Cytomegalovirus Immunoglobulin Research Articles

Conquering CMV Viremia with CMV immunoglobulin, triumph in Renal Transplant Patients: A Case Series

This case series offers the successful management of cytomegalovirus (CMV) viremia in patients who developed CMV infection post renal transplantation. The patients have been treated with three doses of CMV immunoglobulin and ganciclovir for 21 days. The CMV load in each affected person extensively reduced after treatment, indicating the effectiveness of this regimen in coping with CMV viremia in resource constrains setting

Diffusion Tensor Imaging of the Auditory Pathway in Prelingual Deaf Children in Comparison to Normal Hearing Children in the 1 to 7 Years of Age Group

Abstract Objective This article aims to determine the microstructural alterations in the auditory pathway in prelingual deaf children using diffusion tensor imaging (DTI)-derived parameters—fractional anisotropy (FA) and apparent diffusion coefficient (ADC), and secondarily to evaluate these changes in rubella and cytomegalovirus (CMV) positive cases. Method A consecutive series of consenting deaf and normal children between 1 and 7 years of age, forming the case and control groups, respectively, underwent DTI, audiological tests, and testing for rubella, CMV, and toxoplasma infections. FA and ADC were measured at four locations bilaterally: lateral lemniscus (LL), inferior colliculus, medial geniculate body, and auditory cortex (AC). Result The mean ADC values were higher and the mean FA values were lower in cases (19 males, 21 females, mean age 2.65 years) than the controls (21 males, 19 females, mean age 4.63 years) at all eight sites. Sixteen (40%), 17 (42.5%), and 7 (17.5%) cases had severe, severe to profound, and profound hearing loss, respectively, the FA and ADC values being significantly different for LL. For rubella and CMV immunoglobulin G, 20/40and 17/40 cases were positive, respectively, 11 for both, and none for toxoplasma. Significant decrease in FA was seen at LL and AC in rubella/CMV positive cases. Conclusion Microstructural changes are seen throughout the auditory pathway in prelingual deaf children, especially with rubella and/or CMV positive status. Further studies may pave the path to segregate out patient groups potentially more responsive to cochlear implant.

Cytomegalovirus Retinitis: Clinical Manifestations, Diagnosis and Treatment.

Cytomegalovirus (CMV) retinitis is the most common eye disease associated with CMV infection in immunocompromised individuals. The CMVR may initially be asymptomatic; however, relatively mild vitreous inflammation at the onset may be an important differential point from other diseases in HIV patients. Fundus photography, CD4 T-cell count, and telemedicine could be used to screen and monitor the high-risk population, particularly in resource-limited regions. Retinitis generally starts in the peripheral retina and advances toward the posterior pole, which could develop to the characteristic "pizza pie" appearance marked by central retinal necrosis and intraretinal hemorrhage. CMVR causes vision loss if left untreated, and early antiviral therapy significantly reduces the risk of vision loss. Alongside traditional antiviral treatments, immunotherapies including CMV-specific adoptive T-cell therapy and CMV immunoglobulin (CMVIG) are emerging as promising treatment options due to their favorable tolerability and reduced mortality. This review comprehensively examines CMV retinitis, encompassing the clinical features, differential diagnosis, laboratory tests, and updated treatment strategies to inform clinical management.

Overview of latent tuberculosis-related central serous chorioretinopathy: Review and case report

We present a case of multifocal central serous chorioretinopathy (CSCR) in a 40-year-old male who presented with gradual loss of vision in both of his eyes during the previous 3 months. The anterior segment examination was normal; the dilated fundus examination revealed severe retinal elevation in the macular area in both eyes. Optical coherence tomography confirmed the presence of subretinal fluid with a central macular thickness of 353 μm OD and 356 μm OS. On the basis of ocular findings, a diagnosis of multifocal CSCR was made. One month later, the patient complained of further vision loss. His erythrocyte sedimentation rate was elevated, and the Mantoux test (22 mm × 22 mm), the QuantiFERON TB gold (5 IU/ml), and the cytomegalovirus immunoglobulin G (2277.92 AU/ml) yielded positive results. A diagnosis of latent tuberculosis infection was made. After 2 months of starting antitubercular treatment, the patient’s visual acuity improved.

