [44.4 (12/27) vs. 17.4% (31/178), P=0.001]. Regarding cough duration prior to diagnosis, 13 patients (48.1%, 13/27) in the severe group had a duration of less than 1 week, compared with 64 (36.0%, 64/178) in the non-severe group. Twelve patients (44.4%, 12/27) in the severe group had a duration of 1–2 weeks, compared with 66 (37.1%, 66/178) in the non-severe group. 2 cases (7.4%, 2/27) with a cough duration greater than 2 weeks occurred in the severe group, compared with 48 (27.0%, 48/178) in the non-severe group. The duration of cough prior to diagnosis did not differ significantly between the severe and non-severe groups (P=0.08).

No statistically significant differences were observed between the two groups with respect to sex, body weight at admission, preterm birth, history of contact with individuals with cough, paroxysmal cough, post-tussive vomiting, wheezing, or concurrent pneumonia (P>0.05), as presented in Table 2.

Multivariate logistic regression analysis demonstrated that fever [odds ratio (OR) =6.874, 95% confidence interval (CI): 2.155–21.931], whooping cough (OR =0.155, 95% CI: 0.032–0.764), cyanotic episodes (OR =18.82, 95% CI: 4.013–88.252), maximum WBC count >30×10⁹/L (OR =15.755, 95% CI: 1.650–150.437), and pulmonary consolidation (OR =7.772, 95% CI: 1.376–43.908) were independently associated with severe pertussis, as presented in Table 3.

Treatment and outcomes

Before admission, 109 (53.2%) patients had received macrolides and 110 (53.7%) had received cephalosporins. These antibiotics were initiated empirically at primary or secondary hospitals based on cough or suspected respiratory infection, as pertussis PCR was not widely available in those settings. The exact duration of pre‑hospital treatment could not be reliably retrieved from the referral records and is therefore not reported. Among the 27 severe cases, 18 (66.7%) had received macrolides before admission, compared with 91 (51.1%) of non‑severe cases (P=0.13). Pre-hospital macrolide therapy was not associated with a lower risk of severe pertussis. After admission, 27 patients (13.2%, 27/205) were treated with macrolides alone. A total of 114 patients (55.6%, 114/205) showed no clinical improvement after 3–5 days of macrolide therapy and subsequently received either monotherapy or combination therapy with cefoperazone-sulbactam, trimethoprim-sulfamethoxazole, or other β-lactam antibiotics. Additionally, 32 patients (15.6%, 32/205) who had failed to respond to 3–5 days of outpatient macrolide treatment were admitted and received cefoperazonesulbactam alone. Ventilatory support was required in 9 patients (4.4%). No deaths occurred in this cohort. All patients were discharged with clinical improvement. The median length of hospital stay was 10.0 (IQR, 8.0–14.0) days.

Discussion

In this study, 46.3% of patients had a documented history of contact with family members who had a cough, with a higher proportion observed in the neonatal group than in the non-neonatal group. Pathogen testing conducted among accompanying family members of hospitalized patients with pertussis in 2024 demonstrated a detection rate of 77.1% (10). Along with the recent absence of pertussis vaccination history among family members, these findings suggest that a substantial proportion of relatives may have experienced subclinical or asymptomatic infection. Infants aged less than 3 months are more susceptible to pertussis following exposure due to immunologic immaturity and ineligibility for routine vaccination. Screening of suspected cases and close contacts during seasonal peaks should therefore be undertaken.

In 2024, the largest outbreak in nearly 40 years was reported, with a cumulative total of 494,321 cases (11). Vaccination against pertussis remains the primary strategy for prevention and control in China.

In response to evolving epidemiological characteristics, the first dose of pertussis vaccination was advanced to 2 months of age beginning in 2025; however, this adjustment does not provide timely protection for infants aged less than 2 months. Enhanced preventive measures are therefore required for this population (12). In the study by Chen et al., nearly all pregnant women and their neonates exhibited low anti-pertussis toxin IgG levels and were highly susceptible to infection (13). Given the low antibody levels in the Chinese population, the implementation of maternal pertussis immunization to indirectly protect infants aged less than 3 months is of particular importance. The recent adjustment to the immunization schedule added one dose of acellular pertussis vaccine at 6 years of age; however, adolescents and adults remain outside the current vaccination coverage (12). In the future, adolescents and adults may constitute important sources of pertussis transmission to unvaccinated infants in China.

