Objective: To investigate the risk factors and outcomes of cytomegalovirus (CMV) infection post umbilical cord blood stem cell transplantation (UCBT) in children with primary immunodeficiency diseases (PID). Methods: Clinical data of 143 PID children who received UCBT in the Children's Hospital of Fudan University from January 2015 to June 2020 were collected retrospectively. CMV-DNA in the plasma was surveilled once or twice a week within 100 days post-UCBT. According to the CMV-DNA test results, children were divided into the CMV-infected group and the CMV-uninfected group. The incidence and risk factors of CMV infection were analyzed. At 1-month post-UCBT, the absolute lymphocyte count, ratio of lymphocyte subsets and immunoglobulin levels were compared between those whose CMV infection developed 1-month later post-UCBT and those not. Mann-Whitney U test and chi-squared test were used for comparision between groups. Kaplan-Meier survival analysis was used to analyze the impact of CMV infection on survival. Results: Among 143 patients, there were 113 males and 30 females, with a age of 14 (8, 27) months at UCBT. Chronic granulomatosis disease (n=49), very-early-onset inflammatory bowel disease (n=43) and severe combined immunodefiency (n=29) were the three main kinds of PID. The rate of CMV infection was 21.7% (31/143), and the time of infection occurring was 44 (31, 49) days post-UCBT. The incidence of recurrent CMV infection was 4.2% (6/143) and refractory CMV infection was 4.9% (7/143).There was no significant difference in the first time CMV-DNA copy and peak CMV-DNA copy during treatment between the recurrent CMV infection group and the non-recurrent CMV infection group (32.8 (18.3, 63.1)×10⁶ vs. 22.5 (13.2, 31.9)×10⁶ copies/L, Z=-0.95, P=0.340;35.2 (20.2, 54.6)×10⁶ vs. 28.4 (24.1, 53.5)×10⁶copies/L, Z=-0.10, P=0.920), so were those between the refractory CMV infection group and non-refractory CMV infection group (21.8 (13.1, 32.2)×10⁶ vs. 25.9 (14.2, 12.2)×10⁶copies/L, Z=-1.04, P=0.299; 47.7 (27.9, 77.6)×10⁶ vs. 27.7 (19.7,51.8)×10⁶copies/L, Z=-1.49, P =0.137). The CMV-infected group accepted more reduced-intensity conditioning (RIC) regimen than the CMV-uninfected group (45.2% (14/31) vs. 25.0% (28/112), χ²=4.76, P<0.05). The rate of CMV-seropositive recipients and Ⅱ-Ⅳ acute graft versus host diseases (aGVHD) are significantly higher in the CMV-infected group than the CMV-uninfected group (100% (31/31) vs. 78.6% (88/112), 64.5% (20/31) vs. 26.8% (30/112), χ²=7.98,15.20, both P<0.05). The follow-up time was 31.6 (13.2, 45.9) months, CMV infection had no effect on overall survival (OS) rate (χ²=0.02, P=0.843). There was significant difference in the survival rate among three groups of refractory CMV infection, non-refractory CMV infection and the CMV-uninfected (4/7 vs.95.8% (23/24) vs. 86.6% (97/112), χ²=5.91, P=0.037), while there was no significant difference in the survival rate among three groups of recurrent CMV infection, non-recurrent CMV infection and the CMV-uninfected (5/6 vs. 88.0% (22/25) vs. 86.6% (97/112), χ²=0.43, P=0.896). Children who developed CMV infection after 30 days post-UCBT had lower absolute count and rate of CD4⁺ T cells and immunoglobulin G (IgG) level than those in the CMV-uninfected group (124.1 (81.5, 167.6) ×10⁶ vs. 175.5 (108.3, 257.2) ×10⁶/L, 0.240 (0.164, 0.404) vs. 0.376 (0.222, 0.469), 9.3 (6.2, 14.7) vs. 13.6 (10.7, 16.4) g/L, Z=-2.48, -2.12,-2.47, all P<0.05), but have higher rate of CD8⁺T cells than those in CMV-uninfected group (0.418 (0.281, 0.624) vs. 0.249 (0.154, 0.434), Z=-2.56, P=0.010). Conclusions: RIC regimen, grade Ⅱ-Ⅳ aGVHD and CMV-seropositive recipients are the main risk factors associated with CMV infection in PID patients post-UCBT. Survival rate of children with refractory CMV infection after UCBT is reduced. Immune reconstitution in children after UCBT should be regularly monitored, and frequency of CMV-DNA monitoring should be increased for children with delayed immune reconstitution.
Child ; Cord Blood Stem Cell Transplantation/adverse effects* ; Cytomegalovirus ; Cytomegalovirus Infections/etiology* ; DNA ; Female ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Immunoglobulin G ; Infant ; Male ; Primary Immunodeficiency Diseases ; Prognosis ; Retrospective Studies ; Risk Factors

