The Epidemiological Characteristics of Mycoplasma Pneumoniae Infection and Coinfection among Children in Central China from 2018 to 2023

The Epidemiological Characteristics of Mycoplasma Pneumoniae Infection and Coinfection among Children in Central China from 2018 to 2023 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Epidemiological Characteristics of Mycoplasma Pneumoniae Infection and Coinfection among Children in Central China from 2018 to 2023 Jieyu Mao, Zhili Niu, Mengling Liu, Liangyu Li, Haiyue Zhang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4617945/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Jan, 2025 Read the published version in BMC Pediatrics → Version 1 posted 5 You are reading this latest preprint version Abstract Background Mycoplasm pneumomiae(M. pneumoniae, MP) is a common cause of reapiratory infections in humans, particularly among children and adolescents. This study investigates the epidemiological characteristics of MP infection among children and its relationship with coinfections to provide guidance for local MP prevention strategies. Methods After data screening based on the inclusion and exclusion criteria, a total of 163,058 pediatric patients with Acute Respiratory Tract Infection (ARTI) were enrolled in the study, ranging from January 1, 2018, to December 31, 2023. Results From 2018 to 2023, a total of 49,936 cases tested positive for MP, resulting in an overall positive rate of 30.62%. During this period, the annual positive rates were as follows: 45.92%, 32.23%, 22.84%, 16.22%, 16.26%, and 42.93%, respectively. The highest positive rate was observed in autumn (35.13%, P < 0.001). School-aged children exhibited the highest positive rate (40.09%), while infants had the lowest (25.32%, P < 0.001). Furthermore, the positive rate among girls (34.15%) was higher than that among boys (28.01%, P < 0.001). Among patients with MP infection, 14.27% were found to have coinfection with other pathogens, with viral infections accounting for 71.36% and bacterial infections for 28.64%. Notably, infants were more prone to coinfection with multiple pathogens (48.98%, P < 0.001). Conclusions MP infection is prevalent in children, with notable seasonal and age-dependent variations in positive rates. Coinfection with other pathogens is common, particularly in infants. Children Mycoplasma pneumoniae Acute Respiratory Tract Infection Epidemiology Coinfection Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Background Mycoplasma pneumoniae, also known as M. pneumoniae or MP, is a member of the Mollicutes class and is recognized as the smallest self-sufficient pathogenic microorganism capable of independent survival. It is primarily transmitted through respiratory droplets and is commonly found in densely populated areas, including households, schools, and military bases, with an incubation period ranging from 1 to 3 weeks [1-3]. MP remains active throughout the year and can impact individuals across all age groups, with school-aged children and adolescents being particularly vulnerable. Moreover, it demonstrates a cyclical epidemic pattern, marked by significant outbreaks recurring every 3-7 years and enduring for approximately 1-2 years each time. Certain studies propose that this cyclic trend might stem from subtype alterations or temporary acquisition of herd immunity [4, 5]. Its prolonged latency period and persistence in the respiratory tract after infection may contribute to the prolonged duration of MP outbreaks [1]. MP is one of the most frequent pathogens responsible for upper and lower respiratory tract infections. Research suggests that MP is accountable for 20%-40% of community acquired pneumonia cases, with this percentage increasing during outbreaks, making it a common cause of childhood mortality [1, 5-7]. Research on community-acquired pneumonia in Asian countries found that the rate of positivity for MP was around 11% [8].Monitoring of MP infections in 11 European countries from 2011 to 2016 reported an overall positive rate of 16%, with Norway contributing the highest rate at 26% [9]. A prospective study conducted in 12 centers across seven cities in China found MP to be a dominant pathogen, with a positive rate as high as 20.7% [10].A study in Wuhan from 2020 to 2022 found that 36.6% of children with community acquired pneumonia were confirmed to be MP positive [11].Most studies suggest that illnesses caused by MP infections are self-limiting and often present with mild clinical symptoms such as fever, cough, sore throat, and headache. Rhinitis and wheezing are common in children under 5 years old, with atypical findings on chest imaging [7, 12].Apart from causing common conditions like tracheobronchitis and atypical pneumonia, a nationwide cohort study in Taiwan provided a detailed description of the relationship between MP and asthma, suggesting that toxins produced by MP infection may be causative factors or exacerbate asthma [13].Additionally, MP can manifest extrapulmonary symptoms, including involvement of the central nervous system, skin manifestations, hemolytic anemia, cardiovascular complications, renal dysfunction, gastrointestinal discomfort, and musculoskeletal issues, sometimes leading to fatal consequences. These extrapulmonary manifestations are often associated with the direct impact of MP infection or immune-mediated inflammatory responses [14, 15]. Coinfection of MP with other respiratory pathogens is also quite common, especially in children, and may lead to more severe clinical symptoms. A study on coinfection with Streptococcus pneumoniae in Mycoplasma pneumoniae pneumonia found that patients with combined infections had longer duration of fever and were more likely to develop lobar consolidation and parapneumonic effusion [16].However, the correlation between them still requires further investigation. Other studies suggest that coinfection of MP with respiratory viruses may be associated with refractory Mycoplasma pneumoniae pneumonia, characterized by severe pneumonia and poor response to treatment [17].Therefore, coinfection with other pathogens may significantly influence clinical outcomes. Despite numerous epidemiological studies on MP in the region, data on recent trends in MP outbreaks and associated coinfections analysis are lacking. Thus, this study aims to report on the changing trends, epidemiological characteristics, and coinfection analysis of MP infections from 2018 to 2023, providing evidence for clinical diagnosis and treatment and the development of corresponding prevention and control strategies. 2. Materials and methods 2.1 Sample Source The clinical data for this study were sourced from the Laboratory Information Systems of Renmin Hospital of Wuhan University. A total of 163,058 specimens were collected from children aged 0-14 with ARTI treated at Renmin Hospital of Wuhan University from January 1, 2018, to December 31, 2023. The enrolled children were grouped based on season (spring: March to May, summer: June to August, autumn: September to November, winter: December to February of the following year), age (infants: 0≤Age≤3 years old, preschool age: 3<Age≤7 years old, school age: 7<Age≤14 years old), and gender. Inclusion Criteria:(1) Children exhibiting any of the following clinical symptoms of ARTI : new onset fever,cough,sore throat,dyspnea,and abnormal breath sounds.(2) Patients aged ≤14 years old. Exclusion Criteria:(1) Individuals not meeting the clinical presentation criteria for ARTI as described above. (2) Patients >14 years old. (3) Cases with incomplete information. 2.2 Laboratory Diagnosis All enrolled children had specimens collected promptly (either at the time of outpatient visit or within 3 days of hospitalization for inpatients). The specimen types included whole blood, serum, nasal swabs, nasopharyngeal swabs, sputum, and bronchoalveolar lavage fluid. Whole blood specimens were used for MP specific IgM antibody titer determination, while the remaining specimens were used for MP nucleic acid detection. In addition to MP, eight common viruses and other atypical pathogens (Chlamydia pneumoniae, Legionella pneumophila, and Coxiella burnetii) were tested. Specific IgM antibody detection was performed using the following kits: IIFT: Respiratory Tract Profile (EUROIMMUN Medizinische Labordiagnostika AG, Seekamp, Lubeck, Germany) and Mycoplasma pneumoniae IgM Antibody Test Kit (Colloidal Gold Method) (Beijing Beier Bioengineering Co., Daxing, Beijing, China). Nucleic acid detection was conducted using a 13-Respiratory Pathogen Multiplex Detection kit (HEALTH BioMed Co., Ltd., Ningbo, Zhejiang, China). Additionally, specimens obtained from the lower respiratory tract underwent bacterial testing for 10 respiratory bacteria, using the Respiratory Pathogen Nucleic Acid Detection Test Kit (CapitalBio Technology (Chengdu) Co., Ltd., Wenjiang, Chengdu, China). To ensure the reliability of the results, all tests underwent laboratory internal quality control, and were within the control range. 2.3 Definition of Acute MP infection An MP infection is defined by the presence of symptoms typical of ARTI, such as fever, cough, sore throat, and abnormal breath sounds. Additionally, a positive diagnosis requires either PCR testing indicating the presence of MP nucleic acids or serological testing showing the presence of MP specific IgM antibodies. 2.4 Statistical analysis All statistical analyses were performed using IBM SPSS Statistics, Version 27.0(IBM Corp.,Armonk,NY).Continuous variables are expressed as mean standard deviation （ ）,while categorical variables are presented as numbers (%).Group comparisons between variables were conducted using the Pearson’s chi-square test.Pearson correlation coefficient was employed to investigate the correlation between MP and various respiratory pathogens.P value <0.05was considered significant. 3. Results 3.1 Study population From January 1, 2018, to December 31, 2023, a total of 211,600 patients with acute respiratory tract infections (ARTI) were collected from Renmin Hospital of Wuhan University. Among them, 48, 542 cases did not meet the inclusion criteria, leaving a total of 163,058 cases included in the study, with an average age of 4.25 2.91 years. This included 93,575 males and 69,483 females. Among the included cases, 121,384 underwent MP specific IgM antibody testing on blood specimens, while 41,674 (including nasal swabs, nasopharyngeal swabs, sputum, and bronchoalveolar lavage fluid) underwent MP nucleic acid testing. A total of 49,936 cases tested positive for MP (45,602 positive for MP-IgM and 4,334 positive for MP-DNA), resulting in an overall positive rate of 30.62%. The specific process is detailed in Fig.1. 3.2 Seasonal and Annual Trends of MP Infections From 2018 to 2023, the annual positive rates of MP among ARTI patients were 45.92%, 32.23%, 22.84%, 16.22%, 16.26%, and 42.93%, respectively. The differences in positive rates between each year were statistically significant (P<0.001). Throughout the entire study period, the highest positive rate was observed in autumn (35.13%), while the lowest was in spring (26.28%). The comparison of MP positive rates among seasons showed statistically significant differences (P<0.001). Between 2018 and 2019, spring and summer were the seasonal peaks, with positive rates of 50.24% and 49.20%, and 35.23% and 35.86%, respectively. In January 2020, the positive rate peaked at 27.39%, followed by a decline in February, reaching its lowest point in March (6.38%), gradually increasing in April, and maintaining a relatively stable level thereafter. In 2021 and 2022, the highest positive rates were observed in summer, with rates of 17.79% and 21.51%, respectively. However, in 2023, the highest number of MP cases sent for testing occurred in autumn and winter, consistent with the MP positive rates. Particularly, in late autumn and early winter, the monthly positive rates were 72.32% and 65.35%, respectively. The differences in seasonal positive rates each year were statistically significant (P<0.001). The specific distribution of monthly, seasonal, and annual MP infections during the study period is illustrated in Fig.2, and the detailed numerical values are provided in Table 1. 