Although paroxysmal cough was the predominant symptom in this study, variability in onset and presentation was observed, with approximately one-third of infants exhibiting post-tussive vomiting and whooping cough. The neonatal group demonstrated lower proportions of post-tussive vomiting and whooping cough compared with the non-neonatal group, indicating that pertussis manifestations in infants aged less than 3 months, particularly neonates, are frequently atypical. Enhanced clinical recognition of pertussis in young infants is therefore warranted.

In this study, 75.6% of patients were diagnosed within 2 weeks of cough onset, with most neonates diagnosed within 1 week. The pertussis surveillance protocol in China includes a cough duration ≥2 weeks as one of the criteria for clinical case definition (7). Under the current epidemiological context, this criterion may not be appropriate for the clinical diagnosis of pertussis in infants, particularly neonates. For young infants or neonates presenting with paroxysmal cough, pertussis screening should be performed promptly regardless of cough duration and irrespective of the presence of whooping cough, post-tussive vomiting, apnea, or other associated symptoms. Regarding the temporal sequence of diagnosis, we found that in the majority of neonatal cases, the household contacts (parents or siblings) had already developed cough symptoms and were either diagnosed with pertussis or clinically suspected before the neonate was tested. This prior awareness likely prompted early pertussis testing in the exposed neonate, explaining why most of the neonates were diagnosed within 1 week of cough onset. The higher proportion of contact history in the neonatal group supports the notion that household members are the main source of pertussis transmission to neonates, who have very limited exposure to the outside environment. In a subset of cases, the neonate was diagnosed first, and subsequent backward tracing identified infected contacts in the household. During the study period, increased public awareness of pertussis, improved access to PCR testing, and heightened clinical suspicion among physicians all contributed to earlier diagnosis in neonates with documented household exposure.

Most cases in this study were concentrated in 2024. During the pertussis resurgence in that year, BP nucleic acid testing was implemented at this hospital, and screening among patients presenting with cough was strengthened. With the broader application of molecular diagnostic techniques across healthcare institutions, diagnostic capacity and timeliness of pertussis identification in pediatric settings have improved. BP nucleic acid testing is convenient and demonstrates high sensitivity and specificity, and it has been incorporated into the pertussis diagnostic criteria in China (7).

In this study, 5 infants (2.4%) were co-infected with Mycoplasma pneumoniae. Mycoplasma pneumoniae is traditionally considered a pathogen primarily affecting children aged ≥5 years and is uncommon in infants, especially those younger than 3 months. Several factors may explain this finding. First, the widespread use of sensitive molecular diagnostic techniques (e.g., multiplex PCR and metagenomic sequencing) during the 2024 outbreak may have facilitated detection of pathogens that were previously underrecognized in this age group. Second, false-positive PCR results cannot be completely excluded, as molecular detection does not always distinguish active infection from colonization or transient shedding. Third, household transmission from older siblings—who are common sources of pertussis in this cohort—may also expose young infants to Mycoplasma pneumoniae. Nevertheless, the clinical significance of Mycoplasma pneumoniae detection in infants aged <3 months remain uncertain. We have therefore classified it as a bacterial co-infection but emphasize that its contribution to disease severity in young infants with pertussis requires cautious interpretation.

In this study, the incidence of severe pertussis was 13.2%. Multivariate analysis identified fever, cyanotic episodes, WBC count >30×10⁹/L, and pulmonary consolidation as independent risk factors. Patients with pertussis typically do not present with fever; when fever occurs, co-infection is frequently considered. In this study, fever was observed in 13.7% of patients and co-infection in 47.3%, with a higher proportion of fever in the severe group than in the non-severe group. A higher proportion of cyanotic episodes was identified in the severe group, possibly due to airway obstruction related to narrow airways in young infants, a weak cough reflex, and pertussis toxin-induced delayed ciliary movement (14). Marked leukocytosis reflects the accumulation and increased activity of pertussis toxin in the body. Prior studies have demonstrated that elevated WBC count is a predictor of severe pertussis and is strongly associated with disease progression and increased mortality (6,15-17). In this study, a maximum WBC count >30×10⁹/L was identified as a risk factor for severe pertussis in infants aged less than 3 months. Concurrent pneumonia occurred in 87.8% of patients, and the severe group exhibited a higher incidence of pulmonary consolidation than the non-severe group, suggesting that pulmonary consolidation is associated with more severe pulmonary involvement and warrants heightened vigilance for severe pertussis.

