Epidemiology and clinical profiles of neonates with Mycoplasma pneumoniae infection during the post-COVID-19 era in Chengdu

Introduction

Mycoplasma pneumoniae (MP) is one of the common pathogens causing acute respiratory tract infections in children, accounting for up to 40% of the etiological agents of community-acquired pneumonia (CAP) in children. It can also lead to extrapulmonary manifestations, with infections occurring in children of all age groups, predominantly in school-aged children (1,2). MP infections are typically endemic, with epidemics occurring every 1–7 years. They are relatively rare among the pathogens causing lower respiratory tract infections in newborns (1,3).

However, after coronavirus disease 2019 (COVID-19) control measures ended, 2023–2024 saw MP infection outbreaks in children (especially <15 years) across regions in China, with a parallel rise in neonatal cases (3,4). Studies on neonatal MP infections are scarce, and diagnostic testing for MP often relies on serological or non-standardized molecular methods. As a result, our understanding of the infection burden and clinical epidemiological characteristics of MP in the neonatal population after the COVID-19 pandemic remains limited (2,5). Therefore, we investigated the clinical data of 61 hospitalized newborns with MP-related acute respiratory tract infections in the Chengdu area from January 2023 to April 2025, and further analyzed the incidence, clinical manifestations, and laboratory data of these cases. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-530/rc).

Methods

Subjects and study design

This observational, retrospective study enrolled 61 neonates who were hospitalized with MP-induced acute lower respiratory tract infections (LRTIs) at Chengdu Women’s and Children’s Central Hospital between January 2023 and April 2025. Eligibility required a postnatal age of ≤28 days or a corrected gestational age of ≤44 weeks, along with hospitalization for LRTIs. The diagnosis of LRTI was defined by the presence of at least three of the following criteria: cough, tachypnea, chest retractions, wheezing or crackles on auscultation, or radiologic evidence consistent with infection. The exclusion criteria comprised vertical transmission or intrapartum-acquired infection. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China [No. 2022(66)]. Individual consent for this retrospective analysis was waived.

Nasopharyngeal specimen collection and detection

Using a disposable sampler X104 (Shengxiang Biotechnology Co., Ltd., Changsha, China), the nasopharyngeal secretions were collected by inserting the sampler through the nasal or oral cavity to a depth of approximately 6–7 cm until reaching the pharynx. The swab tip was fully immersed in a 3 mL cell preservation solution tube, the tail was broken off and discarded, and the tube cap was tightly secured before immediate transportation to the laboratory. Samples should be transported for testing as soon as possible. If immediate testing is unavailable, samples can be stored at 15–25 ℃ for no more than 8 hours or at 2–8 ℃ for up to 3 days. Real-time polymerase chain reaction (PCR) was performed using TaqMan PCR technology to detect nucleic acids of six common respiratory pathogens in nasopharyngeal secretions, including MP, respiratory syncytial virus (RSV), adenovirus, rhinovirus, influenza A virus, and influenza B virus. Testing for respiratory pathogens was performed not only on neonates with overt respiratory symptoms but also on those presenting with non-specific signs (e.g., feeding intolerance) or those admitted with other diagnoses (e.g., hyperbilirubinemia) if deemed clinically necessary by the attending physician, particularly in the context of potential nosocomial exposure or elevated inflammatory markers.

Data collection

Patient demographic, clinical, laboratory, and imaging data of patients were retrieved from the hospital’s electronic medical record (EMR) system. Laboratory data including peripheral white blood cell (WBC) counts, platelet (PLT) counts, C-reactive protein (CRP), procalcitonin (PCT), liver and kidney function panels, specific serum immunoglobulin M against Mycoplasma pneumoniae (MP-IgM), respiratory pathogen nucleic acid test results (e.g., MP, viral pathogens) and sputum culture and sensitivity were recorded and further analyzed.

Statistical analysis

We used mean ± standard deviation (SD) for continuous variables with normal distribution or median [interquartile range (IQR)] for those with non-normal distribution and n (%) for categorical variables. Parametric tests (t-test) were used for normally distributed data, whereas non-parametric tests (Mann-Whitney U) were applied to skewed data. We assessed differences in categorical variables with the χ² test and calculated 95% confidence intervals (CIs) for differences in medians with an exact test. Multivariate logistic regression identified variables associated with MP detection. SPSS (version 26.0) software was used for all statistical analyses. All tests were 2-tailed, and P<0.05 was considered statistically significant.

