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The chr12q24.13 locus encoding OAS1–OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454-A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.

Background We examined the relationship between placental histopathology and transplacental antibody transfer in pregnant patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods Differences in plasma concentrations of anti-receptor biding domain (RBD) immunoglobulin (Ig)G antibodies in maternal and cord blood were analyzed according to presence of placental injury. Results Median anti-RBD IgG concentrations in cord blood with placental injury (n = 7) did not differ significantly from those without injury (n = 16) (median 2.7 [interquartile range {IQR}, 1.8–3.6] vs 2.7 [IQR, 2.4–2.9], P = 0.59). However, they were associated with lower transfer ratios (median 0.77 [IQR, 0.61–0.97] vs 0.97 [IQR, 0.80–1.01], P = 0.05). Conclusions SARS-CoV-2 placental injury may mediate reduced maternal-fetal antibody transfer.

Understanding of the immune response following COVID-19 vaccination in pregnancy is limited by small cohort size and little data on neutralizing antibody.This was a prospective cohort study comprising patients with PCR confirmed SARS-CoV-2 infection and patients who received both doses of mRNA COVID-19 vaccine (mRNA-1273, BNT162b2) in pregnancy recruited from two hospitals in Atlanta, Georgia, USA. Maternal and cord blood at delivery was assayed for anti-Receptor Binding Domain (RBD) -IgG, -IgA and -IgM and neutralizing antibody. The detection of antibodies, titers, and maternal-to-fetal transfer ratios were compared.Nearly all patients had detectable RBD-IgG in maternal and cord samples. The vaccinated vs. infected cohort had a significantly greater proportion of cord samples with detectable neutralizing antibody (94% vs 28%, p 0.0001) and significantly higher transfer ratios for RBD-IgG and neutralizing antibodies with a transfer efficiency of 105% (vs 80%, p 0.0001) and 110% (vs 90%, p 0.0001), respectively. There was a significant linear decline in maternal and cord blood RBD-IgG and neutralizing antibody titers as time from vaccination to delivery increased.Those who receive the mRNA COVID-19 vaccine mount an immune response that is equivalent to - if not greater than- those naturally infected by SARS-CoV-2 during pregnancy.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in pregnancy is associated with robust maternal immune response and neutralizing potency; however, antibody transfer across the placenta is less than expected., OBJECTIVE: To characterize maternal immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and quantify the efficiency of transplacental antibody transfer. METHODS: We conducted a prospective cohort study of pregnant patients who tested positive for SARS CoV-2 infection at any point in pregnancy and collected paired maternal and cord blood samples at the time of delivery. An enzyme-linked immunosorbent assay (ELISA) and neutralization assays were performed to measure maternal plasma and cord blood concentrations and neutralizing potency of immunoglobulin (Ig)G, IgA, and IgM antibodies directed against the SARS-CoV-2 spike protein. Differences in concentrations according to symptomatic compared with asymptomatic infection and time from positive polymerase chain reaction (PCR) test result to delivery were analyzed using nonparametric tests of significance. The ratio of cord to maternal anti–receptor-binding domain IgG titers was analyzed to assess transplacental transfer efficiency. RESULTS: Thirty-two paired samples were analyzed. Detectable anti–receptor-binding domain IgG was detected in 100% (n=32) of maternal and 91% (n=29) of cord blood samples. Functional neutralizing antibody was present in 94% (n=30) of the maternal and 25% (n=8) of cord blood samples. Symptomatic infection was associated with a significant difference in median (interquartile range) maternal anti–receptor-binding domain IgG titers compared with asymptomatic infection (log 3.2 [3.5–2.4] vs log 2.7 [2.9–1.4], P=.03). Median (interquartile range) maternal anti–receptor-binding domain IgG titers were not significantly higher in patients who delivered more than 14 days after a positive PCR test result compared with those who delivered within 14 days (log 3.3 [3.5–2.4] vs log 2.67 [2.8–1.6], P=.05). Median (range) cord/maternal antibody ratio was 0.81 (0.67–0.88). CONCLUSIONS: These results demonstrate robust maternal neutralizing and anti–receptor-binding domain IgG response after SARS-CoV-2 infection, yet a lower-than-expected efficiency of transplacental antibody transfer and a significant reduction in neutralization between maternal blood and cord blood. Maternal infection does confer some degree of neonatal antibody protection, but the robustness and durability of protection require further study.

