Clinical significance of cytomegalovirus detection in young children with Mycoplasma pneumoniae-associated community-acquired pneumonia: A retrospective cohort study

Clinical significance of cytomegalovirus detection in young children with Mycoplasma pneumoniae-associated community-acquired pneumonia: A retrospective cohort study | 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 Clinical significance of cytomegalovirus detection in young children with Mycoplasma pneumoniae-associated community-acquired pneumonia: A retrospective cohort study Xiyang Guo, Zhiao Du, Ting Wang, Heting Dong, Jiawei Chen, Peng Mo, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8954666/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Mycoplasma pneumoniae ( M. pneumoniae )-associated community-acquired pneumonia (CAP) is common in children. Cytomegalovirus (CMV) is frequently detected in respiratory samples in this patient population. We aimed to explore the clinical implications of positive CMV DNA in bronchoalveolar lavage fluid (BALF) from immunocompetent children with M. pneumoniae -associated CAP. Methods A retrospective cohort study was conducted for M. pneumoniae -associated CAP children under two years old with CMV DNA test in BALF between January 1, 2022 and September 30, 2025. These children were assigned to the BALF CMV DNA positive group or negative group. Then, the inter-group characteristics were compared. Results Among the 66 children, 28 and 38 children were in the CMV DNA positive and negative groups, respectively. Children in the BALF CMV DNA positive group were more likely to experience duration of fever ≥ 3 days, had higher C-reactive protein and lactate dehydrogenase levels, showed a higher incidence of pulmonary consolidations, and required longer hospital stays. However, these children had a lower incidence of wheezing, when compared to children in the BALF CMV DNA negative group. Furthermore, virus co-infection was common in the BALF CMV DNA negative group, when compared to the BALF CMV DNA positive group (60.5% vs. 35.7%, p = 0.046). All children fully recovered after intravenous azithromycin administration. Conclusions Both BALF CMV DNA positive and negative children with M. pneumoniae -associated CAP can reach full recovery after azithromycin treatment. However, the former group had stronger inflammations and required longer hospital stays, while the latter group were more likely to have virus co-infection. Clinical trial number: Not applicable. Pneumonia Mycoplasma pneumoniae Cytomegalovirus Bronchoalveolar lavage Pediatrics Figures Figure 1 1. Introduction Mycoplasma pneumoniae ( M. pneumoniae ) is the significant cause of pediatric community-acquired pneumonia (CAP), and is responsible for 10–40% of cases( 1 – 3 ). Affected children can present with various clinical presentations, including fever, paroxysmal dry cough, headaches, chest tightness, wheezing, and difficulty in breathing( 4 ). The treatments for severe M. pneumoniae infection include macrolide antibiotics, glucocorticoids, and intravenous immunoglobulin. Flexible fiberoptic bronchoscopy might be performed in children suspected of having mucus plug obstruction, or when routine treatment is ineffective( 5 , 6 ). Cytomegalovirus (CMV) is a prevalent herpes virus. After the initial infection in healthy people, it remains dormant in the body for life, with the lungs acting as a primary reservoir for this latent state( 7 ). Although lung biopsy remains as the gold standard for diagnosing CMV pneumonitis, its invasive nature often limits its application. In clinic, bronchoalveolar lavage fluid (BALF) is frequently employed for detecting CMV in individuals suspected of CMV pneumonitis( 8 , 9 ). CMV reactivation might occur as a consequence of airway inflammation( 10 ). Thus, the detection of CMV in BALF might not always indicate CMV pneumonitis, and suggest CMV replication in immunocompetent hosts( 11 ). A recent study reported that CMV was frequently detected in respiratory samples obtained from hospitalized children( 12 ). However, the clinical implications of the presence of CMV in respiratory secretion obtained from immunocompetent young children with M. pneumoniae -associated CAP remains unclear( 13 ). Therefore, the present retrospective cohort study was conducted, and serum CMV IgG positive immunocompetent young children with M. pneumoniae -associated CAP were categorized into two groups: BALF CMV DNA positive and negative groups. Then, the potential clinical characteristic differences were determined. 2. Materials and Methods 2.1 Study design and participant selection A retrospective cohort study was conducted, and medical records over a 45-month period (from January 1, 2022 to September 30, 2025) at the Children’s Hospital of Soochow University (a tertiary teaching hospital in Suzhou, Jiangsu, China) were reviewed. The present study protocol received approval from the research Ethics Committee of the Children’s Hospital of Soochow University (2025CS062). The informed consent was waived due to the retrospective study design. For the study period, consecutive serum CMV IgG positive immunocompetent children under two years of age, who were diagnosed with M. pneumoniae -associated CAP and underwent a CMV DNA test in BALF, were included. This age cut-off was chosen because old children with mature immune functions can limit viral replication( 14 , 15 ). Children were excluded when they met any of the following conditions: ( 1 ) birthweight < 2,500 g or born prematurely; ( 2 ) age < 28 days old; ( 3 ) severe concomitant disease, such as liver or kidney disease; ( 4 ) congenital or acquired immunodeficiencies; ( 5 ) genetic or neurologic disorders; ( 6 ) congenital heart disease; ( 7 ) bronchopulmonary malformation. 2.2 Data collection The following medical records were reviewed: ( 1 ) demographic data; ( 2 ) clinical data, including the presentation of symptoms before admission, the time of bronchoscopy after hospitalization, fever, and wheezing; ( 3 ) laboratory data, including peripheral blood leukocyte count, neutrophil percentage, platelet count, lactate dehydrogenase, C-reactive protein, alanine aminotransferase, and aspartate aminotransferase, which were obtained within six hours after admission; ( 4 ) BALF cell profile, including neutrophils, alveolar macrophages, lymphocytes percentage and eosinophils, which was recorded as the percentage of the total cell count( 16 ); ( 5 ) radiological findings (chest X-ray or computed tomography [CT]) obtained at 24 hours before or after admission; ( 6 ) M. pneumoniae , Chlamydophila pneumoniae , human metapneumovirus, human rhinovirus (hRV), respiratory syncytial virus, coronaviruses, parainfluenza virus, adenovirus, human bocavirus, and influenza A and B viruses, which were detected from BALF samples using a respiratory pathogen multiple nucleic acid test kit (Health Gene Tech., Ningbo, China)( 17 ); ( 7 ) bacteria detected in the BALF sample culture, in which growth > 10 4 cfu/ml was considered significant( 18 ); ( 8 ) serum IgM and IgG against M. pneumoniae , which were evaluated using a commercial test kit (Shenzhen YHLO Biotech Co., Ltd. Shenzhen, China); ( 9 ) CMV DNA detected from BALF samples using the quantitative detection kit for CMV nucleic acid (Sansure Biotech Co., Ltd. Hunan, China)( 17 ); ( 10 ) serum CMV IgG, which was detected using a CMV antibody test kit (Autobio Diagnostics Co., Ltd. Zhengzhou, China)( 17 ); ( 11 ) hospital course, including medication, admission to the pediatric intensive care unit (PICU), requirement for supplemental oxygen, length of hospital stay, and treatment outcomes( 19 ). 2.3 Definitions CAP was defined as fever or cough with tachypnoea, wheezes or crackles on auscultation, and new infiltrates on chest imaging( 20 ). M. pneumoniae infection was defined as both a positive M. pneumoniae DNA in BALF samples and a positive M. pneumoniae IgM( 21 ). M. pneumoniae -associated CAP was defined as CAP in the presence of M. pneumoniae infection. Co-infection by virus was defined as the occurrence of M. pneumoniae -associated CAP with at least one virus detected from BALF samples. Bacteria co-infection was defined as the occurance of M. pneumoniae -associated CAP, with evidence obtained from the bacterial infection, and detected from BALF samples. 2.4 Statistical analysis Statistical analysis was performed using SPSS 21.0 (IBM, USA). Continuous data were expressed in mean ± standard deviation or median with interquartile range (IQR), and compared using Student t -test or Mann-Whitney U test, depending on the normality examination by the Shapiro-Wilk test. Categorical variables were expressed in frequency and proportion, and compared using Chi-square test or Fisher’s exact test, as appropriate. A p -value of < 0.05 in the two-sided test was considered statistically significant. 