In contrast, whooping cough was negatively associated with severe pertussis (OR =0.155). The finding that whooping cough was negatively associated with severe pertussis should not be misinterpreted as the absence of whooping cough causing severe disease. Rather, this likely reflects a clinical phenomenon: infants with severe pertussis often have weak cough force due to respiratory muscle fatigue, severe tachypnea, or the need for ventilatory support, making the classic inspiratory whoop less audible or absent (6,18).

Furthermore, we also compared the distribution of cough duration (<1, 1–2, >2 weeks) between the severe and non-severe groups. However, the duration of cough prior to diagnosis did not differ significantly between severe and non-severe cases, indicating that delayed diagnosis alone was not a major driver of severity in this cohort. In this cohort, pre-hospital macrolide therapy was not associated with a lower risk of severe pertussis. This lack of protective effect may reflect the predominance of macrolide-resistant strains in Anhui Province, as well as potential delays from symptom onset to treatment initiation. Prospective studies are needed to clarify the impact of early targeted therapy on disease progression. In addition, the severe group had a significantly higher proportion of bacterial co-infection, whereas viral co-infection rates were similar between groups. This suggests that concomitant bacterial respiratory infection may exacerbate the clinical course in pertussis. Clinicians should therefore have a low threshold for evaluating and treating bacterial co-infection in infants with severe pertussis.

Macrolides have long been the first-line antibiotics for pertussis. In this study, half of the patients had already received β-lactam or macrolide therapy before admission, yet still tested positive for Bordetella pertussis infection. Moreover, among the confirmed cases admitted to our hospital, half showed no clinical improvement after macrolide treatment and required a switch to other antibiotics, suggesting the possibility of in vivo macrolide resistance. In recent years, high-level in vitro resistance of Bordetella pertussis to macrolides has been reported in several regions of China, including Anhui, Shanghai, and Beijing (19,20). In 2024, all 186 Bordetella pertussis isolates cultured at our hospital were resistant to azithromycin (10). Therefore, macrolides should no longer be considered the first-line empirical antibiotics for pertussis in China. In contrast, isolates from multiple regions in China have been shown to be sensitive to trimethoprim-sulfamethoxazole (TMP-SMX) in vitro (19,20). However, TMP-SMX is contraindicated in infants younger than 2 months. Previous studies have indicated that cefoperazonesulbactam achieves a higher bacterial clearance rate than macrolides for macrolide‑resistant Bordetella pertussis (21). In the active search for alternative agents to macrolides, antimicrobial susceptibility testing should be performed to avoid inappropriate use or to minimize antibiotic-related adverse effects. During the era of widespread empirical antibiotic use for pertussis, close monitoring for the emergence of new resistant strains is warranted.

The low rate of ventilatory support (4.4%), absence of malignant pertussis, and 100% survival in this cohort of infants aged <3 months are notable. Compared with published series where ventilatory support rates in similar age groups range from 15% to over 40% (22,23), our findings suggest a potentially less severe cohort or selection bias. Several factors may contribute to this discrepancy. First, our hospital is the only provincial‑level referral center for pediatric infectious diseases in Anhui Province, but some critically ill infants may have been directly admitted to the pediatric intensive care units of other large general hospitals in the region, or may have died before transfer, thus not being captured in our study. Second, we excluded infants with severe congenital malformations, genetic disorders, or chromosomal abnormalities, all of which are known to increase the risk of severe pertussis and poor outcomes. The 100% survival rate, while encouraging, should be interpreted cautiously given the potential for selection bias and the retrospective, single-center design. Future multicenter prospective studies are needed to more accurately characterize the full spectrum of disease severity in this vulnerable age group.

Conclusions

In this cohort of 205 hospitalized infants aged <3 months with pertussis, the incidence of severe disease was 13.2%. Multivariate analysis identified fever, cyanotic episodes, a maximum WBC count >30×10⁹/L, and pulmonary consolidation as independent risk factors for severe pertussis. Whooping cough was negatively associated with severe disease. These findings highlight specific clinical and laboratory features that warrant close monitoring for progression to severe pertussis in young infants.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0213/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0213/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0213/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-2026-0213/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. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Anhui Provincial Children’s Hospital (No. EYLL-2026-031). Due to the retrospective nature of the study, the requirement for patient consent for inclusion 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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