Results

Demographics

A total of 61 neonates hospitalized with MP infection were included in this study. Among the 61 children with MP infection, 8 patients (13.1%) were co-infected with RSV, 3 (4.9%) were co-infected with adenovirus, 3 (4.9%) were co-infected with rhinovirus, 1 (1.6%) was co-infected with influenza B virus, and 18 (29.5%) were co-infected with bacterial infections. The bacterial co-infections, identified via sputum culture, were primarily caused by Gram-negative enteric bacilli. Klebsiella pneumoniae subspecies pneumoniae (5 cases, 27.8%), Escherichia coli (4 cases, 22.2%), and Enterobacter cloacae complex (3 cases, 16.7%) were the most common isolates. A wider spectrum of pathogens, each found in one case (5.6%), comprised Haemophilus influenzae, Burkholderia cepacia, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus faecium. Notably, antimicrobial susceptibility testing did not reveal resistance in these isolates.

Age ranged from 1 day to 75 days with a median of 21 days. The ratio of preterm to term infants was 0.39:1, and the male to female ratio was 1.03:1. Gestational age ranged from 29.0 to 41.3 weeks, with a median of 38.6 weeks. The birth weight was 3,033±669 g.

Epidemiology of MP infection

The age distribution of MP infection in neonates is shown in Figure 1. Three (4.9%) cases were aged 1–7 days, 14 (23%) 8–14 days, 14 (23%) 15–21 days, and 30 cases (49.2%) were 22 days or older. Thus, the incidence of MP infection in neonates increases with age.

Figure 1 Age distribution of neonates with MP infection. Bar chart showing the age distribution of 61 neonates with MP infection, categorized into four postnatal age intervals: 1–7, 8–14, 15–21, and >21 days. The y-axis represents the number of participants in each group. Results indicate that MP infection was most prevalent in neonates aged >21 days (n=30, 49.2%), followed by 15–21 days (n=14, 23%) and 8–14 days (n=14, 23%), with the lowest incidence in the 1–7 days group (n=3, 4.9%), reflecting an increasing trend in MP infection frequency with advancing postnatal age. MP, Mycoplasma pneumoniae.

The seasonal distribution of MP infection in neonates is shown in Figure 2. MP infections peaked in autumn (from September to November) and winter (from December to February), involving 27 cases (44.3%) in autumn and 17 cases (27.9%) in winter, respectively, compared with 11 cases (18.0%) in spring (from March to May) and 6 (9.8%) in summer (from June to August). The prevalence of MP infection was higher during autumn and winter and lower in spring and summer.

Figure 2 Seasonal distribution of neonates with MP infection. Bar chart illustrating the seasonal distribution of MP infection among 61 neonates, grouped by seasons: spring (March–May), summer (June–August), autumn (September–November), and winter (December–February). The y-axis denotes the number of participants in each season. MP infections were most common in autumn (n=27, 44.3%) and winter (n=17, 27.9%), with lower prevalence in spring (n=11, 18.0%) and summer (n=6, 9.8%), indicating an autumn-winter predominance of neonatal MP infection in the post-COVID-19 era. COVID-19, coronavirus disease 2019; MP, Mycoplasma pneumoniae.

Clinical manifestations, laboratory and imaging findings

The main clinical manifestations of patients with MP infection are shown in Table 1. Thirty-six patients (59.0%) had cough. Fever (temperature, >37.5 ℃) was observed in 17 (27.9%) patients, dyspnea or tachypnea in 8 (13.1%) patients, and wheezing in two (3.3%) patients. All three patients with wheezing had concurrent RSV infections.

WBC counts ranged from 2.23×10⁹ to 46.35×10⁹ L⁻¹ with a median of 9.12×10⁹ L⁻¹. CRP was >10 mg/mL in 5 (8.1%) patients. PCT was >0.5 ng/mL in 7 (11.5%) patients. Liver enzyme, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level was above the upper limit of normality in 3 (4.9%) patients. Serum creatinine (SCr) ranged from 11.3 to 65.0 µmol/L with a median of 22.6 µmol/L, and all patients had serum creatinine levels below the upper limit of normality.

