Detection of SARS-CoV-2 in placental but not fetal tissues in the second trimester.
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ABSTRACT:
SUBMITTER: Valk JE
PROVIDER: S-EPMC7700914 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Detection of SARS-CoV-2 in placental but not fetal tissues in the second trimester.
Valk Jacob E JE Chong Alexander M AM Uhlemann Anne-Catrin AC Debelenko Larisa L
Journal of perinatology : official journal of the California Perinatal Association 20201130 5
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Project description:Few studies have addressed the impact of maternal mild/asymptomatic SARS-CoV-2 infection on the developing neonatal immune system. In this study, we analyzed umbilical cord blood and placental chorionic villi from newborns of unvaccinated mothers with mild/asymptomatic SARSCoV-2 infection during pregnancy using flow cytometry, single-cell transcriptomics, and functional assays. Despite the lack of vertical transmission, levels of inflammatory mediators were altered in cord blood. Maternal infection was also associated with increased memory T, B cells, and non-classical monocytes as well as increased activation. However, ex vivo responses to stimulation were attenuated. Finally, within the placental villi, we report an expansion of fetal Hofbauer cells and infiltrating maternal macrophages and rewiring towards a heightened inflammatory state. In contrast to cord blood monocytes, placental myeloid cells were primed for heightened antiviral responses. Taken together, this study highlights dysregulated fetal immune cell responses in response to mild maternal SARS-CoV-2 infection during pregnancy.
| S-EPMC10197637 | biostudies-literature
Project description:IntroductionWe demonstrate the nonlinear severity of symptoms of SARS-CoV-2 infection in the mother leading to fetal death after acute placental failure.MethodsCareful clinical evaluation, real-time RT-PCR molecular microbiologic testing, isolation of a viable virus, and autopsy with histologic results were used to investigate the possible vertical transmission of SARS-CoV-2 infection from mother to fetus.ResultsHistologic changes in the placenta correlate with SARS-CoV-2 infection. Total nucleic acid isolated from vaginal swabs, fresh placental tissue, and deparaffinized tissue showed a high viral load of SARS-CoV-2. Complete genome sequencing confirmed the presence of the SARS-CoV-2 Delta variant.DiscussionSeveral methods have been used to confirm SARS-CoV-2-mediated acute placental failure, all of which were conclusive. It should be noted that careful periodic fetal well-being checks are required in women infected with SARS-CoV-2, regardless of the severity of symptoms. Most of the cases described with fetal death occurred in the third trimester.
| S-EPMC10191722 | biostudies-literature
Project description:ObjectiveWe hypothesized that the origins of abruption may extend to the stages of placental implantation; however, there are no reliable markers to predict its development. Based on this hypothesis, we sought to evaluate whether first-trimester and second-trimester serum analytes predict placental abruption.MethodsWe performed a secondary analysis of data of 35,307 women (250 abruption cases) enrolled in the First and Second Trimester Evaluation of Risk cohort (1999-2003), a multicenter, prospective cohort study. Percentiles (based on multiples of the median) of first-trimester (pregnancy-associated plasma protein A and total and free β-hCG) and second-trimester (maternal serum alpha-fetoprotein, unconjugated estriol, and inhibin-A) serum analytes were examined in relation to abruption. Associations are based on risk ratio (RR) and 95% confidence interval (CI).ResultsWomen with an abnormally low pregnancy-associated plasma protein A (fifth percentile or less) were at increased risk of abruption compared with those without abruption (9.6% compared with 5.3%; RR 1.9, 95% CI, 1.2-2.8). Maternal serum alpha-fetoprotein 95th percentile or greater was more common among abruption (9.6%) than nonabruption (5.1%) pregnancies (RR 1.9, 95% CI 1.3-3.0). Inhibin-A fifth percentile or less (8.0% compared with 5.1%; RR 1.8, 95% CI 1.1-2.9), and 95th percentile or greater (9.6% compared with 5.0%; RR 2.0, 95% CI 1.3-3.1) were associated with abruption. Women with all three abnormal pregnancy-associated plasma protein A, maternal serum alpha-fetoprotein, and inhibin-A analytes were at 8.8-fold (95% CI 2.3-34.3) risk of abruption. No associations were seen with other analytes.ConclusionThese data provide support for our hypothesis that the origins of placental abruption may extend to the early stages of pregnancy.
