Cytomegalovirus Load Research Articles

The pediatric gut bacteriome and virome in response to SARS-CoV-2 infection.

Since the beginning of the SARS-CoV-2 pandemic in early 2020, it has been apparent that children were partially protected from both infection and the more severe forms of the disease. Many different mechanisms have been proposed to explain this phenomenon, including children's frequent exposure to other upper respiratory infections and vaccines, and which inflammatory cytokines they are more likely to produce in response to infection. Furthermore, given the presence of SARS-CoV-2 in the intestine and its ability to infect enterocytes, combined with the well described immunomodulatory capabilities of the microbiome, another potential contributing factor may be the presence of certain protective microbial members of the gut microbiota (GM). We performed shotgun metagenomic sequencing and profiled both the bacteriome and virome of the GM of pediatric SARS-CoV-2 patients compared to healthy, age-matched subjects. We found that, while pediatric patients do share some pro-inflammatory microbial signatures with adult patients, they also possess a distinct microbial signature of protective bacteria previously found to be negatively correlated with SARS-CoV-2 infectivity and COVID-19 severity. COVID-19 was also associated with higher fecal Cytomegalovirus load, and with shifts in the relative abundances of bacteriophages in the GM. Furthermore, we address how the preventative treatment of COVID-19 patients with antibiotics, a common practice especially in the early days of the pandemic, affected the bacteriome and virome, as well as the abundances of antimicrobial resistance and virulence genes in these patients. To our knowledge, this is the first study to address the bacteriome, virome, and resistome of pediatric patients in response to COVID-19 and to preventative antibiotics use.

Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients.

Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4-12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV (p = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = -0.553, p = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT (p = 0.03 and p = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation.

Routine breast milk monitoring using automated molecular assay system reduced postnatal CMV infection in preterm infants.

Human cytomegalovirus (CMV) transmitted through breast milk poses fatal risks to preterm infants. However, current molecular assay systems often do not accommodate breast milk samples. In this study, we evaluated the analytical and clinical performance of the measurement procedure of CMV load in breast milk utilizing the Cobas CMV test on the Cobas 6,800 system. This was enabled by incorporating a simple independent sample preparation procedure before the application of samples on the automated assay system. Clinical data from electronic medical records were retrospectively analyzed. Breast milk samples from mothers of preterm infants born before 33 weeks of gestation were screened for CMV using the automated assay system. CMV positivity rates in breast milk and neonatal samples and the CMV transmission rate were calculated. Furthermore, to validate the analytical accuracy of the overall measurement procedure with newly obtained residual breast milk samples, the linearity of the measurement procedure was assessed, and a simplified sample preparation method was validated against a conventional method. The CMV positivity rates in maternal breast milk and neonatal samples were 57.8 and 5.2%, respectively. The CMV transmission rate through breast milk was 7.7%. No significant differences in gestational age or birth weight were found between the CMV-negative and CMV-positive neonates. The linearity of the procedure was observed within a range of 1.87-4.73 log IU/mL. The simplified sample preparation method had an equivalent or even improved CMV detection sensitivity than the conventional method. Incorporating a simple independent sample preparation procedure effectively resolved any potential issues regarding the application of breast milk on the automated assay system. Our approach contributed to reduced vertical transmission of CMV by providing a convenient and reliable method for the monitoring of breast milk CMV positivity for clinicians.

Investigation of Ganciclovir Resistance in Cytomegalovirus Isolates by Phenotypic and Genotypic Methods