3. Results 3.1 Participant selection results A total of 90 children younger than two years old were admitted for M. pneumoniae -associated CAP during the study period. After excluding 24 children with severe concomitant disease or bronchopulmonary malformation, 66 children were included for the analysis. There were 45 boys and 21 girls, and the median age was 14.5 months old. The age distribution is presented in Fig. 1 . Based on the BALF CMV DNA test results, 28 children were assigned to the BALF CMV DNA positive group (median copy number of CMV DNA in BALF: 8,475 copies/ml, IQR: 2,542 − 135,100 copies/mL) and 38 children were assigned to the BALF CMV DNA negative group. 3.2 Clinical characteristics Children in the BALF CMV DNA positive group were more likely to experience duration of fever ≥ 3 days, and had lower incidences of wheezing, when compared to children in the BALF CMV DNA negative group (Table 1 ). There were no statistically significant differences in the other characteristics between the two groups. Table 1 Comparison of clinical characteristics between the BALF CMV DNA positive and negative groups. Characteristics BALF CMV DNA positive ( n = 28) BALF CMV DNA negative ( n = 38) p Demographics Age, months, median (IQR) 14.0 (6.2–18.7) 15.5 (7.0-18.2) 0.840 Male, n (%) 17 (60.7) 28 (73.7) 0.264 Duration of symptoms before admission, day, median (IQR) 7.0 (5.2–18.7) 8.0 (6.0-10.7) 0.830 Length of hospital stay before bronchoscopy, day, median (IQR) 4.0 (3.0–7.0) 4.0 (3.0–7.0) 0.946 Clinical symptoms and signs, n (%) Fever 22 (78.6) 28 (73.7) 0.647 Duration of fever ≥ 3 days 18 (64.3) 14 (36.8) 0.027 Wheezing 12 (42.9) 24 (63.2) 0.038 3.3 Laboratory and radiographic results The laboratory values and chest imaging results are presented in Table 2 . Children in the BALF CMV DNA positive group had higher levels of C-reactive protein and lactate dehydrogenase, and a higher incidence of pulmonary consolidation, when compared to children in the BALF CMV DNA negative group. Table 2 Comparison of laboratory results between the BALF CMV DNA positive and negative groups. Test results BALF CMV DNA positive ( n = 28) BALF CMV DNA negative ( n = 38) p Peripheral blood test, median (IQR) Peripheral leukocyte count, 10 9 /L 8.4 (7.7–11.8) 9.5 (7.1–14.4) 0.345 Neutrophil percentage, % 33.4 (22.7–42.5) 32.9 (24.4–44.6) 0.756 Platelet count, 10 9 /L 333.0 (256.0-381.0) 390.0 (276.0-525.0) 0.052 C-reactive protein, mg/L 5.3 (1.1–9.2) 3.1 (0.7–6.8) 0.047 Lactate dehydrogenase, U/L 382.4 (347.4-425.6) 363.9 (333.0-394.8) 0.013 Alanine aminotransferase, U/L 18.6 (13.9–29.9) 19.0 (16.2–25.9) 0.770 Aspartate aminotransferase, U/L 40.0 (33.8–56.9) 41.2 (36.1–45.8) 0.973 D-dimer, ng/mL 320.0 (259.2-837.5) 380.0 (260.0-630.0) 0.947 Bronchoalveolar lavage fluid cell profile, n (%) Neutrophil 70.0 (30.0–78.0) 55.0 (12.0–83.0) 0.392 Lymphocytes 2.0 (0–4.0) 2.0 (0–4.0) 0.541 Eosinophils 0 (0–0) 0 (0–0) 0.455 Alveolar macrophages 25.0 (20.0–65.0) 15.0 (10.0–50.0) 0.274 Chest imaging findings, n (%) Consolidations 13 (46.4) 5 (13.2) 0.003 Unilateral 5 (38.5) 0 (0) 0.249 Bilateral 8 (61.5) 5 (100.0) - Interstitial changes 4 (14.3) 9 (23.7) 0.343 Pleural effusion 4 (14.3) 1 (2.6) 0.154 3.4 Microbiological diagnosis The positive microbiological results for the 66 children are presented in Table 3 . Co-infection with viruses or bacteria were detected in 37 children, including 13 (19.7%) and 24 (36.4%) children in the BALF CMV DNA positive and negative groups, respectively. Virus co-infection was common in the BALF CMV DNA negative group, when compared to the BALF CMV DNA positive group (60.5% vs. 35.7%, p = 0.046), but there was no significant difference in bacteria co-infection between the two groups (2.6% vs. 10.7%, p > 0.05). Table 3 Etiologic agents for the 66 children with Mycoplasma pneumoniae -associated community-acquired pneumonia. Pathogens Number Bronchoalveolar lavage fluid cytomegalovirus DNA negative group Mycoplasma pneumoniae 14 Mycoplasma pneumoniae + influenza B 1 Mycoplasma pneumoniae + adenovirus 1 Mycoplasma pneumoniae + human metapneumovirus 1 Mycoplasma pneumoniae + respiratory syncytial virus 3 Mycoplasma pneumoniae + coronaviruses 1 Mycoplasma pneumoniae + parainfluenza virus 3 Mycoplasma pneumoniae + human rhinovirus 8 Mycoplasma pneumoniae + human metapneumovirus + respiratory syncytial virus 1 Mycoplasma pneumoniae + respiratory syncytial virus + human rhinovirus 1 Mycoplasma pneumoniae + parainfluenza virus + adenovirus 1 Mycoplasma pneumoniae + parainfluenza virus + human bocavirus 1 Mycoplasma pneumoniae + human rhinovirus + adenovirus 1 Mycoplasma pneumoniae + haemophilus influenzae 1 Bronchoalveolar lavage fluid cytomegalovirus DNA positive group Mycoplasma pneumoniae + cytomegalovirus 15 Mycoplasma pneumoniae + cytomegalovirus + adenovirus 2 Mycoplasma pneumoniae + cytomegalovirus + parainfluenza virus + human rhinovirus + human metapneumovirus 1 Mycoplasma pneumoniae + cytomegalovirus + parainfluenza virus + human rhinovirus + respiratory syncytial virus 1 Mycoplasma pneumoniae + cytomegalovirus + parainfluenza virus 1 Mycoplasma pneumoniae + cytomegalovirus + human bocavirus + human rhinovirus 1 Mycoplasma pneumoniae + cytomegalovirus + human bocavirus 1 Mycoplasma pneumoniae + cytomegalovirus + human rhinovirus 3 Mycoplasma pneumoniae + cytomegalovirus + Streptococcus pneumoniae 3 3.5 Hospital management and outcomes All children received azithromycin administration (intravenous, 10 mg/kg/day) for five consecutive days. None of the children received ganciclovir therapy. All children fully recovered, although children in the BALF CMV DNA positive group spent more time in the hospital, when compared to children in the BALF CMV DNA negative group (Table 4 ). Table 4 Comparison of hospital management between the BALF CMV DNA positive and negative groups. Management BALF CMV DNA positive ( n = 28) BALF CMV DNA negative ( n = 38) p Antimicrobial agents Azithromycin, n (%) 28 (100) 38 (100) > 0.999 Ganciclovir, n (%) 0 (0.0) 0 (0.0) > 0.999 Requirement for supplemental oxygen, n (%) 3 (10.7) 2 (5.3) 0.643 PICU admission, n (%) 1 (3.6) 1 (2.6) > 0.999 Length of hospital stay, day, median (IQR) 10.0 (8.0–13.0) 8.0 (7.0–10.0) 0.021 4. Discussion M. pneumoniae is the common cause for pediatric CAP. CMV is a prevalent herpes virus. The detection of CMV DNA from BALF samples in patients with M. pneumoniae -associated CAP does not necessarily indicate CMV pulmonary disease. There is an unclear clinical significance of detecting CMV DNA in BALF in CAP patients( 13 ), Therefore, the present retrospective cohort study was conducted to compare the clinical characteristics, laboratory results, imaging findings, and treatment outcomes between BALF CMV DNA positive and negative children with M. pneumoniae- associated CAP. The clinical characteristics in children with M. pneumoniae -associated CAP differed between the BALF CMV DNA positive and negative groups. For example, duration of fever ≥ 3 days was common in the BALF CMV DNA positive group, when compared to the BALF CMV DNA negative group. Furthermore, the levels of C-reactive protein and lactate dehydrogenase were higher in the BALF CMV DNA positive group, when compared to the BALF CMV DNA negative group. In addition, consolidations were more frequently reported in the BALF CMV DNA positive group, when compared to the BALF CMV DNA negative group. Longer duration of fever, higher level of C-reactive protein, higher level of lactate dehydrogenase, and consolidations were identified as markers of severe M. pneumoniae pneumonia( 22 ). These results suggest that children with positive BALF CMV DNA had severe clinical presentations, when compared to children with negative BALF CMV DNA. CMV can be a primary pathogen, since CMV induces a direct cytopathic effect by encoding the viral mitochondria-localized inhibitor of apoptosis( 23 ). In addition, CMV exerts its immunosuppressive effects by impairing T-cell proliferation, and interfering with antigen processing( 24 – 26 ). However, it could not be ruled out that the detection of CMV DNA in BALF might be the outcome of a more severe illness. Severe M. pneumoniae infection can induce immunoparalysis, which places children at a high risk for CMV replication in BALF( 27 , 28 ). Patients with severe M. pneumoniae pneumonia were reported to have high levels of TNF-α( 29 ), which can activate NF-κB, with the subsequent translocation into the nucleus to promote CMV replication( 30 ). In the present study, wheezing was more common in the BALF CMV DNA negative group, when compared to the BALF CMV DNA positive group. This might be due to the more common virus co-infection detected in the BALF CMV DNA negative group, when compared to the BALF CMV DNA positive group. The most common detected pathogen was hRV, which is a common pathogen that causes wheezing in young children( 31 , 32 ). The length of hospitalization was longer in the BALF CMV DNA positive group, when compared to the BALF CMV DNA negative group. This was consistent with the more significant inflammation and more frequent pulmonary consolidation observed in the former group, when compared to the latter group. CMV infection can result in the secretion of fibrogenic cytokines and increase in pulmonary fibrosis, as observed in mice experiments( 33 ). This might partly explain the longer length of hospitalization observed in the BALF CMV DNA positive group. The present study has limitations. First, the present study was a retrospective study conducted in a single research institution with a small number of children. Second, the CMV DNA in BALF samples was not dynamically detected, which may provide better insights into the relationship between the CMV DNA in BALF and clinical characteristics. Finally, the benefit of anti-CMV therapy for children with positive CMV DNA in BALF remains unclear, and requires further investigation. 