3.3 Age-related Characteristics and Temporal Trends of MP Infections The 163,058 ARTI patients were divided into three age groups, with the positive rate for each age group: infants (21,436 cases, accounting for 25.32%), pre-school children (19,570 cases, accounting for 34.87%), and school-age children (8,930 cases, accounting for 40.09%). Among these, the school-age children group had the highest MP infection rate. The results for each age group are shown in Table 1. Further stratifying by detection time into three periods: 2018-2019, 2020-2022, and 2023, pre-school and school-age children were more common in all three years. The number of MP positive patients and the positive rates for each year group are shown in Fig.3. It's noteworthy that the positive rate increased with the age of the patients. Furthermore, we observed a linear relationship between the MP infection rates among patients aged 1 to 12 months throughout the months of the year, as depicted in Fig.4. 3.4 Gender Differences in MP Infection Positive Rates Of the 49,936 confirmed infection cases, there were 23,726 females with an average positive rate of 34.15%, and 26,210 males with a positive rate of 28.01%. Despite a higher number of males being tested, the positive rate among females was significantly higher than that of males, with a statistically significant difference between the two groups (p < 0.001). Over the six years from 2018 to 2023, the positive rate among females was consistently higher than that of male patients, with rates of 50.71%, 36.68%, 25.66%, 19.17%, 18.46%, and 46.45%, respectively. The gender differences over the six-year period were statistically significant (p < 0.001). For specific numerical values, please refer to Table 1. 3.5 Prevalence and Patterns of Coinfections in MP Patients In cases of MP infection, 7,126 cases were found to have at least one concurrent infection with another pathogen, with an overall positive rate of 14.27%. The yearly positive rates were 18.62%, 18.30%, 8.06%, 5.32%, 13.10%, and 12.98%, respectively, with statistically significant differences between the years (P<0.001). Among the 7,126 coinfected cases, 5,085 were found to have at least one concurrent viral infection (71.36%), while 2,041 were found to have at least one concurrent bacterial infection (28.64%). The study found that younger children were more likely to have coinfections with other pathogens, with infants (48.98%) > pre-school children (37.29%) > school-age children (13.74%), with statistically significant differences between age groups (P<0.001). The rate of coinfection was similar between genders (14.25% for males, 14.29% for females, P=0.914). Among MP coinfections with viruses, the most commonly detected virus was influenza virus (IFV) (1,933 cases, accounting for 38.01%), followed by respiratory syncytial virus (RSV) (1,545 cases, accounting for 30.38%), human parainfluenza Virus (HPIV) (738 cases, accounting for 14.51%), human rhinovirus (HRV) (424 cases, accounting for 8.34%), human adenovirus (HAdV) (286 cases, accounting for 5.62%), human metapneumovirus (HMPV) (72 cases, accounting for 1.42%), human coronavirus (HCoV) (71 cases, accounting for 1.40%), and human bocavirus (HBoV) (16 cases, accounting for 0.31%). Genetic typing analysis of IFV showed that influenza B virus (FluB) predominated, accounting for 89.91% of all genetically analyzed cases, while influenza A virus (FluA) accounted for 10.09%. Among FluA coinfected patients, 66 cases of coinfection with influenza A subtype H3N2 (H3N2) were found, with no cases of coinfection with influenza A subtype H1N1 (H1N1) detected. Further age-specific analysis revealed that the top two viruses in all three age groups were IFV and RSV (42.10% and 34.53% for infants, 34.04% and 27.93% for pre-school children, 33.68% and 21.50% for school-age children, respectively), while the third-ranked virus in school-age children was HRV (16.84%). The pattern of virus coinfection was generally similar between infants and pre-school children (with HCoV > HMPV for preschool children), as shown in Fig.5. Among MP coinfections with bacteria, the most commonly detected was Chlamydia pneumoniae (C.pneumoniae, CP) (1,286 cases, accounting for 63.01%), followed by Haemophilus influenzae (H.influenzae, Hi) (297 cases, accounting for 14.55%), Streptococcus pneumoniae (S.pneumoniae, Sp) (273 cases, accounting for 13.38%), Staphylococcus aureus (S.aureus, Sa) (81 cases, accounting for 3.97%), Acinetobacter baumannii (A.baumannii, Ab) (25 cases, accounting for 1.22%), Methicillin-Resistant Staphylococcus aureus (MRSA) (23 cases, accounting for 1.13%), Klebsiella pneumoniae (K.pneumoniae, Kp) (14 cases, accounting for 0.69%), Legionella pneumophila (L.pneumophila, Lp) (14 cases, accounting for 0.69%), Pseudomonas aeruginosa (P.aeruginosa, Pa) (12 cases, accounting for 0.59%), Coxiella burnetii (Coxiella burnetii, Cox) (7 cases, accounting for 0.34%), Escherichia coli (E.coli) (6 cases, accounting for 0.29%), Mycobacterium tuberculosis (M.tuberculosis, MTB) (2 cases, accounting for 0.10%), and Stenotrophomonas maltophilia (Stenotrophomonas maltophilia, Sm) (1 case, accounting for 0.05%). Further age-specific analysis showed that among the top three coinfection bacteria in all three age groups were C.pneumoniae, H.influenzae, and S.pneumoniae, albeit with slightly different orderings. In pre-school children, the order was C.pneumoniae > S.pneumoniae > H.influenzae. The ranking of coinfection patterns with other bacteria varied across different age groups, as shown in Fig.5. Among the MP positive patients, 5,775 cases had single pathogen infections, while 641 cases exhibited coinfections involving at least two pathogens. The most common coinfection patterns with viruses were MP, HPIV and HAdV. The most common coinfection patterns with bacteria were MP, H. influenzae and S. pneumoniae. The most common coinfection patterns with bacterial and viruses were MP, RSV and C. pneumoniae. In addition, there were 64 cases with coinfections involving at least three pathogens. Among them, 7 cases involved MP mixed with 4 other pathogens, and 2 cases involved MP mixed with 5 other pathogens. The specific distribution and mutual relationships of coinfection pathogens can be found in Fig.6. Discussion In this study, we provide a detailed description of the trend changes in MP infection among children under 14 years old in Wuhan from 2018 to 2023. We found that MP infection occurred continuously throughout the study period, with a monthly positive rate consistently above 10% (except in March 2020 and December 2022). Particularly notable was a significant outbreak observed from 2018 to 2019, similar to trends seen in other regions of China[18-22].During this outbreak, peaks of infection were mainly concentrated in the spring and summer, consistent with previous studies in the region[23].However, from 2020 to 2022, there was a notable decline in positive rates following the peak in January 2020 (27.39%), with both the total number of MP tests and positive rates significantly decreasing in February, reaching a low point in March (47 cases, 6.38%), representing declines of 82.64% and 78.71% compared to the same periods in 2018 and 2019, respectively.Positive rates gradually rebounded in April and remained stable and relatively low thereafter, with the highest rates occurring in the summer months of 2021-2022 (17.79% and 21.51%, respectively).We attribute this decline partly to reduced patient visits to healthcare facilities (particularly in 2020, when testing numbers were lowest) following the outbreak of the worldwide coronavirus disease (COVID-19), as well as the non-pharmaceutical interventions (NPIs) implemented in Wuhan at the time (including reducing gatherings, mask-wearing, hand hygiene, and disinfection), which likely effectively reduced the transmission of respiratory pathogens, including MP. However, despite the relaxation or cessation of NPI measures, MP infection rates continued to show a long-term decrease, while infections by other pathogens re-emerged during the same period, indicating an increase in community transmission[24, 25].By 2023, Wuhan experienced another localized MP outbreak, becoming a significant public health concern, consistent with multiple research findings[26, 27].We observed that in January 2023, positive rates remained low as in previous years, gradually increasing from February and peaking in the autumn and winter seasons. Particularly during late autumn and early winter, monthly positive rates reached 72.32% and 65.35%, respectively, consistent with findings from some European studies[22, 28, 29].Throughout the period from 2018 to 2023, there were fluctuations in the peak seasons of MP outbreaks in Wuhan, which we attribute to the influence of NPI measures adopted during the COVID-19 pandemic, altering people's behavior patterns and social activities, thereby affecting the transmission pattern of MP, either prolonging the epidemic period or due to changes in MP genotypes. MP typically experiences a major outbreak every 3-7 years, thus the resurgence of the epidemic in Wuhan in 2023 conforms to its cyclical epidemic pattern. Most studies indicate that MP infection is more common in children aged 5 and above. Consistent with this, our study found that MP is more prevalent in pre-school and school-age children, in line with the findings of Meyer et al[30-34].We believe this could be due to the broader social contacts of children in this age group. In China, children typically start attending kindergarten around the age of 3 and begin primary school at 6-7 years old, spending most of their daytime in school,a densely populated places . This further supports the notion that MP infections often occur in places like schools and military bases through close contact and droplet transmission.Additionally, numerous studies suggest that after infecting host cells, MP can stimulate immune cells to produce a large number of cytokines and mediators, leading to clinical illness and lung injury[4, 35].Therefore, as children's immune function matures, their bodies can mount a more effective immune response against this pathogen. Our study results indicate that this trend is particularly pronounced in infants under 1 year old, with MP infection positive rates increasing with age. We speculate that breastfed infants may acquire protective antibodies from breast milk, which could be one reason for the lower infection rates in younger infants. Research has shown that antibodies induced in the mother's body during the perinatal period undergo specific post-translational modifications. When these antibodies are transferred to newborns through blood or breastfeeding, they can help young infants resist a wider range of pathogen infections[36].Overall, there is a general linear trend in the age distribution of MP infections in children. In our study, the gender difference in MP infection is significant, with a notably higher positive rate among female patients compared to males, consistent with several previous domestic studies[20, 37-39]. We speculate that