Ganciclovir-resistant cytomegalovirus (CMV) strains are reported following long-term antiviral agent use, especially for immune-suppressive patients. In this study, it was aimed to investigate the mutations in the UL97 gene of CMV, which causes ganciclovir (GCV) resistance by genotypic and phenotypic methods in patients who developed CMV infection following hematopoietic cell (HCT) or solid organ transplantation (SOT). Thirty patients who had HCT or SOT in Mediterranean University Hospital and developed CMV infection during routine follow-up with a viral load of CMV over 1000 copies/mL were included in the study. CMV DNA was analyzed by an automated system (Cobas Ampliprep/COBAS TaqMan CMV Test, Roche Diagnostics, Germany) quantitatively. DNA sequence analysis of the regions including codons 420-664 in the UL97 gene region was done by the Sanger sequencing method to detect mutations causing antiviral resistance and compared with defined mutations. In order to investigate antiviral resistance by phenotypic methods, heparinized blood samples of the patients were collected, 'buffy coat (leukocyte layer)' was inoculated into MRC-5 cells by centrifugation method and CMV growth in these cells was controlled with monoclonal antibodies when growth was detected, virus titer was determined and plaque reduction test was applied as recommended. It was determined that 22 of the 30 patients were HCT recipients and eight were SOT (five kidney, three liver) recipients. When the CMV serology pattern of the patients was evaluated before transplantation, 29 (96.7%) patients were found to be seropositive and one (3.3%) patient was found to be seronegative. Totally, nine CMV UL97 mutations were detected in seven (23.3%) pediatric patients who had HCT, including six seropositive and one seronegative case. In addition, one mutation (D605E) not known to cause GCV resistance was detected in a seronegative recipient and three previously unidentified mutations were detected (1474T, F499S, V559A) in a seronegative recipient. Five of the mutations defined were UL97 mutations with a defined clinical resistance against GCV in each of the five recipients (C603W, C592G, H520Q, M460V, A594T). In the plaque reduction test using 3 µM, 12 µM, 48 µM and 96 µM concentrations of GCV in CMV strains, the IC50 value was determined to be ≥ 8 µM for the five CMV strains, and the phenotypic presence of GCV resistance was shown. Clinical resistance associated with CMV UL97 mutation was detected in five (22.7%) of 22 patients who had HCT. GCV resistance was also demonstrated in these patients by phenotypic methods. No UL97 mutation was detected in the patients who had SOT.

Cytomegalovirus reactivation with high viral load in a patient of coronavirus disease 2019 acute respiratory distress syndrome: a case report

IntroductionCytomegalovirus establishes life-long latency after primary infection in childhood. Cytomegalovirus reactivation has been well reported in immune-compromised patients; however, in the last few years it has been observed that cytomegalovirus reactivation also occurs in critically ill patients without exogenous immunosuppression, which increases length of intensive care unit stay and mortality rate.Case reportA 63-year-old Indian male, without any known comorbidity, developed severe coronavirus disease 2019 and was admitted to the intensive care unit. He received remdesivir, tocilizumab, steroids, anticoagulants, and empiric antibiotics over the next 3 weeks. However, his clinical condition did not improve much, and during the 9th week of illness his condition started deteriorating and routine bacterial cultures, fungal cultures, and cytomegalovirus real-time polymerase chain reaction on blood were negative. His clinical condition worsened rapidly, which led to the need for invasive mechanical ventilation. Tracheal aspirate bacterial and fungal culture showed no growth, but cytomegalovirus real-time polymerase chain reaction showed 21,86,000 copies/mL in tracheal aspirates. After 4 weeks of ganciclovir treatment, the patient improved clinically and was discharged. Currently he is doing well and able to do his routine activity without the need of oxygen.ConclusionTimely management with ganciclovir is associated with favorable outcome in cytomegalovirus infection. Thus, it can be suggested that treatment should be initiated with ganciclovir if a patient with coronavirus disease 2019 has high cytomegalovirus load in tracheal aspirates, along with unexplained and prolonged clinical and/or radiological features.

Cytomegalovirus Glycoprotein B Genotype in Patients with Anterior Segment Infection

(1) The glycoprotein B (gB) on the viral envelope, encoded by the most widely characterised polymorphic gene, gpUL55, is responsible for cytomegalovirus (CMV) entry into the host and could serve as a potential marker of pathogenicity. The aim of the present study is to investigate the distribution of the CMV gB genotype in anterior segment infection in Taiwan and its correlation with clinical manifestations and outcomes. (2) Fifty-seven patients with CMV anterior segment infection were identified according to clinical features and positivity for CMV DNA in aqueous humour samples. CMV gB genotyping was performed through polymerase chain reaction assays. Patients' medical records were retrospectively reviewed. (3) Among the 57 aqueous humour samples tested for gB, 40 (70.28%) had multiple gB genotypes, and only 17 (29.82%) had a single gB genotype. Compared with single-genotype infection, multiple-genotype infection was correlated with higher CMV loads (p < 0.001) but not correlated with outcome. A higher proportion of patients with the gB3 genotype had received filtering surgery before antiviral treatment than those without the gB3 genotype (p = 0.046). (4) Multiple-genotype infection was highly prevalent in CMV anterior segment infection in Taiwan, and gB1 and gB3 were predominant. Multiple-genotype infection was correlated with higher CMV loads but not with specific clinical manifestations or prognostic outcomes. The gB3 genotype may be correlated with poor intraocular pressure control.

