Clinical characteristics of Mycoplasma pneumoniae pneumonia in children during the post-coronavirus disease 2019 era: a retrospective study in Chongqing, China

Introduction

Background

Mycoplasma pneumoniae (MP) is among the leading pathogens causing community-acquired pneumonia in Chinese children (1). Recently, the global prevalence of MP infections has increased, particularly in China (2,3). MP outbreaks follow cyclical patterns, typically peaking every 3–7 years, with higher incidence in the summer and lower rates in spring, and primarily affecting school-aged children (4).

The non-pharmaceutical interventions (NPIs) implemented during the coronavirus disease 2019 (COVID-19) pandemic not only contained the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also profoundly altered the epidemiological patterns of other respiratory pathogens. Extensive research indicates a widespread “immunity debt” phenomenon in the post-pandemic era, leading to significant shifts in the infection dynamics of multiple pathogens. For instance, in six European countries following the COVID-19 pandemic, the respiratory syncytial virus (RSV) hospitalization burden exhibited an age distribution shift and increased severity among children (5). Similarly, studies from South Korea demonstrated seasonal delays and age-specific burden shifts in influenza and RSV infections attributable to the “immunity debt” (6). In response to the RSV threat, new immunoprophylaxis strategies such as nirsevimab and the maternal RSV vaccine [respiratory syncytial virus prefusion F protein vaccine (RSVpreF)] have been implemented in multiple countries and have shown significant effectiveness (7). However, these changes are not confined to viral pathogens; bacterial and atypical pathogens, including MP, have also demonstrated significant epidemiological rebounds, though their specific clinical progression patterns and underlying drivers remain incompletely understood. During the implementation of NPIs in 2020–2022, MP infection rates declined to remarkably low levels (below 5%). However, following the relaxation of NPIs in 2023, global MP resurgence has been documented (2-4,8-10). Countries in Asia, such as China and Japan, and Europe, such as Denmark and Sweden, experienced particularly significant resurgences exhibiting novel characteristics, with a shift in peak incidence to younger individuals (from 5–15 to 3–8 years) and increased severe disease rates (2,4,8,10). While existing studies have demonstrated the epidemiological rebound of MP, they are limited by short observation periods, which fail to capture complete post-peak fluctuation patterns, and their inability to document peak intensity and subsequent epidemiological troughs. These limitations prevent a comprehensive assessment of how the COVID-19 pandemic and/or NPIs impact MP transmission, thereby hindering the development of targeted control measures.

Early diagnosis of MP pneumonia (MPP) faces three major challenges. First, it exhibits non-specific clinical manifestations that are easily confused with viral pneumonia (1,11). Second, in radiographic evaluation, chest X-rays exhibit limited sensitivity for early lesions. High-resolution computed tomography (CT) is more accurate than X-rays; however, it poses radiation risks (1,12). Third, although nucleic acid amplification tests (NAATs) are the gold standard (13,14), their limited availability in primary care leads to clinical reliance on serological tests [e.g., MP-immunoglobin M (MP-IgM)], potentially resulting in missed early diagnoses. These diagnostic limitations have been further amplified in the context of multiple pathogen co-circulation, such as COVID-19 and RSV, following the discontinuation of NPIs, exacerbating the difficulty of early MPP differentiation. Concurrently, the proportion of severe MPP (SMPP) cases has markedly increased in recent years (12,15). Collectively, these challenges highlight the urgent need for a systematic investigation into the novel clinical phenotypes and severe disease characteristics of MPP in the post-pandemic era.

Rationale and knowledge gap

Recent methodological advances have provided new support for research on COVID-19 sequelae (long COVID) and pandemic-related diseases. A nationwide Korean cohort study demonstrated that recurrent intestinal infections may increase the risk of long-term mental illness, highlighting the importance of persistent symptom assessment after acute infection—this methodology is also applicable for analyzing “long COVID-like” symptoms in patients with MPP (16). Another study comparing Bell’s palsy incidence before and after COVID-19 revealed how pandemic interventions affected traditional infectious disease cycles, providing a reference framework for analyzing MP epidemic patterns before and after the relaxation of NPIs (17).

Respiratory symptoms such as persistent cough following COVID-19 constitute manifestations of “long COVID” (18-21), warranting particular attention in pediatric patients (21,22). Currently, the epidemiological evolution, disease burden, and immunoprophylaxis of viruses like RSV and influenza have become research priorities (23). However, systematic evidence remains inadequate for MP as an important atypical pathogen. Significant knowledge gaps persist regarding the effect of the COVID-19 pandemic on the epidemiological characteristics of MP, the evolution of clinical phenotypes, and correlation with “long COVID”. In high-resistance regions like China, where macrolide resistance rates remain persistently high, determining whether clinical management strategies for MPP require adaptation to the post-pandemic era and how to optimize treatment in this high-resistance context has become an urgent critical issue.