| S-EPMC5367463 | biostudies-literature
Project description:BackgroundSARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes, including fetal death and preterm birth. It is not known whether that risk occurs only during the time of acute infection or whether the risk persists later in pregnancy.ObjectiveThis study aimed to evaluate whether the risk of SARS-CoV-2 infection during pregnancy persists after an acute maternal illness.Study designA retrospective cohort study of pregnant patients with and without SARS-CoV-2 infection delivering at 17 hospitals in the United States between March 2020 and December 2020. Patients experiencing a SARS-CoV-2-positive test at or before 28 weeks of gestation with a subsequent delivery hospitalization were compared with those without a positive SAR-CoV-2 test at the same hospitals with randomly selected delivery days during the same period. Deliveries occurring at <20 weeks of gestation in both groups were excluded. The study outcomes included fetal or neonatal death, preterm birth at <37 weeks of gestation and <34 weeks of gestation, hypertensive disorders of pregnancy (HDP), any major congenital malformation, and size for gestational age of <5th or <10th percentiles at birth based on published standards. HDP that were collected included HDP and preeclampsia with severe features, both overall and with delivery at <37 weeks of gestation.ResultsOf 2326 patients who tested positive for SARS-CoV-2 during pregnancy and were at least 20 weeks of gestation at delivery from March 2020 to December 2020, 402 patients (delivering 414 fetuses or neonates) were SARS-CoV-2 positive before 28 weeks of gestation and before their admission for delivery; they were compared with 11,705 patients without a positive SARS-CoV-2 test. In adjusted analyses, those with SARS-CoV-2 before 28 weeks of gestation had a subsequent increased risk of fetal or neonatal death (2.9% vs 1.5%; adjusted relative risk, 1.97; 95% confidence interval, 1.01-3.85), preterm birth at <37 weeks of gestation (19.6% vs 13.8%; adjusted relative risk, 1.29; 95% confidence interval, 1.02-1.63), and HDP with delivery at <37 weeks of gestation (7.2% vs 4.1%; adjusted relative risk, 1.74; 95% confidence interval, 1.19-2.55). There was no difference in the rates of preterm birth at <34 weeks of gestation, any major congenital malformation, and size for gestational age of <5th or <10th percentiles. In addition, there was no significant difference in the rate of gestational hypertension overall or preeclampsia with severe features.ConclusionThere was a modest increase in the risk of adverse pregnancy outcomes after SARS-CoV-2 infection.
| S-EPMC9374493 | biostudies-literature
Project description:To date, mother-to-fetus transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, remains controversial. Although placental COVID-19 infection has been documented in some cases during the second- and third-trimesters, no reports are available for the first trimester of pregnancy, and no SARS-CoV-2 protein has been found in fetal tissues. We studied the placenta and fetal organs from an early pregnancy miscarriage in a COVID-19 maternal infection by immunohistochemical, reverse transcription quantitative real-time polymerase chain reaction, immunofluorescence, and electron microscopy methods. SARS-CoV-2 nucleocapsid protein, viral RNA, and particles consistent with coronavirus were found in the placenta and fetal tissues, accompanied by RNA replication revealed by double-stranded RNA (dsRNA) positive immunostain. Prominent damage of the placenta and fetal organs were associated with a hyperinflammatory process identified by histological examination and immunohistochemistry. The findings provided in this study document that congenital SARS-CoV-2 infection is possible during the first trimester of pregnancy and that fetal organs, such as lung and kidney, are targets for coronavirus. The infection and multi-organic fetal inflammation produced by SARS-CoV-2 during early pregnancy should alert clinicians in the assessment and management of pregnant women for possible fetal consequences and adverse perinatal outcomes.
| S-EPMC8250563 | biostudies-literature
Project description:ObjectiveThe aim of the study was to evaluate the diagnostic potential of placental shear wave elastography in predicting preeclampsia at 16 to 20 weeks of gestation.Materials and methodsA total of 230 pregnant women between 16 and 20 weeks of gestation were observed for the study. These women underwent shear wave elastography ElastPQ (Philips Healthcare, Bothell, Washington, USA) of the placenta. The mean value of placental shear modulus was obtained for each participant. These participants were followed up for the development of preeclampsia and were divided into two groups; group A included those who developed preeclampsia and group B included those who remained normotensive until delivery. The elasticity values of the two groups were compared, and the ROC curve was drawn to obtain the best cut-off value that would predict the onset of preeclampsia.ResultsPlacental shear modulus varied from 1.03 kPa to 7.4 kPa at 16 to 20 weeks of gestation with an average of 2.74 ± 0.87 kPa. There was a statistically significant difference in the mean value of elasticity between two groups, being 4.61 kPa in group A and 2.51 kPa in group B. Maximum diagnostic accuracy was obtained at 2.9667 kPa with area under the curve 0.970, sensitivity 92%, specificity 91.71%, positive predictive value 57.5% and negative predictive value 98.9%.ConclusionStiffness of placenta, quantitatively measured by SWE at 16 to 20 weeks of gestation, is higher in the women who develop preeclampsia and hence may be used for predicting preeclampsia.
| S-EPMC9354178 | biostudies-literature
Project description:The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS-CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case.