Cytomegalovirus disease in immunosuppressed patients with necrotizing pauci-immune glomerulonephritis.

Renal involvement due to necrotizing pauci-immune glomerulonephritis (PIGN) associated with small vessel vasculitis requires the use of immunosuppressive. Associated side effects include an increased risk of infectious processes, such as cytomegalovirus (CMV) disease; therefore, there are no recommendations on its management in the various clinical practice guidelines (CPG). To study the incidence of CMV disease and its determinants. Patients with histological diagnosis of necrotizing pauci-immune glomerulonephritis in the last 10 years, who were determined the viral load of CMV, analyzing the determinants of its occurrence. Forty-four biopsies were performed during the study period. Eleven patients (25%) developed CMV disease; all had received immunosuppressive treatment. Four (30.8%) died during admission. The determinants of CMV disease were age (for every 10 years OR: 3.0, 95% CI: 1.0-8.9, p = 0.012), and plasma albumin (for each g/L OR: 0.8, 95% CI: 0.6-1.0, p = 0.012). The incidence of CMV disease in immunocompromised patients due to PIGN is high, with high mortality. It would be necessary to include strategies in the CPGs to prevent it.

Evaluation of Platelet Parameters in Patients With Secondary Failure of Platelet Recovery and Cytomegalovirus Infection After Hematopoietic Stem Cell Transplantation.

To investigate the clinical significance of changes in platelet parameters in patients with secondary failure of platelet recovery (SFPR) and cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT). In this retrospective study, 79 patients who had undergone allogeneic HSCT (allo-HSCT), including 40 patients with SFPR and 39 patients without SFPR, were recruited. The evaluated parameters were platelet count (PLT), plateletcrit (PCT), platelet-large cell ratio (P-LCR), mean platelet volume (MPV), platelet distribution width (PDW), the incidence of CMV infection after allo-HSCT, and the correlation of SFPR and CMV infection in patients who had undergone allo-HSCT. The control group included 107 healthy donors. The SFPR group had significantly lower megakaryocyte counts, PLT, and PCT and significantly higher P-LCR, MPV, and PDW than the healthy donor and non-SFPR groups. The incidence of CMV infection was higher in SFPR patients than in non-SFPR patients. Among the patients with SFPR, P-LCR, MPV, and PDW were lower in those with CMV DNA >8000 copies/mL than in those with CMV DNA <8000 copies/mL (P < .05 for all); the CMV viral load was slightly negatively correlated with MPV (P = .0297) and P-LCR (P = .0280). We demonstrate for the first time that the level of platelet activation in SFPR patients, which was closely related to CMV infection, was higher than that in that in non-SFPR patients, and higher CMV load was associated with the inhibition of platelet activation.

Fifteen-Year Surveillance of LTR Receiving Pre-Emptive Therapy for CMV Infection: Prevention of CMV Disease and Incidence of CLAD.

The efficacy of pre-emptive therapy in the prevention of cytomegalovirus (CMV) disease and the potential association of CMV infection with the occurrence of chronic lung allograft dysfunction (CLAD) was evaluated in 129 lung transplant recipients receiving pre-emptive therapy based on pp65-antigenemia or CMV-DNA in the blood and in the bronchoalveolar lavage. Seventy-one (55%) patients received pre-emptive ganciclovir/valganciclovir (GCV/VGCV) for CMV infection for a median of 28 (9-191) days. Possible CMV disease occurred in six (5%) patients and was healed after the GCV/VGCV therapy. The cumulative incidence of CLAD was 38% and 54% at 5 and 10 years. Acute rejection and CMV load in the blood (but not in the lung) were independent predictors of the occurrence of CLAD. Pre-emptive therapy is highly effective in preventing CMV disease in lung recipients and does not induce a superior incidence of CLAD compared to what reported for other cohorts of patients who received an extended antiviral prophylaxis.