Objective

To address these research gaps regarding post-pandemic MPP, this retrospective study analyzed clinical data from Chinese children with MP infection at a tertiary hospital in Chongqing, China, from January 2018 to December 2024. This study aimed to: (I) systematically evaluate whether the epidemiological rebound of MPP in the post-pandemic era in southwestern China aligns with the internationally reported “immunity debt” pattern; (II) investigate the impact of COVID-19 and/or NPIs on the clinical phenotypes of MPP, including fever duration, extrapulmonary complications, and treatment patterns (such as the use of tetracycline-class antibiotics); and (III) analyze the adaptation and safety of current treatment strategies (e.g., tetracycline and corticosteroid use) in settings with high macrolide resistance rates. By systematically delineating the epidemiological evolution of MPP in Southwest China during the post-pandemic era, this study addresses critical regional data gaps and provides a clinical evidence base for the prevention and treatment of COVID-19-associated MPP. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-435/rc).

Methods

Data collection

Data for this cohort study were obtained from The Second Affiliated Hospital of Army Medical University (Xinqiao Hospital). Electronic medical records were retrieved using the keyword “Mycoplasma,” covering the period from January 1, 2018, to December 31, 2024, yielding 826 medical records. The extracted data included the admission date, discharge date, name, home address, ID, hospitalization frequency, sex, age, weight, height, diagnosis, and auxiliary test results (Table S1).

Inclusion criteria: (I) treated at Xinqiao hospital; (II) treatment administered between January 1, 2018, and December 31, 2024; (III) aged 0–14 years; and (IV) positive MP nucleic acid test results.

Exclusion criteria: (I) incomplete medical records; (II) co-infection with other atypical pathogens (e.g., Chlamydia and Legionella); or (III) history of COVID-19 infection in the control group.

Based on these criteria, 285 cases were excluded, resulting in the final inclusion of 541 cases (Figure 1). A standardized case registration form was created, and patient data were manually collected by reviewing medical records. The clinical features, imaging findings, pulmonary function test results, and treatment regimens were recorded (Table S2).

Figure 1 Research flowchart. MP, Mycoplasma pneumoniae.

Grouping and clinical classification

The patients were divided into two groups based on hospitalization dates.

• Observation group: patients hospitalized between January 1, 2023, and December 31, 2024.
• Control group: patients hospitalized between January 1, 2018, and December 31, 2022.

Severity classification was based on objective criteria from the 2023 National Health Commission guidelines (11) and was independently adjudicated by two pediatric pulmonologists. Imaging studies were independently interpreted by two radiologists blinded to group assignment. The specific criteria were as follows:

• Mild cases: the disease course lasted for 7–10 days. These cases had good prognoses without sequelae.
• Severe cases: the patients experienced persistent high fever (>39 °C for ≥5 days) or fever lasting >7 days; symptoms, including wheezing, tachypnea, dyspnea, chest pain, and hemoptysis; multilobar involvement (≥2 lobes) or pulmonary consolidation/atelectasis; oxygen saturation <93% at rest (in room air) or requiring oxygen therapy; and presence of pleural effusion or extrapulmonary complications (e.g., myocarditis, encephalitis) not meeting critical criteria.
• Critical cases:respiratory failure and/or life-threatening extrapulmonary complications requiring mechanical ventilation or other life support measures.

The main reagent kits and methodologies used for laboratory tests are detailed in Table S3. Chest radiography and pulmonary CT examinations, including specific examination protocols and equipment models, are provided in Table S4.

Definitions, result interpretation, medication guidelines, and handling of missing data

• Previous positive medical history: a history of asthma, allergic rhinitis, congenital heart disease, or hematologic disorders.
• Severe cough: this was defined as cough that significantly impaired the child’s sleep, daily activities, or play ability, or nocturnal cough disturbing other family members’ sleep.
• MP-IgM result interpretation:
  • Positive: both the test (T) and control lines (C) are visible.
  • Weakly positive: the test line (T) is faint but clearly discernible.
• Medication dosages and administration used in this study are detailed in Table S5.
• Handling of missing data: missing data were directly excluded due to the low proportion of missing values (<5%) and to avoid bias introduced by imputation.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. As this retrospective study posed no potential harm to participants’ privacy, rights, or welfare, it was approved by the Ethics Committee of The Second Affiliated Hospital of Army Medical University (No. 2024-Research-010-03), and the requirement for informed consent was waived.