Congenital transmission is the most important mode of transmission of Chagas disease (CD) in non-endemic countries. Identifying CD in reproductive-aged women is essential to reduce the risk of transmitting the disease to their children and offer treatment to women and their children, which could cure the disease. We evaluated the use of point-of-care (POC) testing for CD in postpartum patients. In our patient population, 16.7% (23/138) tested positive by POC testing, but confirmatory testing was negative for all patients. Among those considered high risk, 30% declined participation. Our results suggest limited utility of the point-of-care test used in our study and identify an opportunity for improvement to broaden diagnostic testing options. Our study also highlights the need to develop strategies to increase subject participation in future research.

Pregnancy is an independent risk factor for severe covid-19. Vaccination is the best way to reduce the risk for SARS-CoV-2 infection and limit its morbidity and mortality. The current recommendations from the World Health Organization, Centers for Disease Control and Prevention, and professional organizations are for pregnant, postpartum, and lactating women to receive covid-19 vaccination. Pregnancy specific considerations involve potential effects of vaccination on fetal development, placental transfer of antibodies, and safety of maternal vaccination. Although pregnancy was an exclusion criterion in initial clinical trials of covid-19 vaccines, observational data have been rapidly accumulating and thus far confirm that the benefits of vaccination outweigh the potential risks. This review examines the evidence supporting the effectiveness, immunogenicity, placental transfer, side effects, and perinatal outcomes of maternal covid-19 vaccination. Additionally, it describes factors associated with vaccine hesitancy in pregnancy. Overall, studies monitoring people who have received covid-19 vaccines during pregnancy have not identified any pregnancy specific safety concerns. Additional information on non-mRNA vaccines, vaccination early in pregnancy, and longer term outcomes in infants are needed. To collect this information, vaccination during pregnancy must be prioritized in vaccine research.

Trichomonas vaginalis (TV) is the most prevalent nonviral sexually transmitted infection globally, but routine screening is not recommended in HIV-negative individuals. There is a significant racial/ethnic health disparity in TV infection rates. Evidence regarding the association between TV and adverse perinatal outcomes is conflicting, but a recent large meta-analysis found a modest increased risk of preterm birth with TV infection (odds ratio, 1.27; 95% confidence interval, 1.08-1.50). The current study was undertaken to evaluate whether TV infection increases the risk of spontaneous preterm birth (sPTB) in a high-risk obstetric cohort in Atlanta, GA.We conducted a retrospective cohort study of women delivering at a safety-net hospital in Atlanta between July 2016 and June 2018. Women delivering a singleton live fetus at20 weeks' gestation were included. The diagnosis of TV was by nucleic acid amplification testing. The outcome of interest was sPTB before 37 weeks' gestation. Multivariable Cox proportional hazards modeling was used to estimate the effect of TV on sPTB, controlling for confounding variables, including clinical and demographic characteristics. Several sensitivity analyses were undertaken.There were 3723 deliveries during the study period, and approximately half (46%) were screened for TV with nucleic acid amplification testing. After exclusions, the analytic cohort included 1629 women. Median age was 26 years (interquartile range, 22-31 years), and 70% of participants were listed as non-Hispanic Black in the electronic medical record. The prevalence of TV was 16% (n = 257). The sPTB rate was 7% (n = 112). In multivariable Cox proportional hazards modeling, TV infection was not associated with a statistically significantly increased risk of sPTB (hazard ratio, 1.34; 95% confidence interval, 0.84-2.13; P = 0.22). Factors associated with sPTB included history of PTB, adequate plus or transfer of prenatal care (vs. adequate/intermediate prenatal care utilization using the Kotelchuck index), recreational substance use, and Chlamydia trachomatis diagnosed during the current pregnancy. Results were not substantively different in sensitivity analyses.The prevalence of TV was high in this cohort. Its infection was not associated with a statistically significantly increased risk of sPTB. Nevertheless, the magnitude of effect is consistent with prior meta-analyses.

We examined the relationship between placental histopathology and transplacental antibody transfer in pregnant patients following SARS-CoV-2 infection. Differences in plasma concentrations of anti-Receptor Biding Domain (RBD) Immunoglobulin (Ig) G antibodies in maternal and cord blood were analyzed according to presence of placental injury. Median [IQR] anti-RBD IgG concentrations in cord blood with placental injury (n = 7) did not differ significantly from those without injury (n= 16) [(2.7 [1.8,3.6] vs 2.7[2.4, 2.9], p= 0.59). However, they were associated with lower transfer ratios (median [IQR] 0.77[0.61, 0.97] vs. 0.97[0.80, 1.01], p = 0.05) suggesting that SARS-CoV-2 placental injury mediates reduced maternal-fetal antibody transfer.