Clinical presentation and transmission of postnatal cytomegalovirus infection in preterm infants.

Preterm infants are at greater risk of developing postnatal cytomegalovirus (CMV) infection with serious symptoms. Breast milk is the main route of CMV transmission in populations with a high seroprevalence. This study aimed to investigate the clinical presentation and transmission of postnatal CMV (pCMV) infection via breast milk in preterm infants under the specific setting of our neonatal intensive care unit (NICU). The medical records of 147 preterm infants were reviewed retrospectively, and their clinical characteristics and outcomes were analyzed. Breast milk and infant urine samples were collected every two weeks until discharge, and the kinetics of CMV loads were evaluated using a polymerase chain reaction assay. Seventeen infants (11.6%) were diagnosed with pCMV infection during the study period. In comparison between the pCMV and control groups, the mean birth weight was significantly lower in the pCMV group than in the control group (1084.1 ± 404.8 g vs. 1362.5 ± 553.8 g, P = 0.047). Four (23.5%) patients had leukocytopenia, six (35.3%) had neutropenia, three (17.6%) had thrombocytopenia, and two (11.8%) had hyperbilirubinemia in the pCMV group. Five patients were treated with antiviral agents, and their CMV load in the urine decreased after treatment. CMV loads peaked at 3-5 weeks in breast milk, whereas they peaked at 8-12 weeks of postnatal age in infants' urine. A comparison between the median CMV load in breast milk from the pCMV and control groups revealed a significant difference (P = 0.043). Most preterm infants with pCMV infection present a favorable clinical course and outcomes. A high CMV viral load in breast milk is associated with transmission. Further studies are warranted to prevent transmission and severe pCMV infections in preterm infants.

Changes in cytomegalovirus load in the breast milk of very/extremely premature infants and the effect of pasteurization and freeze-thawing on reducing viral load.

ObjectiveThis study aimed to clarify the change in Cytomegalovirus (CMV) loads in breast milk (BM) of very/extremely premature infants (VPI/EPI) with birth weight < 1,500 g after birth, and to compare the effectiveness of pasteurization and freeze–thawing methods in reducing the CMV load of BM.MethodsBreast milk samples were collected and tested every 2 weeks by fluorescence quantitative polymerase chain reaction (FQ-PCR). We determined CMV load in BM before and after pasteurizing, and freeze-thawing.ResultsCytomegalovirus DNA can already be detected in colostrum. The viral load gradually increased in the first 4 weeks, peaked in the 4th to 6th weeks, and gradually decreased thereafter. The viral load gradually returned to the initial level approximately 10–12 weeks postpartum. During the peak period of the CMV load in BM, the viral load was higher in the EPI than the VPI (P < 0.05). The average CMV load (logarithmic [LG]) in the pasteurization group was significantly lower than that in the raw BM group. The average CMV load in the freeze-thawed BM group was significantly lower than that in the raw BM group. The mean CMV load in the pasteurized BM group was lower than that in the freeze–thawed BM group, but the difference was not statistically significant. The CMV-DNA clearance rate in pasteurized was higher than in freeze–thawed (P < 0.05).ConclusionThe CMV detoxification rate in BM is high and the peak load period is mainly between 4 and 6 weeks. The CMV load values detected are higher than the threshold values (7 × 103 copy number/mL) of CMV infection that are reported in the literature as a concern. Both the freeze-thaw and pasteurization techniques can effectively reduce the CMV load.

Comparative real-time PCR quantification of cytomegalovirus in severe early childhood caries and caries-free children

The present study was undertaken to evaluate cytomegalovirus (CMV) load in carious lesions in children with severe early childhood caries (S-ECC) and compare it with caries-free (CF), healthy children, by quantitative real-time polymerase chain reaction (PCR). Dental plaque samples were collected from 57 subjects including S-ECC (n = 33) and CF (n = 24) patients. The two groups were matched in terms of age, gender, and socioeconomic status. After deoxyribonucleic acid (DNA) extraction, SYBR Green real-time PCR was used to quantify CMV DNA. The CMV DNA was detected in seven patients in theS-ECC group. The mean of decayed, missing, and filled tooth surfaces (dmfs) was 11.90 ± 5.95 in the S-ECC group. There was no significant difference in gender between the two groups. There was a significant relationship between CMV positivity in children and theS-ECC group (p = 0.043). Results of this study suggest a relationship between the presence of CMV in the oral cavity and S-ECC. We can design clinical trials to confirm these results and improve children's dental care.