this difference may be due to genetic and hormonal factors. Sara et al. suggested that females have two X chromosomes, which contain multiple genes regulating immune function, such as interleukin-1 receptor-associated kinase 1 (IRAK1) and interleukin-2 receptor gamma chain. While one X chromosome is usually inactivated to prevent gene overexpression, this inactivation is only partial[40].They proposed that males may be more susceptible to bacterial and viral infections, while females may exhibit stronger immune responses. However, our study primarily detected MP IgM, which could potentially influence the detection results. Estradiol affects cellular immunity in a concentration-dependent manner. Susan and Sabra et al. suggested that low concentrations of estradiol can stimulate TH1-type responses, promoting the production of pro-inflammatory cytokines such as interleukin-1 and interferon-gamma[41, 42]. Respiratory tract infections caused by MP are difficult to distinguish from infections caused by other respiratory pathogens in terms of clinical symptoms and radiological findings. In pediatric ARTI, most MP infected patients are often co-detected with other viruses or bacteria, and this co-detection is associated with the severity of the disease[43, 44].In 14.27% of specimens collected from MP positive children, one or more other respiratory pathogens were detected. These pathogens may play a role in the pathogenesis of MP induced respiratory diseases, but their specific roles remain unclear. In our study, the most common viral coinfection was with IFV (mainly FluB), followed by RSV and HPIV. This differs from the findings of Maureen et al., who reported a lower coinfection rate of MP with influenza virus, RSV, and HPIV (<3.0%)[43]. For patients with combined viral infections, there may be no need to adjust their primary antibacterial treatment regimen. The most common bacterial coinfection was with C.pneumoniae, followed by H.influenzae and S.pneumoniae, similar to previous studies[45, 46].C. pneumoniae, like MP, is an atypical pathogen, and there is no significant difference in treatment regimens between the two. However, H. influenzae and S. pneumoniae are common strains, and MP is primarily treated with macrolide antibiotics. For children with combined infections of these two pathogens, additional antibiotics such as cephalosporins or fluoroquinolones may be needed for combination therapy. We also found that the incidence of coinfections is negatively correlated with age, with infants and young children being more commonly affected. This is consistent with the findings of Maureen et al[17, 43]. The interactions between MP and co-detected microorganisms and their potential impact on the severity of clinical symptoms in affected children require further research for deeper exploration. Our study has several limitations. Firstly, being a retrospective study conducted in a single region and center, the representativeness of our sample may be biased. However, despite this limitation, the analysis of our large dataset over the past six years can still serve as guidance for preventing MP outbreaks in the region. Secondly, the sensitivity of PCR methods is higher than that of MP serological testing, especially for infants and young children, whose immune function may not be fully matured. As a result, some children may have false-negative results due to their serum antibody titers not being elevated. Directly using PCR methods for MP detection seems more reasonable. Unfortunately, due to potential cost-saving reasons, some patients in this study did not have both methods used in combination. This may have affected the positive rate of MP. Furthermore, we did not conduct genotyping or drug resistance analysis of MP, and thus could not determine whether the prevalent genotypes of MP had changed compared to previous outbreaks. Future studies could analyze data from more regions and incorporate clinical research to further explore the mechanisms and influencing factors of MP infections. Conclusions In summary, our study revealed the epidemiological trends, clinical characteristics, and coinfection relationships of MP among children in Wuhan. Two MP outbreaks occurred in Wuhan from 2018 to 2023, specifically in 2018-2019 and 2023. The NPI measures implemented during the COVID-19 pandemic also contributed to the delayed appearance of MP infections in Wuhan. However, MP re-emerged in 2023, becoming a significant contributor to the autumn and winter epidemics in the city. The high rate of coinfection between MP and other pathogens may lead to more severe clinical symptoms or the development of severe pneumonia, thereby increasing the burden on healthcare systems. These findings hold significant implications for informing clinical diagnosis and treatment, as well as shaping prevention and control strategies. Moreover, they offer valuable insights for future research endeavors related to this topic. Abbreviations MP: Mycoplasma pneumoniae, M. pneumoniae ARTI: Acute Respiratory Tract Infection IFV: Influenza virus Flu B: Influenza B virus Flu A: Influenza A virus H3N2: Influenza A subtype H3N2 H1N1: Influenza A subtype H1N1 RSV: Respiratory syncytial virus HPIV: Human parainfluenza HRV: Human rhinovirus HAdV: Human adenovirus HMPV: Human metapneumovirus HCoV: Human coronavirus HBoV: Human bocavirus CP: Chlamydia pneumoniae, C.pneumoniae Hi: Haemophilus influenzae, H.influenzae Sp: Streptococcus pneumoniae, S.pneumoniae Sa: Staphylococcus aureus, S.aureus Ab: Acinetobacter baumannii, A.baumannnii Kp: Klebsiella pneumoniae, K.pneumoniae Lp: Legionella pneumophila, L.pneumophila Pa: Pseudomonas aeruginosa, P.aeruginosa Cox: Coxiella burnetii E.coil: Escherichia coli MTB: Mycobacterium tuberculosis, M.tuberculosis Sm: Stenotrophomonas maltophilia MRSA: Methicillin-Resistant Staphylococcus aureus COVID-19: Coronavirus disease NPI: Non-pharmaceutical interventions Declarations Ethics approval and consent to participate The procedures followed in this study were in accordance with principles of the Declaration of Helsinki (1964,amended most recently in 2008) of the World Medical Association.The protocol was approved by the Ethics Commission of Renmin Hospital of Wuhan University, and the requirement for patient informed consent was waived by the Ethics Commission of Renmin Hospital of Wuhan University due to the observational nature of the study. Consent for publication Not Applicable. Availability of data and materials Demographic and clinical data of patients which involved in this study were extracted from the Laboratory Information Systems of Renmin Hospital of Wuhan University. The datasets generated or analyzed during this study are not publicly available due to privacy or ethical restrictions but are available from the corresponding author on reasonable request. Competing Interests The authors declare that there was no conflict of interest. Funding This work was supported by The National Natural Science Foundation of China(82370008). Author Contributions JieYu Mao and ZhiLi Niu designed the study, conducted data organization and analysis, and drafted the initial manuscript. MengLing Liu and LiangYu Li participated in data organization and verification.HaiYue Zhang and RuiYun Li contributed to the study design and data interpretation. Pingan Zhang and XiaoJun Wu contributed to the study design, data interpretation, manuscript revisions, and final draft editing. All authors read and approved the final report. Acknowledgements This study was conducted at the Renmin Hospital of Wuhan University. We sincerely thank all the staff and participants for their important contributions. Authors’ information 1 Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University Wuhan, Hubei, China. 2 Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. Clinical Trial Number This study is a retrospective analysis using clinical data for statistical purposes. It does not involve patient privacy or human trials and is therefore exempt from the requirement for a clinical trial registration number. 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Frontiers in cellular and infection microbiology 2022, 12:843463. Meyer Sauteur PM, Beeton ML, Uldum SA, Bossuyt N, Vermeulen M, Loens K et al : Mycoplasma pneumoniae detections before and during the COVID-19 pandemic: results of a global survey, 2017 to 2021. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2022, 27(19). Wang X, Li M, Luo M, Luo Q, Kang L, Xie H et al : Mycoplasma pneumoniae triggers pneumonia epidemic in autumn and winter in Beijing: a multicentre, population-based epidemiological study between 2015 and 2020. Emerging microbes & infections 2022, 11(1):1508-1517. Tang M, Dong W, Yuan S, Chen J, Lin J, Wu J et al : Comparison of respiratory pathogens in children with community-acquired pneumonia before and during the COVID-19 pandemic. BMC pediatrics 2023, 23(1):535. Wang F, Cheng Q, Duo H, Wang J, Yang J, Jing S et al : Childhood Mycoplasma pneumoniae: epidemiology and manifestation in Northeast and Inner Mongolia, China. Microbiology spectrum 2024, 12(5):e0009724. Wu Z, Li Y, Gu J, Zheng H, Tong Y, Wu Q: Detection of viruses and atypical bacteria associated with acute respiratory infection of children in Hubei, China. Respirology (Carlton, Vic) 2014, 19(2):218-224. Meyer Sauteur PM, Chalker VJ, Berger C, Nir-Paz R, Beeton ML: Mycoplasma pneumoniae beyond the COVID-19 pandemic: where is it? The Lancet Microbe 2022, 3(12):e897. Meyer Sauteur PM, Beeton ML: Mycoplasma pneumoniae: gone forever? The Lancet Microbe 2023, 4(10):e763. Larcher R, Boudet A, Roger C, Villa F, Loubet P: Mycoplasma pneumoniae is back! Is it the next pandemic? Anaesthesia, critical care & pain medicine 2024, 43(1):101338. Meyer Sauteur PM, Beeton ML: Mycoplasma pneumoniae: delayed re-emergence after COVID-19 pandemic restrictions. The Lancet Microbe 2024, 5(2):e100-e101. Wreghitt T: Mycoplasma pneumoniae: current outbreak. Epidemiology and infection 2024, 152:e47. Yan C, Xue GH, Zhao HQ, Feng YL, Cui JH, Yuan J: Current status of Mycoplasma pneumoniae infection in China. World journal of pediatrics : WJP 2024, 20(1):1-4. Chen K, Jia R, Li L, Yang C, Shi Y: The aetiology of community associated pneumonia in children in Nanjing, China and aetiological patterns associated with age and season. BMC public health 2015, 15:113. Kawakami N, Namkoong H, Saito F, Ishizaki M, Yamazaki M, Mitamura K: Epidemiology of macrolide-resistant Mycoplasma pneumoniae by age distribution in Japan. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2021, 27(1):45-48. Zhang L, Lai M, Ai T, Liao H, Huang Y, Zhang Y et al : Analysis of mycoplasma pneumoniae infection among children with respiratory tract infections in hospital in Chengdu from 2014 to 2020. Translational pediatrics 2021, 10(4):990-997. Cheng Y, Cheng Y, Dai S, Hou D, Ge M, Zhang Y et al : The Prevalence of Mycoplasma Pneumoniae Among Children in Beijing Before and During the COVID-19 Pandemic. Frontiers in cellular and infection microbiology 2022, 12:854505. Ma J, Guo P, Mei S, Li M, Yu Z, Zhang Y et al : Influence of COVID-19 pandemic on the epidemiology of Mycoplasma pneumoniae infections among hospitalized children in Henan, China. Heliyon 2023, 9(11):e22213. Yang J, Hooper WC, Phillips DJ, Talkington DF: Cytokines in Mycoplasma pneumoniae infections. Cytokine & growth factor reviews 2004, 15(2-3):157-168. Erickson JJ, Archer-Hartmann S, Yarawsky AE, Miller JLC, Seveau S, Shao TY et al : Pregnancy enables antibody protection against intracellular infection. Nature 2022, 606(7915):769-775. Lv YT, Sun XJ, Chen Y, Ruan T, Xu GP, Huang JA: Epidemic characteristics of Mycoplasma pneumoniae infection: a retrospective analysis of a single center in Suzhou from 2014 to 2020. Annals of translational medicine 2022, 10(20):1123. Huang BX, Cai DF, Zhang JS, Lei M, Chen YS: Epidemiological characteristics of a single center for mycoplasma pneumoniae infection in a Children's Hospital in Shenzhen from 2011 to 2018 %J MolDiagnTher. 