Serological screening for cytomegalovirus in a leucodepleted blood supply: A systematic review.

Optimal blood donation screening annotation.

CMV Infection after Transplant from Cord Blood Compared to Other Alternative Donors: The Importance of Donor-Negative CMV Serostatus

Leukocyte-reduced blood transfusions: perioperative indications, adverse effects, and cost analysis.

Measures to prevent transfusion-transmitted cytomegalovirus (TT-CMV) infection after hematopoietic stem cell transplantation (HSCT) include transfusion of CMV antibody-negative blood units and/or transfusion of leukoreduced cellular blood products. We assessed the incidence of TT-CMV in CMV-seronegative patients receiving CMV-seronegative HSC transplants, who were transfused with leukoreduced cellular blood products not tested for anti-CMV. In a prospective observational study between 1999 and 2009, all HSCT patients received leukoreduced cellular blood products not tested for anti-CMV. Patients were screened for CMV serostatus and CMV-negative recipients of CMV-negative transplants were systematically monitored for TT-CMV clinically and by CMV nucleic acid testing. Anti-CMV antibodies (immunoglobulin [Ig]G and IgM) were assessed after three time intervals (Interval 1, study inclusion to Day +30 after HSCT; Interval 2, Day +30-Day +100; Interval 3, after Day +100). Among 142 patients treated with allogeneic HSCT, 23 CMV-negative donor-patient pairs were identified. These 23 patients received 1847 blood products from 3180 donors. All patients remained negative for CMV DNA and none developed CMV-associated clinical complications. This results in a risk for TT-CMV per donor exposure of 0% (95% confidence interval, 0.0%-0.12%). However, 17 of 23 patients seroconverted for anti-CMV IgG, but none for anti-CMV IgM. CMV IgG seroconverters received significantly more transfusions per week than nonconverters. The risk of TT-CMV is low in high-risk CMV(neg/neg) HSCT patients transfused with leukoreduced blood products not tested for anti-CMV. The cause of anti-CMV IgG seroconversion is most likely passive antibody transmission by blood products.

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.

Recent studies show that 14-30% of newborn infants with prolonged hospitalizations in intensive care nurseries (ICNs) develop infections with cytomegalovirus (CMV). These infections can be associated with fever, hepatitis and pneumonia. Maternal-infant transmission at the time of birth, and acquisition of CMV through blood products appear to be the major routes of viral transmission. Although most cases of CMV infections occur sporadically in ICNs, our surveillance program has identified several clusters of 2 to 4 infants excreting CMV at the same time in one ICN. These multiple groups of infants with temporally related nosocomial CMV infections suggest that infant-infant transmission of CMV may occur. Using restriction endonuclease analyses, I have compared the DNA fragment migration patterns of the CMV isolates of infants with epidemiologically related infections. In addition, the viruses of a nosocomially infected baby and his mother who developed a primary CMV infection after the discharge home of her infant were compared. At present the analyses indicate that no 2 infants excreting CMV were infected with the same strain virus. However, the DNA digestion pattern of the mother's isolate is identical to her infant's CMV strain. These findings suggest that although nosocomially infected infants are capable of transmitting CMV to other individuals that the risk of infant-infant CMV transmission in ICNs is low with routine methods of handwashing and isolation.

Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)-exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined. CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1-infected women to define correlates of maternal CMV replication and infant CMV acquisition. Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (β = 0.47; P = .005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P = .003) and maternal CD4 < 450 cells/mm(3) (HR, 1.8; P = .008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm(3) to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm(3). Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.

Cytomegalovirus Infection and Lymphopenia Are Associated with Increased Mortality Post Autologous Stem Cell Transplantation