| S-EPMC7999228 | biostudies-literature
Project description:Ex vivo studies with first trimester placental tissues are crucial for understanding human placental development, and culturing placental villi in floating conditions is vital to mimic the natural setting. Moreover, being able to cryopreserve these scarce materials for ex vivo studies would open unprecedented avenues, as they are very limited to research and the need to culture freshly adds further hurdles while limiting efficient use. Here we showed that hanging drop method is a simple yet effective approach to culture placental floating villi. We also revealed that these functional units of the early-stage human placenta can be cryopreserved for culturing, and that frozen-thawed villi can regenerate the syncytial layer following denudation. We further illustrated the utility of frozen-thawed tissues to study syncytialization, while validating the importance of HtrA4 in the process which was shown previously in cell models. These represent significant new knowledge to the field of placental biology.
| S-EPMC11810994 | biostudies-literature
Project description:ObjectiveTo estimate the risk of adverse perinatal outcomes among women with isolated fetal growth restriction from 17 to 22 weeks of gestation.MethodsThis was a retrospective cohort study of all singleton, nonanomalous pregnancies undergoing ultrasonography to assess fetal anatomy between 17 and 22 weeks of gestation at a single center from 2010 to 2014. After excluding patients with fetal structural malformations, chromosomal abnormalities, or identified infectious etiologies, we compared perinatal outcomes between pregnancies with and without fetal growth restriction, defined as estimated fetal weight less than the 10th percentile for gestational age. Our primary outcome was small for gestational age (SGA) at birth, defined as birth weight less than the 10th percentile. Secondary outcomes included preterm delivery at less than 37 and less than 28 weeks of gestation, preeclampsia, abruption, stillbirth, neonatal death, neonatal intensive care unit admission, intraventricular hemorrhage, need for respiratory support, and necrotizing enterocolitis.ResultsOf 12,783 eligible patients, 355 (2.8%) had early second-trimester fetal growth restriction. Risk factors for growth restriction were African American race and tobacco use. Early second-trimester growth restriction was associated with a more than fivefold increase in risk of SGA at birth (36.9% compared with 9.1%, adjusted odds ratio [OR] 5.5, 95% CI 4.3-7.0), stillbirth (2.5% compared with 0.4%, OR 6.2, 95% CI 2.7-12.8), and neonatal death (1.4% compared with 0.3%, OR 5.2, 95% CI 1.6-13.5). Rates of indicated preterm birth at less than 37 weeks of gestation (7.3% compared with 3.3%, OR 2.3, 95% CI 1.5-3.5) and less than 28 weeks of gestation (2.5% compared with 0.2%, OR 10.8, 95% CI 4.5-23.4), neonatal need for respiratory support (16.9% compared with 7.8%, adjusted OR 1.6, 95% CI 1.1-2.2), and necrotizing enterocolitis (1.4% compared with 0.2%, OR 7.7, 95% CI 2.3-20.9) were also significantly higher for those with growth restriction. Rates of preeclampsia, abruption, and other neonatal outcomes were not significantly different.ConclusionAlthough fetal growth restriction in the early second trimester occurred in less than 3% of our cohort and most of those with isolated growth restriction did not have adverse outcomes, it is a strong risk factor for SGA, stillbirth, neonatal death, and indicated preterm birth.
| S-EPMC5659275 | biostudies-literature
Project description:Epigenetic mechanisms such as genomic imprinting have a fundamental role in embryo and fetal development. Hence, we here studied expression levels of epigenetic modifiers and imprinted genes in cases of ididopathic spontaneous abortion (SA). Thirty-five placental samples and 35 matched fetal tissues from second trimester SA were analysed; including 16 controls (placental and fetal infections as the known cause of spontaneous abortion) and 19 idiopathic SA cases. Transcript levels of epigenetic regulators and imprinted genes were measured by qRT-PCR and methylation at imprinted genes was studied by bisulfite genomic sequencing and MS-MLPA. Global DNA hydroxymethylation (5-hmC) levels were measured by an ELISA-based assay. We observed an upregulation of TET2 and TET3 in placental samples from idiopathic SA cases; however, no significant difference in global 5-hmC levels was observed. On the contrary, in fetal tissues, TET3 was markedly downregulated in idiopathic SA, showing an opposite trend to that observed in placental tissue. IGF2 and CDKN1C were upregulated and MEST downregulated in placentas from idiopathic SA cases; concordantly, IGF2 was also upregulated in fetal tissues from idiopathic SA cases. Although not reaching statistical significance, an increase in methylation levels of MEST, KvDMR1 and H19 DMRs was observed in idiopathic SA cases, concordantly with the observed changes in expression. Our study reveals, for the first time, deregulation of epigenetic modifiers and imprinted genes in both placental and fetal tissues from idiopathic SA cases in the second trimester of pregnancy, indicating a critical role during pregnancy.
| S-EPMC6791697 | biostudies-literature