Pregnant patients with SARS-CoV-2 infection are at increased risk for severe disease including hospitalization, intensive care admission, ventilatory support, and death. Although pregnant patients were excluded from investigational trials for pharmacologic treatments for COVID-19 illness, the National Institutes of Health treatment guidelines state that efficacious treatments should not be withheld from pregnant patients. An infusion of casirivimab and imdevimab (REGEN-COV), a monoclonal antibody therapy, was shown to reduce the risk of COVID-19-related hospitalization or death from any cause and resolved symptoms and reduced SARS-CoV-2 viral load more rapidly than placebo. In July of 2021, the Food and Drug Administration released an Emergency Use Authorization for REGEN-COV. Although pregnant persons were not included in the original trials, given the higher risk of morbidity and mortality in the pregnant population, our institution offered REGEN-COV to our pregnant patients beginning in August of 2021. Side effects after REGEN-COV administration are rare and thought to be secondary to COVID-19 rather than REGEN-COV.This study aimed to track safety and clinical outcomes in unvaccinated pregnant patients who received REGEN-COV and to compare these outcomes with those of a contemporary cohort of patients who tested positive for SARS-CoV-2 and were eligible but did not receive REGEN-COV. Our hypothesis was that REGEN-COV administration during pregnancy is safe, and that pregnant persons who received REGEN-COV would experience less severe COVID-19 respiratory illness, with decreased length of hospital stay, rates of intensive care unit admission, and need for oxygen and other COVID-19 therapeutics.This is a retrospective cohort study of pregnant patients who either tested positive for SARS-CoV-2 or had a known exposure to a COVID-19-positive person, and were therefore eligible for REGEN-COV at our institution. Within this cohort, we compared those who received REGEN-COV with those who did not between March and October of 2021 at Grady Memorial Hospital in Atlanta, Georgia. The main outcomes studied were perinatal outcomes, safety data, and the clinical course of SARS-CoV-2 infection.From March to October of 2021, 86 pregnant people tested positive for SARS-CoV-2 via real-time polymerase chain reaction or had a confirmed exposure. In this group, 36 received REGEN-COV and 50 did not. There were no instances of infusion rate adjustment or discontinuation, anaphylaxis, or death among individuals who received REGEN-COV. One individual experienced worsening shortness of breath24 hours after administration, which was classified as an infusion-related reaction. There were no significant differences in perinatal outcomes, length of hospitalization, rates of intensive care unit admission, additional pharmacologic treatment for COVID-19, or oxygen requirement between the 2 groups.Administration of REGEN-COV is safe in pregnancy and did not increase adverse maternal, neonatal, or obstetrical outcomes. There was not a statistically significant difference in COVID-19-related outcomes in our high-risk population. Given the likely safety of this drug in pregnancy and its known benefits in the nonpregnant population, we advocate for the continued use of this therapy and encourage the development of future studies to enroll a larger and more diverse cohort to explore its efficacy further.

BACKGROUND Treating chlamydia and gonorrhea in pregnancy has been shown to decrease the associated risk of preterm birth in some studies. Delayed treatment of these infections among nonpregnant patients carries known consequences. It is unclear whether delayed treatment in pregnancy similarly increases adverse outcomes. METHODS We conducted a retrospective cohort study of women who delivered at a safety-net hospital from July 2016 to June 2018. Women with at least one visit who were tested for chlamydia and gonorrhea were included. Women diagnosed after 36 weeks (preterm analysis) or 31 weeks (early preterm analysis) were excluded. We used multivariable logistic regression to examine the association between no infection, timely treatment ( 1 week, not treated) with preterm (

Objective The natural history of women with a short cervix and a low-risk obstetric history remains poorly defined. In our study, we sought to better characterize the impact of previous obstetric history on the delivery outcomes in women diagnosed with a mid-trimester sonographic short cervix. Study Design We performed a retrospective cohort study of women with singleton gestations who underwent transvaginal cervical length screening between 16 and 24 weeks at two urban hospitals in Philadelphia between January 2013 and March 2018 and were found to have a short cervix (defined as ≤2 cm). Women were excluded from the cohort if there were major fetal anomalies noted or if delivery outcome information was not available. The cohort was then divided into three groups based on obstetric history: nulliparous, history of full-term birth only, or history of spontaneous preterm birth (sPTB). The primary outcome was sPTB Results Our cohort included a total of 384 singleton pregnancies that were diagnosed with a sonographic short cervix: 165 women were nulliparous, 119 women had a history of full-term birth, and 100 women with a history of sPTB. We found that women with a short sonographic cervix had a sPTB rate of 39.6% with no differences found between the three groups. Only two-thirds of nulliparous women and women with a history of full-term birth received the recommended preventative treatment, compared with almost 100% of women with a history of sPTB. Conclusion Women with and without a history of sPTB are at comparable risk of sPTB in the presence of a sonographically short cervix. Preventative therapies should be recommended to both nulliparous women and women with a history of full-term birth since uptake in this population are not as high.