Seroprevalence and age-related susceptibility of TORCH infections in childbearing age women: A 5-year cross-sectional retrospective study and a literature review

BackgroundSerodiagnosis of TORCH infections should be performed in pre-pregnancy and reproductive-age women to prevent vertical transmission. Herein, we conducted a 5-year cross-sectional retrospective study in childbearing age women to provide prevalence data. Also, stratifying the cohort into three age groups, we identified those most susceptible to acute TORCH infections. MethodsBetween 2019 and 2023, serum samples from 2286 childbearing age women attending the “R. Dulbecco” University Hospital of Catanzaro were collected. Screening for TORCH pathogens, such as: Toxoplasma gondii (TOX), Cytomegalovirus (CMV), Rubella Virus (RUB), Parvovirus B19 (ParvoB19), Herpes Simplex Virus types 1 and 2 (HSV1, HSV2) and Treponema pallidum was carried out using serological tests. Chemiluminescent immunoassay was performed to detect TOX, CMV and ParvoB19 Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies, while Enzyme Linked Fluorescent Assay was performed to detect RUB IgM and IgG antibodies and CMV and TOX IgG Avidity. Enzyme Linked Immunosorbent Assay was performed to detect HSV1 IgG, HSV2 IgG, HSV1/2 IgM, T. pallidum total antibodies and RUB IgG Avidity. Binomial logistic regression models were developed to compare seroprevalence rates among different age groups. ResultsThe highest immunological protection was observed for RUB infection (87 %), probably associated with vaccination practice, followed by HSV1 and CMV (82 % and 63 %). The 16–25 year age group results as the most susceptible to acute infections as demonstrated by odds of CMV IgM positivity (primary infection) which decreased with age. ConclusionsThe TORCH serological screening program should be implemented in women before pregnancy to formulate strategies for serological screening of childbearing age women and guiding clinicians in making decisions.

The embodiment of the neighborhood socioeconomic environment in the architecture of the immune system.

There is growing recognition of the importance of immune health for understanding the origins of ageing-related disease and decline. Numerous studies have demonstrated consistent associations between the social determinants of health and immunosenescence (i.e. ageing of the immune system). Yet few studies have interrogated the relationship between neighborhood socioeconomic status (nSES) and biologically specific measures of immunosenescence. We used data from the US Health and Retirement Study to measure immunosenescence linked with neighborhood socioeconomic data from the National Neighborhood Data Archive to examine associations between indicators of nSES and immunosenescence. We found associations between both the ratio of terminally differentiated effector memory to naïve (EMRA:Naïve) CD4+ T cells and cytomegalovirus (CMV) immunoglobulin G (IgG) levels and nSES. For the CD4+ EMRA:Naïve ratio, each 1% increase in the neighborhood disadvantage index was associated with a 0.005 standard deviation higher value of the EMRA:Naïve ratio (95% CI: 0.0003, 0.01) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.05 higher standardized value of the CD4+ EMRA:Naïve ratio. The results were fully attenuated when adjusting for both individual-level SES and race/ethnicity. For CMV IgG antibodies, a 1% increase in neighborhood disadvantage was associated a 0.03 standard deviation higher value of CMV IgG antibodies (β = 0.03; 95% CI: 0.002, 0.03) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.3 higher standardized value of CMV. This association was attenuated though still statistically significant when controlling for individual-level SES and race/ethnicity. The findings from this study provide compelling initial evidence that large, nonspecific social exposures, such as neighborhood socioeconomic conditions, can become embodied in cellular processes of immune ageing.

Impact of cytomegalovirus (CMV) seroconversion pre-allogeneic hematopoietic cell transplantation on posttransplant outcomes.

Cytomegalovirus (CMV) reactivation post-allogeneic hematopoietic cell transplantation (post-alloHCT) increases morbidity and mortality. We sought to determine the frequency of CMV seroconversion in patients pre-alloHCT and to investigate the impact on posttransplant outcomes. We retrospectively investigated 752 adult patients who underwent alloHCT at our center from January 2015 to February 2020 before the adoption of letermovir prophylaxis. CMV serology was assessed at consult and pretransplant. The cohort was divided into four groups based on pretransplant CMV seroconversion: negative to positive (Group 1), positive to negative (Group 2), consistently negative (Group 3), and consistently positive (Group 4). Eighty-nine patients (12%) had seroconverted from negative to positive, 17 (2%) from positive to negative, 151 (20%) were consistently seronegative, and 495 (66%) were consistently seropositive pretransplant. For the four CMV serostatus groups, cumulative incidence of CMV reactivation at 6 months posttransplant was 4.5%, 47.1%, 6.6%, and 76.6% for Groups 1, 2, 3, and 4, respectively (p < .0001). No differences between groups were seen regarding Grade III-IV acute graft-versus-host disease (GVHD) (p = .91), moderate/severe chronic GVHD (p = .41), or graft failure (p = .28). On multivariable analysis, there was no impact of CMV serostatus group on overall survival (p = .67), cumulative incidence of relapse (p = .83) or non-relapse mortality. alloHCT patients who demonstrate CMV seroconversion pretransplant from negative to positive have a very low risk of CMV reactivation posttransplant. The observed seroconversion may be due to passive CMV immunity acquired through blood products. Quantitative CMV immunoglobulin G/immunoglobulin M pretransplant may help differentiate between true seroconversion and passively transmitted CMV immunoglobulin.

