The Value of Hyperimmune Globulin in Pregnancies Complicated by Cytomegalovirus Infection: A Continuing Saga.
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ABSTRACT:
SUBMITTER: Schleiss MR
PROVIDER: S-EPMC7486836 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
The Value of Hyperimmune Globulin in Pregnancies Complicated by Cytomegalovirus Infection: A Continuing Saga.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20200901 6
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Project description:BackgroundPrimary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection.MethodsIn this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed.ResultsFrom 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo.ConclusionsAmong pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).
| S-EPMC8363945 | biostudies-literature
Project description:Cytomegalovirus (CMV) is a major cause of allogeneic hematopoietic stem cell transplant (HSCT)-related morbidity and mortality. Treatment failure continues to be a major issue in patients with CMV infection due to both drug resistance and intolerance. This single-center brief retrospective analysis of a case series aims to investigate the safety and efficacy of CMV-hyperimmune globulin as salvage therapy for CMV infection in children undergoing HSCT. Fifteen pediatric patients received human CMV-specific immunoglobulin (CMVIG) between July 2018 and December 2021 as a salvage therapy for refractory or recurrent CMV infection. At the time of CMVIG prescription, eight children presented with recurrent CMV infection and seven with refractory CMV infection. The overall response rate was 67% at 50 days from the CMVIG administration [95% confidence interval (CI): 44-88]. Overall survival (OS) from CMVIG administration at 100 days was 87% (95% CI: 56-96), and OS from HSCT at 1 year was 80% (95% CI: 50-93). Four patients died, three unrelated to CMV infection and one due to CMV pneumonia. CMVIG as salvage therapy was well tolerated, and no infusion-related adverse events were observed.
| S-EPMC10405925 | biostudies-literature
Project description:DNA methylation, a partially reversible process, is critical in tissue development and aging. The discrepancy between biological age, as estimated from methylation, and chronological age has been proposed as a potential indicator of health and disease. Epigenetic age acceleration has been implicated as a contributing mechanism in obstetric conditions such as preeclampsia and small-for-gestational-age, yet future studies could benefit from more accurate models. Herein, we curated 1,842 placental methylomes from the public domain and organized a DREAM challenge to develop models that infer gestational age. Challenge participants were blinded to the test data that we generated from 384 placentas encompassing normal and complicated pregnancies. The mean absolute error of the top performing model (0.99 weeks of gestation) and of a post-challenge placental clock model (PCPC, 1.04 weeks) compared favorably to the accuracy of existing models. Moreover, predictions obtained with new models were better calibrated across the gestational age spectrum and suggest that previous reports of accelerated aging in preterm preeclampsia were likely due to modeling artifacts. Based on predictions from previous and newly developed epigenetic models we found that accelerated placental ageing was associated with a decrease in birthweight percentiles in male neonates delivered at term in our test cohort (about 10 birthweight percentiles drop per week of age acceleration for PCPC model, p<0.001). By contrast, preterm accelerated aging was protective against delivery of a small-for-gestational-age neonate regardless of fetal sex.
2025-07-10 | GSE287219 | GEO
Project description:Information on treatment of COVID-19 infection in renal transplant recipients is scarce, especially in symptomatic patients and patients with recent major clinical events. This group of patients suffers from different opportunistic infections which may coexist with COVID-19. Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 infection with either antiviral drugs, hydroxychloroquine and/or azithromycin. Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. Besides the immunosuppression reduction which is supposed to be beneficial, immunoglobulins with their immunomodulatory effects and possible antiviral role, may increase a possibility for favorable outcome.
| S-EPMC7261461 | biostudies-literature
Project description:The aim of this randomized, controlled trial is to determine whether anti-SARS-CoV-2 hyperimmune globulin protects against severe COVID-19 in severely immunocompromised, hospitalized, COVID-19 patients. Patients were randomly assigned to receive anti-SARS-CoV-2 hyperimmune globulin (COVIG) or intravenous immunoglobulin without SARS-CoV-2 antibodies. Severe COVID-19 was observed in two out of ten (20%) patients treated with COVIG compared to seven out of eight (88%) in the IVIG control group (p = 0.015, Fisher's exact test). COVIG may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available. The trial was registered at www.trialregister.nl (#NL9436).
| S-EPMC9384649 | biostudies-literature
Project description:Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus.
| S-EPMC9320065 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.