Objective To compare the mean transvaginal ultrasound (TVU) cervical length (CL) at midtrimester screening for spontaneous preterm birth in asymptomatic monochorionic diamniotic versus dichorionic diamniotic twin pregnancies Study design This was a multicenter retrospective cohort study. Study subjects were identified at the time of a routine second trimester fetal ultrasound exam at 18 0/7–23 6/7 weeks gestation. We excluded women that received progesterone, pessary, or cerclage. Distribution of CL was determined and normality was examined. Mean of TVU CL were compared between monochorionic diamniotic and dichorionic diamniotic pregnancies. The relationship of TVU CL with gestational age (GA) at delivery and incidence of spontaneous preterm birth (SPTB) at different TVU CL cut offs were assessed. Incidence of short TVU CL, defined as TVU CL ≤30 mm, was also calculated in the two groups. Results 580 women with diamniotic twin pregnancies underwent TVU CL screening between 18 0/6 and 23 6/7 weeks. 175 (30.2%) were monochorionic diamniotic pregnancies, and 405 (69.8%) were dichorionic pregnancies. The demographic characteristics were similar on both groups. The mean GA at TVU CL was about 20 week in both groups. The mean TVU CL was significantly lower in the monochorionic diamniotic (32.8 ± 10.1) compared to the dichorionic (34.9 ± 8.6) group (MD −2.10 mm, 95% CI −3.91 to −0.29). TVU CL ≤30 mm was 16.6% (29/175) in the monochorionic group, and 11.9% (48/405) in the dichorionic group (aOR 1.48, 95% CI 1.03–2.43). Twins with a monochorionic diamniotic pregnancy had a significantly higher incidence of SPTB (53.1% vs 44.9%; aOR 1.22, 95% CI 1.22–1.79). For any given CL measured between 18 0–7 and 23 6/7 weeks, gestational age at delivery for monochorionic diamniotic pregnancies was about 2 weeks earlier compared to dichorionic pregnancies (MD -2.1 weeks; ANCOVA P Conclusion Monochorionic diamniotic twin pregnancies had a higher rate of spontaneous preterm birth than dichorionic diamniotic pregnancies. The higher rate of spontaneous preterm delivery in monochorionic pregnancies is associated with lower midtrimester TVU CL when compared to dichorionic pregnancies.

Recent human clinical studies have identified Mobiluncus mulieris, a fastidious strict anaerobic bacterium present in the cervicovaginal (CV) space, as being strongly associated with spontaneous preterm birth (sPTB). However, the molecular mechanisms that underlie this association remain unknown. As disruption of the cervical epithelial barrier has been shown to contribute to the premature cervical remodeling that precedes sPTB, we hypothesize that M. mulieris, a microbe strongly associated with sPTB in humans, has the ability to alter cervical epithelial function. We investigated if bacteria-free supernatants of M. mulieris were able to disrupt the cervical epithelial barrier through immunological and epigenetic based mechanisms in an in vitro model system. Ectocervical cells were treated with supernatant from cultured M. mulieris and epithelial cell permeability, immune cytokines and microRNAs (miRNAs) were investigated. M. mulieris supernatant significantly increased cell permeability and the expression of two inflammatory mediators associated with cervical epithelial breakdown, IL-6 and IL-8. Moreover, treatment of the ectocervical cells with the M. mulieris supernatant also increased the expression of miRNAs that have been associated with either sPTB or a shorter gestational length in humans. Collectively, these results suggest that M. mulieris induces molecular and functional changes in the cervical epithelial barrier thought to contribute to the pathogenesis of sPTB, which allows us to hypothesize that targeting CV bacteria such as M. mulieris could provide a therapeutic opportunity to reduce sPTB rates.

Congenital transmission is the most important mode of transmission of Chagas disease (CD) in non-endemic countries. Identifying CD in reproductive-aged women is essential to reduce the risk of transmitting the disease to their children and offer treatment to women and their children, which could cure the disease. We evaluated the use of point-of-care (POC) testing for CD in postpartum patients. In our patient population, 16.7% (23/138) tested positive by POC testing, but confirmatory testing was negative for all patients. Among those considered high risk, 30% declined participation. Our results suggest limited utility of the point-of-care test used in our study and identify an opportunity for improvement to broaden diagnostic testing options. Our study also highlights the need to develop strategies to increase subject participation in future research.

