Analysis Of Pathogen Characteristics And Risk Factors In Children With Hematologic Diseases Concomitant With Pulmonary Infection Using Metagenomic Next-generation Sequencing Of Alveolar Lavage Fluid

ObjectivePulmonary infection is the most common site of infection in children after hematopoietic stem cell transplantation and hematopoietic tumor chemotherapy.It has complex etiology and can lead to severe clinical adverse prognosis such as related death and respiratory dysfunction.At present,there are few clinical reports on pulmonary infection after transplantation.In this study,the pathogens and risk factors of metagenomic next-generation sequencing(mNGS)and in alveolar lavage fluid in children with pulmonary infection were analyzed to provide clinical diagnostic ideas and treatment strategies.MethodsA total of 135 children with hematologic diseases hospitalized in our department from December 2017 to February 2022 were retrospectively analyzed,including 93 cases in the transplantation group and 42 cases in the chemotherapy group.All the children completed preoperative blood drawing test,imaging examination and bronchoscopic alveolar lavage,and underwent postoperative alveolar lavage fluid mNGS and conventional microbiological tests(CMTs).Information collected in this study included baseline data such as age,transplant time,donor type,blood routine,infection indicators,and chest imaging.SPSS software was used for rank-sum test and logistic regression analysis of relevant clinical data.Results1.mNGS and CMTs have high consistency in cytomegalovirus(CMV)and EB virus(EBV)detection;In fungi,polyomavirus and some bacteria(such as Pseudomonas aeruginosa),mNGS were more sensitive than CMTs.In addition to mycoplasma,the specificity of CMTs was higher than mNGS.2.Umbilical cord blood transplantation and low platelet count were independent risk factors for herpes virus 6B infection in the transplantation group(p=0.014,0.05).Time of infection after transplantation and CD34+cell count of stem cells were independent risk factors for infection with EBV(p=0.027,0.023).High monocyte count was an independent risk factor for bacterial and viral infection(p=0.024).3.The cumulative incidence of CMV disease,and EB viremia diagnosed within 6 months after transplantation was about 43%,38%,and 30%,respectively.The cumulative incidence of gram-negative bacteria infection within 6 months after transplantation was about 90%,while gram-positive bacteria infection was about 75%,and the median time of infection was 2 and 3 months after transplantation,respectively.4.Low lymphocyte count was an independent risk factor for pneumocystis infection in chemotherapy group.Conclusion1.mNGS is more sensitive to rare pathogen diagnosis than CMTs,enriching detection and diagnosis methods.2.In the transplant group,the risk of infection with Human Herpesvirus 6B was 14 times higher in umbilical cord blood transplantation than in non-umbilical cord blood transplantation patients;The lower the platelet count,the more susceptible to infection with Human Herpesvirus 6B;The longer the infection time span after transplantation,the more susceptible to infection with EBV,and the lower the CD34+cell count of stem cells,the more susceptible to infection with EBV.The higher the monocyte count,the more susceptible to bacterial and viral infection.3.In the chemotherapy group,the lower the lymphocyte count was,the more susceptible to infection with Pneumocystis jirovecii.4.The cumulative incidence of Cytomegaloviremia,CMV disease,and EB viremia within 6 months after transplantation was about 43%,38%and 30%,respectively.The cumulative incidence of gram-negative bacteria infection within 6 months after transplantation was about 90%,while gram-positive bacteria infection was about 75%,and the median time of infection was 2 and 3 months after transplantation,respectively.