A boy, aged 6 years and 11 months, was admitted due to nephrotic syndrome for 2 years, cough for 1 month, and shortness of breath for 15 days. The boy had a history of treatment with hormone and immunosuppressant. Chest CT after the onset of cough and shortness of breath showed diffuse ground-glass opacities in both lungs. Serum (1, 3)-beta-D glucan was tested positive, and the nucleic acid of cytomegalovirus was detected in respiratory secretions. After the anti-fungal and anti-viral treatment, the child improved temporarily but worsened again within a short period of time.
Child ; Cough/etiology* ; Cytomegalovirus Infections/therapy* ; Dyspnea/etiology* ; Extracorporeal Membrane Oxygenation ; Humans ; Male ; Nephrotic Syndrome/complications* ; Pneumonia, Pneumocystis/therapy* ; Respiratory Distress Syndrome/therapy*

Objective: To investigate the relationship between human cytomegalovirus (HCMV) infection and peripheral blood CD14 CD16 monocytes in the pathogenesis of coronary heart disease (CHD), and to elucidate the mechanism of pathogenesis in CHD by analyzing the correlation between infection, inflammation, and CHD, to provide a basis for the prevention, evaluation, and treatment of the disease. Methods: In total, 192 patients with CHD were divided into three groups: latent CHD, angina pectoris, and myocardial infarction. HCMV-IgM and -IgG antibodies were assessed using ELISA; CD14 CD16 monocytes were counted using a five-type automated hematology analyzer; mononuclear cells were assessed using fluorescence-activated cell sorting; and an automatic biochemical analyzer was used to measure the levels of triglyceride, cholesterol, high- and low-density lipoprotein cholesterols, lipoprotein, hs-CRp and Hcy. Results: The positive rates of HCMV-IgM and -IgG were significantly higher in the CHD groups than in the control group. HCMV infection affects lipid metabolism to promote immune and inflammatory responses. Conclusion HCMV infection has a specific correlation with the occurrence and development of CHD. The expression of CD14 CD16 mononuclear cells in the CHD group was increased accordingly and correlated with acute HCMV infection. Thus, HCMV antibody as well as peripheral blood CD14 CD16 mononuclear cells can be used to monitor the occurrence and development of CHD.
Angina Pectoris ; epidemiology ; virology ; China ; epidemiology ; Coronary Disease ; epidemiology ; virology ; Cytomegalovirus ; physiology ; Cytomegalovirus Infections ; complications ; Humans ; Incidence ; Inflammation ; epidemiology ; etiology ; Leukocyte Count ; Monocytes ; metabolism ; Myocardial Infarction ; epidemiology ; virology

OBJECTIVETo study the relationship between the expression of peripheral blood HLA-DR, CD4CD25 regulatory T cells, IL-17 and IL-27 with liver damage in children with human cytomegalovirus (HCMV) infection.

METHODSTwenty-one HCMV children with liver damage and twenty-one HCMV children without liver damage were enrolled in this study. The expression of peripheral blood HLA-DR and CD4CD25 regulatory T cells was detected by flow cytometry. Plasma levels of IL-17 and IL-27 were measured using ELISA.