5. Conclusion In conclusion, the clinical characteristics, laboratory test results, and imaging reports differed between BALF CMV DNA positive and negative children with M. pneumoniae -associated CAP. All affected children recovered from the infection. Children with BALF CMV DNA positive results had stronger inflammation, and required longer hospital stays, implying increased medical demand and expenses. Abbreviations M. pneumoniae Mycoplasma pneumoniae CAP community-acquired pneumonia CMV Cytomegalovirus BALF bronchoalveolar lavage fluid CT computed tomography hRV human rhinovirus PICU pediatric intensive care unit IQR interquartile range Declarations Ethical approval and consent to participate This study performed in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of the Children’s Hospital of Soochow University (2025CS062). Because this study presented no more than minimal risk of harm to patient subjects, the Ethics Committee of the Children’s Hospital of Soochow University approved a waiver of patient informed consent. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare no competing interests. Funding This work was supported by the Gusu Health Talent Project (grant number GSWS2023047), the 2025 Suiyuan clinical research project of the Children’s Hospital of Soochow University (grant number 2025SYLCYJ09), the natural science foundation of the Jiangsu higher education institutions of China (grant number 23KJB320017), and the natural science foundation of Jiangsu province (grant number BK20230218). Author contributions XYG was responsible for collecting the data and drafting the manuscript. ZAD was responsible for statistical analysis and drafting the manuscript. TW and ZRC were responsible for literature retrieval. HTD, JWC and PM were responsible for collecting the data. YQW and HMS were responsible for critical reading of a final version of the manuscript. All authors reviewed the manuscript. Acknowledgements The authors thank all participants involved in this research. References Tsai TA, Tsai CK, Kuo KC, Yu HR. Rational stepwise approach for Mycoplasma pneumoniae pneumonia in children. J Microbiol Immunol Infect. 2021;54(4):557-65. Xu W, Guo L, Dong X, Li X, Zhou P, Ni Q, et al. Detection of Viruses and Mycoplasma pneumoniae in Hospitalized Patients with Severe Acute Respiratory Infection in Northern China, 2015-2016. Jpn J Infect Dis. 2018;71(2):134-9. Zhu YG, Tang XD, Lu YT, Zhang J, Qu JM. Contemporary Situation of Community-acquired Pneumonia in China: A Systematic Review. J Transl Int Med. 2018;6(1):26-31. Yan C, Xue GH, Zhao HQ, Feng YL, Cui JH, Yuan J. Current status of Mycoplasma pneumoniae infection in China. World J Pediatr. 2024;20(1):1-4. Wang YS, Zhou YL, Bai GN, Li SX, Xu D, Chen LN, et al. Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children. World J Pediatr. 2024;20(9):901-14. Gao L, Sun Y. Laboratory diagnosis and treatment of Mycoplasma pneumoniae infection in children: a review. Ann Med. 2024;56(1):2386636. Balthesen M, Messerle M, Reddehase MJ. Lungs are a major organ site of cytomegalovirus latency and recurrence. J Virol. 1993;67(9):5360-6. Tan SK, Burgener EB, Waggoner JJ, Gajurel K, Gonzalez S, Chen SF, Pinsky BA. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis. Open Forum Infect Dis. 2016;3(1):ofv212. Bewig B, Haacke TC, Tiroke A, Bastian A, Bottcher H, Hirt SW, et al. Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells. Respiration. 2000;67(2):166-72. Huang L, Zhang X, Pang L, Sheng P, Wang Y, Yang F, et al. Viral reactivation in the lungs of patients with severe pneumonia is associated with increased mortality, a multicenter, retrospective study. J Med Virol. 2023;95(1):e28337. Mansfield S, Dwivedi V, Byrd S, Trgovcich J, Griessl M, Gutknecht M, Cook CH. Broncholaveolar lavage to detect cytomegalovirus infection, latency, and reactivation in immune competent hosts. J Med Virol. 2016;88(8):1408-16. Ding Y, Liu G, Li Q, Zou L, Dai J, Chongsuvivatwong V. Distribution characteristics of human herpes viruses in the lower respiratory tract and their impact on 30-day mortality in community-acquired pneumonia patients. Front Cell Infect Microbiol. 2024;14:1436509. Escribano A, Chilet M, Clari MA, Lucas R, Costa E, Bravo D, et al. Frequent detection of cytomegalovirus (CMV) DNA in the lower respiratory tract in CMV-seropositive pediatric patients with underlying chronic bronchopulmonary diseases lacking canonical immunosuppression. J Med Virol. 2013;85(5):888-92. Gordon CL, Miron M, Thome JJ, Matsuoka N, Weiner J, Rak MA, et al. Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection. J Exp Med. 2017;214(3):651-67. Jackson SE, Sedikides GX, Okecha G, Wills MR. Generation, maintenance and tissue distribution of T cell responses to human cytomegalovirus in lytic and latent infection. Med Microbiol Immunol. 2019;208(3-4):375-89. Sun H, Li S, Yan Y, Chen Z, Wang Y, Hao C, Ji W. Associations between patient clinical characteristics and the presence of cytomegalovirus DNA in the bronchoalveolar lavage fluid of children with recurrent wheezing. BMC Infect Dis. 2018;18(1):458. Wang X, Lu Y, Chen F, Ruan L, Gu L, Wang T, et al. Clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia and cytomegalovirus DNA detected in bronchoalveolar lavage fluid. Front Pediatr. 2024;12:1407174. De Schutter I, De Wachter E, Crokaert F, Verhaegen J, Soetens O, Pierard D, Malfroot A. Microbiology of bronchoalveolar lavage fluid in children with acute nonresponding or recurrent community-acquired pneumonia: identification of nontypeable Haemophilus influenzae as a major pathogen. Clin Infect Dis. 2011;52(12):1437-44. Gilca R, De Serres G, Tremblay M, Vachon ML, Leblanc E, Bergeron MG, et al. Distribution and clinical impact of human respiratory syncytial virus genotypes in hospitalized children over 2 winter seasons. J Infect Dis. 2006;193(1):54-8. Subspecialty Group of Respiratory Diseases TSoPCMA, Editorial Board CJoP. [Guidelines for management of community acquired pneumonia in children (the revised edition of 2013) (I)]. Zhonghua Er Ke Za Zhi. 2013;51(10):745-52. Defilippi A, Silvestri M, Tacchella A, Giacchino R, Melioli G, Di Marco E, et al. Epidemiology and clinical features of Mycoplasma pneumoniae infection in children. Respir Med. 2008;102(12):1762-8. Subspecialty Group of Respiratory tSoPCMA, China National Clinical Research Center of Respiratory D, Editorial Board CJoP. Evidence-based guideline for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children (2023). Pediatr Investig. 2025;9(1):1-11. Poncet D, Pauleau AL, Szabadkai G, Vozza A, Scholz SR, Le Bras M, et al. Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA. J Cell Biol. 2006;174(7):985-96. Filteau S, Rowland-Jones S. Cytomegalovirus Infection May Contribute to the Reduced Immune Function, Growth, Development, and Health of HIV-Exposed, Uninfected African Children. Front Immunol. 2016;7:257. Barry SM, Johnson MA, Janossy G. Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited. Bone Marrow Transplant. 2000;26(6):591-7. Wikby A, Johansson B, Olsson J, Lofgren S, Nilsson BO, Ferguson F. Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Exp Gerontol. 2002;37(2-3):445-53. Schildermans J, De Vlieger G. Cytomegalovirus: A Troll in the ICU? Overview of the Literature and Perspectives for the Future. Front Med (Lausanne). 2020;7:188. Giamarellos-Bourboulis EJ, Siampanos A, Bolanou A, Doulou S, Kakavoulis N, Tsiakos K, et al. Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2024;12(4):294-304. Deng F, Cao H, Liang X, Li Q, Yang Y, Zhao Z, et al. Analysis of cytokine levels, cytological findings, and MP-DNA level in bronchoalveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia. Immun Inflamm Dis. 2023;11(5):e849. Docke WD, Prosch S, Fietze E, Kimel V, Zuckermann H, Klug C, et al. Cytomegalovirus reactivation and tumour necrosis factor. Lancet. 1994;343(8892):268-9. Rossi GA, Colin AA. Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing. Eur Respir J. 2015;45(3):774-89. Jartti T, Korppi M. Rhinovirus-induced bronchiolitis and asthma development. Pediatr Allergy Immunol. 2011;22(4):350-5. Cook CH, Zhang Y, Sedmak DD, Martin LC, Jewell S, Ferguson RM. Pulmonary cytomegalovirus reactivation causes pathology in immunocompetent mice. Crit Care Med. 2006;34(3):842-9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 17 Mar, 2026 Reviews received at journal 16 Mar, 2026 Reviewers agreed at journal 01 Mar, 2026 Reviews received at journal 27 Feb, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers invited by journal 26 Feb, 2026 Editor invited by journal 26 Feb, 2026 Editor assigned by journal 26 Feb, 2026 Submission checks completed at journal 26 Feb, 2026 First submitted to journal 24 Feb, 2026 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. 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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-8954666","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":600241312,"identity":"ba430b7b-28ec-4a17-9251-a9824d9f589f","order_by":0,"name":"Xiyang Guo","email":"","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xiyang","middleName":"","lastName":"Guo","suffix":""},{"id":600241314,"identity":"5aa01b40-eeec-420d-b1f6-127c6f90d2f8","order_by":1,"name":"Zhiao Du","email":"","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":false,"prefix":"","firstName":"Zhiao","middleName":"","lastName":"Du","suffix":""},{"id":600241320,"identity":"7237cb2a-5060-48d9-8f68-2ff0e57e633a","order_by":2,"name":"Ting Wang","email":"","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":false,"prefix":"","firstName":"Ting","middleName":"","lastName":"Wang","suffix":""},{"id":600241322,"identity":"bd0fe70f-e724-422d-bec9-9fe0e1d95154","order_by":3,"name":"Heting Dong","email":"","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":false,"prefix":"","firstName":"Heting","middleName":"","lastName":"Dong","suffix":""},{"id":600241325,"identity":"81a9f413-bafd-4ef2-9376-c14fbdc557eb","order_by":4,"name":"Jiawei Chen","email":"","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":false,"prefix":"","firstName":"Jiawei","middleName":"","lastName":"Chen","suffix":""},{"id":600241332,"identity":"7b8cc8d3-e14b-4dfa-90c0-41892ea71735","order_by":5,"name":"Peng Mo","email":"","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Mo","suffix":""},{"id":600241341,"identity":"c20e1043-7ed6-4afb-ad37-c7dab8a0acf6","order_by":6,"name":"Zhengrong Chen","email":"","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":false,"prefix":"","firstName":"Zhengrong","middleName":"","lastName":"Chen","suffix":""},{"id":600241346,"identity":"4e8373a4-4c50-4fa5-901d-3a47e04ba9b9","order_by":7,"name":"Yuqing Wang","email":"","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yuqing","middleName":"","lastName":"Wang","suffix":""},{"id":600241347,"identity":"71d6eb12-636a-4341-8f48-1241ee2ad3cf","order_by":8,"name":"Huiming Sun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYDACCSBOqLCp52dmPviAeC0PzqQlSLazJRsQrYXxYdvhBIPzPGYCROmQn92dwJDYlpZnfJjBjIGhxiaaoBaDO2c3MCScsyk2O8yQ9oDhWFpuA0EtErlALWVpjNsOMxw3YGw4TFiL/AyQFrbDjJubGdskiNLCcAOkpe1w4gZmZjbitBiAtZxJM5Y4zMZskECMX0AOY/xRYSPH33/+44MPNTZEOIyBgf0HnJlAhPJRMApGwSgYBUQAABz5QQncGk41AAAAAElFTkSuQmCC","orcid":"","institution":"Children's Hospital of Suzhou University","correspondingAuthor":true,"prefix":"","firstName":"Huiming","middleName":"","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2026-02-24 08:25:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8954666/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8954666/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104173208,"identity":"274ae309-c159-43ce-80c5-52729552cf87","added_by":"auto","created_at":"2026-03-08 15:28:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25634,"visible":true,"origin":"","legend":"\u003cp\u003eAge distribution of the enrolled children, which were grouped by BALF cytomegalovirus DNA results.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8954666/v1/2bc9c2ed40a32a5d2f529374.png"},{"id":104173212,"identity":"28981c89-5bfb-4e7f-842a-460b1d8b3f92","added_by":"auto","created_at":"2026-03-08 15:28:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":889102,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8954666/v1/1d13caad-f0a7-4b93-abfe-453fa4bdf527.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical significance of cytomegalovirus detection in young children with Mycoplasma pneumoniae-associated community-acquired pneumonia: A retrospective cohort study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e (\u003cem\u003eM. pneumoniae\u003c/em\u003e) is the significant cause of pediatric community-acquired pneumonia (CAP), and is responsible for 10\u0026ndash;40% of cases(\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Affected children can present with various clinical presentations, including fever, paroxysmal dry cough, headaches, chest tightness, wheezing, and difficulty in breathing(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The treatments for severe \u003cem\u003eM. pneumoniae\u003c/em\u003e infection include macrolide antibiotics, glucocorticoids, and intravenous immunoglobulin. Flexible fiberoptic bronchoscopy might be performed in children suspected of having mucus plug obstruction, or when routine treatment is ineffective(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCytomegalovirus (CMV) is a prevalent herpes virus. After the initial infection in healthy people, it remains dormant in the body for life, with the lungs acting as a primary reservoir for this latent state(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Although lung biopsy remains as the gold standard for diagnosing CMV pneumonitis, its invasive nature often limits its application. In clinic, bronchoalveolar lavage fluid (BALF) is frequently employed for detecting CMV in individuals suspected of CMV pneumonitis(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). CMV reactivation might occur as a consequence of airway inflammation(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Thus, the detection of CMV in BALF might not always indicate CMV pneumonitis, and suggest CMV replication in immunocompetent hosts(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). A recent study reported that CMV was frequently detected in respiratory samples obtained from hospitalized children(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). However, the clinical implications of the presence of CMV in respiratory secretion obtained from immunocompetent young children with \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP remains unclear(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTherefore, the present retrospective cohort study was conducted, and serum CMV IgG positive immunocompetent young children with \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP were categorized into two groups: BALF CMV DNA positive and negative groups. Then, the potential clinical characteristic differences were determined.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study design and participant selection\u003c/h2\u003e \u003cp\u003e A retrospective cohort study was conducted, and medical records over a 45-month period (from January 1, 2022 to September 30, 2025) at the Children\u0026rsquo;s Hospital of Soochow University (a tertiary teaching hospital in Suzhou, Jiangsu, China) were reviewed. The present study protocol received approval from the research Ethics Committee of the Children\u0026rsquo;s Hospital of Soochow University (2025CS062). The informed consent was waived due to the retrospective study design.