2023, 15(04):686-689. Liaon SQ, Tan H, Zhang XM, Wan K, Lu XF, Zhu HC et al : Multicenter epidemiological characteristics of Mycoplasma pneumoniae infection in children in Hainan Province, 2012- 2020 %J China Tropical Medicine. 2023, 23(05):511-515+533. Dias SP, Brouwer MC, van de Beek D: Sex and Gender Differences in Bacterial Infections. Infection and immunity 2022, 90(10):e0028322. Kovats S: Estrogen receptors regulate innate immune cells and signaling pathways. Cellular immunology 2015, 294(2):63-69. Klein SL, Flanagan KL: Sex differences in immune responses. Nature reviews Immunology 2016, 16(10):626-638. Diaz MH, Cross KE, Benitez AJ, Hicks LA, Kutty P, Bramley AM et al : Identification of Bacterial and Viral Codetections With Mycoplasma pneumoniae Using the TaqMan Array Card in Patients Hospitalized With Community-Acquired Pneumonia. Open forum infectious diseases 2016, 3(2):ofw071. Jiang W, Wu M, Zhou J, Wang Y, Hao C, Ji W et al : Etiologic spectrum and occurrence of coinfections in children hospitalized with community-acquired pneumonia. BMC infectious diseases 2017, 17(1):787. Ma L, Wang W, Le Grange JM, Wang X, Du S, Li C et al : Coinfection of SARS-CoV-2 and Other Respiratory Pathogens. Infection and drug resistance 2020, 13:3045-3053. Shin S, Koo S, Yang YJ, Lim HJ: Characteristics of the Mycoplasma pneumoniae Epidemic from 2019 to 2020 in Korea: Macrolide Resistance and Co-Infection Trends. Antibiotics (Basel, Switzerland) 2023, 12(11). Table Table 1. Total number of cases and MP positive cases in different groups from 2018 to 2023 Group Year n(%) 2018 2019 2020 2021 2022 2023 Season Spring 2 668(50.24%) 2 942(35.23%) 37(15.88%) 1 236(17.35) 1 005(12.63%) 2 243(23.44%) Summer 2 534(49.20%) 2 836(35.86%) 284(22.42%) 1 259(17.79%) 2 180(21.51%) 3 326(35.71%) Autumn 2 149(39.27%) 2 349(27.67%) 1 009(22.35%) 1 405(16.26) 891(16.47%) 9 925(55.30%) Winter 2 655(45.34%) 2 093(30.08%) 854(24.06%) 822(13.11%) 574(11.25%) 2 660(48.74%) c 2 160.582 177.627 10.124 64.114 376.093 2878.993 P <0.001 <0.001 0.018 <0.001 <0.001 <0.001 Age 0≤Age≤3 6 181(43.61) 5 305(27.51%) 1 074（18.76%） 2 380(14.09%) 1 904(13.01) 4 592(32.92%) 3<Age≤7 3 008(51.84%) 3 792(40.06%) 841（29.33%） 1 894(18.93%) 2 015(18.97%) 8 020(46.19%) 7<Age≤14 817(45.06%) 1 123(37.99%) 269(27.65%) 448(20.33%) 731(21.80%) 5 542(50.48%) c 2 112.808 507.613 135.360 138.030 246.363 900.917 P <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 Sex Male 5 438(42.54%) 5 296(28.97%) 1 168(20.84%) 2 325(14.00%) 2 417(14.64%) 9 566(40.19%) Female 4 568(50.71%) 4 924(36.68%) 1 016(25.66%) 2 397(19.17%) 2 233(18.46%) 8 588(46.45%) c 2 141.899 210.300 30.521 140.219 74.597 166.255 P <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 28 Jan, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 07 Aug, 2024 Editor invited by journal 01 Jul, 2024 Editor assigned by journal 28 Jun, 2024 Submission checks completed at journal 28 Jun, 2024 First submitted to journal 21 Jun, 2024 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4617945","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":325091923,"identity":"105262ad-5c04-4a48-805b-babd71f13cc5","order_by":0,"name":"Jieyu Mao","email":"","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Jieyu","middleName":"","lastName":"Mao","suffix":""},{"id":325091924,"identity":"8cf5ac23-a5c8-4b74-b208-801d2b71a805","order_by":1,"name":"Zhili Niu","email":"","orcid":"","institution":"Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Zhili","middleName":"","lastName":"Niu","suffix":""},{"id":325091925,"identity":"9f9326db-dd55-4ca3-9c69-446c6a6ca1ad","order_by":2,"name":"Mengling Liu","email":"","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Mengling","middleName":"","lastName":"Liu","suffix":""},{"id":325091926,"identity":"82649dbf-eae9-4fb8-b2a6-57c38d3a270f","order_by":3,"name":"Liangyu Li","email":"","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Liangyu","middleName":"","lastName":"Li","suffix":""},{"id":325091927,"identity":"ac2d7d6e-870f-4a0c-81b7-963d23ee2e5e","order_by":4,"name":"Haiyue Zhang","email":"","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Haiyue","middleName":"","lastName":"Zhang","suffix":""},{"id":325091928,"identity":"bb762408-088d-46f2-bc55-656fe66fd46f","order_by":5,"name":"Ruiyun Li","email":"","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Ruiyun","middleName":"","lastName":"Li","suffix":""},{"id":325091929,"identity":"b3ea0507-fa71-481b-97ad-232c6d863705","order_by":6,"name":"Pingan Zhang","email":"","orcid":"","institution":"Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Pingan","middleName":"","lastName":"Zhang","suffix":""},{"id":325091931,"identity":"3c7d99a3-e898-4a81-8103-7b4be4640d73","order_by":7,"name":"Xiaojun Wu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYJCCAwwMbFBmhYQcP4lazlgYSzaQZB9jW0XiBkJaDG7kGB74UcGXuF36dJo07zwJxg0MzA8f3cCrJS3hYM8ZtsSdfbnbpHm3STCbM7AZG+fg0WJ2I/nAAd42tsQNZ3jBWtgsG3jYpPFrSWw4+BeuZY4Ej8EBglqSDxxG2NIgIUFQi/2ZZwmHZc6wGQO1bLacc0zCQLKZgF8k23OMP76pOCYL1LLxxpuauvp+9uaHj/FpgYJjIIJFigdEMRNWDgI1YLUffxCnehSMglEwCkYYAAB5Ik6INjPCoQAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University","correspondingAuthor":true,"prefix":"","firstName":"Xiaojun","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2024-06-21 14:21:51","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4617945/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4617945/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-05435-9","type":"published","date":"2025-01-28T15:57:23+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60811619,"identity":"e15f951c-d452-45ad-8902-b08bfe49d868","added_by":"auto","created_at":"2024-07-22 10:57:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":49243,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart outlining the study's methodology. Between January 1, 2018, and December 31, 2023, a total of 211,600 patients were collected; however, after data screening, 48,542 cases that did not meet the inclusion criteria were excluded, leaving 163,058 patients who were included in this study. Additionally, 49,936 patients tested positive for MP.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4617945/v1/f1b580ed2f009fd56b3949e7.png"},{"id":60811622,"identity":"aa93ad40-5749-4a78-a4f9-67f66209dd84","added_by":"auto","created_at":"2024-07-22 10:57:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":53493,"visible":true,"origin":"","legend":"\u003cp\u003eMonthly, Seasonal, and Annual Distribution of MP Infection in Children. \u003cstrong\u003ea\u003c/strong\u003e From 2018 to 2023, the number of ARTI patients and the number of MP positive cases categorized by month. The blue bars represent MP positive cases, the gray bars represent MP negative cases, and the orange line represents the MP positive rate; The gray background area indicates the period of the COVID-19 pandemic, while the red background area indicates the lockdown period in Wuhan. \u003cstrong\u003eb\u003c/strong\u003e Distribution of MP positive in different seasons from 2018 to 2023 (Numbers and proportion).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4617945/v1/3fba2030163ac063e97699a7.png"},{"id":60811620,"identity":"04017ec0-58f9-4fe0-b61d-9623a6d9c8cb","added_by":"auto","created_at":"2024-07-22 10:57:14","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":45688,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of MP Infection in Children by Age. \u003cstrong\u003ea\u003c/strong\u003e Yellow blocks represent ARTI patients with negative MP tests, while orange blocks represent ARTI patients with positive MP tests. The stacked bar chart illustrates the proportion of MP positive patients by age. \u003cstrong\u003eb\u003c/strong\u003e The number of MP positive children in each age group for the years 2018-2019, 2020-2022, and 2023. \u003cstrong\u003ec\u003c/strong\u003e The proportion of MP positive children in each age group for the years 2018-2019, 2020-2022, and 2023.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4617945/v1/e5516486a45316397f2326b5.png"},{"id":60812372,"identity":"3408de47-bef8-4df6-864d-ebcc3b335133","added_by":"auto","created_at":"2024-07-22 11:05:14","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":38225,"visible":true,"origin":"","legend":"\u003cp\u003eThe Specific Distribution of MP Positive Patients by Age from 1 to 12 Months\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4617945/v1/c1b5d9111287d0d50dd8c7f2.png"},{"id":60812373,"identity":"6d060fdf-4182-46de-abf4-45fc68100898","added_by":"auto","created_at":"2024-07-22 11:05:14","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":87584,"visible":true,"origin":"","legend":"\u003cp\u003eThe composition of coinfection viruses and bacteria among MP positive patients from 2018 to 2023.The overall viral composition of 5,085 MP positive patients who had all the eight viral pathogens tested, with further subtyping for IFV. The overall bacterial composition of 2,041 MP positive patients who had all the thirteen bacterial pathogens tested (including three atypical pathogens). Furthermore, we stratified the patients into age groups, displaying the coinfection pathogen composition for each age group. The length of bars and the number behind indicate the proportion of each pathogen.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4617945/v1/5b4ee44905391a0a143ae1a5.png"},{"id":60811621,"identity":"c80792d7-d7ec-4f63-8a35-7d3d5965b439","added_by":"auto","created_at":"2024-07-22 10:57:14","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":148130,"visible":true,"origin":"","legend":"\u003cp\u003eCoinfection Patterns and Pathogen Interactions among Patients Infected with MP in the Wuhan Region from 2018 to 2023. \u003cstrong\u003ea\u003c/strong\u003e Coinfection patterns among MP infected patients. The x-axis represents log2(patient+ 1); larger blue circles indicate higher case counts, while smaller red circles indicate lower case counts, with darker shades denoting more cases. \u003cstrong\u003eb\u003c/strong\u003e Interactions among coinfection pathogens. Positive interactions with bilateral P-values \u0026lt; 0.05 are depicted in blue, while negative interactions with bilateral P-values \u0026lt; 0.05 are depicted in red. Larger circles represent higher numbers of coinfection cases, while darker shades indicate stronger interactions between the pathogens.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-4617945/v1/c2c858cffe06e7cfb6672f4f.png"},{"id":75351422,"identity":"6320e4ed-37e2-43d8-a95a-0125ec96e735","added_by":"auto","created_at":"2025-02-03 16:11:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1162909,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4617945/v1/a3ce9867-8515-4b69-9653-16081deb26db.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Epidemiological Characteristics of Mycoplasma Pneumoniae Infection and Coinfection among Children in Central China from 2018 to 2023","fulltext":[{"header":"1. Background","content":"\u003cp\u003eMycoplasma pneumoniae, also known as M. pneumoniae or MP, is a member of the Mollicutes class and is recognized as the smallest self-sufficient pathogenic microorganism capable of independent survival. It is primarily transmitted through respiratory droplets and is commonly found in densely populated areas, including households, schools, and military bases, with an incubation period ranging from 1 to 3 weeks [1-3].