| S-EPMC9108634 | biostudies-literature
Project description:Aims: This study was aimed at assessing the association of oral glucose tolerance test (OGTT) glucose threshold levels and the requirement of insulin therapy in twin pregnancies with gestational diabetes mellitus (GDM). Methods: In this post hoc analysis of a cohort study spanning 18 years, 446 patients with twin pregnancy and GDM (246 managed with lifestyle modification and 200 requiring pharmacotherapy) were included. We collected and evaluated maternal characteristics, as well as fasting, 1-h, and 2-h glucose concentrations from a standardized 75-g OGTT. The assessment methods included logistic regression analysis, positive and negative predictive values, area under the curve (AUC), and random forest analysis. Results: The fasting (p < 0.01, OR: 1.03 [95% CI 1.01-1.05]) and 1-h (p < 0.01; OR: 1.01 [95% CI 1.00-1.02]) glucose levels during the OGTT were significantly associated with the subsequent need for insulin therapy, with thresholds of 95 mg/dL for fasting glucose and 184 mg/dL for the 1-h OGTT. Additionally, indications for insulin therapy were marked by thresholds of 108 mg/dL at G0, 215 mg/dL at G60, and 86 mg/dL at G120. Conclusion: Identifying threshold values for insulin therapy and risk stratification in twin pregnancy are crucial for optimal patient management.
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Project description:Although the conventional prevalence of myotonic dystrophy is 1:8,000, the prevalence in Korean population was recently reported as 1:1,245. With higher domestic result than expected, we aimed to investigate the clinical characteristics of pregnancies complicated by congenital myotonic dystrophy in our institution.We have reviewed 11 paired cases of neonates diagnosed with congenital myotonic dystrophy and their mothers between July 2004 and May 2014, with clinical features including maternal history of infertility, prenatal ultrasonographic findings, and neonatal outcomes. Cytosine-thymine-guanine (CTG) repeat expansion in the myotonic dystrophy protein kinase gene of both neonates and their mothers was also examined.None of mother was aware of their myotonic dystrophy traits before pregnancy. History of infertility followed by assisted reproductive technology accounted for 57.1% (4/7). Distinctive prenatal ultrasonographic finding was severe idiopathic polyhydramnios (66.7%, 4/6) with median amniotic fluid index of 43 (range, 37 to 66). In 37.5% (3/8) cases, decreased fetal movement was evident during prenatal ultrasound examination. For neonatal outcomes, more than half (6/11) were complicated with preterm birth and the proportion of 1-minute Apgar score <4 and 5-minute Apgar score <7 was 44.4% (4/9) and 66.7% (6/9), respectively. Most of neonates were admitted to the neonatal intensive care unit (9/10) because of hypotonia with respiratory problems and there was one infant death. Median number of cytosine-thymine-guanine repeats in mothers and neonates was 400 (range, 166 to 1,000) and 1,300 (range, 700 to 2,000), respectively.Our data suggest that severe idiopathic polyhydramnios with decreased fetal movement in pregnant women, especially with a history of infertility, requires differential diagnosis of congenital myotonic dystrophy.
| S-EPMC5547078 | biostudies-other
Project description:This study aims to characterize the intermediates, and the final product (FP) obtained during the production of human intramuscular hyperimmune gamma globulin anti-SARS-CoV-2 (hIHGG anti-SARS-CoV-2) and to determine its stability. Material and methods: hIHGG anti-SARS-CoV-2 was fractionated from 270 convalescent plasma donations with the Cohn method. Prior to fractionation, the plasma was inactivated (Theraflex MB Plasma). Samples were defined using enzyme immunoassays (EIA) for anti-S1, anti-RBD S1, and anti-N antibodies, and neutralization assays with SARS-CoV-2 (VN) and pseudoviruses (PVN, decorated with SARS-CoV-2 S protein). Results were expressed as a titer (EIA) or 50% of the neutralization titer (IC50) estimated in a four-parameter nonlinear regression model. Results: Concentration of anti-S1 antibodies in plasma was similar before and after inactivation. Following fractionation, the anti-S1, anti-RBD, and anti-N (total tests) titers in FP were concentrated approximately 15-fold from 1:4 to 1:63 (1800 BAU/mL), 7-fold from 1:111 to 1:802 and from 1:13 to 1:88, respectively. During production, the IgA (anti-S1) antibody titer was reduced to an undetectable level and the IgM (anti-RBD) titer from 1:115 to 1:24. The neutralizing antibodies (nAb) titer increased in both VN (from 1:40 to 1:160) and PVN (IC50 from 63 to 313). The concentration of specific IgG in the FP did not change significantly for 14 months. Conclusions: The hIHGG anti-SARS-CoV-2 was stable, with concentration up to approximately 15-fold nAb compared to the source plasma pool.
| S-EPMC9227433 | biostudies-literature