Epstein-Barr Virus and Human Cytomegalovirus Infection in Intestinal Mucosa of Chinese Patients With Inflammatory Bowel Disease.

ObjectiveThis study aimed to determine the frequency of Epstein–Barr virus (EBV), cytomegalovirus (CMV) in mucosa and blood of inflammatory bowel disease (IBD) patients in China and evaluate their correlation with the clinical disease activities.MethodsPeripheral blood and endoscopic fresh colonic mucosal samples were collected from a cohort of 287 IBD patients and 50 controls. Viral DNA load was analyzed through quantitative real-time PCR. The clinical disease activity of ulcerative colitis (UC) and Crohn’s disease (CD) was assessed by the Mayo Clinic Score and Crohn’s disease activity index, respectively.ResultsAmong 287 IBD patients, 228 (79.4%) were positive for EBV and 99 (34.5%) were positive for CMV. EBV and CMV infection rates are significantly higher than those in the control group (28.0%, p < 0.05; 4.0%, p < 0.05). In addition, EBV/CMV prevalence increases as clinical activities progress [For EBV infection, the prevalence was 53.93% (48/89) in the mild group, 87.00% (87/100) in the moderate group, and 94.90% (93/98) in the severe group; and for CMV infection, the prevalence was 3.37% (3/89) in the mild group, 27.00% (27/100) in the moderate group, and 70.41% (69/98) in the severe group]. EBV and CMV loads are related to clinical disease activities (p < 0.05). In addition, viral load in the intestinal mucosa of patients with acute exacerbation of IBD is higher than that of patients in remission.ConclusionHigh prevalence of EBV and CMV is found in patients with IBD, and their prevalence is related to clinical disease activities. In addition, the viral load in the intestinal mucosa is associated with the status of mucosa in the same patients (active phase versus remission phase). Detection of viral load on mucosal specimens with quantitative real-time PCR is a feasible method to monitor EBV and CMV infection in IBD patients.

Molecular Detection and Glycoprotein B (UL55) Genotyping of Cytomegalovirus among Sudanese Renal Transplant Recipients.

Background Cytomegalovirus (CMV) is the most common opportunistic pathogen among renal transplants with significant morbidity and mortality. This study was designed to detect CMV DNA and to determine the frequency of different glycoprotein B (UL55) genotypes among Sudanese renal transplant recipients. Methods One hundred and four renal transplant recipients were included in this study. A blood specimen was collected from each recipient. DNA was extracted from plasma using the QIAamp DNA mini kit. CMV amplification and quantification were performed using CMV Real-RT Quant kits. Genotyping of human CMV gB was carried out by nested PCR and sequencing of the highly diverse region of gB. Results CMV DNA was detected in 40/104 (38.5%) of renal transplant recipients. The average of the CMV DNA viral load was 358 × 104 copies/ml (6.5 log10) ranging from 62 copies/ml (1.8 log10) to 1.43 × 108 copies/ml (9 log10). CMV viremia was detected in 60% of recipients of less than 1–12 months, 17% of 13–24, 10% of 25–36, 5% of 37–48, and 8% in more than 48 months posttransplantation with no association (p = 0.296) between CMV viremia and postrenal transplantation time. The association between the type of immunosuppressive drugs and high viral loads (>1000 copies/ml) showed a significant difference (p = 0.05). The association between CMV loads of >1000 copies/ml and symptoms of CMV disease was highly significant (p ≤ 0.001). Fever 7 (41%), fever and leucopenia 6 (35%), and gastrointestinal disease 4 (24%) were the most common symptoms of CMV disease. CMV genotyping revealed 8 cases (80%) for gB3 and 2 cases (20%) for gB4 genotypes. The most frequent genotype among Sudanese renal transplant recipients was gB3. Conclusions The frequency of CMV DNA is high among Sudanese renal transplant recipients. CMV gB3 is the most predominant glycoprotein B genotype in Sudanese renal transplant recipients.