RESULTSThe plasma levels of IL-17 and IL-27 in children with liver damage were significantly higher than in those without liver damage, while the expression of peripheral blood CD4CD25 regulatory T cells was lower than in those without liver damage (P<0.05). Plasma IL-17 and IL-27 levels were negatively correlated with the expression of peripheral blood CD4CD25 regulatory T cells (P<0.01).

CONCLUSIONSImmune imbalance mediated by CD4CD25 regulatory T cells and over-expression of IL-17 and IL-27 may be involved in the pathogenesis of liver damage in children with HCMV infection.

CD4 Antigens ; immunology ; Cytomegalovirus ; physiology ; Cytomegalovirus Infections ; blood ; complications ; genetics ; Female ; Flow Cytometry ; HLA-DR Antigens ; genetics ; immunology ; Humans ; Infant ; Interleukin-17 ; blood ; genetics ; Interleukin-2 Receptor alpha Subunit ; immunology ; Interleukins ; blood ; genetics ; Liver ; injuries ; metabolism ; Liver Diseases ; blood ; etiology ; immunology ; Male ; T-Lymphocytes, Regulatory ; immunology

Breast milk is considered ideal food for premature infants, but it can also be the main source of cytomegalovirus (CMV) infection in premature infants. CMV infection may cause serious clinical symptoms, such as sepsis-like syndrome, thrombocytopenia, neutropenia, jaundice, hepatitis, and pneumonitis. This article reviews the research advances in symptoms, treatment strategies, prognosis and the prevention of breast milk-acquired CMV infection in premature infants.
Breast Feeding ; Cytomegalovirus Infections ; etiology ; prevention & control ; therapy ; Humans ; Infant, Newborn ; Infant, Premature ; Infectious Disease Transmission, Vertical ; prevention & control ; Milk, Human ; virology

OBJECTIVETo study the possible immunological mechanism of wheezing attack in children with cytomegalovirus (CMV) infection.

METHODSA total of 25 under-5-year-old children with wheezing following CMV infection were enrolled. The expression of serum regulatory T cells (Treg)/T helper 17 (Th17) cytokines interleukin (IL)-10, IL-6, and IL-17, and peripheral blood lymphocyte subsets were determined. Twenty age-matched healthy children were selected as the control group.

RESULTSThe wheezing group had a significantly reduced serum IL-10 level, significantly increased IL-6 and IL-17 levels, significantly reduced levels of natural killer cells, and significantly increased levels of CD8+ T cells and CD19+ B cells, as compared with the control group.

CONCLUSIONSWheezing children with CMV infection have Treg/Th17 imbalance and cellular immune dysfunction, which may be an important immunological mechanism of the development of wheezing in children after CMV infection.

Child, Preschool ; Cytokines ; blood ; Cytomegalovirus Infections ; immunology ; Female ; Humans ; Infant ; Male ; Respiratory Sounds ; etiology ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

OBJECTIVETo investigate the risk factors for hearing impairment induced by cytomegalovirus (CMV) infection in children.

METHODSOne hundred and fifty-eight children diagnosed with CMV infection were enrolled as subjects. Based on the results of the brainstem auditory evoked potential (BAEP) test, patients were classified into normal hearing group (n=117; BAEP≤35) and abnormal hearing group (n=41; BAEP>35). A retrospective analysis was performed on the general information, routine blood indices, liver function, copy number of CMV-DNA in urine and breast milk. The receiver operating characteristic (ROC) curve was used to predict the copy number of CMV-DNA resulting in abnormal BAEP. The Spearman rank correlation analysis was used to test the correlations of the copy number of CMV-DNA in urine with the degree of hearing impairment and platelet count.

RESULTSThe incidence rates of platelet abnormality and abnormal liver function and the copy number of CMV-DNA in urine were significantly higher in the abnormal hearing group than in the normal hearing group (P<0.01). According to the ROC curve, the copy number of CMV-DNA in urine had a sensitivity of 46.3% and a specificity of 93.2% in predicting hearing impairment when it reached 1.415×10(6) per mL. The results of correlation analysis showed that the degree of hearing impairment was positively correlated with the copy number of CMV-DNA (r=0.382, P<0.01); the platelet count was negatively correlated with the copy number of CMV-DNA in urine (r=-0.233, P=0.003).