Statistical analysis

The data were processed and analyzed using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) and SPSS 19.0 (IBM Corporation, Armonk, NY, USA). Quantitative variables were analyzed using the Shapiro-Wilk normality test (P>0.05, indicating normal distribution). Normally distributed data are presented as mean ± standard deviation (SD) (independent t-test), while non-normal data are presented as median [interquartile range (IQR)] [M (Q1, Q3)] (Mann-Whitney U test). Categorical data are shown as counts (%) (Chi-squared test). Statistical significance was set at P<0.05.

Results

Epidemiological characteristics of MP over the past 7 years

From 2018 to 2024, 43,792 MP-IgM tests were performed, showing a “bimodal rebound” pattern in positivity rates (Figure 2). The MPP hospitalization rate in 2023 was 5.1 times higher than the pre-pandemic level (11.16% vs. 2.29%), with a slight decrease to 9.38% in 2024 (Table S6). Between January 2023 and December 2024, the MP-PCR positivity rate was 12.30%, exceeding 20% in July, August, and November 2023 (Figure 3, Table S7).

Figure 2 MP-IgM positive rate, weakly positive rate, and MPP hospitalization proportion from 2018 to 2024. MP-IgM, Mycoplasma pneumoniae immunoglobin M; MPP, Mycoplasma pneumoniae pneumonia.

Figure 3 Monthly distribution of positive rates for MP nucleic acid testing and antibody testing from 2023 to 2024. MP-IgM, Mycoplasma pneumoniae immunoglobin M; MP-PCR, Mycoplasma pneumoniae polymerase chain reaction.

General characteristics and clinical features upon admission

Significant differences were observed between the observation [2023–2024] and control [2018–2022] groups in age, weight, height, and history of epidemiological exposure (all P<0.05). The observation group demonstrated significantly higher frequencies of fever, cough, severe cough, and SMPP compared to the control group (all P<0.05, Table 1). Further details are provided in Tables S8-S10.

Chest radiography and pulmonary CT findings

The observation group underwent significantly more chest radiographs and pulmonary CT examinations than the control group (P<0.05). Radiographically, localized lesions, multilobar involvement (66.89%), and pulmonary consolidation and/or atelectasis (22.81%) were more common in the observation group, whereas increased bilateral lung markings were the predominant findings in the control group (48.24%, Table S11).

Laboratory findings

No statistically significant differences in C-reactive protein, procalcitonin, white blood cell count, and other indicators were observed between the groups. However, the observation group had significantly higher neutrophil percentage (NEUT%) and globulin (GLB) levels, and lower lymphocyte percentage (LYM%), albumin (ALB) levels, and ALB/GLB ratio (all P<0.05, Table S12).

Comparison of medications administered during hospitalization

The utilization rates of tetracycline antibiotics (26.75% vs. 1.18%) and corticosteroids (63.82% vs. 23.53%) were significantly higher in the observation group, which also had a longer treatment duration (all P<0.05). Notably, 57.38% of tetracycline recipients in the observation group were children aged <8 years. No significant difference in azithromycin administration was observed between the groups (Table 2, Tables S13,S14).

Comparison of hospital stay, discharge status, and auxiliary examinations between the observation and control groups

At discharge, the observation group had a significantly higher proportion of patients with persistent cough (64.69% vs. 20.00%) and a higher chest X-ray re-examination rate (35.09% vs. 9.41%) compared to the control group (both P<0.001). No significant difference in hospitalization duration (P=0.18) was found. The control group had a significantly higher rate of pulmonary function re-examinations (P<0.05; Table 3, Table S15).

Discussion

Key findings

After a multiperiod cohort analysis, we identified three major shifts in MPP during the post-pandemic era: (I) an explosive rebound in epidemiology; (II) a trend toward severe disease in younger age groups; and (III) a shift in treatment strategies for intensified regimens combining doxycycline and corticosteroids. These findings provide critical evidence for understanding the long-term effects of emerging respiratory infectious diseases on the transmission patterns of traditional pathogens.