Cytomegalovirus (CMV) infections occur worldwide and primary infection usually occurs in early childhood and is often asymptomatic whereas primary infection in adults may result in symptomatic illness. CMV establishes a chronic latent infection with intermittent periods of reactivation. Primary infection or reactivation associate with increased mortality and morbidity in those who are immunocompromised. Transplacental transmission may result in significant birth defects or long-term sensorineural hearing loss.We performed a study to determine the CMV seroprevalence and the association between HLA Class I alleles and frequency of CMV infection in Ireland. The presence of CMV IgG, a marker of previous CMV infection, was determined for a cohort of 1849 HLA typed solid organ transplant donors between 1990 and 2013. The presence of CMV IgG was correlated with HLA type.The CMV seroprevalence in solid organ transplant donors was 33.4% (range 22–48% per annum) over the time period 1990 to 2013. Multivariate logistic regression analysis showed that both age and HLA alleles were associated with CMV seropositivity. A significant and positive relationship between age and CMV seropositivity was observed (OR = 1.013, P < 0.001, CI [1.007, 1.019]). Chi-square analysis revealed that the female gender was independently associated with CMV seropositivity (P < 0.01). Seroprevalence in women of reproductive age (20–39 years) was significantly higher than men of the same age (37% vs 26%, P < 0.01). The frequencies of HLA-A1, HLA-A2, and HLA-A3 in our cohort were 40.8%, 48.8%, and 25.9%, respectively. Logistic regression analysis showed that the presence of HLA-A1 but not HLA-A2 or HLA-A3 was independently associated with CMV seronegativity (P < 0.01). Interestingly, individuals who co-expressed HLA-A2 and HLA-A3 alleles were significantly more likely to be CMV seropositive (P < 0.02). The frequencies of HLA-B5, HLA-B7, and HLA-B8 in our cohort were 6.1%, 31.2%, and 30.8%, respectively. The presence of the most common inherited haplotype in the Irish population, HLA-A1, B8 was significantly associated with CMV seronegativity (OR = 1.278, P < 0.001, CI [1.049, 1.556]).CMV seroprevalence is lower in Ireland compared with other countries. The high frequency of HLA-A1 in the Irish population may, in part, have a role in the reduced susceptibility to CMV infection.

Use of SARS-CoV-2-infected deceased organ donors: Should we always "just say no?"

Leukocyte depletion (LD) by blood product filtration has been shown to be similarly effective to the use of screened, CMV seronegative blood products to prevent CMV disease in CMV seronegative allogeneic stem cell transplant (SCT) patients with CMV seronegative donors. The aim of this retrospective study was to determine the risk for development of CMV infection requiring preemptive therapy and for CMV disease if unscreened products treated by prestorage LD is used. Forty-nine consecutive patients transplanted after June 1995 were included. As a control group, 33 patients transplanted from January 1992 to June 1995 in whom a combination of CMV seronegative and LD blood products were given. All patients were monitored weekly by a leukocyte-based PCR for CMV DNA detection. Preemptive therapy was initiated after two consecutively positive tests. No patient developed CMV disease in either group. CMV DNA was detected in 6/49 (p = NS) in the study group and in 3/33 patients in the historical control group. Two patients in the study group were given preemptive therapy compared to one patient in the control group. This study suggests that the risk for CMV disease and the need for preemptive therapy against CMV is low in CMV seronegative allogeneic SCT patients receiving grafts from CMV seronegative stem cell donors receiving LD blood products. Thus, this strategy can be safely used together with PCR monitoring and preemptive therapy.

Granulocyte-Colony Stimulating Factor Reactivates Human Cytomegalovirus in a Latently Infected Humanized Mouse Model

Cytomegalovirus (CMV) infection is common among people with HIV (PWH), and may be associated with negative outcomes. We aimed to identify the seroprevalence of CMV between 01 January 1998 and 01 June 2022 among PWH accessing care at the Southern Alberta Clinic (SAC) and the associated risk factors. We also aimed to assess the impact of CMV seropositivity on CD4+ T-cells and CD4+/CD8+ ratio recovery among PWH who maintain HIV viral suppression. Poisson regression models with robust variance estimated crude and adjusted prevalence ratios and 95% confidence intervals to identify risk factors for CMV seronegativity. Among PWH maintaining viral suppression, trends in the median CD4+ T-cell count and CD4+/CD8+ ratio were visualized, and continuous time-to-event Cox proportional hazard models estimated hazards ratios (aHR) for CD4+ cell count recovery to ≥500 cells/mm3 and CD4+/CD8+ ratio of >1 at 10 years by CMV serostatus. Among 3249 PWH, 2954 (91%) were CMV seropositive. CMV seronegativity was associated with younger ages, male sex, non-Hispanic white race and an education of ≥12 years. While CMV seronegativity did not affect CD4+ T-cell recovery following HIV viral suppression (aHR 1.15 [0.89-1.48]), it was associated with a greater likelihood of CD4+/CD8+ ratio normalization (aHR 2.38 [1.85-3.07]) at 10 years of follow-up. CMV is a common coinfection among PWH. We found that CMV positivity among PWH maintaining HIV viral suppression, while not associated with CD4+ T-cell recovery, was associated with a reduced CD4+/CD8+ ratio recovery. This suggests an association with chronic CMV infection-mediated immune activation and inflammation among PWH.

