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
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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: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: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: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:BackgroundThe aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients.MethodsPatients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies.ResultsSevere COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher's exact test).ConclusionsAntisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.
| S-EPMC9384649 | biostudies-literature
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:Placental insufficiency leading to intrauterine growth restriction demonstrates perturbed gene expression affecting placental angiogenesis and nutrient transfer from mother to fetus. To understand the post-transcriptional mechanisms underlying such placental gene expression changes, our objective was to identify key non-coding microRNAs that express biological function. To this end, we undertook microarray targeting microRNAs in placentas of appropriate (AGA, n=3) versus small for gestational age (SGA, n=3) weight infants and observed upregulation of 97 miRs in SGA versus AGA. In a larger cohort of samples, we validated by qRT-PCR, differential expression of three specific microRNAs that target genes mediating angiogenesis and nutrient transfer. We performed microarray on a small cohort of samples in order to identify differential expression in pathways involved with angiogenesis and nutrient transfer, essential processes for placental function that when perturbed, may result in intrauterine growth restriction.
2017-01-06 | GSE93174 | GEO
Project description:IntroductionCyclophilin A was reported to be increased in the serum of mothers with preeclampsia, and is implicated in its pathogenesis. This study aimed to determine the expression of cyclophilin A in the placenta of mothers with and without hypertension, and to correlate its expression with maternal complications and adverse perinatal outcomes.Materials and methodsThis study consisted of a total of 70 cases (35 cases of mothers with hypertension, and 35 normotensive mothers as a control). Cyclophilin A immunohistochemistry was performed on a paraffin-embedded tissue section of placenta submitted at full thickness in order to evaluate the expression in fetal endothelial cells, cytotrophoblasts, syncytiotrophoblasts, maternal endothelial cells and decidual cells. The cyclophilin A expression was scored as weak, moderate or strong intensity.ResultsThe hypertensive group was more likely to have preterm deliveries (p < 0.0001), caesarean sections (p < 0.0001), and infants admitted to the intensive care unit (p < 0.001). Fifty-one percent of the fetal endothelial cells and cytotrophoblasts expressed cyclophilin A in the hypertensive group, compared to only 28.6% in the normotensive group. However, the difference was not statistically significant (p = 0.086).ConclusionWe found no significant difference in placental cyclophilin A expression between hypertensive and normotensive mothers. There was also no difference in expression in mothers with and without maternal complications and adverse perinatal outcomes.
| S-EPMC9101619 | biostudies-literature
Project description:Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55-13.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection.
| S-EPMC11359551 | biostudies-literature
Project description:BackgroundMaternal obesity complicates a high number of pregnancies. The degree to which neonatal outcomes are adversely affected is unclear.ObjectiveThis study aimed to evaluate neonatal outcomes of pregnancies complicated by maternal obesity.Study designThis study was a secondary analysis of a cohort of deliveries occurring on randomly selected days at 25 hospitals from 2008 to 2011. Data were collected by certified abstractors. This analysis included singleton deliveries between 24 and 42 weeks of gestation. Body mass index was calculated on the basis of maternal height and most recent weight before delivery. Normal and overweight (reference group; body mass index, 18.5-29.9 kg/m2), obese (body mass index, 30.0-39.9 kg/m2), morbidly obese (body mass index, 40.0-49.9 kg/m2), and super morbidly obese (body mass index, ≥50 kg/m2) patients were compared. Patients in the reference group were matched in a 1:1 ratio with those in all other groups with obesity using the baseline characteristics of age, race and ethnicity, previous cesarean delivery, preexisting diabetes mellitus, chronic hypertension, parity, cigarette use, and insurance status. The primary outcome was composite neonatal morbidity, including fetal or neonatal death, hypoxic-ischemic encephalopathy, respiratory distress syndrome, intraventricular hemorrhage grade 3 or 4, necrotizing enterocolitis, sepsis, birth injury, seizures, or ventilator use. We used a modified Poisson regression to examine the associations between body mass index and composite neonatal outcome. Preterm delivery at <37 weeks of gestation and the presence of maternal preeclampsia or eclampsia were included in the final model because of their known associations with neonatal outcomes.ResultsOverall, 52,162 patients and their neonates were included after propensity score matching. Of these, 21,704 (41.6%) were obese, 3787 (7.3%) were morbidly obese, and 590 (1.1%) were super morbidly obese. A total of 2103 neonates (4.0%) had the composite outcome. Neonates born to pregnant people with morbid obesity had a 33% increased risk of composite neonatal morbidity compared with those in the reference group (adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.52), but no significant association was observed for persons with obesity (adjusted odds ratio, 1.05; 95% confidence interval, 0.97-1.14) or with super morbid obesity (adjusted odds ratio, 1.18; 95% confidence interval, 0.86-1.64).ConclusionCompared with the reference group, gravidas with morbid obesity were at higher risk of composite neonatal morbidity.
| S-EPMC10065915 | biostudies-literature