Progressive Thrombocytopenia, Splenomegaly, and Abnormal Tone in an Infant With Growth Faltering.

A 4-month-old full-term female presented with growth faltering associated with progressive feeding difficulty, rash, abdominal distension, and developmental delays. She was found to have disconjugate gaze, abnormal visual tracking, mixed tone, bruising, and splenomegaly on examination. Initial workup was notable for thrombocytopenia and positive cytomegalovirus (CMV) immunoglobulin G and immunoglobulin M antibodies. She initially presented to the infectious diseases CMV clinic, where she was noted to have severe malnutrition, prompting referral to the emergency department for hospital admission to optimize nutrition with nasogastric tube feeding and facilitate additional evaluation. An active CMV infection with viruria and viremia was confirmed, but elements of her presentation and workup including brain magnetic resonance imaging were not consistent with isolated CMV infection. To avoid premature diagnostic closure, a multidisciplinary workup was initiated and ultimately established her diagnosis.

Reexploring cytomegalovirus serology in allogeneic hematopoietic cell transplantation.

Discuss the recent evidence on cytomegalovirus (CMV) serology in allogeneic hematopoeic cell transplant (HCT) recipients. Whereas the role CMV-specific cellular mediated immunity has recently emerged as an important factor of CMV DNAemia posttransplant, the value of CMV serology has remained unchanged through decades, associated with donor selection and posttransplant prophylactic and monitoring strategies. In this review, we describe and discuss the emerging reports on the association between the magnitude of pretransplant CMV immunoglobulin G (IgG) titer and the posttransplant incidence of CMV DNAemia, as CMV IgG titer could become an additional tool in CMV risk assessment in the future. Pretransplant recipient CMV serology may have significant implications in posttransplant CMV reactivation in allogeneic HCT recipients.

Delphi Method Analysis and Consensus of Prevalent Distinctive Practices for Biliary Atresia Management after Kasai Portoenterostomy.

Extrahepatic biliary atresia (BA) is seen in infants, with an incidence of 1 in 15,000 live births. The presentation is progressive jaundice, dark-colored urine, and clay-colored stools. Kasai portoenterostomy (KPE) is the commonly performed surgical procedure in these patients. Postoperatively, phenobarbitone, ursodeoxycholic acid (UDCA), steroids, and other drugs are given to improve bile drainage and prevent inflammation and fibrosis. However, a definitive protocol regarding the need for different drugs, dosage, and duration varies across individual surgeons and centers. No universally accepted protocol exists for postoperative management after KPE. The aim of this study was to know the prevailing postoperative management of BA by subject experts and use the Delphi process to know if the experts want to change their practice based on the results from the survey. A questionnaire was made after discussing with two experts in the field of BA. The questionnaire was mailed to 25 subject experts. The first survey data were analyzed and shared with all responders. In the second survey, change in the management based on the results from the first survey was assessed. The Delphi questionnaire was answered by 17 experts. Postoperatively, prophylactic antibiotics are prescribed for 6-12 weeks by around 40% and >12 weeks by 30% of respondents. Phenobarbitone is prescribed for <3 months by nearly 50%. UDCA is prescribed for <3 months, ≤6 months, and 6 months-1 year by 47.1%, 23.5%, and 23.5% responders, respectively. Nearly 50% prescribe steroids (mostly prednisolone), and among them, two-thirds prescribe it for 6-12 weeks. Approximately 60% give antiviral drugs to children who are cytomegalovirus immunoglobulin M positive. In our survey, 50% of experts perform 5-10 KPE per year, and 25% each perform 10-15 and >15 KPE per year. The second survey noted that a significant percentage of responders want to change their practice according to consensus. From our Delphi survey, an overview of the postoperative management of BA could be made. However, multicentric studies are required for uniform protocol on the postoperative management of BA.