Cranial placodes are ectodermal regions that contribute extensively to the vertebrate peripheral sensory nervous system. The development of the ophthalmic trigeminal (opV) placode, which gives rise only to sensory neurons of the ophthalmic lobe of the trigeminal ganglion, is a useful model of sensory neuron development. While key differentiation processes have been characterized at the tissue and cellular levels, the signaling pathways governing opV placode development have not. Here we tested in chick whether the canonical Wnt signaling pathway regulates opV placode development. By introducing a Wnt reporter into embryonic chick head ectoderm, we show that the canonical pathway is active in Pax3+ opV placode cells as, or shortly after, they are induced to express Pax3. Blocking the canonical Wnt pathway resulted in the failure of targeted cells to adopt or maintain an opV fate, as assayed by the expression of various markers including Pax3, FGFR4, Eya2, and the neuronal differentiation markers Islet1, neurofilament, and NeuN, although, surprisingly, it led to upregulation of Neurogenin2, both in the opV placode and elsewhere in the ectoderm. Activating the canonical Wnt signaling pathway, however, was not sufficient to induce Pax3, the earliest specific marker of the opV placode. We conclude that canonical Wnt signaling is necessary for normal opV placode development, and propose that other molecular cues are required in addition to Wnt signaling to promote cells toward an opV placode fate.

Vertebrate cranial neurogenic placodes are relatively simple model systems for investigating the control of sensory neurogenesis. The ophthalmic trigeminal (opV) placode, for which the earliest specific marker is the paired domain homeodomain transcription factor Pax3, forms cutaneous sensory neurons in the ophthalmic lobe of the trigeminal ganglion. We previously showed that Pax3 expression in avian opV placode cells correlates with specification and commitment to a Pax3+, cutaneous sensory neuron fate. Pax3 can act as a transcriptional activator or repressor, depending on the cellular context. We show using mouse Splotch2H mutants that Pax3 is necessary for the normal neuronal differentiation of opV placode cells. Using an electroporation construct encoding a Pax3–Engrailed fusion protein, which represses Pax3 target genes, we show that activation of Pax3 target genes is required cell-autonomously within chick opV placode cells for expression of the opV placode markers FGFR4 and Ngn2, maintenance of the preplacodal marker Eya2, expression of Pax3 itself (suggesting that Pax3 autoregulates), neuronal differentiation and delamination. Mis-expression of Pax3 in head ectoderm is sufficient to induce FGFR4 and Ngn2 expression, but neurons do not differentiate, suggesting that additional signals are necessary to enable Pax3+ cells to differentiate as neurons. Mis-expression of Pax3 in the Pax2+ otic and epibranchial placodes also downregulates Pax2 and disrupts otic vesicle closure, suggesting that Pax3 is sufficient to alter the identity of these cells. Overall, our results suggest that activation of Pax3 target genes is necessary but not sufficient for neurogenesis in the opV placode.

Vertebrate cranial ectodermal placodes are transient, paired thickenings of embryonic head ectoderm that are crucial for the formation of the peripheral sensory nervous system: they give rise to the paired peripheral sense organs (olfactory organs, inner ears and anamniote lateral line system), as well as the eye lenses, and most cranial sensory neurons. Here, we present the first detailed spatiotemporal fate-maps in any vertebrate for the ophthalmic trigeminal (opV) and maxillomandibular trigeminal (mmV) placodes, which give rise to cutaneous sensory neurons in the ophthalmic and maxillomandibular lobes of the trigeminal ganglion. We used focal DiI and DiO labelling to produce eight detailed fate-maps of chick embryonic head ectoderm over approximately 24 h of development, from 0–16 somites. OpV and mmV placode precursors arise from a partially overlapping territory; indeed, some individual dyespots labelled both opV and mmV placode-derived cells. OpV and mmV placode precursors are initially scattered within a relatively large region of ectoderm adjacent to the neural folds, intermingled both with each other and with future epidermal cells, and with geniculate and otic placode precursors. Although the degree of segregation increases with time, there is no clear border between the opV and mmV placodes even at the 16-somite stage, long after neurogenesis has begun in the opV placode, and when neurogenesis is just beginning in the mmV placode. Finally, we find that occasional cells in the border region between the opV placode and mmV placode express both Pax3 (an opV placode specific marker) and Neurogenin1 (an mmV placode specific marker), suggesting that a few cells are responding to both opV and mmV placode-inducing signals. Overall, our results fill a large gap in our knowledge of the early stages of development of both the opV and mmV placodes, providing an essential framework for subsequent studies of the molecular control of their development.