The Potential Association of Delayed T Lymphocyte Reconstitution Within Six Months Post-Transplantation With the Risk of Cytomegalovirus Retinitis in Severe Aplastic Anemia Recipients.

BackgroundDelayed immune reconstitution after allogeneic hematopoietic stem cell transplantation (HSCT) is significantly associated with cytomegalovirus (CMV) infection. The aim of this study was to observe the recovery trend of peripheral lymphocyte subsets and immunoglobulins in HSCT recipients who developed CMV retinitis (CMVR).MethodsWe identified 37 CMVR cases and 303 non-CMVR controls in this case-control study from a database of 404 consecutive severe aplastic anemia patients who received allogeneic HSCT at a single center between 2015 and 2020. We analyzed the transplant outcomes and immune reconstitution principles with a focus on lymphocyte CD series and immunoglobulin series within the first year post-HSCT.ResultsThirty-seven patients (55 eyes) were diagnosed with CMVR, with a mean onset time of 155 days post-HSCT. Among the 37 patients, one never had CMV detected in his blood but had a high CMV load in his intraocular fluid at the time of CMVR diagnosis. In the controls, 195 had CMV viremia and 108 did not. Compared with controls, CMVR cases had a longer duration of CMV viremia and a higher peak number of CMV load. T lymphocyte subsets including CD3, CD4 and CD8 were significantly lower in CMVR cases within six months after HSCT (all p < 0.05). Immunoglobulins also showed a slower recovery trend in CMVR cases. The recovery of B lymphocytes and natural killer cells exhibited no significant differences between the two groups.ConclusionsIt is not enough to develop fundus screening strategies by merely relying on the CMV serostatus of recipients. Dynamic and continuous monitoring of T lymphocyte subsets, especially within six months post-HSCT, as well as serum immunoglobulin levels, can provide assistance with screening program of CMVR in HSCT recipients with severe aplastic anemia.

Cytomegalovirus infection after renal transplantation.

Renal transplant patients show a high prevalence of cytomegalovirus (CMV) infection after the procedure. This study was conducted to assess the prevalence and factors associated with the incidence of CMV infection among renal transplant patients. A total of 100 patients were recruited in this study. The CMV load in the blood of each patient was assessed using the technique of polymerase chain reaction (PCR). The serostatus of all recipients and donors was examined preoperatively and those of the recipients again postoperatively. The association of CMV load was assessed with the following factors: age, gender, alanine aminotransferase (ALT) and serum creatinine levels, types of immunosuppressive and induction regimens, preoperative diabetes status, and serological virologic response (SVR) at 12 weeks postoperatively. Our findings showed that CMV incidence was significantly higher in middle-aged patients (62 of 66 patients, 93.9%; p=0.0001). Furthermore, about 88.2% of patients induced by anti-thymocyte globulin (ATG) showed a high viral load, significantly higher than the proportion of CMV-positive patients induced by basiliximab (p=0.001). In addition, a higher proportion of CMV-negative recipients who received the graft from CMV-positive donors and vice-versa were CMV-positive postoperatively. Administration of Valcyte 450 showed 100% efficiency in decreasing the CMV load in the patients. Among all the assessed factors, only the age of the recipients, type of induction therapy used, and the preoperative serostatus of both donors and recipients were significantly associated with the postoperative CMV incidence among the patients.

Comparative Effects of Valganciclovir and Ganciclovir on the Congenital Cytomegalovirus Infection and Hearing Loss: A Randomized Controlled Trial