Cytomegalovirus Immunoglobulin G Levels and Subclinical Arterial Disease among People Living with HIV in Botswana: A Cross-Sectional Study.

Cytomegalovirus (CMV) has been linked with increased cardiovascular risk and monocyte activation in people living with HIV (PLWH). This cross-sectional study aimed to compare CMV immunoglobulin G (IgG) levels between combined antiretroviral therapy (cART)-treated PLWH versus ART-naïve PLWH and those without HIV, and to investigate their associations with biomarkers of endothelial injury and carotid atherosclerosis, in Gaborone, Botswana. All participants were between 30 and 50 years old. Carotid intimal media thickness (cIMT) and biomarkers of endothelial injury and monocyte activation were also assessed. The association between quantitative CMV IgG and cardiovascular disease risk was assessed in multivariate logistic regression analysis. The results showed that the mean CMV IgG level among ART-naïve participants was significantly higher than both the cART group and controls. However, CMV IgG levels did not differ significantly between the controls and cART groups. Among PLWH, CMV IgG levels were associated with ICAM-1 levels and cIMT. Increases in CMV IgG among ART-naïve participants were significantly associated with increases in log VCAM-1. In conclusion, CMV IgG levels are elevated among PLWH in sub-Saharan Africa, and higher levels are associated with biomarkers of endothelial injury and cIMT. Future research should investigate the long-term impact of elevated CMV IgG among PLWH.

(977) - Efficacy of CMV Immunoglobulin as Cytomegalovirus Prophylaxis in High Risk Lung Transplant Recipients

(977) - Efficacy of CMV Immunoglobulin as Cytomegalovirus Prophylaxis in High Risk Lung Transplant Recipients

Evaluation of Three Cytomegalovirus IgG Lateral Flow Assays for Rapid Determination of CMV Serostatus.

Cytomegalovirus (CMV) serostatus is a major determinant of CMV infection, disease risk, and transplant outcomes. Current clinical serology assays are limited by relatively slow turnaround time, design for batched testing, need for trained personnel, and/or specialized equipment. Rapid diagnostic assays in development have a role in emerging settings, such as critically ill patients, but have not been systematically evaluated. We assessed the performance of 3 rapid lateral flow assays (LFAs) for the detection of CMV immunoglobulin (Ig)G antibodies compared with a reference commercially available CMV IgG enzyme-linked immunosorbent assay in residual serum samples from 200 consecutive adults who underwent clinical CMV serology testing. Samples with discrepant results between the LFA and reference assay were tested by a second reference assay. A subset of serum samples was assessed for interoperator variability. Operating characteristics of the QooLabs LFA were separately assessed in plasma samples. The sensitivity and specificity of the individual LFA assays using serum varied significantly: 86%/83%, 99/93%, and 57/97%, for Healgen, QNow automated reader, and nanoComposix, respectively, compared with the reference assay. Results for the QNow assay were comparable between automated and manual reads. Among a subset of 10 serum samples assessed by 5 individual operators, 44 of 50 (88%) results were concordant. Among 50 plasma samples assessed by the QooLabs LFA, the sensitivity and specificity were 72% and 96%. The ease of performance, rapid turnaround time, and good operating characteristics provide the rationale for further evaluation of the Qoolabs QNow LFA in specialized settings where rapid assessment of CMV serostatus would be advantageous.

Cytomegalovirus immunoglobulin serology prevalence in patients with newly diagnosed multiple myeloma treated within the GMMG-MM5 phase III trial

ABSTRACT Objectives The seroprevalence of antibodies against Cytomegalovirus (CMV) is an established poor prognostic factor for patients receiving an allogeneic stem cell transplantation. However, the impact of CMV serology on outcome after autologous stem cell transplantation remains unknown. Methods Here, we analyzed the CMV immunoglobulin (Ig) serology of 446 newly-diagnosed multiple myeloma (MM) patients of the GMMG-MM5 phase III trial with a median follow-up of 58 months. Results CMV IgG and IgM positivity was seen in 51% and 6% of the patients, respectively. In multivariate analysis CMV IgG and CMV IgM serology show an age-depending effect for PFS. We identified positive CMV IgG/positive CMV IgM serology as an age-depending beneficial factor on PFS. Discussion Younger patients with a positive CMV IgG/positive CMV IgM serology experienced a favorable effect on PFS, whereas a positive CMV IgG/positive CMV IgM serology at older age has a disadvantageous effect on PFS.