\u0026nbsp;MP remains active throughout the year and can impact individuals across all age groups, with school-aged children and adolescents being particularly vulnerable. Moreover, it demonstrates a cyclical epidemic pattern, marked by significant outbreaks recurring every 3-7 years and enduring for approximately 1-2 years each time. Certain studies propose that this cyclic trend might stem from subtype alterations or temporary acquisition of herd immunity [4, 5]. Its prolonged latency period and persistence in the respiratory tract after infection may contribute to the prolonged duration of MP outbreaks [1].\u003c/p\u003e\n\u003cp\u003eMP is one of the most frequent pathogens responsible for upper and lower respiratory tract infections. Research suggests that MP is accountable for 20%-40% of community acquired pneumonia cases, with this percentage increasing during outbreaks, making it a common cause of childhood mortality [1, 5-7]. Research on community-acquired pneumonia in Asian countries found that the rate of positivity for MP was around 11% [8].Monitoring of MP infections in 11 European countries from 2011 to 2016 reported an overall positive rate of 16%, with Norway contributing the highest rate at 26% [9]. A prospective study conducted in 12 centers across seven cities in China found MP to be a dominant pathogen, with a positive rate as high as 20.7% [10].A study in Wuhan from 2020 to 2022 found that 36.6% of children with community acquired pneumonia were confirmed to be MP positive [11].Most studies suggest that illnesses caused by MP infections are self-limiting and often present with mild clinical symptoms such as fever, cough, sore throat, and headache. Rhinitis and wheezing are common in children under 5 years old, with atypical findings on chest imaging [7, 12].Apart from causing common conditions like tracheobronchitis and atypical pneumonia, a nationwide cohort study in Taiwan provided a detailed description of the relationship between MP and asthma, suggesting that toxins produced by MP infection may be causative factors or exacerbate asthma [13].Additionally, MP can manifest extrapulmonary symptoms, including involvement of the central nervous system, skin manifestations, hemolytic anemia, cardiovascular complications, renal dysfunction, gastrointestinal discomfort, and musculoskeletal issues, sometimes leading to fatal consequences. These extrapulmonary manifestations are often associated with the direct impact of MP infection or immune-mediated inflammatory responses [14, 15].\u003c/p\u003e\n\u003cp\u003eCoinfection of MP with other respiratory pathogens is also quite common, especially in children, and may lead to more severe clinical symptoms. A study on coinfection with Streptococcus pneumoniae in Mycoplasma pneumoniae pneumonia found that patients with combined infections had longer duration of fever and were more likely to develop lobar consolidation and parapneumonic effusion [16].However, the correlation between them still requires further investigation. Other studies suggest that coinfection of MP with respiratory viruses may be associated with refractory Mycoplasma pneumoniae pneumonia, characterized by severe pneumonia and poor response to treatment [17].Therefore, coinfection with other pathogens may significantly influence clinical outcomes. Despite numerous epidemiological studies on MP in the region, data on recent trends in MP outbreaks and associated coinfections analysis are lacking. Thus, this study aims to report on the changing trends, epidemiological characteristics, and coinfection analysis of MP infections from 2018 to 2023, providing evidence for clinical diagnosis and treatment and the development of corresponding prevention and control strategies.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cp\u003e\u003cstrong\u003e2.1 Sample Source\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical data for this study were sourced from the Laboratory Information Systems of Renmin Hospital of Wuhan University. A total of 163,058 specimens were collected from children aged 0-14 with ARTI treated at Renmin Hospital of Wuhan University from January 1, 2018, to December 31, 2023. The enrolled children were grouped based on season (spring: March to May, summer: June to August, autumn: September to November, winter: December to February of the following year), age (infants: 0≤Age≤3 years old, preschool age: 3\u0026lt;Age≤7 years old, school age: 7\u0026lt;Age≤14 years old), and gender.\u003c/p\u003e\n\u003cp\u003eInclusion Criteria:(1) Children exhibiting any of the following clinical symptoms of ARTI : new onset fever,cough,sore throat,dyspnea,and abnormal breath sounds.(2) Patients aged ≤14 years old.\u0026nbsp;Exclusion Criteria:(1) Individuals not meeting the clinical presentation criteria for ARTI as described above. (2) Patients \u0026gt;14 years old. (3) Cases with incomplete information.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Laboratory Diagnosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll enrolled children had specimens collected promptly (either at the time of outpatient visit or within 3 days of hospitalization for inpatients). The specimen types included whole blood, serum, nasal swabs, nasopharyngeal swabs, sputum, and bronchoalveolar lavage fluid. Whole blood specimens were used for MP specific IgM antibody titer determination, while the remaining specimens were used for MP nucleic acid detection. In addition to MP, eight common viruses and other atypical pathogens (Chlamydia pneumoniae, Legionella pneumophila, and Coxiella burnetii) were tested. Specific IgM antibody detection was performed using the following kits: IIFT: Respiratory Tract Profile (EUROIMMUN Medizinische Labordiagnostika AG, Seekamp, Lubeck, Germany) and Mycoplasma pneumoniae IgM Antibody Test Kit (Colloidal Gold Method) (Beijing Beier Bioengineering Co., Daxing, Beijing, China). Nucleic acid detection was conducted using a 13-Respiratory Pathogen Multiplex Detection kit (HEALTH BioMed Co., Ltd., Ningbo, Zhejiang, China). Additionally, specimens obtained from the lower respiratory tract underwent bacterial testing for 10 respiratory bacteria, using the Respiratory Pathogen Nucleic Acid Detection Test Kit (CapitalBio Technology (Chengdu) Co., Ltd., Wenjiang, Chengdu, China). To ensure the reliability of the results, all tests underwent laboratory internal quality control, and were within the control range.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Definition of Acute MP infection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn MP infection is defined by the presence of symptoms typical of ARTI, such as fever, cough, sore throat, and abnormal breath sounds. Additionally, a positive diagnosis requires either PCR testing indicating the presence of MP nucleic acids or serological testing showing the presence of MP specific IgM antibodies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4 Statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using IBM SPSS Statistics, Version 27.0(IBM Corp.,Armonk,NY).Continuous variables are expressed as mean\u0026nbsp;standard deviation\u0026nbsp;（\u0026nbsp;）,while categorical variables are presented as numbers (%).Group comparisons between variables were conducted using the Pearson’s chi-square\u0026nbsp;test.Pearson correlation coefficient was employed to investigate the correlation between MP and various respiratory pathogens.P value \u0026lt;0.05was considered significant.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Study population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom January 1, 2018, to December 31, 2023, a total of 211,600 patients with acute respiratory tract infections (ARTI) were collected from Renmin Hospital of Wuhan University. Among them, 48, 542 cases did not meet the inclusion criteria, leaving a total of 163,058 cases included in the study, with an average age of 4.25\u0026nbsp;2.91 years. This included 93,575 males and 69,483 females. Among the included cases, 121,384 underwent MP specific IgM antibody testing on blood specimens, while 41,674 (including nasal swabs, nasopharyngeal swabs, sputum, and bronchoalveolar lavage fluid) underwent MP nucleic acid testing. A total of 49,936 cases tested positive for MP (45,602 positive for MP-IgM and 4,334 positive for MP-DNA), resulting in an overall positive rate of 30.62%. The specific process is detailed in Fig.1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Seasonal and Annual Trends of MP Infections\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom 2018 to 2023, the annual positive rates of MP among ARTI patients were 45.92%, 32.23%, 22.84%, 16.22%, 16.26%, and 42.93%, respectively. The differences in positive rates between each year were statistically significant (P\u0026lt;0.001). Throughout the entire study period, the highest positive rate was observed in autumn (35.13%), while the lowest was in spring (26.28%). The comparison of MP positive rates among seasons showed statistically significant differences (P\u0026lt;0.001). Between 2018 and 2019, spring and summer were the seasonal peaks, with positive rates of 50.24% and 49.20%, and 35.23% and 35.86%, respectively. In January 2020, the positive rate peaked at 27.39%, followed by a decline in February, reaching its lowest point in March (6.38%), gradually increasing in April, and maintaining a relatively stable level thereafter. In 2021 and 2022, the highest positive rates were observed in summer, with rates of 17.79% and 21.51%, respectively. However, in 2023, the highest number of MP cases sent for testing occurred in autumn and winter, consistent with the MP positive rates. Particularly, in late autumn and early winter, the monthly positive rates were 72.32% and 65.35%, respectively. The differences in seasonal positive rates each year were statistically significant (P\u0026lt;0.001). The specific distribution of monthly, seasonal, and annual MP infections during the study period is illustrated in Fig.2, and the detailed numerical values are provided in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Age-related Characteristics and Temporal Trends of MP Infections\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 163,058 ARTI patients were divided into three age groups, with the positive rate for each age group: infants (21,436 cases, accounting for 25.32%), pre-school children (19,570 cases, accounting for 34.87%), and school-age children (8,930 cases, accounting for 40.09%). Among these, the school-age children group had the highest MP infection rate. The results for each age group are shown in Table 1. Further stratifying by detection time into three periods: 2018-2019, 2020-2022, and 2023, pre-school and school-age children were more common in all three years. The number of MP positive patients and the positive rates for each year group are shown in Fig.3. It's noteworthy that the positive rate increased with the age of the patients. Furthermore, we observed a linear relationship between the MP infection rates among patients aged 1 to 12 months throughout the months of the year, as depicted in Fig.4.