\u003c/p\u003e \u003cp\u003eFor the study period, consecutive serum CMV IgG positive immunocompetent children under two years of age, who were diagnosed with \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP and underwent a CMV DNA test in BALF, were included. This age cut-off was chosen because old children with mature immune functions can limit viral replication(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eChildren were excluded when they met any of the following conditions: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) birthweight\u0026thinsp;\u0026lt;\u0026thinsp;2,500 g or born prematurely; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) age\u0026thinsp;\u0026lt;\u0026thinsp;28 days old; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) severe concomitant disease, such as liver or kidney disease; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) congenital or acquired immunodeficiencies; (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) genetic or neurologic disorders; (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) congenital heart disease; (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) bronchopulmonary malformation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data collection\u003c/h2\u003e \u003cp\u003eThe following medical records were reviewed: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) demographic data; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) clinical data, including the presentation of symptoms before admission, the time of bronchoscopy after hospitalization, fever, and wheezing; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) laboratory data, including peripheral blood leukocyte count, neutrophil percentage, platelet count, lactate dehydrogenase, C-reactive protein, alanine aminotransferase, and aspartate aminotransferase, which were obtained within six hours after admission; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) BALF cell profile, including neutrophils, alveolar macrophages, lymphocytes percentage and eosinophils, which was recorded as the percentage of the total cell count(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e); (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) radiological findings (chest X-ray or computed tomography [CT]) obtained at 24 hours before or after admission; (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) \u003cem\u003eM. pneumoniae\u003c/em\u003e, \u003cem\u003eChlamydophila pneumoniae\u003c/em\u003e, human metapneumovirus, human rhinovirus (hRV), respiratory syncytial virus, coronaviruses, parainfluenza virus, adenovirus, human bocavirus, and influenza A and B viruses, which were detected from BALF samples using a respiratory pathogen multiple nucleic acid test kit (Health Gene Tech., Ningbo, China)(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e); (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) bacteria detected in the BALF sample culture, in which growth\u0026thinsp;\u0026gt;\u0026thinsp;10\u003csup\u003e4\u003c/sup\u003e cfu/ml was considered significant(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e); (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) serum IgM and IgG against \u003cem\u003eM. pneumoniae\u003c/em\u003e, which were evaluated using a commercial test kit (Shenzhen YHLO Biotech Co., Ltd. Shenzhen, China); (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) CMV DNA detected from BALF samples using the quantitative detection kit for CMV nucleic acid (Sansure Biotech Co., Ltd. Hunan, China)(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e); (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) serum CMV IgG, which was detected using a CMV antibody test kit (Autobio Diagnostics Co., Ltd. Zhengzhou, China)(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e); (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) hospital course, including medication, admission to the pediatric intensive care unit (PICU), requirement for supplemental oxygen, length of hospital stay, and treatment outcomes(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Definitions\u003c/h2\u003e \u003cp\u003eCAP was defined as fever or cough with tachypnoea, wheezes or crackles on auscultation, and new infiltrates on chest imaging(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). \u003cem\u003eM. pneumoniae\u003c/em\u003e infection was defined as both a positive \u003cem\u003eM. pneumoniae\u003c/em\u003e DNA in BALF samples and a positive \u003cem\u003eM. pneumoniae\u003c/em\u003e IgM(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP was defined as CAP in the presence of \u003cem\u003eM. pneumoniae\u003c/em\u003e infection. Co-infection by virus was defined as the occurrence of \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP with at least one virus detected from BALF samples. Bacteria co-infection was defined as the occurance of \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP, with evidence obtained from the bacterial infection, and detected from BALF samples.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS 21.0 (IBM, USA). Continuous data were expressed in mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median with interquartile range (IQR), and compared using Student \u003cem\u003et\u003c/em\u003e-test or Mann-Whitney U test, depending on the normality examination by the Shapiro-Wilk test. Categorical variables were expressed in frequency and proportion, and compared using Chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. A \u003cem\u003ep\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.05 in the two-sided test was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Participant selection results\u003c/h2\u003e \u003cp\u003eA total of 90 children younger than two years old were admitted for \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP during the study period. After excluding 24 children with severe concomitant disease or bronchopulmonary malformation, 66 children were included for the analysis. There were 45 boys and 21 girls, and the median age was 14.5 months old. The age distribution is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBased on the BALF CMV DNA test results, 28 children were assigned to the BALF CMV DNA positive group (median copy number of CMV DNA in BALF: 8,475 copies/ml, IQR: 2,542\u0026thinsp;\u0026minus;\u0026thinsp;135,100 copies/mL) and 38 children were assigned to the BALF CMV DNA negative group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Clinical characteristics\u003c/h2\u003e \u003cp\u003eChildren in the BALF CMV DNA positive group were more likely to experience duration of fever\u0026thinsp;\u0026ge;\u0026thinsp;3 days, and had lower incidences of wheezing, when compared to children in the BALF CMV DNA negative group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There were no statistically significant differences in the other characteristics between the two groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical characteristics between the BALF CMV DNA positive and negative groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBALF CMV DNA positive (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBALF CMV DNA negative (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eDemographics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, months, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14.0 (6.2\u0026ndash;18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.5 (7.0-18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.840\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (60.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (73.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.264\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of symptoms before admission, day, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.0 (5.2\u0026ndash;18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.0 (6.0-10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.830\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay before bronchoscopy, day, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.0 (3.0\u0026ndash;7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.0 (3.0\u0026ndash;7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.946\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eClinical symptoms and signs, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (78.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (73.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.647\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of fever\u0026thinsp;\u0026ge;\u0026thinsp;3 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (64.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (36.