ObjectiveThe objectives are to estimate the vertical transmission rate in twins relative to singleton pregnancies, to evaluate whether discordance within twin pairs is rare, and to characterize concordance within monozygotic and dizygotic twin pairs in relation to hereditability.MethodsWe first sought to estimate the vertical transmission rate of congenital CMV infection in twins by gathering cohort-based studies of congenital CMV in which vertical transmission in both singleton and twin pregnancies was reported. This also allowed us to compare singleton and twin infection rates. From the above studies and other large cohorts of congenitally infected infants, the percentage of discordantly infected twin pairs determined whether this is a rare phenomenon. Theorizing discordance is not rare, we then analyzed data from cases with twin outcomes for congenital CMV infection, according to whether the twins were monozygotic or dizygotic, and calculated their corresponding concordance rates to estimate the broad-sense heritability. Lastly, we described other factors that might affect vertical transmission.ResultsFrom five articles following at-risk pregnancies, the rate of vertical transmission in twin pregnancies is 58.7% (95% CI 43.3-72.3%) whereas in singleton pregnancies it is 31.4% (95% CI: 29.0-34.0%) p = 0.0002. Of ten studies of larger cohorts of infants with congenital CMV infection, 21 of 42 twin pairs with at least one twin infected were discordant for congenital CMV (50.0%, 95% CI: 34.4–65.6%) indicating discordance of congenital CMV infection in twin pairs is not rare. Of 28 studies covering 37 twin pairs where at least one twin had congenital CMV, and zygosity was known, eleven of thirteen monozygotic twin pairs (84.6%; 95% CI: 53.7-97.3%) were concordant for CMV infection, and nine of twenty-four dizygotic twin pairs (37.5%; 95% CI: 19.6-59.2%) were concordant for infection giving an estimated hereditability of 94.2%. Within these 37 twin pairs, factors such as primary or recurrent maternal infection, prematurity, growth discordance, and sex are described; however, in many of these cases these factors are unknown.ConclusionThe rate of vertical transmission of congenital CMV is higher for twins than singletons. Discordance of congenital CMV in twins is not rare and suggests a possible genetic susceptibility to congenital CMV.

Cytomegalovirus (CMV) is the most common viral infection after solid organ transplantation (SOT). Safe and effective prophylactic regimens that decrease its incidence after SOT are essential for long-term graft survival. Although valganciclovir is not Food and Drug Administration-approved for CMV prophylaxis in liver transplant recipients, postmarketing studies have shown valganciclovir to be as effective as ganciclovir in high-risk adult patients undergoing SOT. Currently, data are lacking for pediatric liver transplantation. The purpose of this study was to compare the efficacy and safety of valganciclovir and ganciclovir for CMV infection prophylaxis in pediatric liver transplant recipients. This was a retrospective study of 56 pediatric liver transplant recipients who were prescribed either oral ganciclovir (n = 37) or valganciclovir (n = 19). Patients were followed until 200 days after transplantation or death. The primary outcome measure compared the rates of early-onset CMV infection and CMV disease in the 2 medication groups. Secondary outcome measures identified patient-specific factors that contributed to CMV acquisition and the incidence of late-onset CMV infection or disease. The rates of adverse drug effects and discontinuation were also evaluated. Early-onset CMV disease was documented in 0% of valganciclovir patients and in 5.4% of ganciclovir patients (P = 0.54). There were no statistically significant differences in the secondary outcomes. An increased incidence of late-onset CMV disease was seen in the valganciclovir group versus the ganciclovir group (22.2% versus 8.1%, P = 0.23). No differences in adverse events were reported. In conclusion, no statistically significant differences were found in the incidence of CMV infection or disease between patients receiving oral valganciclovir and patients receiving oral ganciclovir.