Chest radiographs or lung ultrasonography of all patients were available for review. Specifically, 51 patients underwent chest X-ray (CXR), while the remaining 10 underwent lung ultrasound due to clinical availability and considerations to minimize radiation exposure. Among the 51 patients with CXR results, the most predominant radiographic abnormality was the presence of patchy or linear opacities (n=40, 78.4%), followed by increased lung markings (n=8, 15.7%). Segmental consolidation affecting a small portion of a lung lobe was observed in the remaining 3 cases (5.9%). These imaging features are highly consistent with the patterns of pneumonia commonly associated with MP infection, thereby corroborating the clinical diagnosis. Among the 10 patients who underwent lung ultrasonography, B-lines with blurred anterior pleural lines were observed in 5 cases (8.2% of the total cohort; 50% of those scanned). The remaining 5 cases manifested as patchy opacities on imaging. No cases of lobar pneumonia or pleural effusion were identified in the entire cohort.

Prognosis

Of the 61 patients with MP infection, 8 (13.1%) required oxygen therapy, including 4 (6.6%) children with concurrent RSV coinfection and 3 (4.9%) who needed mechanical ventilation. The median length of hospital stay was 7 (IQR, 6–11) days. Duration of follow-up was 1 week for 57 children. No patients had residual pulmonary disease.

Variables associated with extended hospital stay with MP infection

Demographic and clinical characteristics in Table 1 were compared between neonates with mycoplasma infection categorized by hospital stay duration: ≥10 days (n=21) versus <10 days (n=40). From this univariate analysis, three predictor variables, fever (temperature ≥37.5 ℃), multiple pathogens and supplemental oxygen were evaluated in a logistic regression model (adjusted OR =5.92, 5.33, and 11.84, respectively, all P<0.05). Cases with hospital stay ≥10 days had higher rates of fever (47.6% vs. 17.5%), multiple pathogens (76.2% vs. 40.0%), and oxygen use (28.6% vs. 5.0%) versus those with <10 days (Table 2).

Comparison between asymptomatic and symptomatic groups

Patients were categorized into symptomatic and asymptomatic groups based on the presence or absence of clinical symptoms (Table 3). In the symptomatic and asymptomatic groups with MP infection, there were no significant differences in age, gender, or seasonal distribution of onset. Birth mode, birth weight, and gestational age also showed no statistical significance between groups. However, the symptomatic group had a significantly higher proportion of preterm infants (P<0.05).

In laboratory tests, WBC, PLT, PCT, ALT, AST, total bilirubin (TBil), SCr, and rates of co-infection with other pathogens did not differ significantly between groups. Conversely, CRP levels were significantly higher in the symptomatic group (P<0.05). Among 13 asymptomatic MP-infected children, 1 case (7.7%) was co-infected with adenovirus and required oxygen therapy. In the symptomatic group, 7 (14.6%) children received oxygen therapy: three underwent invasive mechanical ventilation due to disease exacerbation, and four co-infected with RSV received conventional oxygen therapy. The median hospital stay was longer in the symptomatic group [8 (IQR, 6–11) days] than in the asymptomatic group [6 (IQR, 5–7) days], with a statistically significant difference (P<0.01). All 13 children in the asymptomatic group were discharged after cure. In the symptomatic group, 44 children were discharged after cure, while only 4 were signed out of the hospital during treatment due to parental personal reasons.

Discussion

Over the past decade, the diagnostic and therapeutic capabilities of neonatal intensive care medicine have been significantly enhanced, yet respiratory infections remain one of the leading causes of morbidity and mortality in newborns. MP is typically an infectious agent of respiratory tract infections in children aged over 5 years and adolescents (6,7). In recent years, increasing reports have documented MP infections in children under 5 years old and infants (8). Notably, the “immune debt” resulting from the global COVID-19 pandemic has profoundly influenced alterations in the epidemic patterns of respiratory pathogens (9,10). During the pandemic, non-pharmaceutical interventions (NPIs), such as mask-wearing and social distancing, reduced not only the transmission of COVID-19, but also the circulation of other respiratory infection pathogens, including MP and RSV, across the general population (11). The protective effect of NPIs on neonates, who do not practice these measures themselves, was likely indirect, mediated through reduced infection rates among caregivers and enhanced hospital infection control. The subsequent withdrawal of these measures arguably contributed to a rebound in MP exposure for this susceptible population. Following the lifting of COVID-19 measures in China, multiple regions reported an MP epidemic among children during 2023–2024, with hospitalizations due to MP pneumonia showing a sharp increase (12-14). Yet, few studies have examined neonatal MP infection in the post-COVID-19 era over the past two years. This retrospective study described the epidemiological and clinical characteristics of neonatal MP infection in Chengdu, China, more than two years after the end of the pandemic.