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWheezing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Laboratory and radiographic results\u003c/h2\u003e \u003cp\u003eThe laboratory values and chest imaging results are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Children in the BALF CMV DNA positive group had higher levels of C-reactive protein and lactate dehydrogenase, and a higher incidence of pulmonary consolidation, when compared to children in the BALF CMV DNA negative group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of laboratory results between the BALF CMV DNA positive and negative groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest results\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBALF CMV DNA positive (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBALF CMV DNA negative (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003ePeripheral blood test, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral leukocyte count, 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.4 (7.7\u0026ndash;11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.5 (7.1\u0026ndash;14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil percentage, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.4 (22.7\u0026ndash;42.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.9 (24.4\u0026ndash;44.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.756\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count, 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e333.0 (256.0-381.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e390.0 (276.0-525.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.3 (1.1\u0026ndash;9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.1 (0.7\u0026ndash;6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate dehydrogenase, U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e382.4 (347.4-425.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e363.9 (333.0-394.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlanine aminotransferase, U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.6 (13.9\u0026ndash;29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.0 (16.2\u0026ndash;25.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.770\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspartate aminotransferase, U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.0 (33.8\u0026ndash;56.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.2 (36.1\u0026ndash;45.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.973\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer, ng/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e320.0 (259.2-837.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e380.0 (260.0-630.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.947\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eBronchoalveolar lavage fluid cell profile, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.0 (30.0\u0026ndash;78.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.0 (12.0\u0026ndash;83.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.392\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.0 (0\u0026ndash;4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.0 (0\u0026ndash;4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.541\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEosinophils\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.455\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlveolar macrophages\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.0 (20.0\u0026ndash;65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.0 (10.0\u0026ndash;50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.274\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eChest imaging findings, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConsolidations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (46.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (61.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterstitial changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (23.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.343\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePleural effusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.154\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Microbiological diagnosis\u003c/h2\u003e \u003cp\u003eThe positive microbiological results for the 66 children are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Co-infection with viruses or bacteria were detected in 37 children, including 13 (19.7%) and 24 (36.4%) children in the BALF CMV DNA positive and negative groups, respectively. Virus co-infection was common in the BALF CMV DNA negative group, when compared to the BALF CMV DNA positive group (60.5% \u003cem\u003evs.\u003c/em\u003e 35.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.046), but there was no significant difference in bacteria co-infection between the two groups (2.6% \u003cem\u003evs.\u003c/em\u003e 10.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEtiologic agents for the 66 children with \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e-associated community-acquired pneumonia.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathogens\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBronchoalveolar lavage fluid cytomegalovirus DNA negative group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;influenza B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;adenovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;human metapneumovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;respiratory syncytial virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;coronaviruses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;parainfluenza virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;human rhinovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;human metapneumovirus\u0026thinsp;+\u0026thinsp;respiratory syncytial virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;respiratory syncytial virus\u0026thinsp;+\u0026thinsp;human rhinovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;parainfluenza virus\u0026thinsp;+\u0026thinsp;adenovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;parainfluenza virus\u0026thinsp;+\u0026thinsp;human bocavirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;human rhinovirus\u0026thinsp;+\u0026thinsp;adenovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;haemophilus influenzae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBronchoalveolar lavage fluid cytomegalovirus DNA positive group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;cytomegalovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;cytomegalovirus\u0026thinsp;+\u0026thinsp;adenovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;cytomegalovirus\u0026thinsp;+\u0026thinsp;parainfluenza virus\u0026thinsp;+\u0026thinsp;human rhinovirus\u0026thinsp;+\u0026thinsp;human metapneumovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;cytomegalovirus\u0026thinsp;+\u0026thinsp;parainfluenza virus\u0026thinsp;+\u0026thinsp;human rhinovirus\u0026thinsp;+\u0026thinsp;respiratory syncytial virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;cytomegalovirus\u0026thinsp;+\u0026thinsp;parainfluenza virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;cytomegalovirus\u0026thinsp;+\u0026thinsp;human bocavirus\u0026thinsp;+\u0026thinsp;human rhinovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;cytomegalovirus\u0026thinsp;+\u0026thinsp;human bocavirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;cytomegalovirus\u0026thinsp;+\u0026thinsp;human rhinovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplasma pneumoniae\u0026thinsp;+\u0026thinsp;cytomegalovirus\u0026thinsp;+\u0026thinsp;Streptococcus pneumoniae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Hospital management and outcomes\u003c/h2\u003e \u003cp\u003eAll children received azithromycin administration (intravenous, 10 mg/kg/day) for five consecutive days. None of the children received ganciclovir therapy. All children fully recovered, although children in the BALF CMV DNA positive group spent more time in the hospital, when compared to children in the BALF CMV DNA negative group (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of hospital management between the BALF CMV DNA positive and negative groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eManagement\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBALF CMV DNA positive (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBALF CMV DNA negative (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntimicrobial agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAzithromycin, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGanciclovir, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRequirement for supplemental oxygen, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePICU admission, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay, day, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.0 (8.0\u0026ndash;13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.0 (7.0\u0026ndash;10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e \u003cem\u003eM. pneumoniae\u003c/em\u003e is the common cause for pediatric CAP. CMV is a prevalent herpes virus. The detection of CMV DNA from BALF samples in patients with \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP does not necessarily indicate CMV pulmonary disease. There is an unclear clinical significance of detecting CMV DNA in BALF in CAP patients(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), Therefore, the present retrospective cohort study was conducted to compare the clinical characteristics, laboratory results, imaging findings, and treatment outcomes between BALF CMV DNA positive and negative children with \u003cem\u003eM. pneumoniae-\u003c/em\u003eassociated CAP.