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Gender Differences in MP Infection Positive Rates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 49,936 confirmed infection cases, there were 23,726 females with an average positive rate of 34.15%, and 26,210 males with a positive rate of 28.01%. Despite a higher number of males being tested, the positive rate among females was significantly higher than that of males, with a statistically significant difference between the two groups (p \u0026lt; 0.001). Over the six years from 2018 to 2023, the positive rate among females was consistently higher than that of male patients, with rates of 50.71%, 36.68%, 25.66%, 19.17%, 18.46%, and 46.45%, respectively. The gender differences over the six-year period were statistically significant (p \u0026lt; 0.001). For specific numerical values, please refer to Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5 Prevalence and Patterns of Coinfections in MP Patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn cases of MP infection, 7,126 cases were found to have at least one concurrent infection with another pathogen, with an overall positive rate of 14.27%. The yearly positive rates were 18.62%, 18.30%, 8.06%, 5.32%, 13.10%, and 12.98%, respectively, with statistically significant differences between the years (P\u0026lt;0.001). Among the 7,126 coinfected cases, 5,085 were found to have at least one concurrent viral infection (71.36%), while 2,041 were found to have at least one concurrent bacterial infection (28.64%). The study found that younger children were more likely to have coinfections with other pathogens, with infants (48.98%) \u0026gt; pre-school children (37.29%) \u0026gt; school-age children (13.74%), with statistically significant differences between age groups (P\u0026lt;0.001). The rate of coinfection was similar between genders (14.25% for males, 14.29% for females, P=0.914).\u003c/p\u003e\n\u003cp\u003eAmong MP coinfections with viruses, the most commonly detected virus was influenza virus (IFV) (1,933 cases, accounting for 38.01%), followed by respiratory syncytial virus (RSV) (1,545 cases, accounting for 30.38%), human parainfluenza Virus (HPIV) (738 cases, accounting for 14.51%), human rhinovirus (HRV) (424 cases, accounting for 8.34%), human adenovirus (HAdV) (286 cases, accounting for 5.62%), human metapneumovirus (HMPV) (72 cases, accounting for 1.42%), human coronavirus (HCoV) (71 cases, accounting for 1.40%), and human bocavirus (HBoV) (16 cases, accounting for 0.31%). Genetic typing analysis of IFV showed that influenza B virus (FluB) predominated, accounting for 89.91% of all genetically analyzed cases, while influenza A virus (FluA) accounted for 10.09%. Among FluA coinfected patients, 66 cases of coinfection with influenza A subtype H3N2\u0026nbsp;(H3N2) were found, with no cases of coinfection with influenza A subtype H1N1 (H1N1) detected. Further age-specific analysis revealed that the top two viruses in all three age groups were IFV and RSV (42.10% and 34.53% for infants, 34.04% and 27.93% for pre-school children, 33.68% and 21.50% for school-age children, respectively), while the third-ranked virus in school-age children was HRV (16.84%). The pattern of virus coinfection was generally similar between infants and pre-school children (with HCoV \u0026gt; HMPV for preschool children), as shown in Fig.5.\u003c/p\u003e\n\u003cp\u003eAmong MP coinfections with bacteria, the most commonly detected was Chlamydia pneumoniae (C.pneumoniae, CP) (1,286 cases, accounting for 63.01%), followed by Haemophilus influenzae (H.influenzae, Hi) (297 cases, accounting for 14.55%), Streptococcus pneumoniae (S.pneumoniae, Sp) (273 cases, accounting for 13.38%), Staphylococcus aureus (S.aureus, Sa) (81 cases, accounting for 3.97%), Acinetobacter baumannii (A.baumannii, Ab) (25 cases, accounting for 1.22%), Methicillin-Resistant Staphylococcus aureus (MRSA) (23 cases, accounting for 1.13%), Klebsiella pneumoniae (K.pneumoniae, Kp) (14 cases, accounting for 0.69%), Legionella pneumophila (L.pneumophila, Lp) (14 cases, accounting for 0.69%), Pseudomonas aeruginosa (P.aeruginosa, Pa) (12 cases, accounting for 0.59%), Coxiella burnetii (Coxiella burnetii, Cox) (7 cases, accounting for 0.34%), Escherichia coli (E.coli) (6 cases, accounting for 0.29%), Mycobacterium tuberculosis (M.tuberculosis, MTB) (2 cases, accounting for 0.10%), and Stenotrophomonas maltophilia (Stenotrophomonas maltophilia, Sm) (1 case, accounting for 0.05%). Further age-specific analysis showed that among the top three coinfection bacteria in all three age groups were C.pneumoniae, H.influenzae, and S.pneumoniae, albeit with slightly different orderings. In pre-school children, the order was C.pneumoniae \u0026gt; S.pneumoniae \u0026gt; H.influenzae. The ranking of coinfection patterns with other bacteria varied across different age groups, as shown in Fig.5.\u003c/p\u003e\n\u003cp\u003eAmong the MP positive patients, 5,775 cases had single pathogen infections, while 641 cases exhibited coinfections involving at least two pathogens.\u0026nbsp;The most common coinfection patterns with viruses were MP, HPIV and HAdV. The most common coinfection patterns with bacteria were MP, H. influenzae and S. pneumoniae. The most common coinfection patterns with bacterial\u0026nbsp;and\u0026nbsp;viruses were MP, RSV and C. pneumoniae.\u0026nbsp;In addition, there were 64 cases with coinfections involving at least three pathogens. Among them, 7 cases involved MP mixed with 4 other pathogens, and 2 cases involved MP mixed with 5 other pathogens. The specific distribution and mutual relationships of coinfection pathogens can be found in Fig.6.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we provide a detailed description of the trend changes in MP infection among children under 14 years old in Wuhan from 2018 to 2023. We found that MP infection occurred continuously throughout the study period, with a monthly positive rate consistently above 10% (except in March 2020 and December 2022). Particularly notable was a significant outbreak observed from 2018 to 2019, similar to trends seen in other regions of China[18-22].During this outbreak, peaks of infection were mainly concentrated in the spring and summer, consistent with previous studies in the region[23].However, from 2020 to 2022, there was a notable decline in positive rates following the peak in January 2020 (27.39%), with both the total number of MP tests and positive rates significantly decreasing in February, reaching a low point in March (47 cases, 6.38%), representing declines of 82.64% and 78.71% compared to the same periods in 2018 and 2019, respectively.Positive rates gradually rebounded in April and remained stable and relatively low thereafter, with the highest rates occurring in the summer months of 2021-2022 (17.79% and 21.51%, respectively).We attribute this decline partly to reduced patient visits to healthcare facilities (particularly in 2020, when testing numbers were lowest) following the outbreak of the\u0026nbsp;worldwide coronavirus disease (COVID-19), as well as the\u0026nbsp;non-pharmaceutical interventions (NPIs)\u0026nbsp;implemented in Wuhan at the time (including reducing gatherings, mask-wearing, hand hygiene, and disinfection), which likely effectively reduced the transmission of respiratory pathogens, including MP. However, despite the relaxation or cessation of NPI measures, MP infection rates continued to show a long-term decrease, while infections by other pathogens re-emerged during the same period, indicating an increase in community transmission[24, 25].By 2023, Wuhan experienced another localized MP outbreak, becoming a significant public health concern, consistent with multiple research findings[26, 27].We observed that in January 2023, positive rates remained low as in previous years, gradually increasing from February and peaking in the autumn and winter seasons. Particularly during late autumn and early winter, monthly positive rates reached 72.32% and 65.35%, respectively, consistent with findings from some European studies[22, 28, 29].Throughout the period from 2018 to 2023, there were fluctuations in the peak seasons of MP outbreaks in Wuhan, which we attribute to the influence of NPI measures adopted during the COVID-19 pandemic, altering people's behavior patterns and social activities, thereby affecting the transmission pattern of MP, either prolonging the epidemic period or due to changes in MP genotypes. MP typically experiences a major outbreak every 3-7 years, thus the resurgence of the epidemic in Wuhan in 2023 conforms to its cyclical epidemic pattern.\u003c/p\u003e\n\u003cp\u003eMost studies indicate that MP infection is more common in children aged 5 and above. Consistent with this, our study found that MP is more prevalent in pre-school and school-age children, in line with the findings of Meyer et al[30-34].We believe this could be due to the broader social contacts of children in this age group. In China, children typically start attending kindergarten around the age of 3 and begin primary school at 6-7 years old, spending most of their daytime in school,a densely populated places . This further supports the notion that MP infections often occur in places like schools and military bases through close contact and droplet transmission.Additionally, numerous studies suggest that after infecting host cells, MP can stimulate immune cells to produce a large number of cytokines and mediators, leading to clinical illness and lung injury[4, 35].Therefore, as children's immune function matures, their bodies can mount a more effective immune response against this pathogen. Our study results indicate that this trend is particularly pronounced in infants under 1 year old, with MP infection positive rates increasing with age. We speculate that breastfed infants may acquire protective antibodies from breast milk, which could be one reason for the lower infection rates in younger infants. Research has shown that antibodies induced in the mother's body during the perinatal period undergo specific post-translational modifications. When these antibodies are transferred to newborns through blood or breastfeeding, they can help young infants resist a wider range of pathogen infections[36].Overall, there is a general linear trend in the age distribution of MP infections in children.\u003c/p\u003e\n\u003cp\u003eIn our study, the gender difference in MP infection is significant, with a notably higher positive rate among female patients compared to males, consistent with several previous domestic studies[20, 37-39]. We speculate that this difference may be due to genetic and hormonal factors. Sara et al. suggested that females have two X chromosomes, which contain multiple genes regulating immune function, such as interleukin-1 receptor-associated kinase 1 (IRAK1) and interleukin-2 receptor gamma chain. While one X chromosome is usually inactivated to prevent gene overexpression, this inactivation is only partial[40].They proposed that males may be more susceptible to bacterial and viral infections, while females may exhibit stronger immune responses. However, our study primarily detected MP IgM, which could potentially influence the detection results. Estradiol affects cellular immunity in a concentration-dependent manner. Susan and Sabra et al. suggested that low concentrations of estradiol can stimulate TH1-type responses, promoting the production of pro-inflammatory cytokines such as interleukin-1 and interferon-gamma[41, 42].