CONCLUSIONSAn increased copy number of CMV-DNA in urine might be a risk factor for hearing impairment induced by CMV infection. Children are likely to have hearing impairment when the copy number of CMV-DNA reaches 1.415×10(6) per mL. The monitoring of hearing should be strengthened in CMV-infected children with a decreased platelet count.

Cytomegalovirus Infections ; complications ; DNA, Viral ; urine ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Loss ; etiology ; Humans ; Infant ; Infant, Newborn ; Male ; Platelet Count ; ROC Curve ; Retrospective Studies ; Risk Factors

This study was purposed to investigate the cytomegalovirus (CMV) infection and its related factors after allogenic hematopoietic stem cell transplantation (allo-HSCT). A total of 108 patients who received allo-HSCT in zhongda hospital from January 1, 2004 to March 31, 2014 were enrolled in this study. The CMV infection rate and the median time when the CMV-DNA was positive for the first time, and the risk factors related with CMV infection, CMV disease distribution and mortality after allo-HSCT were analyzed. The results showed that the infection rate of CMV was 52.78% (57/108), the median time of CMV infection was 44 d, especially during 30 d-100 d after transplantation. The univariate analysis showed that CMV infection rate was related with the HLA-identical situation between the donor and the recipient, and whether the use of anti-human thymus globulin(ATG) in conditioning regimen, neutropenic period after transplantation exceeded 10 d and graft-versus-host disease (GVHD). Multivariate analysis showed that CMV infection rate was related with neutropenic period longer than 10 d after transplantation and graft-versus-host disease (GVHD). The mortality of the patients with CMV disease was 58.82% (10/17), in which the mortality of CMV interstitial pneumonia was highest. The CMV infection was one of the most commonly happened infection after allo-HSCT. It is concluded that to reduce the incidence of CMV disease and mortality, the best choice of allo-HSCT is HLA-identical donor, ATG should be used during the conditioning process, and neutropenic period should be reduced less than 10 days. Moreover, it is necessary to strengthen the preemptive therapy of CMV infection actively.
Allografts ; Cytomegalovirus Infections ; etiology ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Risk Factors ; Transplantation Conditioning

No abstract available.
Adult ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Appendicitis/diagnosis/*etiology/therapy ; Bacteremia/*etiology/therapy ; Consolidation Chemotherapy/adverse effects ; Cytomegalovirus Infections/diagnosis/*etiology/therapy ; Humans ; Immunocompromised Host ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/immunology/therapy

This study was aimed to explore the potential association of HLA-E polymorphism with the incidence of cytomegalovirus (CMV) infection after HLA-matched hematopoietic stem cell transplantation, 119 HLA-genoidentical sibling pairs for HLA-E polymorphism were analyzed, HLA-E DNA was amplified by polymerase chain reaction (PCR), and the amplified DNA products was also sequenced directly after purification to confirm the genotype. The results showed that the homozygous HLA-E*0101/0101 accounted for 20.17%, the homozygous HLA-E*0103/0103 accounted for 27.73%; heterozygous HLA-E*0101/0103 accounted for 52.10%; in homozygous HLA-E*0101/0101 group, 15 cases were infected with CMV and the CMV infection rate was 62.50%; in homozygous HLA-E*0103/0103 group, 16 cases were infected with CMV and the CMV infection rate was 48.48%; in heterozygous HLA-E*0101/0103 group 20 cases were infected with CMV and the CMV infection rate was 32.25%. As compared with the homozygous HLA-E*0101/0101 group, the CMV infection rate in HLA-E*0103 group displays statistical significance (P = 0.0295). The CMV infection rate occurred higher and its significance is statistical (P = 0.0074). It is concluded that the HLA-E gene polymorphism is associated with CMV infection after HLA-genoidentical bone marrow transplantation.
Adolescent ; Adult ; Cytomegalovirus Infections ; etiology ; genetics ; Female ; Genotype ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Histocompatibility Antigens Class I ; genetics ; Humans ; Incidence ; Male ; Middle Aged ; Polymorphism, Genetic ; Siblings ; Young Adult