\u003c/p\u003e \u003cp\u003eThe clinical characteristics in children with \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP differed between the BALF CMV DNA positive and negative groups. For example, duration of fever\u0026thinsp;\u0026ge;\u0026thinsp;3 days was common in the BALF CMV DNA positive group, when compared to the BALF CMV DNA negative group. Furthermore, the levels of C-reactive protein and lactate dehydrogenase were higher in the BALF CMV DNA positive group, when compared to the BALF CMV DNA negative group. In addition, consolidations were more frequently reported in the BALF CMV DNA positive group, when compared to the BALF CMV DNA negative group. Longer duration of fever, higher level of C-reactive protein, higher level of lactate dehydrogenase, and consolidations were identified as markers of severe \u003cem\u003eM. pneumoniae\u003c/em\u003e pneumonia(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). These results suggest that children with positive BALF CMV DNA had severe clinical presentations, when compared to children with negative BALF CMV DNA. CMV can be a primary pathogen, since CMV induces a direct cytopathic effect by encoding the viral mitochondria-localized inhibitor of apoptosis(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In addition, CMV exerts its immunosuppressive effects by impairing T-cell proliferation, and interfering with antigen processing(\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). However, it could not be ruled out that the detection of CMV DNA in BALF might be the outcome of a more severe illness. Severe \u003cem\u003eM. pneumoniae\u003c/em\u003e infection can induce immunoparalysis, which places children at a high risk for CMV replication in BALF(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Patients with severe \u003cem\u003eM. pneumoniae\u003c/em\u003e pneumonia were reported to have high levels of TNF-α(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), which can activate NF-κB, with the subsequent translocation into the nucleus to promote CMV replication(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the present study, wheezing was more common in the BALF CMV DNA negative group, when compared to the BALF CMV DNA positive group. This might be due to the more common virus co-infection detected in the BALF CMV DNA negative group, when compared to the BALF CMV DNA positive group. The most common detected pathogen was hRV, which is a common pathogen that causes wheezing in young children(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe length of hospitalization was longer in the BALF CMV DNA positive group, when compared to the BALF CMV DNA negative group. This was consistent with the more significant inflammation and more frequent pulmonary consolidation observed in the former group, when compared to the latter group. CMV infection can result in the secretion of fibrogenic cytokines and increase in pulmonary fibrosis, as observed in mice experiments(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). This might partly explain the longer length of hospitalization observed in the BALF CMV DNA positive group.\u003c/p\u003e \u003cp\u003eThe present study has limitations. First, the present study was a retrospective study conducted in a single research institution with a small number of children. Second, the CMV DNA in BALF samples was not dynamically detected, which may provide better insights into the relationship between the CMV DNA in BALF and clinical characteristics. Finally, the benefit of anti-CMV therapy for children with positive CMV DNA in BALF remains unclear, and requires further investigation.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion, the clinical characteristics, laboratory test results, and imaging reports differed between BALF CMV DNA positive and negative children with \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP. All affected children recovered from the infection. Children with BALF CMV DNA positive results had stronger inflammation, and required longer hospital stays, implying increased medical demand and expenses.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cem\u003eM. pneumoniae Mycoplasma pneumoniae\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCAP community-acquired pneumonia\u003c/p\u003e\n\u003cp\u003eCMV Cytomegalovirus\u003c/p\u003e\n\u003cp\u003eBALF bronchoalveolar lavage fluid\u003c/p\u003e\n\u003cp\u003eCT computed tomography\u003c/p\u003e\n\u003cp\u003ehRV human rhinovirus\u003c/p\u003e\n\u003cp\u003ePICU pediatric intensive care unit\u003c/p\u003e\n\u003cp\u003eIQR interquartile range\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study performed in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of the Children\u0026rsquo;s Hospital of Soochow University (2025CS062). Because this study presented no more than minimal risk of harm to patient subjects, the Ethics Committee of the Children\u0026rsquo;s Hospital of Soochow University approved a waiver of patient informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Gusu Health Talent Project (grant number GSWS2023047), the 2025 Suiyuan clinical research project of the Children\u0026rsquo;s Hospital of Soochow University (grant number 2025SYLCYJ09), the natural science foundation of the Jiangsu higher education institutions of China (grant number 23KJB320017), and the natural science foundation of Jiangsu province (grant number BK20230218).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXYG was responsible for collecting the data and drafting the manuscript. ZAD was responsible for statistical analysis and drafting the manuscript. TW and ZRC were responsible for literature retrieval. HTD, JWC and PM were responsible for collecting the data. YQW and HMS were responsible for critical reading of a final version of the manuscript.\u0026nbsp;All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all participants involved in this research.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTsai TA, Tsai CK, Kuo KC, Yu HR. Rational stepwise approach for Mycoplasma pneumoniae pneumonia in children. J Microbiol Immunol Infect. 2021;54(4):557-65.\u003c/li\u003e\n\u003cli\u003eXu W, Guo L, Dong X, Li X, Zhou P, Ni Q, et al. Detection of Viruses and Mycoplasma pneumoniae in Hospitalized Patients with Severe Acute Respiratory Infection in Northern China, 2015-2016. Jpn J Infect Dis. 2018;71(2):134-9.\u003c/li\u003e\n\u003cli\u003eZhu YG, Tang XD, Lu YT, Zhang J, Qu JM. Contemporary Situation of Community-acquired Pneumonia in China: A Systematic Review. J Transl Int Med. 2018;6(1):26-31.\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. World J Pediatr. 2024;20(1):1-4.\u003c/li\u003e\n\u003cli\u003eWang YS, Zhou YL, Bai GN, Li SX, Xu D, Chen LN, et al. Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children. World J Pediatr. 2024;20(9):901-14.\u003c/li\u003e\n\u003cli\u003eGao L, Sun Y. Laboratory diagnosis and treatment of Mycoplasma pneumoniae infection in children: a review. Ann Med. 2024;56(1):2386636.\u003c/li\u003e\n\u003cli\u003eBalthesen M, Messerle M, Reddehase MJ. Lungs are a major organ site of cytomegalovirus latency and recurrence. J Virol. 1993;67(9):5360-6.\u003c/li\u003e\n\u003cli\u003eTan SK, Burgener EB, Waggoner JJ, Gajurel K, Gonzalez S, Chen SF, Pinsky BA. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis. Open Forum Infect Dis. 2016;3(1):ofv212.\u003c/li\u003e\n\u003cli\u003eBewig B, Haacke TC, Tiroke A, Bastian A, Bottcher H, Hirt SW, et al. Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells. Respiration. 2000;67(2):166-72.\u003c/li\u003e\n\u003cli\u003eHuang L, Zhang X, Pang L, Sheng P, Wang Y, Yang F, et al. Viral reactivation in the lungs of patients with severe pneumonia is associated with increased mortality, a multicenter, retrospective study. J Med Virol. 2023;95(1):e28337.\u003c/li\u003e\n\u003cli\u003eMansfield S, Dwivedi V, Byrd S, Trgovcich J, Griessl M, Gutknecht M, Cook CH. Broncholaveolar lavage to detect cytomegalovirus infection, latency, and reactivation in immune competent hosts. J Med Virol. 2016;88(8):1408-16.