\u003c/p\u003e\n\u003cp\u003eRespiratory tract infections caused by MP are difficult to distinguish from infections caused by other respiratory pathogens in terms of clinical symptoms and radiological findings. In pediatric ARTI, most MP infected patients are often co-detected with other viruses or bacteria, and this co-detection is associated with the severity of the disease[43, 44].In 14.27% of specimens collected from MP positive children, one or more other respiratory pathogens were detected. These pathogens may play a role in the pathogenesis of MP induced respiratory diseases, but their specific roles remain unclear. In our study, the most common viral coinfection was with IFV (mainly FluB), followed by RSV and HPIV. This differs from the findings of Maureen et al., who reported a lower coinfection rate of MP with influenza virus, RSV, and HPIV (\u0026lt;3.0%)[43]. For patients with combined viral infections, there may be no need to adjust their primary antibacterial treatment regimen. The most common bacterial coinfection was with C.pneumoniae, followed by H.influenzae and S.pneumoniae, similar to previous studies[45, 46].C. pneumoniae, like MP, is an atypical pathogen, and there is no significant difference in treatment regimens between the two. However, H. influenzae and S. pneumoniae are common strains, and MP is primarily treated with macrolide antibiotics. For children with combined infections of these two pathogens, additional antibiotics such as cephalosporins or fluoroquinolones may be needed for combination therapy. We also found that the incidence of coinfections is negatively correlated with age, with infants and young children being more commonly affected. This is consistent with the findings of Maureen et al[17, 43]. The interactions between MP and co-detected microorganisms and their potential impact on the severity of clinical symptoms in affected children require further research for deeper exploration.\u003c/p\u003e\n\u003cp\u003eOur study has several limitations. Firstly, being a retrospective study conducted in a single region and center, the representativeness of our sample may be biased. However, despite this limitation, the analysis of our large dataset over the past six years can still serve as guidance for preventing MP outbreaks in the region. Secondly, the sensitivity of PCR methods is higher than that of MP serological testing, especially for infants and young children, whose immune function may not be fully matured. As a result, some children may have false-negative results due to their serum antibody titers not being elevated. Directly using PCR methods for MP detection seems more reasonable. Unfortunately, due to potential cost-saving reasons, some patients in this study did not have both methods used in combination. This may have affected the positive rate of MP. Furthermore, we did not conduct genotyping or drug resistance analysis of MP, and thus could not determine whether the prevalent genotypes of MP had changed compared to previous outbreaks. Future studies could analyze data from more regions and incorporate clinical research to further explore the mechanisms and influencing factors of MP infections.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, our study revealed the epidemiological trends, clinical characteristics, and coinfection relationships of MP among children in Wuhan. Two MP outbreaks occurred in Wuhan from 2018 to 2023, specifically in 2018-2019 and 2023. The NPI measures implemented during the COVID-19 pandemic also contributed to the delayed appearance of MP infections in Wuhan. However, MP re-emerged in 2023, becoming a significant contributor to the autumn and winter epidemics in the city. The high rate of coinfection between MP and other pathogens may lead to more severe clinical symptoms or the development of severe pneumonia, thereby increasing the burden on healthcare systems. These findings hold significant implications for informing clinical diagnosis and treatment, as well as shaping prevention and control strategies. Moreover, they offer valuable insights for future research endeavors related to this topic.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMP: Mycoplasma pneumoniae,\u0026nbsp;M. pneumoniae\u003c/p\u003e\n\u003cp\u003eARTI: Acute Respiratory Tract Infection\u003c/p\u003e\n\u003cp\u003eIFV: Influenza virus\u003c/p\u003e\n\u003cp\u003eFlu B: Influenza B virus\u003c/p\u003e\n\u003cp\u003eFlu A: Influenza A virus\u003c/p\u003e\n\u003cp\u003eH3N2: Influenza A subtype H3N2\u003c/p\u003e\n\u003cp\u003eH1N1: Influenza A subtype H1N1\u003c/p\u003e\n\u003cp\u003eRSV: Respiratory syncytial virus\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHPIV: Human parainfluenza\u003c/p\u003e\n\u003cp\u003eHRV: Human rhinovirus\u003c/p\u003e\n\u003cp\u003eHAdV: Human adenovirus\u003c/p\u003e\n\u003cp\u003eHMPV: Human metapneumovirus\u003c/p\u003e\n\u003cp\u003eHCoV: Human coronavirus\u003c/p\u003e\n\u003cp\u003eHBoV: Human bocavirus\u003c/p\u003e\n\u003cp\u003eCP: Chlamydia pneumoniae, C.pneumoniae\u003c/p\u003e\n\u003cp\u003eHi: Haemophilus influenzae, H.influenzae\u003c/p\u003e\n\u003cp\u003eSp: Streptococcus pneumoniae, S.pneumoniae\u003c/p\u003e\n\u003cp\u003eSa: Staphylococcus aureus, S.aureus\u003c/p\u003e\n\u003cp\u003eAb: Acinetobacter baumannii, A.baumannnii\u003c/p\u003e\n\u003cp\u003eKp: Klebsiella pneumoniae, K.pneumoniae \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLp: Legionella pneumophila, L.pneumophila\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePa: Pseudomonas aeruginosa, P.aeruginosa\u003c/p\u003e\n\u003cp\u003eCox: Coxiella burnetii\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eE.coil: Escherichia coli\u003c/p\u003e\n\u003cp\u003eMTB: Mycobacterium tuberculosis, M.tuberculosis\u003c/p\u003e\n\u003cp\u003eSm: Stenotrophomonas maltophilia\u003c/p\u003e\n\u003cp\u003eMRSA: Methicillin-Resistant Staphylococcus aureus\u003c/p\u003e\n\u003cp\u003eCOVID-19: Coronavirus disease\u003c/p\u003e\n\u003cp\u003eNPI: Non-pharmaceutical interventions\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe procedures followed in this study were in accordance with principles of the Declaration of Helsinki (1964,amended most recently in 2008) of the World Medical Association.The protocol was approved by the Ethics Commission of Renmin Hospital of Wuhan University, and the requirement for patient informed consent was waived by the Ethics Commission of Renmin Hospital of Wuhan University due to the observational nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDemographic and clinical data of patients which involved in this study were extracted from the Laboratory Information Systems of Renmin Hospital of Wuhan University. The datasets\u0026nbsp;generated or analyzed during this study are not publicly available due to privacy or ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there was no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by The National Natural Science Foundation of China(82370008).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJieYu Mao and ZhiLi Niu designed the study, conducted data organization and analysis, and drafted the initial manuscript. MengLing Liu and LiangYu Li participated in data organization and verification.HaiYue Zhang and RuiYun Li contributed to the study design and data interpretation. Pingan Zhang and XiaoJun Wu contributed to the study design, data interpretation, manuscript revisions, and final draft editing. All authors read and approved the final report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted at the Renmin Hospital of Wuhan University. We sincerely thank all the staff and participants for their important contributions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University Wuhan, Hubei, China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eDepartment of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a retrospective analysis using clinical data for statistical purposes. It does not involve patient privacy or human trials and is therefore exempt from the requirement for a clinical trial registration number.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAtkinson TP, Balish MF, Waites KB: Epidemiology, clinical manifestations, pathogenesis and laboratory detection of Mycoplasma pneumoniae infections. \u003cem\u003eFEMS microbiology reviews\u0026nbsp;\u003c/em\u003e2008, 32(6):956-973.\u003c/li\u003e\n \u003cli\u003eJacobs E, Ehrhardt I, Dumke R: New insights in the outbreak pattern of Mycoplasma pneumoniae. \u003cem\u003eInternational journal of medical microbiology : IJMM\u0026nbsp;\u003c/em\u003e2015, 305(7):705-708.\u003c/li\u003e\n \u003cli\u003eMeyer Sauteur PM, Unger WWJ, van Rossum AMC, Berger C: The Art and Science of Diagnosing Mycoplasma pneumoniae Infection. \u003cem\u003eThe Pediatric infectious disease journal\u0026nbsp;\u003c/em\u003e2018, 37(11):1192-1195.\u003c/li\u003e\n \u003cli\u003eWaites KB, 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Is it the next pandemic? \u003cem\u003eAnaesthesia, critical care \u0026amp; pain medicine\u0026nbsp;\u003c/em\u003e2024, 43(1):101338.\u003c/li\u003e\n \u003cli\u003eMeyer Sauteur PM, Beeton ML: Mycoplasma pneumoniae: delayed re-emergence after COVID-19 pandemic restrictions. \u003cem\u003eThe Lancet Microbe\u0026nbsp;\u003c/em\u003e2024, 5(2):e100-e101.\u003c/li\u003e\n \u003cli\u003eWreghitt T: Mycoplasma pneumoniae: current outbreak. \u003cem\u003eEpidemiology and infection\u0026nbsp;\u003c/em\u003e2024, 152:e47.\u003c/li\u003e\n \u003cli\u003eYan C, Xue GH, Zhao HQ, Feng YL, Cui JH, Yuan J: Current status of Mycoplasma pneumoniae infection in China. \u003cem\u003eWorld journal of pediatrics : WJP\u0026nbsp;\u003c/em\u003e2024, 20(1):1-4.\u003c/li\u003e\n \u003cli\u003eChen K, Jia R, Li L, Yang C, Shi Y: The aetiology of community associated pneumonia in children in Nanjing, China and aetiological patterns associated with age and season. \u003cem\u003eBMC public health\u0026nbsp;\u003c/em\u003e2015, 15:113.\u003c/li\u003e\n \u003cli\u003eKawakami N, Namkoong H, Saito F, Ishizaki M, Yamazaki M, Mitamura K: Epidemiology of macrolide-resistant Mycoplasma pneumoniae by age distribution in Japan. \u003cem\u003eJournal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy\u0026nbsp;\u003c/em\u003e2021, 27(1):45-48.\u003c/li\u003e\n \u003cli\u003eZhang L, Lai M, Ai T, Liao H, Huang Y, Zhang Y\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: Analysis of mycoplasma pneumoniae infection among children with respiratory tract infections in hospital in Chengdu from 2014 to 2020. \u003cem\u003eTranslational pediatrics\u0026nbsp;\u003c/em\u003e2021, 10(4):990-997.\u003c/li\u003e\n \u003cli\u003eCheng Y, Cheng Y, Dai S, Hou D, Ge M, Zhang Y\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: The Prevalence of Mycoplasma Pneumoniae Among Children in Beijing Before and During the COVID-19 Pandemic. \u003cem\u003eFrontiers in cellular and infection microbiology\u0026nbsp;\u003c/em\u003e2022, 12:854505.\u003c/li\u003e\n \u003cli\u003eMa J, Guo P, Mei S, Li M, Yu Z, Zhang Y\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: Influence of COVID-19 pandemic on the epidemiology of Mycoplasma pneumoniae infections among hospitalized children in Henan, China. \u003cem\u003eHeliyon\u0026nbsp;\u003c/em\u003e2023, 9(11):e22213.\u003c/li\u003e\n \u003cli\u003eYang J, Hooper WC, Phillips DJ, Talkington DF: Cytokines in Mycoplasma pneumoniae infections. \u003cem\u003eCytokine \u0026amp; growth factor reviews\u0026nbsp;\u003c/em\u003e2004, 15(2-3):157-168.\u003c/li\u003e\n \u003cli\u003eErickson JJ, Archer-Hartmann S, Yarawsky AE, Miller JLC, Seveau S, Shao TY\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: Pregnancy enables antibody protection against intracellular infection. \u003cem\u003eNature\u0026nbsp;\u003c/em\u003e2022, 606(7915):769-775.\u003c/li\u003e\n \u003cli\u003eLv YT, Sun XJ, Chen Y, Ruan T, Xu GP, Huang JA: Epidemic characteristics of Mycoplasma pneumoniae infection: a retrospective analysis of a single center in Suzhou from 2014 to 2020. \u003cem\u003eAnnals of translational medicine\u0026nbsp;\u003c/em\u003e2022, 10(20):1123.