Background: Cytomegalovirus (CMV) is a highly specific herpes virus spreading only from person to person. Valganciclovir (VGCV) and ganciclovir (GCV) are effective in the treatment of neonatal congenital CMV infection. Objectives: This study aimed to compare the curative effects of VGCV and GCV among neonates with CMV infection and evaluate their effects on hearing. Methods: A total of 48 neonates with congenital CMV infection admitted to Huaian Maternal and Child Health Care Hospital, China, were selected from January 2016 to December 2019 and randomly divided into two equal groups of intervention and group (n = 24 each). While the control group received intravenous injection of GCV, the intervention group received oral VGCV. After a 6-week course of treatment, polymerase chain reaction (PCR) was applied to detect the CMV load in both urine and blood. We used the ELISA method to detect the serum CMV-IgM expression level before and after treatment. Moreover, we compared the positive rates of CMV-DNA and CMV-IgM, hyperbilirubinemia, retinitis, hepatosplenomegaly, thrombocytopenia, neutropenia, as well as the results of hearing screening and brainstem auditory evoked potentials (BAEP). Results: Before treatment, there was no statistical difference in blood/urine CMV-DNA expression level and positive expression rates of blood/urine CMV-DNA and CMV-IgM between the groups (P &gt; 0.05). After treatment, blood/urine CMV-DNA expression and the positive expression rates of blood/urine CMV-DNA and CMV-IgM significantly decreased in both groups compared to before treatment (P &lt; 0.05), but there was no statistical significance between the two groups (P &gt; 0.05). Before treatment, there was no significant difference in hearing abnormality rates between the control (50%) and intervention (62.5%) groups (P &gt; 0.05). After treatment, both the control (20.83%) and intervention (29.17%) groups had significantly decreased hearing abnormality rates, and the difference was statistically significant compared with before treatment (P &lt; 0.05), but the difference between the two groups was not statistically significant (P &gt; 0.05). After treatment, the results of comparing BAEP showed that both groups had no statistically significant differences in the number of neonates with normal hearing, mild hearing loss, moderate to severe hearing loss, severe hearing loss, and extremely severe hearing loss (P &gt; 0.05). Before treatment, both groups had no statistically significant differences in the number of neonates with hyperbilirubinemia, retinitis, hepatosplenomegaly, thrombocytopenia, and neutropenia (P &gt; 0.05). After treatment, while the number of neonates with hyperbilirubinemia, retinitis, hepatosplenomegaly, and thrombocytopenia decreased, neutropenia cases increased, and the difference before and after treatment was statistically significant (P &lt; 0.05); however, the difference between the two groups was not statistically significant (P &gt; 0.05). Conclusions: VGCV is similar to GCV in the treatment of neonatal congenital CMV infection, but the oral route of administration of VGCV is more acceptable among neonates.

Nanomembrane-based Apheresis as Safe and Effective Therapy for Cytomegalovirus and Epstein-Barr Virus Reactivation

BACKGROUND: Heavy training schedules or endurance competitions in marathon are forms of extreme physical stress and lead to immunodepression in runners which could be associated with increased susceptibility to viral reactivation by ubiquitous viral infection such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Lately, it was confirmed presence of elevated CMV and EBV loads and the lower antibody titers in competitive athletes. The most common clinical features are fatigue and adynamia accompanied with liver damage, varying from mild and transient elevation of aminotransferases to serious acute hepatitis and liver failure. CASE REPORT: Bearing in mind that a professional practice of marathon running is hazardous for the liver, therapeutic action is necessary as soon as possible to avoid serious complications and even cessation of professional competition. In our case report of professional female marathon runner, we need to treat CMV and EBV reactivation which caused liver damage, prevented regular trainings, and upcoming competitions. We opted for four sessions of nanomembrane based apheresis performed every other day for removal pathological products resulting from virus reactivation to break through the course of the disease and to prevent complications. After completing the whole procedure control laboratory tests and abdominal ultrasound were in physiological ranges. CONCLUSION: Hence, nanomembrane based apheresis can be effective and safe treatment of liver damages for elite marathon runners as well as for athletes.

Cytomegalovirus acquisition in infancy and the risk of tuberculosis disease in childhood: a longitudinal birth cohort study in Cape Town, South Africa