\u003c/li\u003e\n\u003cli\u003eDing Y, Liu G, Li Q, Zou L, Dai J, Chongsuvivatwong V. Distribution characteristics of human herpes viruses in the lower respiratory tract and their impact on 30-day mortality in community-acquired pneumonia patients. Front Cell Infect Microbiol. 2024;14:1436509.\u003c/li\u003e\n\u003cli\u003eEscribano A, Chilet M, Clari MA, Lucas R, Costa E, Bravo D, et al. Frequent detection of cytomegalovirus (CMV) DNA in the lower respiratory tract in CMV-seropositive pediatric patients with underlying chronic bronchopulmonary diseases lacking canonical immunosuppression. J Med Virol. 2013;85(5):888-92.\u003c/li\u003e\n\u003cli\u003eGordon CL, Miron M, Thome JJ, Matsuoka N, Weiner J, Rak MA, et al. Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection. J Exp Med. 2017;214(3):651-67.\u003c/li\u003e\n\u003cli\u003eJackson SE, Sedikides GX, Okecha G, Wills MR. Generation, maintenance and tissue distribution of T cell responses to human cytomegalovirus in lytic and latent infection. Med Microbiol Immunol. 2019;208(3-4):375-89.\u003c/li\u003e\n\u003cli\u003eSun H, Li S, Yan Y, Chen Z, Wang Y, Hao C, Ji W. Associations between patient clinical characteristics and the presence of cytomegalovirus DNA in the bronchoalveolar lavage fluid of children with recurrent wheezing. BMC Infect Dis. 2018;18(1):458.\u003c/li\u003e\n\u003cli\u003eWang X, Lu Y, Chen F, Ruan L, Gu L, Wang T, et al. Clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia and cytomegalovirus DNA detected in bronchoalveolar lavage fluid. Front Pediatr. 2024;12:1407174.\u003c/li\u003e\n\u003cli\u003eDe Schutter I, De Wachter E, Crokaert F, Verhaegen J, Soetens O, Pierard D, Malfroot A. Microbiology of bronchoalveolar lavage fluid in children with acute nonresponding or recurrent community-acquired pneumonia: identification of nontypeable Haemophilus influenzae as a major pathogen. Clin Infect Dis. 2011;52(12):1437-44.\u003c/li\u003e\n\u003cli\u003eGilca R, De Serres G, Tremblay M, Vachon ML, Leblanc E, Bergeron MG, et al. Distribution and clinical impact of human respiratory syncytial virus genotypes in hospitalized children over 2 winter seasons. J Infect Dis. 2006;193(1):54-8.\u003c/li\u003e\n\u003cli\u003eSubspecialty Group of Respiratory Diseases TSoPCMA, Editorial Board CJoP. [Guidelines for management of community acquired pneumonia in children (the revised edition of 2013) (I)]. Zhonghua Er Ke Za Zhi. 2013;51(10):745-52.\u003c/li\u003e\n\u003cli\u003eDefilippi A, Silvestri M, Tacchella A, Giacchino R, Melioli G, Di Marco E, et al. Epidemiology and clinical features of Mycoplasma pneumoniae infection in children. Respir Med. 2008;102(12):1762-8.\u003c/li\u003e\n\u003cli\u003eSubspecialty Group of Respiratory tSoPCMA, China National Clinical Research Center of Respiratory D, Editorial Board CJoP. Evidence-based guideline for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children (2023). Pediatr Investig. 2025;9(1):1-11.\u003c/li\u003e\n\u003cli\u003ePoncet D, Pauleau AL, Szabadkai G, Vozza A, Scholz SR, Le Bras M, et al. Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA. J Cell Biol. 2006;174(7):985-96.\u003c/li\u003e\n\u003cli\u003eFilteau S, Rowland-Jones S. Cytomegalovirus Infection May Contribute to the Reduced Immune Function, Growth, Development, and Health of HIV-Exposed, Uninfected African Children. Front Immunol. 2016;7:257.\u003c/li\u003e\n\u003cli\u003eBarry SM, Johnson MA, Janossy G. Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited. Bone Marrow Transplant. 2000;26(6):591-7.\u003c/li\u003e\n\u003cli\u003eWikby A, Johansson B, Olsson J, Lofgren S, Nilsson BO, Ferguson F. Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Exp Gerontol. 2002;37(2-3):445-53.\u003c/li\u003e\n\u003cli\u003eSchildermans J, De Vlieger G. Cytomegalovirus: A Troll in the ICU? Overview of the Literature and Perspectives for the Future. Front Med (Lausanne). 2020;7:188.\u003c/li\u003e\n\u003cli\u003eGiamarellos-Bourboulis EJ, Siampanos A, Bolanou A, Doulou S, Kakavoulis N, Tsiakos K, et al. Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2024;12(4):294-304.\u003c/li\u003e\n\u003cli\u003eDeng F, Cao H, Liang X, Li Q, Yang Y, Zhao Z, et al. Analysis of cytokine levels, cytological findings, and MP-DNA level in bronchoalveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia. Immun Inflamm Dis. 2023;11(5):e849.\u003c/li\u003e\n\u003cli\u003eDocke WD, Prosch S, Fietze E, Kimel V, Zuckermann H, Klug C, et al. Cytomegalovirus reactivation and tumour necrosis factor. Lancet. 1994;343(8892):268-9.\u003c/li\u003e\n\u003cli\u003eRossi GA, Colin AA. Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing. Eur Respir J. 2015;45(3):774-89.\u003c/li\u003e\n\u003cli\u003eJartti T, Korppi M. Rhinovirus-induced bronchiolitis and asthma development. Pediatr Allergy Immunol. 2011;22(4):350-5.\u003c/li\u003e\n\u003cli\u003eCook CH, Zhang Y, Sedmak DD, Martin LC, Jewell S, Ferguson RM. Pulmonary cytomegalovirus reactivation causes pathology in immunocompetent mice. Crit Care Med. 2006;34(3):842-9.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pneumonia, Mycoplasma pneumoniae, Cytomegalovirus, Bronchoalveolar lavage, Pediatrics","lastPublishedDoi":"10.21203/rs.3.rs-8954666/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8954666/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e (\u003cem\u003eM. pneumoniae\u003c/em\u003e)-associated community-acquired pneumonia (CAP) is common in children. Cytomegalovirus (CMV) is frequently detected in respiratory samples in this patient population. We aimed to explore the clinical implications of positive CMV DNA in bronchoalveolar lavage fluid (BALF) from immunocompetent children with \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort study was conducted for \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP children under two years old with CMV DNA test in BALF between January 1, 2022 and September 30, 2025. These children were assigned to the BALF CMV DNA positive group or negative group. Then, the inter-group characteristics were compared.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 66 children, 28 and 38 children were in the CMV DNA positive and negative groups, respectively. Children in the BALF CMV DNA positive group were more likely to experience duration of fever\u0026thinsp;\u0026ge;\u0026thinsp;3 days, had higher C-reactive protein and lactate dehydrogenase levels, showed a higher incidence of pulmonary consolidations, and required longer hospital stays. However, these children had a lower incidence of wheezing, when compared to children in the BALF CMV DNA negative group. Furthermore, virus co-infection was common in the BALF CMV DNA negative group, when compared to the BALF CMV DNA positive group (60.5% \u003cem\u003evs.\u003c/em\u003e 35.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.046). All children fully recovered after intravenous azithromycin administration.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eBoth BALF CMV DNA positive and negative children with \u003cem\u003eM. pneumoniae\u003c/em\u003e-associated CAP can reach full recovery after azithromycin treatment. However, the former group had stronger inflammations and required longer hospital stays, while the latter group were more likely to have virus co-infection.\u003c/p\u003e\u003ch2\u003eClinical trial number:\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e","manuscriptTitle":"Clinical significance of cytomegalovirus detection in young children with Mycoplasma pneumoniae-associated community-acquired pneumonia: A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 15:27:46","doi":"10.21203/rs.3.rs-8954666/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-17T06:20:35+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-16T19:20:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"177703173180606971325918747736425449051","date":"2026-03-02T01:21:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-27T07:12:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"37966672554504748894930973994389644794","date":"2026-02-27T00:53:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-26T22:34:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-26T17:27:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-26T06:56:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-26T06:48:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2026-02-24T08:19:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d38b4bd8-59cc-459a-857d-4c043f058c0a","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T14:39:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 15:27:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8954666","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8954666","identity":"rs-8954666","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}