Strengths and limitations

This study is the first to systematically document the “bimodal rebound” phenomenon of MP infections in Southwest China. This study has some limitations: (I) the control group asymmetrically excluded patients with COVID-19 because COVID-19 transmission was negligible during 2018–2022 due to NPI implementation. This precluded direct quantification of the impact of COVID-19 on MPP severity, as temporal changes in medical practices (e.g., increased vigilance for severe cases) and pathogen characteristics (e.g., antimicrobial resistance) may have independently influenced outcomes; (II) the increased post-pandemic use of imaging introduced a potential detection bias, which was effectively mitigated by the consistent severity assessment criteria; (III) the single-center study design may have introduced potential selection bias; (IV) data on antimicrobial resistance gene detection were lacking; (V) the dynamic changes in immune markers were not assessed.

Comparison with similar research

Changes in the epidemiological characteristics of MP infection

Further analysis of this study revealed (Figure 3 and Table S7) that within the first 24 months following the lifting of NPIs, 10,130 MP-PCR tests were performed, with an overall positivity rate of 12.30%. The positivity rate peaked between months 7 and 19 (July 2023 to July 2024) and deviated from the traditional seasonal epidemic pattern, consistent with reported non-seasonal peaks of respiratory pathogens post-NPIs relaxation (24). Notably, this study is the first to reveal a unique “bimodal rebound” pattern of MP infection in southwestern China. This pattern differs from the single-wave resurgence reported in European adult cohorts (25) and the sustained high prevalence observed in Japan (26). While these studies confirm the global rebound trend of MP infection after NPI withdrawal, the biphasic peak observed in Chongqing—characterized by an initial rapid outbreak in 2023 followed closely by a sustained high plateau—suggests a potentially more complex transmission dynamic. This phenomenon might be attributed to the background of exceptionally high macrolide-resistant MP (MRMP) rates in China (2,3,9,15), consequently influencing herd immunity landscape and transmission pathways. Specifically, the first peak likely reflects the rapid release of the “immunity debt” accumulated during the NPI period. The subsequent persistent wave might result from the combined effects of multiple factors, including waning immune protection over time, potential antigenic variation of local MP strains, and increased indoor activities during winter facilitating transmission. Furthermore, the intersecting curves of weakly positive and positive MP-IgM during 2020–2021 suggest a phase shift in immune dynamics: the immunity gap created by NPIs, superimposed with accelerated antibody waning due to repeated exposures after lockdowns were lifted, might have collectively led to a “dammed lake effect” in the susceptible population.

Trend toward severe diseases in younger age groups

This study identified a shift in the peak incidence toward preschool-aged children (3–7 years) and a significant increase in disease severity within the cohort, which aligns with reports from Denmark (10) and suggests a global trend. However, the proportion of severe cases in the observation group (74.34%) and the intensity of the inflammatory response were notably higher. This increasing trend was corroborated by elevated biomarkers (increased NEUT%, hyperglobulinemia) and treatment intensification (corticosteroid use), reducing the likelihood of bias due to diagnostic drift. This contrasts with a domestic study by Zhou et al. (27), which reported a lower incidence of fever among patients with MRMP. This discrepancy may be explained by the inclusion of patients with differing prior immune exposure histories—including SARS-CoV-2 infection—in the post-pandemic cohort. The high proportion of multilobar involvement in severe cases, along with biochemical markers of inflammation and tissue damage (e.g., elevated GLB), corresponds with the severe MRMP risk factors identified by Ding et al. (28) (such as elevated lactate dehydrogenase), underscoring a common pathway of excessive immunopathological responses driving severe disease in younger children.

Adaptive changes in treatment strategies

In response to the high prevalence of MRMP, the treatment strategy at our center has evolved significantly, mirroring adjustments reported in other high-resistance settings globally. The substantial increase in the use of tetracycline-class antibiotics (26.75%), particularly among children under 8 years of age (57.38%), represents a direct response to macrolide treatment failures. This approach is supported by Japanese studies demonstrating the superior efficacy of non-macrolide antibiotics, such as lascufloxacin and minocycline, against MRMP (26). Furthermore, the 2.7-fold increase in corticosteroid use (63.82%) is justified by the marked systemic inflammatory response observed in severe cases, a finding consistent with studies on refractory and SMPP that emphasize the role of hyperinflammation and immune dysregulation (27,28). Despite traditional concerns about dental staining, the use of tetracycline antibiotics (such as doxycycline) in children under 8 years of age with severe or macrolide-resistant MPP continues to increase, reflecting pressing clinical needs and prudent risk-benefit assessments. Recent evidence indicates that the risk of dental staining from short-term doxycycline use is minimal (29), a perspective now supported by authoritative guidelines (30). This demonstrates a shift in the risk-benefit profile: for SMPP, the therapeutic benefits of doxycycline clearly outweigh its significantly reduced dental staining risks.