\u003c/li\u003e\n \u003cli\u003eHuang BX, Cai DF, Zhang JS, Lei M, Chen YS: Epidemiological characteristics of a single center for \u003cem\u003emycoplasma pneumoniae\u0026nbsp;\u003c/em\u003einfection in a Children\u0026apos;s Hospital in Shenzhen from 2011 to 2018 %J MolDiagnTher. 2023, 15(04):686-689.\u003c/li\u003e\n \u003cli\u003eLiaon SQ, Tan H, Zhang XM, Wan K, Lu XF, Zhu HC\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: Multicenter epidemiological characteristics of \u003cem\u003eMycoplasma pneumoniae\u0026nbsp;\u003c/em\u003einfection in children in Hainan Province, 2012- 2020 %J China Tropical Medicine. 2023, 23(05):511-515+533.\u003c/li\u003e\n \u003cli\u003eDias SP, Brouwer MC, van de Beek D: Sex and Gender Differences in Bacterial Infections. \u003cem\u003eInfection and immunity\u0026nbsp;\u003c/em\u003e2022, 90(10):e0028322.\u003c/li\u003e\n \u003cli\u003eKovats S: Estrogen receptors regulate innate immune cells and signaling pathways. \u003cem\u003eCellular immunology\u0026nbsp;\u003c/em\u003e2015, 294(2):63-69.\u003c/li\u003e\n \u003cli\u003eKlein SL, Flanagan KL: Sex differences in immune responses. \u003cem\u003eNature reviews Immunology\u0026nbsp;\u003c/em\u003e2016, 16(10):626-638.\u003c/li\u003e\n \u003cli\u003eDiaz MH, Cross KE, Benitez AJ, Hicks LA, Kutty P, Bramley AM\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: Identification of Bacterial and Viral Codetections With Mycoplasma pneumoniae Using the TaqMan Array Card in Patients Hospitalized With Community-Acquired Pneumonia. \u003cem\u003eOpen forum infectious diseases\u0026nbsp;\u003c/em\u003e2016, 3(2):ofw071.\u003c/li\u003e\n \u003cli\u003eJiang W, Wu M, Zhou J, Wang Y, Hao C, Ji W\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: Etiologic spectrum and occurrence of coinfections in children hospitalized with community-acquired pneumonia. \u003cem\u003eBMC infectious diseases\u0026nbsp;\u003c/em\u003e2017, 17(1):787.\u003c/li\u003e\n \u003cli\u003eMa L, Wang W, Le Grange JM, Wang X, Du S, Li C\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: Coinfection of SARS-CoV-2 and Other Respiratory Pathogens. \u003cem\u003eInfection and drug resistance\u0026nbsp;\u003c/em\u003e2020, 13:3045-3053.\u003c/li\u003e\n \u003cli\u003eShin S, Koo S, Yang YJ, Lim HJ: Characteristics of the Mycoplasma pneumoniae Epidemic from 2019 to 2020 in Korea: Macrolide Resistance and Co-Infection Trends. \u003cem\u003eAntibiotics (Basel, Switzerland)\u0026nbsp;\u003c/em\u003e2023, 12(11).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Total number of cases and MP positive cases in different groups from 2018 to 2023\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"88.88888888888889%\" colspan=\"11\" valign=\"top\"\u003e\n \u003cp\u003eYear n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.666666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSeason\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSpring\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 668(50.24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 942(35.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e37(15.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 236(17.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 005(12.63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003e2 243(23.44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSummer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 534(49.20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 836(35.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e284(22.42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 259(17.79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 180(21.51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003e3 326(35.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAutumn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 149(39.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 349(27.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 009(22.35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 405(16.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e891(16.47%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003e9 925(55.30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eWinter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 655(45.34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 093(30.08%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e854(24.06%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e822(13.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e574(11.25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003e2 660(48.74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ec\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e160.582\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e177.627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e10.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e64.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e376.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e2878.993\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0\u0026le;Age\u0026le;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e6 181(43.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e5 305(27.51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 074（18.76%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 380(14.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 904(13.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003e4 592(32.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e3\u0026lt;Age\u0026le;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e3 008(51.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e3 792(40.06%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e841（29.33%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 894(18.93%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 015(18.97%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003e8 020(46.19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e7\u0026lt;Age\u0026le;14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e817(45.06%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 123(37.99%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e269(27.65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e448(20.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e731(21.80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\"\u003e\n \u003cp\u003e5 542(50.48%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003ec\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e112.808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e507.613\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e135.360\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e138.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e246.363\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e900.917\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e5 438(42.54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e5 296(28.97%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 168(20.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 325(14.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 417(14.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e9 566(40.19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e4 568(50.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e4 924(36.68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e1 016(25.66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 397(19.17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e2 233(18.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\"\u003e\n \u003cp\u003e8 588(46.45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003ec\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e141.899\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e210.300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e30.521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e140.219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e74.597\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e166.255\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.578947368421053%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.736842105263158%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\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":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Children, Mycoplasma pneumoniae, Acute Respiratory Tract Infection, Epidemiology, Coinfection","lastPublishedDoi":"10.21203/rs.3.rs-4617945/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4617945/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eMycoplasm pneumomiae(M. pneumoniae, MP) is a common cause of reapiratory infections in humans, particularly among children and adolescents. This study investigates the epidemiological characteristics of MP infection among children and its relationship with coinfections to provide guidance for local MP prevention strategies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAfter data screening based on the inclusion and exclusion criteria, a total of 163,058 pediatric patients with Acute Respiratory Tract Infection (ARTI) were enrolled in the study, ranging from January 1, 2018, to December 31, 2023.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFrom 2018 to 2023, a total of 49,936 cases tested positive for MP, resulting in an overall positive rate of 30.62%. During this period, the annual positive rates were as follows: 45.92%, 32.23%, 22.84%, 16.22%, 16.26%, and 42.93%, respectively. The highest positive rate was observed in autumn (35.13%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). School-aged children exhibited the highest positive rate (40.09%), while infants had the lowest (25.32%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Furthermore, the positive rate among girls (34.15%) was higher than that among boys (28.01%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Among patients with MP infection, 14.27% were found to have coinfection with other pathogens, with viral infections accounting for 71.36% and bacterial infections for 28.64%. Notably, infants were more prone to coinfection with multiple pathogens (48.98%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eMP infection is prevalent in children, with notable seasonal and age-dependent variations in positive rates. Coinfection with other pathogens is common, particularly in infants.\u003c/p\u003e","manuscriptTitle":"The Epidemiological Characteristics of Mycoplasma Pneumoniae Infection and Coinfection among Children in Central China from 2018 to 2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-22 10:57:09","doi":"10.21203/rs.3.rs-4617945/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-07T06:36:15+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-01T07:17:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-28T11:35:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-28T11:33:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2024-06-21T14:20:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d3987446-b428-461a-8128-67b2f125c66c","owner":[],"postedDate":"July 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T16:05:32+00:00","versionOfRecord":{"articleIdentity":"rs-4617945","link":"https://doi.org/10.1186/s12887-025-05435-9","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-01-28 15:57:23","publishedOnDateReadable":"January 28th, 2025"},"versionCreatedAt":"2024-07-22 10:57:09","video":"","vorDoi":"10.1186/s12887-025-05435-9","vorDoiUrl":"https://doi.org/10.1186/s12887-025-05435-9","workflowStages":[]},"version":"v1","identity":"rs-4617945","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4617945","identity":"rs-4617945","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}