PCR is a highly sensitive early diagnostic tool and the gold standard for MP detection (15-19). However, previous studies have shown that asymptomatic MP carriers are common in children with acute respiratory infections (5,20). Therefore, PCR does not represent the sole method for diagnosing MP infection. Specific serum immunoglobulin MP-IgM can typically be detected within about 1 week after infection, and peak titer in the third week, serving as a diagnostic indicator of recent pulmonary infection (15,21-23). In this retrospective study, we combined PCR and serological IgM testing, with a positive result in either test indicating MP infection to avoid missed cases.

MP infection can occur sporadically throughout the year or in seasonal outbreaks. Previous studies have shown that during the pre-pandemic and COVID-19 control periods (2018–2022), summer (June–August) was the peak season for pediatric MP infection, with the lowest positive detection rate in winter (December–February) (24,25). Consistently, another study found that the positivity rate of MP infection in children was higher in summer and autumn, predominantly from August to October (26). However, conflicting reports showed that between 2011–2014, neonatal MP pneumonia cases peaked in winter (December–February) and spring (March–May), with lower rates in summer and autumn (5). While the epidemic seasons of MP infection vary across regions with different climates and pediatric age groups, the epidemiological characteristics of MP may have indeed changed in the post-COVID-19 era. In this study, neonatal MP infections were most prevalent in autumn and winter and least common in summer, differing from some pre-pandemic findings but aligning with post-pandemic reports. A study in eastern China showed that the positive detection rate of pediatric MP infection peaked at 33.16% in autumn 2023 (24). Cough was the most common symptom, followed by fever. Additionally, we found that neonatal MP infection was associated with older age, consistent with other reports indicating that the risk of MP infection increases with age, including in the neonatal population (5,24,26).

Fever, co-infection with other pathogens, and oxygen therapy are associated with prolonged hospital stay exceeding 10 days. A comparison of baseline characteristics and clinical features between MP-infected patients with different lengths of hospital stay showed that children with a hospital stay exceeding 10 days were more likely to present with fever, have higher proportions of co-infection with other pathogens, and receive oxygen therapy. A comparison of clinical manifestations between symptomatic and asymptomatic MP-infected patients showed that symptomatic patients had a higher proportion of preterm infants, elevated CRP levels, and longer hospital stays. Preterm birth is a well-recognized risk factor for neonatal respiratory infections. Beyond immature lung structure and function, prematurity reduces maternally derived antibodies in neonates, compromising their defense against pathogens, which leads to more pronounced infection symptoms (27). In this study, half of MP-infected children with RSV co-infection received oxygen therapy.

Neonatal immune systems are inherently immature, resulting in blunted inflammatory responses to pathogens. Higher CRP in symptomatic children may reflect stronger inflammatory responses from bacterial or viral co-infections. Although a CRP level of 10 mg/L is the most commonly used cut-off value for neonates, it lacks specificity for bacterial infection, as viral infections can also lead to mild elevations (typically <5 mg/L) (28), consistent with our findings. More severe symptoms require neonatologists to spend additional time alleviating clinical signs to meet discharge criteria, consequently extending the treatment duration for symptomatic infants. Previous studies have reported that MP can cause severe pneumonia in neonates with poor resolution (29,30). However, such cases were not observed in our study. All neonatal MP infections were generally mild in course, and neither case with isolated MP infection nor those with co-infection of multiple pathogens developed lobar pneumonia with lung consolidation or pleural effusion.

There are several limitations in this study. First, it was a single-center retrospective analysis, with data restricted to those retrievable from the EMR system, which may have introduced bias. Second, the sample size was insufficient, reducing the statistical power for some analyses and failing to include all neonates with MP infection in Chengdu. Finally, we only enrolled hospitalized patients with MP infection, whereas many MP-infected individuals were treated as outpatients. As a result, patients with more severe symptoms might have been overrepresented.

Conclusions

The epidemiological characteristics of MP infection in neonates may have changed in the post-COVID-19 era, with epidemic seasons predominantly in autumn and winter. Prolonged hospital stay is typically associated with fever, co-infection with other pathogens, and oxygen therapy. Neonates with prematurity or elevated CRP are more likely to develop clinical symptoms.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-530/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-530/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-530/prf

Funding: The study was supported by The Key Research and Development Project of the Science and Technology Department of Sichuan Province (No. 2022YFS0241).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-530/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China [No. 2022(66)], and individual consent for this retrospective analysis was waived.

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

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