Demographic and Clinical Characteristics of Kidney Donors at First Check: A Single-Center Experience.

Kidney transplant is the best treatment for patients with end-stage kidney disease. In many regions of the world, including the Middle East, most kidney transplants are from living donors. In contrast to recipients, data for living donors remain scarce. Here, we describe living donor baseline characteristics at first hospital check at a single center in Baghdad, Iraq. We collected and analyzed demographic, laboratory, imaging, and histocompatibility data from donor records at the Nephrology and Renal Transplantation Center, Medical City-Baghdad, Baghdad, Iraq, from July 2022 to September 2022. We included 124 kidney donors (56.4% male) who donated their kidneys 1 to 3 years previous to our study, with a mean age of 34.84 ± 10.04 years and mean body mass index (weight in kilograms divided by height in meters squared) of 27.11 ± 2.12. Most donors donated their kidneys to a firstdegree relative (69.2%); blood group O was the most prevalent (47.5%). More than half of the donors were unemployed. Histocompatibility testing showed that 40% of the donors had >3 human leukocyte antigen mismatches with their recipients, and 30% of the recipients were high-risk sensitized patients with a calculated panel reactive antibody >50%. Regarding the virus status, 68.5% of the donors tested positive for cytomegalovirus immunoglobulin G, 8% of the transplants were high-risk cytomegalovirus status, and 43.5% tested positive for Epstein-Barr virus immunoglobulin G. Renal imaging showed that 75.8% of donors had a single artery and 24.1% had a double artery (26.6% double left, 40% double right, and 33.3% both). For living transplant procedures at a single center in Iraq, most were from related donors. Most donors are unemployed, which mandates future health and social support. High immunological and viral risks must not be ignored in a single center with living related donors.

Impact of COVID-19 on Cytomegalovirus Immunoglobulin M Antibody Index

Background: Coronavirus disease 2019 (COVID-19) influenced the prevalence of other infectious diseases, including congenital cytomegalovirus (CMV) infection. However, the effect of COVID-19 on antibody titers has not been reported. This study aimed to explore the influence of COVID-19 on levels of CMV immunoglobulin M (IgM) in pregnant women. Methods: This cross-sectional study included pregnant women who visited the University Hospital due to CMV IgM positivity during the 7th and 8th waves of COVID-19. Data, including maternal characteristics, history of COVID-19, CMV immunoglobulin G (IgG) and IgM index, and IgG avidity index (AI) were collected. Chemiluminescent immunoassay was performed to measure levels of IgG and IgM. Polymerase chain reaction using neonatal urine was performed to confirm congenital infection. Results: Of the 89 pregnant women, 36 (40%) (low IgG AI: n = 10; high IgG AI: n = 26) contracted COVID-19. Among 21 women with low IgG AI, 9 (false IgM positive: n = 8; primary infection: n = 1) had an IgG AI of 0. Among the eight women with false IgM positivity, six (75%) contracted COVID-19. The IgM index of pregnant women with false IgM positivity was 12.6 ± 10.9. Meanwhile, the CMV IgM index of pregnant women with false IgM positivity in the non-COVID-19-infected group was 1.7 ± 0.5. When the IgM indices of women who contracted (n = 36) and did not contract (n = 53) COVID-19 were compared, the IgM index of infected women (4.4 ± 5.7) was higher than those of non-infected women (2.7 ± 3.0) (p = 0.01). Regarding IgM and IgG AI, multiple logistic regression analysis revealed that there were no significantly different variables between the two groups. Conclusions: High prevalence of false IgM positivity was observed among women who contracted COVID-19. The IgM index of pregnant women with false IgM positivity was high. Caution should be exercised in interpreting CMV IgM indices in pregnant women with a history of COVID-19.