SummaryBackgroundThe risk of tuberculosis disease after recent exposure is greatest before age 5 years; however, the mechanisms explaining this increased risk are not well elucidated. Acquisition of viral infections, such as cytomegalovirus, in early life might modulate the immune system. We aimed to evaluate the acquisition of cytomegalovirus infection in infancy and the development of tuberculosis disease in children.MethodsIn this prospective, birth cohort study we enrolled pregnant women who were between 20 and 28 weeks of gestation attending antenatal care in Paarl, a periurban setting outside of Cape Town, South Africa. Participants were recruited from two clinics (TC Newman and Mbekweni). Infants were given Bacillus Calmette–Guérin vaccination at birth as per national policy. Nasopharyngeal swabs for cytomegalovirus detection using qPCR were done for infants at birth, age 3 and 6 weeks, and age 3, 6, 12, and 24 months. Children were prospectively followed up for tuberculosis disease until age 9 years using tuberculin skin testing, radiographic examinations, GeneXpert, and sputum testing. Tuberculin skin tests were done at the 6-month visit and then at age 12, 24, 36, 48, and 60 months, and at the time of lower respiratory tract infection. We compared tuberculosis disease incidence after age 1 year or after age 6 months in children with and without cytomegalovirus infection using Cox regression and hazard ratios (HRs) with 95% CIs.FindingsBetween March 5, 2012, and March 31, 2015, 1225 pregnant women were recruited and enrolled in the birth cohort. 88 (7%) women were excluded because of loss to antenatal follow-up or pregnancy losses. Of 1143 livebirths, 68 (6%) mother–infant pairs were excluded. In total, 963 children were serially tested for cytomegalovirus (7186 cytomegalovirus measurements taken; median six tests per child, IQR 2–11). The prevalence of congenital cytomegalovirus at age younger than 3 weeks was 2% (18 of 816). Cytomegalovirus positivity increased continuously with age from 3% (27 of 825) by age 6 weeks to 21% (183 of 882) by 3 months, 35% (315 of 909) by 6 months, and 42% (390 of 933) by 12 months. Mother–infant pairs were followed up for a median of 6·9 years (IQR 6·0–7·8). The risk of tuberculosis disease in children after age 1 year was higher in those with cytomegalovirus infection by age 6 weeks (adjusted HR 4·1, 95% CI 1·2–13·8; p=0·022), 3 months (2·8, 1·4–5·8; p=0·0040), 6 months (3·6, 1·7–7·3; p<0·0001), 12 months (3·2, 1·6–6·4; p=0·0010), and 24 months (4·2, 2·0–8·8; p<0·0001). The risk of microbiologically confirmed tuberculosis disease was also higher among children acquiring cytomegalovirus infection before age 3 months (adjusted HR 3·2, 95% CI 1·0–10·6; p=0·048), 6 months (3·9, 1·2–13·0; p=0·027), 12 months (4·4, 1·2–16·3; p=0·027), and 24 months (6·1, 1·3–27·9; p=0·020). In children older than 1 year, the risk of tuberculosis disease was consistently greater in those with high cytomegalovirus loads than in those with low cytomegalovirus loads that were acquired before age 3 months (adjusted HR 2·0 vs 3·7; ptrend=0·0020; both groups compared with cytomegalovirus negative reference) and before age 12 months (2·7 vs 3·7; ptrend=0·0009).InterpretationInfants that acquire cytomegalovirus in the first year of life are at high risk of subsequently developing tuberculosis disease. Efforts to prevent tuberculosis in early childhood in high-burden countries might need to deter or delay acquisition of cytomegalovirus perinatally or in the first months of life.FundingBill & Melinda Gates Foundation, MRC South Africa, National Research Foundation South Africa, and Wellcome Trust.

High Blood Cytomegalovirus Load Suggests Cytomegalovirus Retinitis in HIV/AIDS Patients: A Cross-Sectional Study

ABSTRACT Purpose To clarify the cut off value of blood CMV load to indicate CMV retinitis and its relationships with ocular features. Methods Patients were divided into non-CMV and CMV retinitis groups. A logistic regression model was applied to estimate the association of each variable with CMV retinitis. Spearman correlation was used to estimate the correlation between the blood and aqueous CMV load. Results Blood CMV load higher than 4log10 (OR, 6.897; CI: 2.813–16.910; P < .001) was the major predictor of CMV retinitis. Blood CMV load wasn’t different between the initial and early stage (P = .066). No correlation was observed between the blood and aqueous CMV load (P = .083, r = 0.228). Conclusions Blood CMV load higher than 4log10 is an important predictor for CMV retinitis in HIV/AIDS patients, but it couldn’t indicate the ocular features. Ophthalmologic screening is still necessary. Abbreviations: CMV: Cytomegalovirus; CMVR: Cytomegalovirus retinitis; HIV: Human Immunodeficiency Virus; AIDS: Acquired Immune Deficiency Syndrome; ART: Antiretroviral therapy; EOD: End-organ diseases; PCR: Polymerase Chain Reaction; OR: Odds Ratio; CI: 95% Confidence Interval; IQR: Interquartile range