Explanations of findings

Potential mechanisms of immune interaction

While a temporal association between the relaxation of NPIs, SARS-CoV-2 transmission, and SMPP was observed in this study, the underlying mechanisms require further investigation. The “immune-dam effect” hypothesis, although consistent with our epidemiological observations, remains a plausible model that requires validation through integrated immunological and virological data. In the observation group, 14.91% of pediatric patients had a clear history of MP epidemiological exposure, and their plasma ALB levels (114 vs. 111 mg/L) were significantly lower than the reference values, suggesting that the nutrition-immune axis may play a regulatory role in infection susceptibility. Animal experiments have confirmed that SARS-CoV-2 infection can remodel the pulmonary microenvironment (31). This study found a 22.81% lung CT consolidation rate in patients with MPP, further supporting the “immune scarring” hypothesis—where prior viral infection may induce long-term immunological alterations that influence the pathogenic process of subsequent pathogens. These findings provide clinical evidence for the “twindemic” theory (i.e., the synergistic epidemic of COVID-19 and MPP) and highlight the need for future prospective cohort studies to further elucidate the molecular interaction mechanisms between MP and SARS-CoV-2.

Delayed recovery

The observation group demonstrated significantly higher rates of residual cough at discharge compared to controls (64.69% vs. 20.00%, P<0.001), with a longer post-treatment cough duration (7 vs. 5 days, P=0.001). This highlights the necessity of respiratory function monitoring (27). Notable differences were observed in the radiographic follow-up, with the observation group showing significantly higher chest radiographic reexamination rates (35.09% vs. 9.41%, P<0.001). Partial inflammatory resolution without consolidation was observed in 80.63% of cases. Complete radiographic resolution was achieved in 13.75% of patients. These results confirmed the characteristic radiographic lag behind clinical improvement in MPP (1,12,13). Potential mechanisms include the following (32). (I) Extensive pulmonary tissue inflammation and damage caused by lobar consolidation. (II) Small airway inflammation and mucus plug obstruction due to diffuse bronchiolitis. (III) Increased airway injury and immune response from sequential or co-infections with various respiratory pathogens after the relaxation of NPIs. (IV) Th2 immune response and airway hyperreactivity due to atopic predisposition. (V) Delayed tissue repair due to MP-induced cellular immune response (33). Interestingly, no significant difference was found in hospitalization duration between the groups (P=0.18), suggesting that the observation group may require extended outpatient follow-up management.

Implications and actions needed

To enhance the diagnosis and treatment of pediatric MPP, the findings of this study provide critical evidence for optimizing management strategies. Accordingly, subsequent research should focus on. (I) Establishing a multicenter drug resistance surveillance network and exploring the mechanisms of MP and SARS-CoV-2 co-infection; (II) developing machine learning-based early warning models for severe cases. The latter particularly requires the incorporation of explainable artificial intelligence (AI) principles to ensure clinical credibility (34) and should draw upon smart healthcare development frameworks to advance AI capabilities—evolving from performing predictive tasks to supporting clinical workflow integration and personalized management (35). A core future objective lies in constructing truly interpretable AI tools capable of directly guiding clinical practice, thereby enabling precise prevention and management of MPP.

Conclusions

This study systematically demonstrated three paradigm shifts in MP infections during the post-pandemic era: a new epidemiological pattern of explosive outbreak-sustained transmission, the evolution of clinical phenotypes toward more severe manifestations in younger children, and a therapeutic strategy transition to doxycycline-corticosteroid combination regimens. These findings provide crucial evidence for optimizing MPP management protocols. We recommend establishing regional antimicrobial resistance surveillance and early warning systems, developing age-stratified anti-infective treatment guidelines, conducting mechanistic studies on MP-viral co-infections, and implementing efficient risk stratification using readily available clinical indicators for the early identification of SMMP. These results may inform decision-making to address the resurgence of traditional pathogens in emerging infectious diseases.

Acknowledgments

The authors thank the nurses at The Second Affiliated Hospital of Army Medical University for sample collection, and Prof. En Liu for statistical advice.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-435/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-435/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-435/prf

Funding: This work was supported by Chongqing Municipal Health Commission Medical Field Master Teacher Program (No. CQYC20220203178).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-435/coif). All authors report that this work was supported by Chongqing Municipal Health Commission Medical Field Master Teacher Program (No. CQYC20220203178). The authors have no other 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.As this retrospective study posed no potential harm to participants’ privacy, rights, or welfare, it was approved by the Ethics Committee of The Second Affiliated Hospital of Army Medical University (No. 2024-Research-010-03), and the required for informed consent 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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