Possible roles of human cytomegalovirus immunoglobulin G and its avidity to specific human cytomegalovirus antigens in the prevention of abortion among pregnant women

Abstract Background: The human cytomegalovirus (HCMV) is a widespread viral pathogen characterized by strict host specificity and is limited to humans. It has been described as an important etiological agent of intrauterine infection during the pregnancy, that causes lifelong infection and may lead to some serious results such as miscarriage, cerebellar malformation stillbirth, and fetus developmental retardation. Objectives: The study was carried out in Kirkuk governorate from the August 2021 to April 2022 to analyze the seroprevalence of HCMV-immunoglobulin G (IgG) against some HCMV antigens and its relation to the history of abortion. Materials and Methods: A total of 220 pregnant women were examined for the seroprevalence of HCMV-IgG by using electro-chemo-luminescence technique and then examined their reactivity and avidity for specific HCMV antigens using line immune assay. Results: The findings of the study showed that among 120 HCMV-IgG seropositive pregnant women, the rates of IgG antibodies were 161 (73.18%). In terms of reactivity and avidity of HCMV-IgG against different HCMV antigens, the rates were as follows: 67 (55.83%) for HCMV IE1, 52 (43.33%) for CM2, 116 (96.66%) for p150, 68 (56.66%) for p65, 117 (97.5%) for gB1, and 82 (68.33%) for gB2 antigens. Among pregnant women with no previous history of abortion, the prevalence of HCMV-IgG reactivity against gB2 was 75.60%. Furthermore, the rates of HCMV-IgG avidity for HCMV antigens were 90.24% for CM2 and 83.05% for p65 antigens. Conclusions: This finding may refer to the possible role of the specificity of HCMV-IgG and its high avidity for specific HCMV antigens in the prevention of abortion among pregnant women infected with HCMV infection.

Body Surface Area Valganciclovir Prophylactic Dosing is Associated with a Higher Rate of Drug-Associated Toxicities Compared to Body Weight Dosing in Pediatric Solid Organ Transplant Recipients

Abstract Background Valganciclovir (VGCV) is used for prevention of cytomegalovirus (CMV) in pediatric solid organ transplant (SOT) recipients who are at moderate or high risk for CMV infection or reactivation. Optimal dosing is not well defined, and both weight-based (WB) (15 mg/kg/dose) and body surface area-based (BSA) dosing (7 x BSA x creatinine clearance with an upper limit of 150 mL/min/1.73 m2) are used. We used a recently completed retrospective study on VGCV toxicity to compare the effects of these 2 dosing strategies on the proportion and the odds of CMV DNAemia, neutropenia, lymphopenia, and toxicity-related VGCV discontinuation or dose modification. Methods Data was collected from 6 US centers. Inclusion criteria were SOT recipients &amp;lt;20 years of age transplanted between January 2016 and December 2019, anticipated to receive VGCV prophylaxis with either dosing method for &amp;gt;/=3 months, and availability of &amp;gt;/=6 months of follow-up data post-transplant. Neutropenia and lymphopenia were defined as absolute neutrophil or lymphocyte count &amp;lt;1000 cells/microL. The number of patients who had premature discontinuation or dosing modification attributed to leukopenia or acute kidney injury (AKI) was quantified. Anticipated VGCV duration, dosing strategy, and threshold for making VGCV changes were at the discretion of each center for each patient. Cytopenias or toxicities that occurred within 15 days of SOT were excluded. Data were collected for one-year post-transplant and analyzed using Stata version 17.0. Groups were compared using Mann Whitney U test for continuous variables and chi-square test for categorical variables; logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) with multivariable analysis. Results 412 patients met inclusion criteria. 312 patients were treated with WB and 100 with BSA dosing. Median age at transplantation was 5.1 (IQR 1.8-11.8) years and 42.7% were female. Transplanted organs included: liver 35.4%, kidney 33.5%, heart 22.3%, lung 6.6%, and other 2.2%. Within one year of transplantation, 23.4% and 12.2% of the WB group and 31.0% and 16% of the BSA group had at least one episode of CMV DNA detection in the plasma (DNAemia) and breakthrough CMV DNAemia while on VGCV prophylaxis, respectively (p=0.1 and p=0.3). There was no statistically significant difference in the odds of CMV DNAemia or breakthrough CMV DNAemia between dosing groups at one year when adjusted for: transplanted organ, CMV risk based on pre-transplant serostatus, duration of anticipated prophylaxis, age, receipt of CMV immunoglobulin, anti-thymocyte globulin, basiliximab, alemtuzumab, mycophenolate and corticosteroid (aOR=1.1, 95% CI: 0.6-1.8, p=0.8 and aOR=1.4, 95% CI: 0.6-2.9, p=0.4). However, the risk of all drug toxicity while on prophylaxis were significantly greater in BSA compared to WB group: neutropenia (50.0% vs 29.3%), lymphopenia (51.0% vs 15.0%), and toxicity-related VGCV discontinuation or modification (21% vs 6.7%) (each p&amp;lt;0.001). The BSA group had higher odds of neutropenia (aOR=2.3, 95% CI: 1.4-3.7, p=0.001), lymphopenia (aOR=7.0, 95% CI: 3.9-12.4, p&amp;lt;0.001), and toxicity-related VGCV discontinuation or modification (aOR=4.6, 95% CI: 2.2-9.3, p&amp;lt;0.001) while on prophylaxis when adjusted for age, organ, anticipated VGCV duration, and receipt of trimethoprim-sulfamethoxazole, anti-thymocyte globulin, basiliximab, alemtuzumab, mycophenolate and corticosteroid. Conclusions Results of this study indicate that BSA dosing of VGCV is associated with a significantly greater risk of toxicity without a decrease in CMV DNAemia.

Evaluation of risk factors for cytomegalovirus DNAemia after end of regular prophylaxis after heart transplantation.

Cytomegalovirus (CMV) infections after heart transplantation (HTx) can cause cardiac allograft vasculopathy. Consequently, monitoring and prophylaxis for cytomegalovirus deoxyribonucleic acid(CMV-DNAemia) within the first weeks after HTx is recommended. All patients who underwent HTx between September 2010 and 2021 surviving the first 90 days (n = 196) were retrospectively reviewed. The patients were divided on the prevalence of CMV-DNAemia during the first postoperative year after the end of the prophylaxis. A total of n = 35 (20.1%) developed CMV-DNAemia (CMV group) and were compared to patients without CMV-DNAemia (controls, n = 139). The remaining patients (n = 22) were excluded due to incomplete data. Positive donors and negative recipients (D+/R-) and negative donors and positive recipients(D-/R+) serology was significantly increased and D-/R- decreased in the CMV group (p < .01). Furthermore, the mean age was 57.7 ± 8.7 years but only 53.6 ± 10.0 years for controls (p = .03). Additionally, the intensive care unit(p = .02) and total hospital stay (p = .03) after HTx were approximately 50% longer. Interestingly, the incidence of CMV-DNAemia during prophylaxis was only numerically increased in the CMV group (5.7%, respectively,0.7%, p = .10), the same effect was also observed for postoperative infections. Multivariate analyses confirmed that D+/R- and D-/R+CMV immunoglobulin Gmatch were independent risk factors for postprophylaxis CMV-DNAemia. Our data should raise awareness of CMV-DNAemia after the termination of regular prophylaxis, as this affects one in five HTx patients. Especially old recipients as well as D+/R- and D-/R+ serology share an elevated risk of late CMV-DNAemia. For these patients, prolongation, or repetition of CMV prophylaxis, including antiviral drugs and CMV immunoglobulins, may be considered.

Role of Preemptive Cytomegalovirus Hyperimmunoglobulin in Cytomegalovirus Viremia Following Stem Cell Transplant: An Integrative Review.

Cytomegalovirus (CMV) is a major cause of morbidity and mortality in stem cell transplant (SCT) patients. Cytomegalovirus hyperimmunoglobulin (CMV-HIG) therapy has been described in the solid organ transplant setting. However, no review has focused on preemptive use of intravenous CMV immunoglobulins in the SCT setting. This review aims to consolidate findings regarding the preemptive use of CMV-HIG for CMV viremia in SCT patients. PubMed and Scopus were searched using specific search criteria for publications from 2011 to 2021. Search terms were: cytomegalovirus, CMV, immunoglobulins, immunoglobulin, IVIG, CMVIG, hematopoietic stem cell transplantation, and stem cell. Included studies discussed stem cell transplantation, immunoglobulins, and cytomegalovirus. 366 articles were identified from the search. Five articles met the inclusion and exclusion criteria. Preemptive CMV-HIG resulted in an overall response in 65% to 100% of patients with a clearance time of 14 to 21 days. Early use of CMV-HIG may shorten clearance time. No treatment-related mortality or serious adverse events were associated. CMV-HIG is an effective treatment option in SCT patients that is as safe as antivirals alone. Preemptive CMV-HIG with antivirals may provide the added advantage of reduced time to viremia clearance without adding renal injury. Larger, prospective studies are needed to evaluate CMV-HIG's impact on time to viremia clearance and the effectiveness of preemptive CMV-HIG use with antivirals.